Patent Publication Number: US-9896446-B2

Title: Azaquinazoline inhibitors of atypical protein kinase C

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation application and claims the benefit under 35 U.S.C. §120 of the priority date of U.S. application Ser. No. 14/038,915, filed Sep. 27, 2013, which claims the benefit under 35 U.S.C. §119(e) of the priority date of U.S. Provisional Application Nos. 61/707,340, filed Sep. 28, 2012 and 61/781,364, filed Mar. 14, 2013, the disclosures of each of which are incorporated herein by reference in their entireties. 
    
    
     BACKGROUND 
     PKCι and PKCζ (accession numbers NM_002740 and NM_002744 respectively) together define the atypical sub-class of the protein kinase C (PKC) family. The aPKCs are structurally and functionally distinct from the other PKC sub-classes, classic/conventional and novel, as their catalytic activity is not dependent on diacylglycerol and calcium (Ono, Y., Fujii, T., Ogita, K., Kikkawa, U., Igarashi, K., and Nishizuka, Y. (1989). Protein kinase C zeta subspecies from rat brain: its structure, expression, and properties. Proc Natl Acad Sci USA 86, 3099-3103). Structurally, PKCι and PKCζ contain a C-terminal serine/threonine kinase domain (AGC class) and an N-terminal regulatory region containing a Phox Bem 1 (PB 1) domain involved in mediating protein:protein interactions critical for aPKC function. At the amino acid level the aPKCs share 72% overall homology, however, the kinase domains share 84% identity and differ in the active site by just a single amino acid. This striking homology suggests an ATP-competitive ligand would not be expected to exhibit significant aPKC isoform selectivity. 
     The aPKCs have been implicated in a diverse number of signalling pathways, demonstrating both redundant and distinct signalling functions. Both isoforms have emerged as central players in the mechanisms that regulate the establishment and maintenance of cellular polarity in multiple cell types (reviewed in Suzuki, A., and Ohno, S. (2006). The PAR-aPKC system: lessons in polarity. J Cell Sci 119, 979-987). Genetic dissection of their functions using knockout mice have also revealed preferential roles for PKCζ in the regulation of NF-kB signalling (Leitges, M., Sanz, L., Martin, P., Duran, A., Braun, U., Garcia, J. F., Camacho, F., Diaz-Meco, M. T., Rennert, P. D., and Moscat, J. (2001). Targeted disruption of the zetaPKC gene results in the impairment of the NF-kappaB pathway. Mol Cell 8, 771-780), and PKCι in insulin secretion and action (Farese, R. V., Sajan, M. P., Yang, H., Li, P., Mastorides, S., Gower, W. R., Jr., Nimal, S., Choi, C. S., Kim, S., Shulman, G. I., et al. (2007). Muscle-specific knockout of PKC-lambda impairs glucose transport and induces metabolic and diabetic syndromes. J Clin Invest 117, 2289-2301). In addition, both isoforms have been implicated in the pathogenesis of cancer making a strong case for the inhibition of the aPKCs as a novel therapeutic avenue. 
     PKCι is a known oncogene in non-small cell lung cancer (NSCLC). In one study it was shown to be overexpressed in 69% of NSCLC cases at the protein level. Consistent with this, the PKCι gene (PRKCI residing on chromosome 3q26) was shown to be amplified in 36.5% of NSCLC tumours examined, including 96% of the squamous cell carcinoma sub-type (Regala, R. P., Weems, C., Jamieson, L., Khoor, A., Edell, E. S., Lohse, C. M., and Fields, A. P. (2005b). Atypical protein kinase C iota is an oncogene in human non-small cell lung cancer. Cancer Res 65, 8905-8911). Amplification of 3q26 has also been reported in 44% of ovarian cancers, including &gt;70% of serous epithelial ovarian cancers where 3q26 amplification is translated into increased PKCι protein expression. Moreover, increased PKCι expression is associated with poor prognosis in NSCLC and ovarian cancer where it may serve as a diagnostic biomarker of aggressive disease (Eder, A. M., Sui, X., Rosen, D. G., Nolden, L. K., Cheng, K. W., Lahad, J. P., Kango-Singh, M., Lu, K. H., Warneke, C. L., Atkinson, E. N., et al. (2005). Atypical PKCiota contributes to poor prognosis through loss of apical-basal polarity and cyclin E overexpression in ovarian cancer. Proc Natl Acad Sci USA 102, 12519-12524; Zhang, L., Huang, J., Yang, N., Liang, S., Barchetti, A., Giannakakis, A., Cadungog, M. G., O&#39;Brien-Jenkins, A., Massobrio, M., Roby, K. F., et al. (2006). Integrative genomic analysis of protein kinase C (PKC) family identifies PKCiota as a biomarker and potential oncogene in ovarian carcinoma. Cancer Res 66, 4627-4635). 3q26 amplifications have been observed in many other cancers including oesophageal squamous cell carcinoma (Yang, Y. L., Chu, J. Y., Luo, M. L., Wu, Y. P., Zhang, Y., Feng, Y. B., Shi, Z. Z., Xu, X., Han, Y. L., Cai, Y., et al. (2008). Amplification of PRKCI, located in 3q26, is associated with lymph node metastasis in esophageal squamous cell carcinoma. Genes Chromosomes Cancer 47, 127-136) and breast cancer (Kojima, Y., Akimoto, K., Nagashima, Y., Ishiguro, H., Shirai, S., Chishima, T., Ichikawa, Y., Ishikawa, T., Sasaki, T., Kubota, Y., et al. (2008). The overexpression and altered localization of the atypical protein kinase C lambda/iota in breast cancer correlates with the pathologic type of these tumors. Hum Pathol 39, 824-831) suggesting that PKCι may also participate in the pathogenesis of these diseases. 
     In NSCLC the primary function of PKCι is to drive transformed growth via a Rac1/PAK/MEK/ERK signalling axis. However, PKCι also functions in NSCLC survival, resistance to chemotherapy, and invasion via distinct pathways (reviewed in Fields, A. P., and Regala, R. P. (2007). Protein kinase C iota: human oncogene, prognostic marker and therapeutic target. Pharmacol Res 55, 487-497). In ovarian cancer transformed growth is correlated with deregulated epithelial cell polarity and increased cycle E expression (Eder et al., 2005) suggesting that PKCι can influence the cancer phenotype through multiple mechanisms. Compelling evidence has emerged to suggest that inhibition of PKCι may be a useful therapeutic approach to combat tumours characterised by increased PKCι expression. In transgenic models, mice with elevated PKCι activity in the colon are more susceptible to carcinogen-induced colon carcinogenesis, and expression of a kinase-dead mutant of PKCι blocks the transformation of intestinal cells by oncogenic Ras (Murray, N. R., Jamieson, L., Yu, W., Zhang, J., Gokmen-Polar, Y., Sier, D., Anastasiadis, P., Gatalica, Z., Thompson, E. A., and Fields, A. P. (2004). Protein kinase Ciota is required for Ras transformation and colon carcinogenesis in vivo. J Cell Biol 164, 797-802). Finally, genetic or pharmacological inhibition of PKCι by a gold derivative—aurothiomalate (ATM)—blocks the growth of NSCLC cells in soft agar and significantly decreases tumour volume in xenograft models of NSCLC(Regala, R. P., Thompson, E. A., and Fields, A. P. (2008). Atypical protein kinase C iota expression and aurothiomalate sensitivity in human lung cancer cells. Cancer Res 68, 5888-5895; Regala, R. P., Weems, C., Jamieson, L., Copland, J. A., Thompson, E. A., and Fields, A. P. (2005a). Atypical protein kinase Ciota plays a critical role in human lung cancer cell growth and tumorigenicity. J Biol Chem 280, 31109-31115). 
     Despite the high degree of similarity between aPKC isoforms, the role of PKCζ in cancer is distinct from that of PKCι. PKCζ plays a role in NSCLC cell survival by phosphorylating and antagonising the pro-apoptotic effects of Bax in response to nicotine (Xin, M., Gao, F., May, W. S., Flagg, T., and Deng, X. (2007). Protein kinase Czeta abrogates the proapoptotic function of Bax through phosphorylation. J Biol Chem 282, 21268-21277). PKCζ activity has also been linked to resistance against a wide range of cytotoxic and genotoxic agents. For instance, in human leukaemia cells, overexpression of PKCζ confers resistance against 1-β-D-arabinofuranosylcytosine (ara-C), daunorubicin, etoposide, and mitoxantrone-induced apoptosis (Filomenko, R., Poirson-Bichat, F., Billerey, C., Belon, J. P., Garrido, C., Solary, E., and Bettaieb, A. (2002). Atypical protein kinase C zeta as a target for chemosensitization of tumor cells. Cancer Res 62, 1815-1821; Plo, I., Hernandez, H., Kohlhagen, G., Lautier, D., Pommier, Y., and Laurent, G. (2002). Overexpression of the atypical protein kinase C zeta reduces topoisomerase II catalytic activity, cleavable complexes formation, and drug-induced cytotoxicity in monocytic U937 leukemia cells. J Biol Chem 277, 31407-31415). Furthermore, inhibition of PKCζ activity through expression of a kinase-dead mutant sensitises leukaemia cells to the cytotoxic effects of etoposide both in vitro and in vivo (Filomenko et al., 2002). Atypical protein kinase C regulates dual pathways for degradation of the oncogenic coactivator SRC-3/AIB1. Mol Cell 29, 465-476), and both of these proteins have been postulated to play a role in tamoxifen resistance in breast cancer (Iorns, E., Lord, C. J., and Ashworth, A. (2009). Parallel RNAi and compound screens identify the PDK1 pathway as a target for tamoxifen sensitization. Biochem J 417, 361-370; Osborne, C. K., Bardou, V., Hopp, T. A., Chamness, G. C., Hilsenbeck, S. G., Fuqua, S. A., Wong, J., Allred, D. C., Clark, G. M., and Schiff, R. (2003). Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer. J Natl Cancer Inst 95, 353-361). Together these studies suggest that inhibition of PKCζ activity may have beneficial therapeutic effects by acting as a chemosensitiser to a wide array of commonly used chemotoxic agents in the clinic. 
     Further evidence that small molecule inhibition of PKCζ could have important therapeutic benefits has recently emerged from tumour models that link PKCζ signalling to the mTOR pathway. PKCζ is constitutively activated in follicular lymphoma and has been identified as a novel target for the anti-CD20 therapeutic antibody rituximab (Leseux, L., Laurent, G., Laurent, C., Rigo, M., Blanc, A., Olive, D., and Bezombes, C. (2008). PKC zeta mTOR pathway: a new target for rituximab therapy in follicular lymphoma. Blood 111, 285-291). Rituximab inhibits follicular lymphoma proliferation by targeting a PKCζ-MAPK-mTOR pathway, suggesting that PKCζ is both a target of Rituximab, and a key regulator of its&#39; anti-leukaemic effect. Regulation of the mTOR/p70S6K pathway by PKCζ has also been implicated in the transition of prostate cancer cells to an androgen-independent state (Inoue, T., Yoshida, T., Shimizu, Y., Kobayashi, T., Yamasaki, T., Toda, Y., Segawa, T., Kamoto, T., Nakamura, E., and Ogawa, O. (2006). Requirement of androgen-dependent activation of protein kinase Czeta for androgen-dependent cell proliferation in LNCaP Cells and its roles in transition to androgen-independent cells. Mol Endocrinol 20, 3053-3069). Finally, mice containing a homozygous deletion of Par4, a negative regulator of PKCζ, exhibit greatly enhanced PKCζ activity. These mice spontaneously develop tumours of the prostate and endometrium, and potentiate Ras-induced lung carcinogenesis consistent with a role for PKCζ in lung cancer (Garcia-Cao, I., Duran, A., Collado, M., Carrascosa, M. J., Martin-Caballero, J., Flores, J. M., Diaz-Meco, M. T., Moscat, J., and Serrano, M. (2005). Tumour-suppression activity of the proapoptotic regulator Par4. EMBO Rep 6, 577-583; Joshi, J., Fernandez-Marcos, P. J., Galvez, A., Amanchy, R., Linares, J. F., Duran, A., Pathrose, P., Leitges, M., Canamero, M., Collado, M., et al. (2008). Par-4 inhibits Akt and suppresses Ras-induced lung tumorigenesis. EMBO J 27, 2181-2193). 
     SUMMARY 
     The application provides a compound of formula (I) 
                         
or a salt thereof, wherein R 7 , R 8 , R 9 , G, and X are as defined herein.
 
     A compound of formula (I) and its salts have aPKC inhibitory activity, and may be used to treat aPKC-dependent disorders or conditions. 
     The present application further provides a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof together with at least one pharmaceutically acceptable carrier, diluent, or excipient therefor. 
     In another aspect, the present application provides a method of treating a subject suffering from an aPKC-dependent disorder or condition comprising: administering to the subject a compound of formula (I) or a pharmaceutically acceptable salt thereof. 
     The present application further provides a method of treating a proliferative disorder in a subject, comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. 
    
    
     DETAILED DESCRIPTION 
     I. Definitions 
     
         
         “About” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass reasonable variations of the value, such as, for example, ±10% from the specified value. For example, the phrase “about 50” encompasses reasonable variations of 50, such as ±10% of the numerical value 50, or from 45 to 55. 
         “Alkyl” or “alkyl group” refers to a monoradical of a branched or unbranched saturated hydrocarbon chain. Examples include, but are not limited to, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, isopropyl, tert-butyl, isobutyl, etc. Alkyl groups typically contain 1-10 carbon atoms, such as 1-6 carbon atoms or 1-4 carbon atoms, and can be substituted or unsubstituted. 
         “Alkylene” or “alkylene group” refers to a diradical of a branched or unbranched saturated hydrocarbon chain. Examples include, but are not limited to, methylene (—CH 2 —), the ethylene isomers (—CH(CH 3 )— and —CH 2 CH 2 —), the propylene isomers (—CH(CH 3 )CH 2 —, —CH(CH 2 CH 3 )—, —C(CH 3 ) 2 —, and —CH 2 CH 2 CH 2 —), etc. Alkylene groups typically contain 1-10 carbon atoms, such as 1-6 carbon atoms, and can be substituted or unsubstituted. 
         “Alkenyl” or “alkenyl group” refers to a monoradical of a branched or unbranched hydrocarbon chain containing at least one double bond. Examples include, but are not limited to, ethenyl, 3-buten-1-yl, 2-ethenylbutyl, and 3-hexen-1-yl. Alkenyl groups typically contain 2-10 carbon atoms, such as 2-6 carbon atoms or 2-4 carbon atoms, and can be substituted or unsubstituted. 
         “Alkynyl” or “alkynyl group” refers to a monoradical of a branched or unbranched hydrocarbon chain containing at least one triple bond. Examples include, but are not limited to, ethynyl, 3-butyn-1-yl, propynyl, 2-butyn-1-yl, and 3-pentyn-1-yl. Alkynyl groups typically contain 2-10 carbon atoms, such as 2-6 carbon atoms or 2-4 carbon atoms, and can be substituted or unsubstituted. 
         “Aryl” or “aryl group” refers to phenyl and 7-15 membered monoradical bicyclic or tricyclic hydrocarbon ring systems, including bridged, spiro, and/or fused ring systems, in which at least one of the rings is aromatic. Aryl groups can be substituted or unsubstituted. Examples include, but are not limited to, naphthyl, indanyl, 1,2,3,4-tetrahydronaphthalenyl, 6,7,8,9-tetrahydro-5H-benzocycloheptenyl, and 6,7,8,9-tetrahydro-5H-benzocycloheptenyl. An aryl group may contain 6 (i.e., phenyl) or 9 to 15 ring atoms, such as 6 (i.e., phenyl) or 9-11 ring atoms, e.g., 6 (i.e., phenyl), 9 or 10 ring atoms. 
         “Arylene” or “arylene group” refers to a phenylene (—C 6 H 4 —) or a 7-15 membered diradical bicyclic or tricyclic hydrocarbon ring systems, including bridged, spiro, and/or fused ring systems, in which at least one of the rings is aromatic. Arylene groups can be substituted or unsubstituted. For example, an arylene group may contain 6 (i.e., phenylene) or 9 to 15 ring atoms; such as 6 (i.e., phenylene) or 9-11 ring atoms; e.g., 6 (i.e., phenylene), 9 or 10 ring atoms. An arylene group can also include ring systems substituted on ring carbons with one or more —OH functional groups (which may further tautomerize to give a ring C═O group). 
         “Arylalkyl” or “arylalkyl group” refers to an alkyl group in which a hydrogen atom is replaced by an aryl group, wherein alkyl group and aryl group are as previously defined (i.e., arylalkyl-). Arylalkyl groups can be substituted or unsubstituted. Examples include, but are not limited to, benzyl (C 6 H 5 CH 2 —). 
         “Cycloalkyl” or “cycloalkyl group” refers to a monoradical non-aromatic carbocyclic ring system, which may be saturated or unsaturated, substituted or unsubstituted, and may be monocyclic, bicyclic, or tricyclic, and may be bridged, spiro, and/or fused. Examples include, but are not limited to, cyclopropyl, cyclopropenyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, norbornyl, norbornenyl, bicyclo[2.2.1]hexane, bicyclo[2.2.1]heptane, bicyclo[2.2.1]heptene, bicyclo[3.1.1]heptane, bicyclo[3.2.1]octane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, bicyclo[3.3.1]nonane, and bicyclo[3.3.2]decane. The cycloalkyl group may contain from 3 to 10 ring atoms, such as 3 to 7 ring atoms (e.g., 3 ring atoms, 5 ring atoms, 6 ring atoms, or 7 ring atoms). 
         “Cycloalkylalkyl” or “cycloalkylalkyl group” refers to an alkyl group in which a hydrogen atom is replaced by a cycloalkyl group, wherein alkyl group and cycloalkyl group are as previously defined (i.e., cycloalkylalkyl-). Cycloalkylalkyl groups can be substituted or unsubstituted. Examples include, but are not limited to, cyclohexylmethyl (C 6 H 11 CH 2 —). 
         “Haloalkyl” or “haloalkyl group” refers to alkyl groups in which one or more hydrogen atoms are replaced by halogen atoms. Haloalkyl includes both saturated alkyl groups and unsaturated alkenyl and alkynyl groups, such as for example —CF 3 , —CHF 2 , —CH 2 F, —CF 2 CF 3 , —CHFCF 3 , —CH 2 CF 3 , —CF 2 CH 3 , —CHFCH 3 , —CF 2 CF 2 CF 3 , —CF 2 CH 2 CH 3 , —CF═CF 2 , —CCl═CH 2 , —CBr═CH 2 , —CI═CH 2 , —C≡C—CF 3 , —CHFCH 2 CH 3  and —CHFCH 2 CF 3 . 
         “Halogen” includes fluorine, chlorine, bromine and iodine atoms. 
         “Heteroaryl” or “heteroaryl group” refers to (a) 5 and 6 membered monocyclic aromatic rings, which contain, in addition to carbon atom(s), at least one heteroatom, such as nitrogen, oxygen or sulfur, and (b) 7-15 membered bicyclic and tricyclic rings, which contain, in addition to carbon atom(s), at least one heteroatom, such as nitrogen, oxygen or sulfur, and in which at least one of the rings is aromatic. Heteroaryl groups can be substituted or unsubstituted, and may be bridged, spiro, and/or fused. Examples include, but are not limited to, 2,3-dihydrobenzofuranyl, 1,2-dihydroquinolinyl, 3,4-dihydroisoquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, benzoxazinyl, benzthiazinyl, chromanyl, furanyl, 2-furanyl, 3-furanyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, oxazolyl, pyridinyl, 2-, 3-, or 4-pyridinyl, pyrimidinyl, 2-, 4-, or 5-pyrimidinyl, pyrazolyl, pyrrolyl, 2- or 3-pyrrolyl, pyrazinyl, pyridazinyl, 3- or 4-pyridazinyl, 2-pyrazinyl, thienyl, 2-thienyl, 3-thienyl, tetrazolyl, thiazolyl, thiadiazolyl, triazinyl, triazolyl, pyridin-2-yl, pyridin-4-yl, pyrimidin-2-yl, pyridazin-4-yl, pyrazin-2-yl, naphthyridinyl, pteridinyl, phthalazinyl, purinyl, alloxazinyl, benzimidazolyl, benzofuranyl, benzofurazanyl, 2H-1-benzopyranyl, benzothiadiazine, benzothiazinyl, benzothiazolyl, benzothiophenyl, benzoxazolyl, cinnolinyl, furopyridinyl, indolinyl, indolizinyl, indolyl, or 2-, 3-, 4-, 5-, 6-, or 7-indolyl, 3H-indolyl, quinazolinyl, quinoxalinyl, isoindolyl, isoquinolinyl, 10-aza-tricyclo[6.3.1.0 2,7 ]dodeca-2(7),3,5-trienyl, 12-oxa-10-aza-tricyclo[6.3.1.0 2,7 ]dodeca-2(7),3,5-trienyl, 12-aza-tricyclo[7.2.1.0 2,7 ]dodeca-2(7),3,5-trienyl, 10-aza-tricyclo[6.3.2.0 2,7 ]trideca-2(7),3,5-trienyl, 2,3,4,5-tetrahydro-1H-benzo[d]azepinyl, 1,3,4,5-tetrahydro-benzo[d]azepin-2-onyl, 1,3,4,5-tetrahydro-benzo[b]azepin-2-onyl, 2,3,4,5-tetrahydro-benzo[c]azepin-1-onyl, 1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-onyl, 2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepinyl, 5,6,8,9-tetrahydro-7-oxa-benzocycloheptenyl, 2,3,4,5-tetrahydro-1H-benzo[b]azepinyl, 1,2,4,5-tetrahydro-benzo[e][1,3]diazepin-3-onyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl, 3,4-dihydro-2H-benzo[f][1,4]oxazepin-5-onyl, 6,7,8,9-tetrahydro-5-thia-8-aza-benzocycloheptenyl, 5,5-dioxo-6,7,8,9-tetrahydro-5-thia-8-aza-benzocycloheptenyl, and 2,3,4,5-tetrahydro-benzo[f][1,4]oxazepinyl. For example, a heteroaryl group may contain 5, 6, or 8-15 ring atoms. As another example, a heteroaryl group may contain 5 to 10 ring atoms, such as 5, 6, 9, or 10 ring atoms. 
         “Heteroarylalkyl” or “heteroarylalkyl group” refers to an alkyl group in which a hydrogen atom is replaced by a heteroaryl group, wherein alkyl group and heteroaryl group are as previously defined (i.e., heteroarylalkyl-). Heteroarylalkyl groups can be substituted or unsubstituted. Examples include, but are not limited to, the pyridinylmethyl isomers 
       
    
     
       
         
         
             
             
         
       
         
         “Heterocycloalkyl” or “heterocycloalkyl group” refers to 3-15 membered monocyclic, bicyclic, and tricyclic non-aromatic rings, which may be saturated or unsaturated, can be substituted or unsubstituted, may be bridged, spiro, and/or fused, and which contain, in addition to carbon atom(s), at least one heteroatom, such as nitrogen, oxygen, sulfur or phosphorus. Examples include, but are not limited to, tetrahydrofuranyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidyl, piperazinyl, indolinyl, isoindolinyl, morpholinyl, thiomorpholinyl, homomorpholinyl, homopiperidyl, homopiperazinyl, thiomorpholinyl-5-oxide, thiomorpholinyl-S,S-dioxide, pyrrolidinyl, tetrahydropyranyl, piperidinyl, tetrahydrothienyl, homopiperidinyl, homothiomorpholinyl-S,S-dioxide, oxazolidinonyl, dihydropyrazolyl, dihydropyrrolyl, dihydropyrazinyl, dihydropyridinyl, dihydropyrimidinyl, dihydrofuryl, dihydropyranyl, tetrahydrothienyl-5-oxide, tetrahydrothienyl-S,S-dioxide, homothiomorpholinyl-5-oxide, quinuclidinyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 8-oxa-3-aza-bicyclo[3.2.1]octanyl, 3,8-diaza-bicyclo[3.2.1]octanyl, 2,5-diaza-bicyclo[2.2.1]heptanyl, 3,8-diaza-bicyclo[3.2.1]octanyl, 3,9-diaza-bicyclo[4.2.1]nonanyl, 2,6-diaza-bicyclo[3.2.2]nonanyl, [1,4]oxaphosphinanyl-4-oxide, [1,4]azaphosphinanyl-4-oxide, [1,2]oxaphospholanyl-2-oxide, phosphinanyl-1-oxide, [1,3]azaphospholidinynl-3-oxide, [1,3]oxaphospholanyl-3-oxide and 7-oxabicyclo[2.2.1]heptanyl. A heterocycloalkyl group may contain, in addition to carbon atom(s), at least one nitrogen, oxygen, or sulfur. For example, a heterocycloalkyl group may contain, in addition to carbon atom(s), at least one nitrogen or oxygen. A heterocycloalkyl group may contain, in addition to carbon atom(s), at least one nitrogen. A heterocycloalkyl group may contain carbon atoms and 1 or 2 nitrogen atoms. A heterocycloalkyl group may contain carbon atoms and an oxygen atom. A heterocycloalkyl group may contain carbon atoms, a nitrogen atom, and an oxygen atom. A heterocycloalkyl group may contain carbon atoms, a nitrogen atom, and a sulfur atom. A heterocycloalkyl group may contain carbon atoms and a sulfur atom. A heterocycloalkyl group may contain from 3 to 10 ring atoms. A heterocycloalkyl group may contain from 3 to 7 ring atoms. A heterocycloalkyl group may contain from 5 to 7 ring atoms, such as 5 ring atoms, 6 ring atoms, or 7 ring atoms. Unless otherwise indicated, the foregoing heterocycloalkyl groups can be C-attached or N-attached where such is possible and results in the creation of a stable structure. For example, piperidinyl can be piperidin-1-yl (N-attached) or piperidin-4-yl (C-attached). 
         “Heterocycloalkylene” or “heterocycloalkylene group” refers to diradical, 3-15 membered monocyclic, bicyclic, or tricyclic non-aromatic ring systems, which may be saturated or unsaturated, can be substituted or unsubstituted, may be bridged, spiro, and/or fused, and which contain, in addition to carbon atom(s), at least one heteroatom, such as nitrogen, oxygen, sulfur or phosphorus. Examples include, but are not limited to, the azridinylene isomers 
       
    
                         
The heterocycloalkylene group may contain, in addition to carbon atom(s), at least one nitrogen, oxygen, or sulfur. The heterocycloalkylene group may contain, in addition to carbon atom(s), at least one nitrogen or oxygen. The heterocycloalkylene group may contain, in addition to carbon atom(s), at least one nitrogen. For example, a heterocycloalkylene group may contain from 3 to 10 ring atoms; such as from 3 to 7 ring atoms. A heterocycloalkylene group may contain from 5 to 7 ring atoms, such as 5 ring atoms, 6 ring atoms, or 7 ring atoms. Unless otherwise indicated, the foregoing heterocycloalkylene groups can be C-attached and/or N-attached where such is possible and results in the creation of a stable structure. A heterocycloalkylene group can also include ring systems substituted on ring carbons with one or more —OH functional groups (which may further tautomerize to give a ring C═O group) and/or substituted on a ring sulfur atom by one (1) or two (2) oxygen atoms to give S═O or SO 2  groups, respectively, and/or substituted on a ring phosphorus by an oxygen atom to give P═O.
     “Heterocycloalkylalkyl” or “heterocycloalkylalkyl group” refers to an alkyl group in which a hydrogen atom is replaced by a heterocycloalkyl group, wherein alkyl group and heterocycloalkyl group are as previously defined (i.e., heterocycloalkylalkyl-). Heteroycloalkylalkyl groups can be substituted or unsubstituted. Examples include, but are not limited to, pyrrolidinylmethyl (C 4 H 8 NCH 2 —).   “Pharmaceutically acceptable” refers to physiologically tolerable materials, which do not typically produce an allergic or other untoward reaction, such as gastric upset, dizziness and the like, when administered to a human.   “Pharmaceutical composition” refers to a composition that can be used to treat a disease, condition, or disorder in a human.   “Pseudohalogen” refers to —OCN, —SCN, —CF 3 , and —CN.   “Stable” or “chemically stable” refers to a compound that is sufficiently robust to be isolated to a useful degree of purity from a reaction mixture. The present application is directed solely to the preparation of stable compounds. When lists of alternative substituents include members which, owing to valency requirements, chemical stability, or other reasons, cannot be used to substitute a particular group, the list is intended to be read in context to include those members of the list that are suitable for substituting the particular group. For example, R 1  can be C 1-6 alkyl optionally substituted by 1-13 R 19 ; when R 1  is methyl, the methyl group is optionally substituted by 1-3 R 19 .   “Therapeutically effective amount” refers to an amount of a compound sufficient to inhibit, halt, or cause an improvement in a disorder or condition being treated in a particular subject or subject population. For example in a human or other mammal, a therapeutically effective amount can be determined experimentally in a laboratory or clinical setting, or may be the amount required by the guidelines of the United States Food and Drug Administration, or equivalent foreign agency, for the particular disease and subject being treated. It should be appreciated that determination of proper dosage forms, dosage amounts, and routes of administration is within the level of ordinary skill in the pharmaceutical and medical arts.   “Treatment” refers to the acute or prophylactic diminishment or alleviation of at least one symptom or characteristic associated or caused by a disorder being treated. For example, treatment can include diminishment of several symptoms of a disorder or complete eradication of a disorder.   

     II. Compounds 
     The compounds of the present application are defined by the following numbered Embodiments. When a higher numbered Embodiment refers back to multiple previous lower numbered Embodiments in the alternative and contains a new limitation not present in the lower numbered Embodiments, the higher numbered Embodiment is intended to be an express description of each and every one of the alternatives. For example, if Embodiment 2 refers back to Embodiment 1 and contains a limitation not present in Embodiment 1, Embodiment 3 refers back Embodiments 1 or 2 and contains a limitation(s) not present in Embodiments 1 or 2, and Embodiment 4 refers back to any of Embodiments 1-3 and contains a limitation(s) not present in Embodiments 1, 2, or 3, then Embodiment 4 is intended to be an explicit description of a genus having the limitations of Embodiments 1 and 4, an explicit description of a genus having the limitations of Embodiments 2 and 4 (i.e., 1, 2, and 4), and an explicit description of a genus having the limitations of Embodiments 3 and 4 (i.e., 1, 3, and 4, and 1, 2, 3 and 4). By way of example, if Embodiment 1 is a compound of formula (I) defining R 7 , R 8  and R 9  independently as alkyl or aryl, Embodiment 2 is a compound of Embodiment 1 defining R 7  as alkyl, Embodiment 3 is a compound of Embodiments 1 or 2 defining R 8  as alkyl, and Embodiment 4 is a compound of any of Embodiments 1-3 defining R 9  as alkyl, then Embodiment 4 is an explicit description of a genus having the limitations of Embodiments 1 and 4 (i.e., a compound of formula (I) in which R 7  and R 8  are alkyl or aryl, and R 9  is alkyl), an explicit description of a genus having the limitations of Embodiments 2 and 4 (i.e., a compound of formula (I) in which R 8  is alkyl or aryl, and R 7  and R 9  are alkyl), an explicit description of a genus having the limitations of Embodiments 3 and 4 (i.e., a compound of formula (I) in which R 7  is alkyl or aryl, and R 8  and R 9  are alkyl; and a compound of formula (I) in which R 7 , R 8  and R 9  are all alkyl). It should be noted in this regard that when a higher numbered Embodiment refers to a lower numbered Embodiment and contains limitations for a group(s) not present in the lower numbered Embodiment, the higher numbered Embodiment should be interpreted in context to ignore the missing group(s). For example, if Embodiment 1 recites a compound of formula (I) in which X is H, C 1-10 alkyl, or —C(═O)R 28 , Embodiment 2 recites a compound of Embodiment 1 in which X is H or C 1-10 alkyl, and Embodiment 3 recites a compound of Embodiments 1 or 2 in which R 28  is alkyl, then Embodiment 3 defines a genus having the limitations of Embodiments 1 and 3 and a genus having the limitation of Embodiments 2 and 3 (i.e., 1, 2, and 3). In the genus defined by the limitations of Embodiments 2 and 3, X cannot be —C(═O)R 28 ; therefore this genus should be interpreted to ignore the Embodiment 3 definition of R 28 =alkyl (i.e., the genus of Embodiments 2 and 3 has the same scope as the genus of Embodiment 2). 
     The compounds of the present application are defined herein using structural formulas that do not specifically recite the mass numbers or the isotope ratios of the constituent atoms. It is intended that the present application includes compounds in which the constituent atoms are present in any ratio of isotope forms. For example, carbon atoms may be present in any ratio of  12 C,  13 C, and  14 C; hydrogen atoms may be present in any ratio of  1 H,  2 H, and  3 H; etc. Preferably, the constituent atoms in the compounds of the present application are present in their naturally occurring ratios of isotope forms. 
     Embodiment 1 
     A compound of formula (I) 
                         
or a salt form thereof,
 
wherein
         G is a group of formula       

     
       
         
         
             
             
         
       
         
         
           
             X is chosen from H, C 1-10 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —C(═O)C(═O)R 28 , —NR 24 R 28 , —NR 24 NR 24 R 28 , —N═NR 28 , —NR 24 OR 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)C(═O)R 28 , —NR 24 C(═O)OR 28 , —NR 24 C(═O)C(═O)OR 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 C(═O)NR 24 C(═O)R 28 , —NR 24 C(═O)NR 24 C(═O)OR 28 , —NR 24 C(═O)C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —NR 24 S(═O) 2 NR 24 R 28 , —OR 28 , —OC(═O)R 28 , —OC(═O)NR 24 R 28 , —OC(═O)OR 28 , —OS(═O)R 28 , —OS(═O) 2 R 28 , —OS(═O) 2 OR 28 , —OS(═O) 2 NR 24 R 28 , —S(═O) n R 28 , —S(═O) 2 NR 24 R 28 , and —S(═O)NR 24 R 28 ; 
             R 7 , R 8 , R 9 , R 12 , R 13 , R 14 , R 15 , R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —(═O)C(═O)R 20 , —C(═NR 25 )R 20 , —C(═NR 25 )NR 22 R 23 , —C(═NOH)NR 22 R 23 , —C(═NOR 26 )R 20 , —C(═NNR 22 R 23 )R 20 , —C(═NNR 24 C(═O)R 21 )R 20 , —C(═NNR 24 C(═O)OR 21 )R 20 , —C(═S)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═NR 25 )NR 22 R 23 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 C(═S)R 20 , —NR 24 C(═S)OR 20 , —NR 24 C(═S)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)(NR 22 R 23 )(NR 22 R 23 ), —NR 24 P(═)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OC(═NR 25 )NR 22 R 23 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 78 R 78 , —OP(═O)(NR 22 R 23 )(NR 22 R 23 ), —OP(═O)(OR 20 )(OR 20 ), —OP(═O)(SR 20 )(SR 20 ), —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 R 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —SP(═O)R 78 R 78 , —SP(═O)(NR 22 R 23 )(NR 22 R 23 ), —SP(═O)(OR 20 )(OR 20 ), —SP(═O)(SR 20 )(SR 20 ), —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), —P(═O)(OR 20 )(OR 20 ), and —P(═O)(SR 20 )(SR 20 );
           or any of R 7  and R 8 , R 12  and R 13 , R 14  and R 15 , R a  and R b , R a  and R e , R a  and R e , R a  and R g , R b  and R d , R b  and R f , R b  and R h , R c  and R d , R c  and R e , R c  and R g , R d  and R f , R d  and R h , R e  and R f , R e  and R g , R f  and R h , and R g  and R h  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 19 ;   
         
             R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 39 , C 2-6 alkenyl optionally substituted by 1-11 R 39 , C 2-6 alkynyl optionally substituted by 1-9 R 39 , C 6-11 aryl optionally substituted by 1-11 R 39 , C 7-16 arylalkyl optionally substituted by 1-19 R 39 , C 3-11 cycloalkyl optionally substituted by 1-21 R 39 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 39 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 39 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 39 , 5-15 membered heteroaryl optionally substituted by 1-15 R 39 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 39 , halogen, —CN, —C(═O)R 30 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —C(═O)C(═O)R 30 , —C(═NR 35 )R 30 , —C(═NR 35 )NR 32 R 33 , —C(═NOH)NR 32 R 33 , —C(═NOR 36 )R 30 , —C(═NNR 32 R 33 )R 30 , —C(═NNR 34 C(═O)R 31 )R 30 , —C(═NNR 34 C(═O)OR 31 )R 30 , —C(═S)NR 32 R 33 , —NC, —NO 2 , —NR 32 R 33 , —NR 34 NR 32 R 33 , —N═NR 34 , ═NR 30 , ═NOR 30 , —NR 34 OR 36 , —NR 34 C(═O)R 30 , —NR 34 C(═O)C(═O)R 30 , —NR 34 C(═O)OR 31 , —NR 34 C(═O)C(═O)OR 31 , —NR 34 C(═O)NR 32 R 33 , —NR 34 C(═O)NR 34 C(═O)R 30 , —NR 34 C(═O)NR 34 C(═O)OR 30 , —NR 34 C(═NR 35 )NR 32 R 33 , —NR 34 C(═O)C(═O)NR 32 R 33 , —NR 34 C(═S)R 30 , —NR 34 C(═S)OR 30 , —NR 34 C(═S)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —NR 34 P(═O)R 78 R 78 , —NR 34 P(═O)(NR 32 R 33 )(NR 32 R 33 ), —NR 34 P(═O)(OR 30 )(OR 30 ), —NR 34 P(═O)(SR 30 )(SR 30 ), —OR 30 , ═O, —OCN, —OC(═O)R 30 , —OC(═O)NR 32 R 33 , —OC(═O)OR 30 , —OC(═NR 35 )NR 32 R 33 , —OS(═O)R 30 , —OS(═O) 2 R 30 , —OS(═O) 2 OR 30 , —OS(═O) 2 NR 32 R 33 , —OP(═O)R 78 R 78 , —OP(═O)(NR 32 R 33 )(NR 32 R 33 ), —OP(═O)(OR 30 )(OR 30 ), —OP(═O)(SR 30 )(SR 30 ), —Si(R 34 ) 3 , —SCN, ═S, —S(═O) n R 30 , —S(═O) 2 OR 30 , —SO 3 R 37 , —S(═O) 2 NR 32 R 33 , —S(═O)NR 32 R 33 , —SP(═O)R 78 R 78 , —SP(═O)(NR 32 R 32 )(NR 32 R 33 ), —SP(═O)(OR 30 )(OR 30 ), —SP(═O)(SR 30 )(SR 30 ), —P(═O)R 78 R 78 , —P(═O)(NR 32 R 33 )(NR 32 R 33 ), —P(═O)(OR 30 )(OR 30 ), and —P(═O)(SR 30 )(SR 30 ); 
             R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 49 , C 2-6 alkenyl optionally substituted by 1-11 R 49 , C 2-6 alkynyl optionally substituted by 1-9 R 49 , C 6-11 aryl optionally substituted by 1-11 R 49 , C 7-16 arylalkyl optionally substituted by 1-19 R 49 , C 3-11 cycloalkyl optionally substituted by 1-21 R 49 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 49 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 49 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 49 , 5-15 membered heteroaryl optionally substituted by 1-15 R 49 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 49 ; 
             R 28  at each occurrence is independently chosen from C 1-10 alkyl optionally substituted by 1-13 R 49 , C 2-10 alkenyl optionally substituted by 1-11 R 49 , C 2-6 alkynyl optionally substituted by 1-9 R 49 , C 6-11 aryl optionally substituted by 1-11 R 49 , C 7-16 arylalkyl optionally substituted by 1-19 R 49 , C 3-11 cycloalkyl optionally substituted by 1-21 R 49 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 49 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 49 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 49 , 5-15 membered heteroaryl optionally substituted by 1-15 R 49 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 49 ; 
             R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 59 , C 2-6 alkenyl optionally substituted by 1-11 R 59 , C 2-6 alkynyl optionally substituted by 1-9 R 59 , C 6-11 aryl optionally substituted by 1-11 R 59 , C 7-16 arylalkyl optionally substituted by 1-19 R 59 , C 3-11 cycloalkyl optionally substituted by 1-21 R 59 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 59 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 59 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 59 , 5-15 membered heteroaryl optionally substituted by 1-15 R 59 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 59 ;
           or any R 22  and R 23  and/or R 32  and R 33  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 69  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 69 ;   
         
             R 39 , R 49 , R 59  and R 69  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 79 , C 2-6 alkenyl optionally substituted by 1-11 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-19 R 79 , C 3-11 cycloalkyl optionally substituted by 1-21 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 79 , 5-15 membered heteroaryl optionally substituted by 1-15 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —C(═O)C(═O)R 70 , —C(═NR 75 )R 70 , —C(═NR 75 )NR 72 R 73 , —C(═NOH)NR 72 R 73 , —C(═NOR 76 )R 70 , —C(═NNR 72 R 73 )R 70 , —C(═NNR 74 C(═O)R 71 )R 70 , —C(═NNR 74 C(═O)OR 71 )R 70 , —C(═S)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 NR 72 R 73 , —N═NR 74 , ═NR 70 , ═NOR 70 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)C(═O)R 70 , —NR 74 C(═)OR 71 , —NR 74 C(═O)C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 C(═O)NR 74 C(═O)OR 70 , —NR 74 C(═NR 75 )NR 72 R 73 , —NR 74 C(═O)C(═O)NR 72 R 73 , —NR 74 C(═S)R 70 , —NR 74 C(═S)OR 70 , —NR 74 C(═S)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —NR 74 P(═O)R 78 R 78 , —NR 74 P(═O)(NR 72 R 73 )(NR 72 R 73 ), —NR 74 P(═O)(OR 70 )(OR 70 ), —NR 74 P(═O)(SR 70 )(SR 70 ), —OR 70 , ═O, —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —OC(═NR 75 )NR 72 R 73 , —OS(═O)R 70 , —OS(═O) 2 R 70 , —OS(═O) 2 R 70 , —OS(═O) 2 NR 72 R 73 , —OP(═O)R 78 R 78 , —OP(═O)(NR 72 R 73 )(NR 72 R 73 ), —OP(═O)(OR 70 )(OR 70 ), —OP(═O)(SR 70 )(SR 70 ), —Si(R 74 ) 3 , —SCN, ═S, —S(═O) n R 70 , —S(═O) 2 OR 70 , —SO 3 R, —S(═O) 2 NR 72 R 73 , —S(═O)NR 72 R 73 , —SP(═O)R 78 R 78 , —SP(═O)(NR 72 R 73 )(NR 72 R 73 ), —SP(═O)(OR 70 )(OR 70 ), —SP(═O)(SR 70 )(SR 70 ), —P(═O)R 78 R 78 , —P(═O)(NR 72 R 73 )(NR 72 R 73 ), —P(═O)(OR 70 )(OR 70 ), and —P(═O)(SR 70 )(SR 70 ); 
             R 70 , R 71 , R 74 , R 7 , R 76  and R 77  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 89 , C 2-6 alkenyl optionally substituted by 1-11 R 89 , C 2-6 alkynyl optionally substituted by 1-9 R 89 , C 6-11 aryl optionally substituted by 1-11 R 89 , C 7-16 arylalkyl optionally substituted by 1-19 R 89 , C 3-11 cycloalkyl optionally substituted by 1-21 R 89 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 89 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 89 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 89 , 5-15 membered heteroaryl optionally substituted by 1-15 R 89 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 89 ; 
             R 72  and R 73  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 99 , C 2-6 alkenyl optionally substituted by 1-11 R 99 , C 2-6 alkynyl optionally substituted by 1-9 R 99 , C 6-11 aryl optionally substituted by 1-11 R 99 , C 7-16 arylalkyl optionally substituted by 1-19 R 99 , C 3-11 cycloalkyl optionally substituted by 1-21 R 99 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 99 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 99 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 99 , 5-15 membered heteroaryl optionally substituted by 1-15 R 99 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 99 ;
           or any R 72  and R 73  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 109  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 109 ;   
         
             R 78  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 89 , C 2-6 alkenyl optionally substituted by 1-11 R 89 , C 2-6 alkynyl optionally substituted by 1-9 R 89 , C 6-11 aryl optionally substituted by 1-11 R 89 , C 7-16 arylalkyl optionally substituted by 1-19 R 89 , C 3-11 cycloalkyl optionally substituted by 1-21 R 89 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 89 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 89 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 89 , 5-15 membered heteroaryl optionally substituted by 1-15 R 89 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 89 ;
           or any two R 78  attached to the same phosphorus atom can, together with the phosphorus atom linking them, form a 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 89 ;   
         
             R 79 , R 89 , R 99  and R 109  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 119 , C 2-6 alkenyl optionally substituted by 1-11 R 119 , C 2-6 alkynyl optionally substituted by 1-9 R 119 , C 6-11 aryl optionally substituted by 1-11 R 119 , C 7-16 arylalkyl optionally substituted by 1-19 R 119 , C 3-11 cycloalkyl optionally substituted by 1-21 R 119 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 119 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 119 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 119 , 5-15 membered heteroaryl optionally substituted by 1-15 R 119 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 119 , halogen, —CN, —C(═O)R 110 , —C(═O)OR 110 , —C(═O)NR 112 R 113 , —C(═O)C(═O)R 110 , —C(═NR 115 )R 110 , —C(═NR 115 )NR 112 R 113 , —C(═NOH)NR 112 R 113 , —C(═NOR 116 )R 110 , —C(═NNR 112 R 113 )R 110 , —C(═NNR 114 C(═O)R 111 )R 110 , —C(═NNR 114 C(═O)OR 111 )R 110 , —C(═S)NR 112 R 113 , —NC, —NO 2 , —NR 112 R 113 , —NR 114 NR 112 R 113 , —N═NR 114 , ═NR 110 , ═NOR 110 , —NR 114 OR 116 , —NR 114 C(═O)R 110 , —NR 114 C(═O)C(═O)R 110 , —NR 114 C(═O)OR 111 , —NR 114 C(═O)C(═O)OR 111 , —NR 114 C(═O)NR 112 R 113 , —NR 114 C(═O)NR 114 C(═O)R 110 , —NR 114 C(═O)NR 114 C(═O)OR 110 , —NR 114 C(═NR 115 )NR 112 R 113 , —NR 114 C(═O)C(═O)NR 112 R 113 , —NR 114 C(═S)R 110 , —NR 114 C(═S)OR 110 , —NR 114 C(═S)NR 112 R 113 , —NR 114 S(═O) 2 R 11 , —NR 114 S(═O) 2 NR 112 R 113 , —NR 114 P(═O)R 118 R 118 , —NR 114 P(═O)(NR 112 R 113 )(NR 112 R 113 ), —NR 114 P(═O)(OR 110 )(OR 110 )—NR 114 P(═O)(SR 110 )(SR 110 ), —OR 110 , ═O, —OCN, —OC(═O)R 110 , —OC(═O)NR 112 R 113 , —OC(═O)OR 110 , —OC(═NR 115 )NR 112 R 113 , —OS(═O)R 110 , —OS(═O) 2 R 110 , —OS(═O) 2 OR 110 , —OS(═O) 2 NR 112 R 113 , —OP(═O)R 118 R 118 , —OP(═O)(NR 112 R 113 )(NR 112 R 113 ), —OP(═O)(OR 110 )(OR 110 ), —OP(═O)(SR 110 )(SR 110 ), —Si(R 114 ) 3 , —SCN, ═S, —S(═O) n R 110 , —S(═O) 2 OR 110 , —SO 3 R 1111 , —S(═O) 2 NR 112 R 113 , —S(═O)NR 112 R 113 , —SP(═O)R 118 R 118 , —SP(═O)(NR 112 R 113 )(NR 112 R 113 ), —SP(═O)(OR 110 )(OR 110 ), —SP(═O)(SR 110 )(SR 110 ), —P(═O)R 118 R 118 , —P(═O)(NR 112 R 113 )(NR 112 R 113 ), —P(═O)(OR 110 )(OR 110 ), and —P(═O)(SR 110 )(SR 110 ); 
             R 110 , R 111 , R 114 , R 115 , R 116  and R 117  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 129 , C 2-6 alkenyl optionally substituted by 1-11 R 129 , C 2-6 alkynyl optionally substituted by 1-9 R 129 , C 6-11 aryl optionally substituted by 1-11 R 129 , C 7-16 arylalkyl optionally substituted by 1-19 R 129 , C 3-11 cycloalkyl optionally substituted by 1-21 R 129 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 129 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 129 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 129 , 5-15 membered heteroaryl optionally substituted by 1-15 R 129 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 129 ; 
             R 112  and R 113  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 139 , C 2-6 alkenyl optionally substituted by 1-11 R 139 , C 2-6 alkynyl optionally substituted by 1-9 R 139 , C 6-11 aryl optionally substituted by 1-11 R 139 , C 7-16 arylalkyl optionally substituted by 1-19 R 139 , C 3-11 cycloalkyl optionally substituted by 1-21 R 139 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 139 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 139 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 139 , 5-15 membered heteroaryl optionally substituted by 1-15 R 139 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 39 ;
           or any R 112  and R 113  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 149  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 149      
         
             R 118  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 129 , C 2-6 alkenyl optionally substituted by 1-11 R 129 , C 2-6 alkynyl optionally substituted by 1-9 R 129 , C 6-11 aryl optionally substituted by 1-11 R 129 , C 7-16 arylalkyl optionally substituted by 1-19 R 129 , C 3-11 cycloalkyl optionally substituted by 1-21 R 129 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 129 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 129 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 129 , 5-15 membered heteroaryl optionally substituted by 1-15 R 129 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 129 ; 
             R 119 , R 129 , R 139  and R 149  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 159 , C 2-6 alkenyl optionally substituted by 1-11 R 159 , C 2-6 alkynyl optionally substituted by 1-9 R 159 , C 6-11 aryl optionally substituted by 1-11 R 159 , C 7-16 arylalkyl optionally substituted by 1-19 R 159 , C 3-11 cycloalkyl optionally substituted by 1-21 R 159 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 159 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 159 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 159 , 5-15 membered heteroaryl optionally substituted by 1-15 R 159 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 159 , halogen, —CN, —C(═O)R 150 , —C(═O)OR 150 , —C(═O)NR 152 R 153 , —C(═O)C(═O)R 150 , —C(═NR 155 )R 150 , —C(═NR 155 )NR 152 R 153 , —C(═NOH)NR 152 R 153 , —C(═NOR 156 )R 150 , —C(═NNR 152 R 153 )R 150 , —C(═NNR 154 C(═O)R 151 )R 150 , —C(═NNR 154 C(═O)OR 151 )R 150 , —C(═S)NR 152 R 153 , —NC, —NO 2 , —NR 152 R 150 , —NR 154 NR 152 R 153 , —N═NR 154 , ═NR 150 , ═NOR 15 , —NR 154 OR 156 , —NR 154 C(═O)R 150 , —NR 154 C(═O)C(═O)R 150 , —NR 154 C(═)OR 151 , —NR 154 C(═O)C(═O)OR 151 , —NR 154 C(═O)NR 152 R 153 , —NR 154 C(═O)NR 154 C(═O)R 150 , —NR 154 C(═O)NR 154 C(═O)OR 150 , —NR 154 C(═NR 155 )NR 152 R 153 , —NR 154 C(═O)C(═O)NR 152 R 153 , —NR 154 C(═S)R 150 , —NR 154 C(═S)OR 150 , —NR 154 C(═S)NR 152 R 153 , —NR 154 S(═O) 2 R 151 , —NR 154 S(═O) 2 NR 152 R 153 , —NR 154 P(═O)R 158 R 158 , —NR 154 P(═O)(NR 152 R 153 )(NR 152 R 153 ), —NR 154 P(═O)(OR 150 )(OR 150 ), —NR 154 P(═O)(SR 150 )(SR 150 ), —OR 150 , ═O, —OCN, —OC(═O)R 150 , —OC(═O)NR 152 R 153 , —OC(═)OR 150 , —OC(═NR 155 )NR 152 R 153 , —OS(═O)R 150 , —OS(═O) 2 R 150 , —OS(═O) 2 OR 15 , —OS(═O) 2 NR 152 R 153 , —OP(═O)R 158 R 158 , —OP(═O)(NR 152 R 153 )(NR 152 R 153 ), —OP(═O)(OR 150 )(OR 150 ), —OP(═O)(SR 150 )(SR 150 ), —Si(R 154 ) 3 , —SCN, ═S, —S(═O) n R 150 , —S(═O) 2 OR 150 , —SO 3 R 1515 , —S(═O) 2 NR 152 R 153 , —S(═O)NR 152 R 153 , —SP(═O)R 158 R 158 , —SP(═O)(NR 152 R 153 )(NR 152 R 153 ), —SP(═O)(OR 150 )(OR 150 ), —SP(═O)(SR 150 )(SR 150 ), —P(═O)R 158 R 158 , —P(═O)(NR 152 R 153 )(NR 152 R 153 ), —P(═O)(OR 150 )(OR 150 ), and —P(═O)(SR 150 )(SR 150 ); 
             R 150 , R 151 , R 154 , R 155 , R 156  and R 157  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 169 , C 2-6 alkenyl optionally substituted by 1-11 R 169 , C 2-6 alkynyl optionally substituted by 1-9 R 169 , C 6-11 aryl optionally substituted by 1-11 R 169 , C 7-16 arylalkyl optionally substituted by 1-19 R 169 , C 3-11 cycloalkyl optionally substituted by 1-21 R 169 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 169 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 169 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 169 , 5-15 membered heteroaryl optionally substituted by 1-15 R 169 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 169 ; 
             R 152  and R 153  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 179 , C 2-6 alkenyl optionally substituted by 1-11 R 179 , C 2-6 alkynyl optionally substituted by 1-9 R 179 , C 6-11 aryl optionally substituted by 1-11 R 179 , C 7-16 arylalkyl optionally substituted by 1-19 R 179 , C 3-11  cycloalkyl optionally substituted by 1-21 R 179 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 179 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 179 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 179 , 5-15 membered heteroaryl optionally substituted by 1-15 R 179 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 179 ;
           or any R 152  and R 153  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 189  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 189 ;   
         
             R 158  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 169 , C 2-6 alkenyl optionally substituted by 1-11 R 169 , C 2-6 alkynyl optionally substituted by 1-9 R 169 , C 6-11 aryl optionally substituted by 1-11 R 169 , C 7-16 arylalkyl optionally substituted by 1-19 R 169 , C 3-11 cycloalkyl optionally substituted by 1-21 R 169 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 169 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 169 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 169 , 5-15 membered heteroaryl optionally substituted by 1-15 R 169 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 69 ; 
             R 159 , R 169 , R 179  and R 189  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 199 , C 2-6 alkenyl optionally substituted by 1-11 R 199 , C 2-6 alkynyl optionally substituted by 1-9 R 199 , C 6-11 aryl optionally substituted by 1-11 R 199 , C 7-16 arylalkyl optionally substituted by 1-19 R 199 , C 3-11 cycloalkyl optionally substituted by 1-21 R 199 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 199 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 199 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 199 , 5-15 membered heteroaryl optionally substituted by 1-15 R 199 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 199 , halogen, —CN, —C(═O)R 190 , —C(═O)OR 190 , —C(═O)NR 192 R 193 , —C(═O)C(═O)R 190 , —C(═NR 195 )R 190 , —C(═NR 195 )NR 192 R 193 , —C(═NOH)NR 192 R 193 , —C(═NOR 196 )R 190 , —C(═NNR 192 R 193 )R 190 , —C(═NNR 194 C(═O)R 191 )R 190 , —C(═NNR 194 C(═O)OR 191 )R 190 , —C(═S)NR 192 R 193 , —NC, —NO 2 , —NR 192 R 193 , —NR 194 NR 192 R 193 , —N═NR 194 , ═NR 190 , ═NOR 190 , —NR 194 OR 196 , —NR 194 C(═O)R 190 , —NR 194 C(═O)C(═O)R 190 , —NR 194 C(═O)OR 191 , —NR 194 C(═O)C(═O)OR 191 , —NR 194 C(═O)NR 192 R 193 , —NR 194 C(═O)NR 194 C(═O)R 190 , —NR 194 C(═O)NR 194 C(═)OR 190 , —NR 194 C(═NR 195 )NR 192 R 193 , —NR 194 C(═O)C(═O)NR 192 R 193 , —NR 194 C(═S)R 190 , —NR 194 C(═S)OR 190 , —NR 194 C(═S)NR 192 R 193 , —NR 194 S(═O) 2 R 191 , —NR 194 S(═O) 2 NR 192 R 192 R 193 , —NR 194 P(═O)R 198 R 198 , —NR 194 P(═O)(NR 192 R 193 )(NR 192 R 193 )—NR 194 P(═)(OR 190 )(OR 190 ), —NR 194 P(═O)(SR 190 )(SR 190 )—OR 190 , ═O, —OCN, —OC(═O)R 190 , —OC(═O)NR 192 R 193 , —OC(═O)OR 190 , —OC(═NR 195 )NR 192 R 193 , —OS(═O)R 190 , —OS(═O) 2 R 190 , —OS(═O) 2 OR 190 , —OS(═O) 2 NR 192 R 193 , —OP(═O)R 198 R 198 , —OP(═O)(NR 192 R 193 )(NR 192 R 193 ), —OP(═O)(OR 190 )(OR 190 ), —OP(═O)(SR 190 )(SR 190 ), —Si(R 194 ) 3 , —SCN, ═S, —S(═O) n R 190 , —S(═O) 2 R 190 , —SO 3 R 1919 , —S(═O) 2 NR 192 R 193 , —S(═O)NR 192 R 193 , —SP(═O)R 198 R 198 , —SP(═O)(NR 192 R 193 )(NR 192 R 193 ), —SP(═O)(OR 190 )(OR 190 ), —SP(═O)(SR 190 )(SR 190 ), —P(═O)R 198 R 198 , —P(═O)(NR 192 R 193 )(NR 192 R 193 ), —P(═O)(OR 190 )(OR 190 ), and —P(═O)(SR 190 )(SR 190 ); 
             R 190 , R 91 , R 94 , R 195 , R 196  and R 197  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 209 , C 2-6 alkenyl optionally substituted by 1-11 R 209 , C 2-6 alkynyl optionally substituted by 1-9 R 209 , C 6-11 aryl optionally substituted by 1-11 R 209 , C 7-16 arylalkyl optionally substituted by 1-19 R 209 , C 3-11 cycloalkyl optionally substituted by 1-21 R 209 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 209 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 209 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 209 , 5-15 membered heteroaryl optionally substituted by 1-15 R 209 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 209    
             R 192  and R 193  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 219 , C 2-6 alkenyl optionally substituted by 1-11 R 219 , C 2-6 alkynyl optionally substituted by 1-9 R 219 , C 6-11 aryl optionally substituted by 1-11 R 219 , C 7-16 arylalkyl optionally substituted by 1-19 R 219 , C 3-11 cycloalkyl optionally substituted by 1-21 R 219 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 219 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 219 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 219 , 5-15 membered heteroaryl optionally substituted by 1-15 R 219 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 219 ;
           or any R 192  and R 193  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 229  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 229 ;   
         
             R 198  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 209 , C 2-6 alkenyl optionally substituted by 1-11 R 209 , C 2-6 alkynyl optionally substituted by 1-9 R 209 , C 6-11 aryl optionally substituted by 1-11 R 209 , C 7-16 arylalkyl optionally substituted by 1-19 R 209 , C 3-11 cycloalkyl optionally substituted by 1-21 R 209 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 209 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 209 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 209 , 5-15 membered heteroaryl optionally substituted by 1-15 R 209 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 209    
             R 199 , R 209 , R 219  and R 229  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 halogen, C 2-6 alkenyl, C 2-6 alkynyl, C 6-11 aryl, C 7-16 arylalkyl, C 3-11 cycloalkyl, C 4-17 cycloalkylalkyl, 3-15 membered heterocycloalkyl, 4-21 membered heterocycloalkylalkyl, 5-15 membered heteroaryl, 6-21 membered heteroarylalkyl, halogen, —CN, —C(═O)R 230 , —C(═)OR 230 , —C(═O)NR 230 R 230 , —C(═O)C(═O)R 230 , —C(═NR 230 )R 230 , —C(═NR 230 )NR 230 R 230 , —C(═NOH)NR 230 R 230 , —C(═NOR 230 )R 230 , —C(═NNR 230 R 230 )R 230 , —C(═NNR 230 C(═O)R 230 )R 230 , —C(═NNR 230 C(═O)OR 230 )R 230 , —C(═S)NR 230 R 230 , —NC, —NO 2 , —NR 230 R 230 , —NR 230 NR 230 R 230 , —N═NR 230 , ═NR 230 , ═NOR 230 , —NR 230 OR 230 , —NR 230 C(═O)R 230 , —NR 230 C(═O)C(═O)R 230 , —NR 230 C(═O)OR 230 , —NR 230 C(═O)C(═O)OR 230 , —NR 230 C(═O)NR 230 R 230 , —NR 230 C(═O)NR 230 C(═O)R 230 , —NR 230 C(═O)NR 230 C(═O)OR 230 , —NR 230 C(═NR 230 )NR 230 R 230 , —NR 230 C(═O)C(═O)NR 230 R 230 , —NR 230 C(═S)R 230 , —NR 230 C(═S)OR 230 , —NR 230 C(═S)NR 230 R 230 , —NR 230 S(═) 2 R 230 , —NR 230 S(═O) 2 NR 230 R 230 , —NR 230 P(═O)R 231 R 231 , —NR 230 P(═O)(NR 230 R 230 )(NR 230 R 230 ), —NR 230 P(═O)(OR 230 )(OR 230 ), —NR 230 P(═O)(SR 230 )(SR 230 ), —OR 230 , ═O, —OCN, —OC(═O)R 230 , —OC(═O)NR 230 R 230 , —OC(═O)OR 230 , —OC(═NR 230 )NR 230 R 230 , —OS(═O)R 230 , —OS(═) 2 R 230 , —OS(═O) 2 OR 230 , —OS(═O) 2 NR 230 R 230 , —OP(═O)R 231 R 231 , —OP(═O)(NR 230 R 230 )(NR 230 R 230 ), —OP(═O)(OR 230 )(OR 230 ), —OP(═O)(SR 230 )(SR 230 ), —Si(R 230 ) 3 , —SCN, ═S, —S(═O) n R 230 , —S(═O) 2 R 230 , —SO 3 R 230 , —S(═O) 2 NR 230 R 230 , —S(═O)NR 230 R 230 , —SP(═O)R 231 R 231 , —SP(═O)(NR 230 R 230 )(NR 230 R 230 ), —SP(═O)(OR 230 )(OR 230 ), —SP(═)(SR 230 )(SR 230 ), —P(═O)R 231 R 231 , —P(═O)(NR 230 R 230 )(NR 230 R 230 ), —P(═O)(OR 230 )(OR 230 ), and —P(═O)(SR 230 )(SR 230 ); 
             R 230  at each occurrence is independently chosen from H, C 1-6 alkyl and C 1-6 -haloalkyl; 
             R 231  at each occurrence is independently chosen from C 1-6 alkyl and C 1-6 -haloalkyl; and 
             n at each occurrence is independently chosen from 0, 1, and 2;
 
with the proviso that the compound is not
 
           
         
       
    
                         
in which D is H or
 
                         
or a salt form thereof;
 
                         
in which D is
 
                         
or a salt form thereof; or
 
                         
in which D is H or —CH 3 , or a salt form thereof.
 
     Embodiment 2 
     The compound of Embodiment 1, wherein G is a group of formula 
     
       
         
         
             
             
         
       
     
     Embodiment 3 
     The compound of Embodiment 1, wherein G is a group of formula 
     
       
         
         
             
             
         
       
     
     Embodiment 4 
     The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-10 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —C(═O)C(═O)R 28 , —NR 24 R 28 , —NR 24 NR 24 R 28 , —N═NR 28 , —NR 24 OR 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)C(═O)R 28 , —NR 24 C(═O)OR 28 , —NR 24 C(═O)C(═O)OR 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 C(═O)NR 24 C(═O)R 28 , —NR 24 C(═O)NR 24 C(═O)OR 28 , —NR 24 C(═O)C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —NR 24 S(═O) 2 NR 24 R 28 , —OR 28 , —OC(═O)R 28 , —OC(═O)NR 24 R 28 , —OC(═O)OR, —OS(═O)R 28 , —OS(═O) 2 R 28 , —OS(═O) 2 OR 28 , —OS(═O) 2 NR 24 R 28 , —S(═O) n R 28 , —S(═O) 2 NR 24 R 28 , and —S(═O)NR 24 R 28 . 
     Embodiment 5 
     The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-10 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)OR 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —NR 24 S(═O) 2 NR 24 R 28 , —OR 28 , —OC(═O)R 28 , —OC(═O)NR 24 R 28 , —OS(═O)R 28 , —OS(═O) 2 R 28 , —OS(═O) 2 NR 24 R 28 , —S(═O) n R 28 , —S(═O) 2 NR 24 R 28 , and —S(═O)NR 24 R 28 . 
     Embodiment 6 
     The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-10 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)OR 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —NR 24 S(═O) 2 NR 24 R 28 , —OR 28 , —OC(═O)R 28 , —OC(═O)NR 24 R 28 , —OS(═O)R 28 , —OS(═O) 2 R 28 , —OS(═O) 2 NR 24 R 28 , —S(═O) n R 28 , —S(═O) 2 NR 24 R 28 , and —S(═O)NR 24 R 28 . 
     Embodiment 7 
     The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , C 4-7 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-7 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , 6-11 membered heteroarylalkyl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)OR 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —NR 24 S(═O) 2 NR 24 R 28 , —OR 28 , —OC(═O)R 28 , —OC(═O)NR 24 R 28 , —OS(═O)R 28 , —OS(═O) 2 R 28 , —OS(═O) 2 NR 24 R 28 , —S(═) n R 28 , —S(═O) 2 NR 24 R 28 , and —S(═O)NR 24 R 28 . 
     Embodiment 8 
     The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , C 4-7 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-7 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , 6-11 membered heteroarylalkyl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —OR 28 , —OC(═O)R 28 , —S(═O) n R 28 , and —S(═O) 2 NR 24 R 28 . 
     Embodiment 9 
     The compound of any of Embodiments 1-3, wherein X is chosen from C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , C 4-7 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-7 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , 6-11 membered heteroarylalkyl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)OR 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —NR 24 S(═O) 2 NR 24 R 28 , —OR 28 , —OC(═O)R 28 , —OC(═O)NR 24 R 28 , —OS(═O)R 28 , —OS(═) 2 R 28 , —OS(═O) 2 NR 24 R 28 , —S(═) n R 28 , —S(═O) 2 NR 24 R 28 , and —S(═O)NR 24 R 28 . 
     Embodiment 10 
     The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , C 4-7 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-7 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , 6-11 membered heteroarylalkyl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O) 2 NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —OR 28 , —OC(═O)R 28 , —S(═O) n R 28 , and —S(═O) 2 NR 24 R 28 . 
     Embodiment 11 
     The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —OR 28 , —OC(═O)R 28 , —S(═O) n R 28 , and —S(═O) 2 NR 24 R 28 . 
     Embodiment 12 
     The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —OR 28 , —OC(═O)R 28 , —S(═O) n R 28 , and —S(═O) 2 NR 24 R 28 . 
     Embodiment 13 
     The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 S(═O) 2 R 28 , and —OR 28 . 
     Embodiment 14 
     The compound of any of Embodiments 1-3, wherein X is chosen from H, 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 S(═O) 2 R 28 , and —OR 28 . 
     Embodiment 15 
     The compound of any of Embodiments 1-3, wherein X is chosen from C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , C 4-7 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-7 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , 6-11 membered heteroarylalkyl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —OR 28 , —OC(═O)R 28 , —S(═O) n R 28 , and —S(═O) 2 NR 24 R 28 . 
     Embodiment 16 
     The compound of any of Embodiments 1-3, wherein X is chosen from C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —OR 28 , —OC(═O)R 28 , —S(═O) n R 28 , and —S(═O) 2 NR 24 R 28 . 
     Embodiment 17 
     The compound of any of Embodiments 1-3, wherein X is chosen from C 1-6 alkyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —OR 28 , —OC(═O)R 28 , —S(═O) n R 28 , and —S(═O) 2 NR 24 R 28 . 
     Embodiment 18 
     The compound of any of Embodiments 1-3, wherein X is chosen from C 1-6 alkyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 S(═O) 2 R 28 , and —OR 28 . 
     Embodiment 19 
     The compound of any of Embodiments 1-3, wherein X is chosen from 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 S(═O) 2 R 28 , and —OR 28 . 
     Embodiment 20 
     The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —NR 24 R 28 , and —OR 28 . 
     Embodiment 21 
     The compound of any of Embodiments 1-3, wherein X is chosen from H, 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —NR 24 R 28 , and —OR 28 . 
     Embodiment 22 
     The compound of any of Embodiments 1-3, wherein X is chosen from C 1-6 alkyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —NR 24 R 28 , and —OR 28 . 
     Embodiment 23 
     The compound of any of Embodiments 1-3, wherein X is chosen from 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —NR 24 R 28 , and —OR 28 . 
     Embodiment 24 
     The compound of any of Embodiments 1-3, wherein X is chosen from H, 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , and —NR 24 R 28 . 
     Embodiment 25 
     The compound of any of Embodiments 1-3, wherein X is chosen from 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , and —NR 24 R 28 . 
     Embodiment 26 
     The compound of any of Embodiments 1-3, wherein X is chosen from H, 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , —NR 24 R 28 , —OR 28 , and —SR 28 . 
     Embodiment 27 
     The compound of any of Embodiments 1-3, wherein X is chosen from 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , and —NR 24 R 28 . 
     Embodiment 28 
     The compound of any of Embodiments 1-3, wherein X is chosen from H, 3-9 membered heterocycloalkyl optionally substituted by 1-6 R 19 , and —NR 24 R 28 . 
     Embodiment 29 
     The compound of any of Embodiments 1-3, wherein X is chosen from 3-9 membered heterocycloalkyl optionally substituted by 1-6 R 19 , and —NR 24 R 28 . 
     Embodiment 30 
     The compound of any of Embodiments 1-3, wherein X is chosen from H, 3-7 membered heterocycloalkyl optionally substituted by 1-6 R 19 , and —NR 24 R 28 . 
     Embodiment 31 
     The compound of any of Embodiments 1-3, wherein X is chosen from 3-7 membered heterocycloalkyl optionally substituted by 1-6 R 19 , and —NR 24 R 28 . 
     Embodiment 32 
     The compound of any of Embodiments 1-3, wherein X is 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 . 
     Embodiment 33 
     The compound of any of Embodiments 1-3, wherein X is 3-9 membered heterocycloalkyl optionally substituted by 1-6 R 19 . 
     Embodiment 34 
     The compound of any of Embodiments 1-3, wherein X is 3-7 membered heterocycloalkyl optionally substituted by 1-6 R 19 . 
     Embodiment 35 
     The compound of any of Embodiments 1-3, wherein X is 5-6 membered heterocycloalkyl optionally substituted by 1-6 R 19 . 
     Embodiment 36 
     The compound of any of Embodiments 1-3, wherein X is 6 membered heterocycloalkyl optionally substituted by 1-6 R 19 . 
     Embodiment 37 
     The compound of any of Embodiments 1-3, wherein X is morpholinyl, piperidinyl, or piperazinyl optionally substituted by 1-6 R 19 . 
     Embodiment 38 
     The compound of any of Embodiments 1-3, wherein X is piperidinyl or piperazinyl optionally substituted by 1-6 R 19 . 
     Embodiment 39 
     The compound of any of Embodiments 1-3, wherein X is piperidinyl optionally substituted by 1-6 R 19 . 
     Embodiment 40 
     The compound of any of Embodiments 1-3, wherein X is piperazinyl optionally substituted by 1-6 R 19 . 
     Embodiment 41 
     The compound of any of Embodiments 1-3, wherein X is —NR 24 R 28 . 
     Embodiment 42 
     The compound of any of Embodiments 1-3, wherein X is chosen from H and 
                         
wherein
         A is —NR 1 R 2 , —CR i R j R k , —OR 18a , or —SR 18b ;   Q is —NR 11 —, —CR m R n —, —O—, or —S—;   R k  is H, halogen, —CN, —NO 2 , —NR 16 R 17 , —OR 18c , —SR 18d , or —CR o R p R q ;   R q  is H, halogen, —CN, —NO 2 , —NR 16a R 17a  or —OR 18e ;   R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 79 , C 2-6 alkenyl optionally substituted by 1-19 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-19 R 79 , C 3-11 cycloalkyl optionally substituted by 1-21 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 79 , 5-15 membered heteroaryl optionally substituted by 1-15 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 79 , and —OR 70 ;   R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 79 , C 2-6 alkenyl optionally substituted by 1-11 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11  aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-19 R 79 , C 3-11 cycloalkyl optionally substituted by 1-21 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 79 , 5-15 membered heteroaryl optionally substituted by 1-15 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —C(═O)C(═O)R 70 , —C(═NR 75 )R 70 , —C(═NR 75 )NR 72 R 73 , —C(═NOH)NR 72 R 73 , —C(═NOR 76 )R 70 , —C(═NNR 72 R 73 )R 70 , —C(═NNR 74 C(═O)R 71 )R 70 , —C(═NNR 74 C(═O)OR 71 )R 70 , —C(═S)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 NR 72 R 73 , —N═NR 74 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)C(═O)R 70 , —NR 74 C(═)OR 71 , —NR 74 C(═O)C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 C(═O)NR 74 C(═O)OR 70 , —NR 74 C(═NR 75 )NR 72 R 73 , —NR 74 C(═O)C(═O)NR 72 R 73 , —NR 74 C(═S)R 70 , —NR 74 C(═S)OR 70 , —NR 74 C(═S)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —NR 74 P(═O)R 78 R 78 , —NR 74 P(═O)(NR 72 R 73 )(NR 72 R 73 ), —NR 74 P(═O)(OR 70 )(OR 70 ), —NR 74 P(═O)(SR 70 )(SR 70 ), —OR 70 , —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —OC(═NR 75 )NR 72 R 73 , —OS(═O)R 70 , —OS(═O) 2 R 70 , —OS(═O) 2 OR 70 , —OS(═O) 2 NR 72 R 73 , —OP(═O)R 78 R 78 , —OP(═O)(NR 72 R 73 )(NR 72 R 73 ), —OP(═O)(OR 70 )(OR 70 ), —OP(═O)(SR 70 )(SR 70 ), —Si(R 74 ) 3 , —SCN, —S(═O) n R 70 , —S(═O) 2 OR 70 , —SO 3 R 77 , —S(═O) 2 NR 72 R 73 , —S(═O)NR 72 R 73 , —SP(═O)R 78 R 78 , —SP(═O)(NR 72 R 73 )(NR 72 R 73 ), —SP(═O)(OR 70 )(OR 70 ), —SP(═O)(SR 70 )(SR 70 ), —P(═O)R 78 R 78 , —P(═O)(NR 72 R 73 )(NR 72 R 73 ), —P(═O)(OR 70 )(OR 70 ), and —P(═O)(SR 70 )(SR 70 );   or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R n , R 18b  and R n , R 18c  and R i , R 18  and R 3 , R 18  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n  can, together with the atoms linking them, form a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 79 ;   or any of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 79 , C 3-11 cycloalkyl optionally substituted by 1-21 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 79 ;   or R 4  and R 5  or R n  and R 5  can together form a double bond;   or any of R 3  and R 4 , R 5  and R 6 , R i  and R j , and R m  and R n  can together form ═O, ═NR 70 , ═NOR 70 , or ═S.       

     Embodiment 43 
     The compound of any of Embodiments 1-3, wherein X is 
                         
wherein
         A is —NR 1 R 2 , —CR i R j R k , —OR 18a , or —SR 18b ;   Q is —NR 11 —, —CR m R n —, —O—, or —S—;   R k  is H, halogen, —CN, —NO 2 , —NR 16 R 17 , —OR 18c , —SR 18d , or —CR o R p R q ;   R q  is H, halogen, —CN, —NO 2 , —NR 16a R 17a  or —OR 18e      R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 79 , C 2-6 alkenyl optionally substituted by 1-11 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11  aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-19 R 79 , C 3-11 cycloalkyl optionally substituted by 1-21 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 79 , 5-15 membered heteroaryl optionally substituted by 1-15 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 79 , and —OR 70 ;   R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 79 , C 2-6 alkenyl optionally substituted by 1-11 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-19 R 79 , C 3-11 cycloalkyl optionally substituted by 1-21 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 79 , 5-15 membered heteroaryl optionally substituted by 1-15 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —C(═O)C(═O)R 70 , —C(═NR 75 )R 70 , —C(═NR 75 )NR 72 R 73 , —C(═NOH)NR 72 R 73 , —C(═NOR 76 )R 70 , —C(═NNR 72 R 73 )R 70 , —C(═NNR 74 C(═O)R 71 )R 70 , —C(═NNR 74 C(═O)OR 71 )R 70 , —C(═S)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 NR 72 R 73 , —N═NR 74 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)C(═)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 C(═O)NR 74 C(═O)OR 70 , —NR 74 C(═NR 75 )NR 72 R 73 , —NR 74 C(═O)C(═O)NR 72 R 73 , —NR 74 C(═S)R 70 , —NR 74 C(═S)OR 70 , —NR 74 C(═S)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —NR 74 P(═O)R 78 R 78 , —NR 74 P(═O)(NR 72 R 73 )(NR 72 R 73 ), —NR 74 P(═)(OR 70 )(OR 70 ), —NR 74 P(═O)(SR 70 )(SR 70 ), —OR 70 , —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —OC(═NR 75 )NR 72 R 73 , —OS(═O)R 70 , —OS(═O) 2 R 70 , —OS(═O) 2 OR 70 , —OS(═O) 2 NR 72 R 73 , —OP(═O)R 78 R 78 , —OP(═O)(NR 72 R 73 )(NR 72 R 73 ), —OP(═O)(OR 70 )(OR 70 ), —OP(═O)(SR 70 )(SR 70 ), —Si(R 74 ) 3 , —SCN, —S(═O) n R 70 , —S(═O) 2 OR 70 , —SO 3 R 77 , —S(═O) 2 NR 72 R 73 , —S(═O)NR 72 R 73 , —SP(═O)R 78 R 78 , —SP(═O)(NR 72 R 73 )(NR 72 R 73 ), —SP(═O)(OR 70 )(OR 70 ), —SP(═O)(SR 70 )(SR 70 ), —P(═O)R 78 R 78 , —P(═O)(NR 72 R 73 )(NR 72 R 73 ), —P(═O)(OR 70 )(OR 70 ), and —P(═O)(SR 70 )(SR 70 );   or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 1 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18C  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n  can, together with the atoms linking them, form a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 79 ;   or any of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 79 , C 3-11 cycloalkyl optionally substituted by 1-21 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 79 ;   or R 4  and R 5  or R n  and R 5  can together form a double bond;   or any of R 3  and R 4 , R 5  and R 6 , R i  and R j , and R m  and R n  can together form ═O, ═NR 70 , ═NOR 70 , or ═S.       

     Embodiment 44 
     The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 2-6 alkenyl optionally substituted by 1-11 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-11 cycloalkyl optionally substituted by 1-10 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-10 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-10 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-10 R 79 , 5-15 membered heteroaryl optionally substituted by 1-10 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-10 R 79 , and —OR 70 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 2-6 alkenyl optionally substituted by 1-10 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-10 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-11 cycloalkyl optionally substituted by 1-10 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-10 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-10 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-10 R 79 , 5-15 membered heteroaryl optionally substituted by 1-10 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-10 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —(═O)C(═O)R 70 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 NR 72 R 73 , —N═NR 74 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)C(═)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 C(═O)NR 74 C(═O)OR 70 , —NR 74 C(═O)C(═O)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —NR 74 P(═O)R 78 R 78 , —NR 74 P(═O)(NR 72 R 73 )(NR 72 R 73 ), —NR 74 P(═O)(OR 70 )(OR 70 ), —OR 70 , —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —OS(═O)R 70 , —OS(═O) 2 R 70 , —OS(═O) 2 OR 70 , —OS(═O) 2 NR 72 R 73 , —OP(═O)R 78 R 78 , —OP(═O)(NR 72 R 73 )(NR 72 R 73 ), —OP(═O)(OR 70 )(OR 70 ), —Si(R 74 ) 3 , —SCN, —S(═O) n R 70 , —S(═O) 2 OR 70 , —SO 3 R 77 , —S(═O) 2 NR 72 R 73 , —S(═O)NR 72 R 73 , —SP(═O)R 78 R 78 , —SP(═O)(NR 72 R 73 )(NR 72 R 73 ), —SP(═O)(OR 70 )(OR 70 ), —SP(═O)(SR 70 )(SR 70 ), —P(═O)R 78 R 78 , —P(═O)(NR 72 R 73 )(NR 72 R 73 ), and —P(═O)(OR 70 )(OR 70 ); or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 11 , R 18e  and R 11 , R 18e  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n  can, together with the atoms linking them, form a 3-15 membered heterocycloalkyl optionally substituted by 1-10 R 79  or a 5-15 membered heteroaryl optionally substituted by 1-10 R 79 ; or any of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-10 R 79 , C 3-11 cycloalkyl optionally substituted by 1-10 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-10 R 79  or a 5-15 membered heteroaryl optionally substituted by 1-10 R 79 ; or R 4  and R 5  or R n  and R 5  can together form a double bond; or any of R 3  and R 4 , R 5  and R 6 , R i  and R j , and R m  and R n  can together form ═O, ═NR 70 , ═NOR 70 , or ═S. 
     Embodiment 45 
     The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 2-6 alkenyl optionally substituted by 1-11 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-11 cycloalkyl optionally substituted by 1-10 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-10 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-10 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-10 R 79 , 5-15 membered heteroaryl optionally substituted by 1-10 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-10 R 79 , and —OR 70 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 2-6 alkenyl optionally substituted by 1-10 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-10 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-11 cycloalkyl optionally substituted by 1-10 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-10 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-10 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-10 R 79 , 5-15 membered heteroaryl optionally substituted by 1-10 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-10 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —C(═O)C(═O)R 70 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 NR 72 R 73 , —N═NR 74 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —NR 74 P(═O)R 78 R 78 , —NR 74 P(═O)(NR 72 R 73 )(NR 72 R 73 ), —NR 74 P(═)(OR 70 )(OR 70 ), —OR 70 , —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —OS(═O)R 70 , —OS(═O) 2 R 70 , —OS(═O) 2 OR 70 , —OS(═O) 2 NR 72 R 73 , —OP(═O)R 78 R 78 , —OP(═O)(NR 72 R 73 )(NR 72 R 73 ), —OP(═O)(OR 70 )(OR 70 ), —SCN, —S(═O) n R 70 , —S(═O) 2 R 70 , —SO 3 R 77 , —S(═O) 2 NR 72 R 73 , —S(═O)NR 72 R 73 , —SP(═O)R 78 R 78 , —SP(═O)(NR 72 R 73 )(NR 72 R 73 ), —SP(═O)(OR 70 )(OR 70 ), —SP(═O)(SR 70 ), —P(═O)R 78 R 78 , —P(═O)(NR 72 R 73 )(NR 72 R 73 ), and —P(═O)(OR 70 )(OR 70 ); or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n  can, together with the atoms linking them, form a 3-15 membered heterocycloalkyl optionally substituted by 1-10 R 79  or a 5-15 membered heteroaryl optionally substituted by 1-10 R 79 ; or any of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-10 R 79 , C 3-11 cycloalkyl optionally substituted by 1-10 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-10 R 79  or a 5-15 membered heteroaryl optionally substituted by 1-10 R 79 ; or R 4  and R 5  or R n  and R 5  can together form a double bond; or any of R 3  and R 4 , R 5  and R 6 , R i  and R j , and R m  and R n  can together form ═O. 
     Embodiment 46 
     The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 2-6 alkenyl optionally substituted by 1-11 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-10 cycloalkyl optionally substituted by 1-10 R 79 , C 4-11 cycloalkylalkyl optionally substituted by 1-10 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-10 R 79 , 4-11 membered heterocycloalkylalkyl optionally substituted by 1-10 R 79 , 5-11 membered heteroaryl optionally substituted by 1-10 R 79 , and 6-12 membered heteroarylalkyl optionally substituted by 1-10 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 2-6 alkenyl optionally substituted by 1-10 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-10 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-10 cycloalkyl optionally substituted by 1-10 R 79 , C 4-11 cycloalkylalkyl optionally substituted by 1-10 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-10 R 79 , 4-11 membered heterocycloalkylalkyl optionally substituted by 1-10 R 79 , 5-11 membered heteroaryl optionally substituted by 1-10 R 79 , 6-12 membered heteroarylalkyl optionally substituted by 1-10 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 NR 72 R 73 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —OR 70 , —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OS(═O)R 70 , —OS(═) 2 R 70 , —OS(═) 2 OR 70 , —OS(═) 2 NR 72 R 73 , —SCN, —S(═O) n R 70 , —S(═O) 2 OR 70 , —SO 3 R 77 , —S(═O) 2 NR 72 R 73 , and —S(═O)NR 72 R 73 ; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-10 R 79  or a 5-11 membered heteroaryl optionally substituted by 1-10 R 79 ; or any of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-10 R 79 , C 3-10 cycloalkyl optionally substituted by 1-10 R 79 , 3-11 membered heterocycloalkyl optionally substituted by 1-10 R 79  or a 5-11 membered heteroaryl optionally substituted by 1-10 R 79 ; or R 4  and R 5  or R n  and R 5  can together form a double bond; or any of R 3  and R 4 , R 5  and R 6 , R i  and R j , and R m  and R n  can together form ═O. 
     Embodiment 47 
     The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 2-6 alkenyl optionally substituted by 1-11 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-10 cycloalkyl optionally substituted by 1-10 R 79 , C 4-11 cycloalkylalkyl optionally substituted by 1-10 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-10 R 79 , 4-11 membered heterocycloalkylalkyl optionally substituted by 1-10 R 79 , 5-11 membered heteroaryl optionally substituted by 1-10 R 79 , and 6-12 membered heteroarylalkyl optionally substituted by 1-10 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 2-6 alkenyl optionally substituted by 1-10 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-10 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-10 cycloalkyl optionally substituted by 1-10 R 79 , C 4-11 cycloalkylalkyl optionally substituted by 1-10 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-10 R 79 , 4-11 membered heterocycloalkylalkyl optionally substituted by 1-10 R 79 , 5-11 membered heteroaryl optionally substituted by 1-10 R 79 , 6-12 membered heteroarylalkyl optionally substituted by 1-10 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —OR 70 , —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —SCN, —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-10 R 79  or a 5-11 membered heteroaryl optionally substituted by 1-10 R 79 ; or any of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-10 R 79 , C 3-10 cycloalkyl optionally substituted by 1-10 R 79 , 3-11 membered heterocycloalkyl optionally substituted by 1-10 R 79  or a 5-11 membered heteroaryl optionally substituted by 1-10 R 79 ; or R 4  and R 5  or R n  and R 5  can together form a double bond; or any of R 3  and R 4 , R 5  and R 6 , R i  and R j , and R m  and R n  can together form ═O. 
     Embodiment 48 
     The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-10 cycloalkyl optionally substituted by 1-10 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-10 R 79 , and 5-11 membered heteroaryl optionally substituted by 1-10 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 2-6 alkenyl optionally substituted by 1-10 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-10 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-10 cycloalkyl optionally substituted by 1-10 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-10 R 79 , 5-11 membered heteroaryl optionally substituted by 1-10 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —OR 70 , —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-10 R 79  or a 5-11 membered heteroaryl optionally substituted by 1-10 R 79 ; or any of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-10 R 79 , C 3-10 cycloalkyl optionally substituted by 1-10 R 79 , 3-11 membered heterocycloalkyl optionally substituted by 1-10 R 79  or a 5-11 membered heteroaryl optionally substituted by 1-10 R 79 ; or R 4  and R 5  or R n  and R 5  can together form a double bond; or any of R 3  and R 4 , R 5  and R 6 , R i  and R j , and R m  and R n  can together form ═O. 
     Embodiment 49 
     The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 6-11 aryl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 79 , and 5-11 membered heteroaryl optionally substituted by 1-6 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkenyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 6-11 aryl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 79 , 5-11 membered heteroaryl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —OR 70 , —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79  or a 5-11 membered heteroaryl optionally substituted by 1-6 R 79 ; or any of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79  or a 5-11 membered heteroaryl optionally substituted by 1-6 R 79 ; or R 4  and R 5  or R n  and R 5  can together form a double bond; or any of R 3  and R 4 , R 5  and R 6 , R i  and R j , and R m  and R n  can together form ═O. 
     Embodiment 50 
     The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NO 2 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 2R; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m  can, together with the atoms linking them, form a C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , or a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3  and R 4 , R 5  and R 6 , R i  and R j , and R m  and R n  can together form ═O. 
     Embodiment 51 
     The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-6 membered heterocycloalkyl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , and R 18c  and R n  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m  can, together with the atoms linking them, form a C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , or a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3  and R 4 , R 5  and R 6 , R i  and R j , and R m  and R n  can together form ═O. 
     Embodiment 52 
     The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , and R 18c  and R n  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3  and R 4 , R 5  and R 6 , R i  and R l , and R m  and R n  can together form ═O. 
     Embodiment 53 
     The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R l , R m , R n , R o , and R p  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 2R; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 1 , R 16  and R n , R j  and R 11 , and R 18a  and R 11  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3  and R 4 , R 5  and R 6 , R i  and R j , and R m  and R n  can together form ═O. 
     Embodiment 54 
     The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R l , R m , R n , R o , and R p  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═) n R 70 , and —S(═O) 2 NR 72 R 73 2R; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 16  and R 5 , R j  and R 11 , and R 18a  and R 11  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or R 3  and R 4  can together form ═O. 
     Embodiment 55 
     The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , —CN, —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , and —OR 70 ; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 16  and R 5 , R j  and R 11 , and R 18a  and R 11  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or R 3  and R 4  can together form ═O. 
     Embodiment 56 
     The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 3  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —OR 70 , —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 18d , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18e  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 1 , and R 18d  and R n  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79  or a 5-11 membered heteroaryl optionally substituted by 1-6 R 79 ; or any of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79  or a 5-11 membered heteroaryl optionally substituted by 1-6 R 79 ; or R 4  and R 5  or R n  and R 5  can together form a double bond; or any of R 3  and R 4 , R 5  and R 6 , R i  and R j , and R m  and R n  can together form ═O. 
     Embodiment 57 
     The compound of Embodiments 42 or 43, wherein R 1 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 2  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 3  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NO 2 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m  can, together with the atoms linking them, form a C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , or a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3  and R 4 , R 5  and R 6 , R i  and R j , and R m  and R n  can together form ═O. 
     Embodiment 58 
     The compound of Embodiments 42 or 43, wherein R 1 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 2  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 3  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-6 membered heterocycloalkyl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , and R 18c  and R n  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m  can, together with the atoms linking them, form a C 3-10 -cycloalkyl optionally substituted by 1-6 R 79 , or a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3  and R 4 , R 5  and R 6 , R i  and R j , and R m  and R n  can together form ═O. 
     Embodiment 59 
     The compound of Embodiments 42 or 43, wherein R 1 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 2  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 3  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , and R 18c  and R n  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3  and R 4 , R 5  and R 6 , R i  and R j , and R m  and R n  can together form ═O. 
     Embodiment 60 
     The compound of any of Embodiments 42-59, wherein 0-3 of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl or an optionally substituted heteroaryl. 
     Embodiment 61 
     The compound of any of Embodiments 42-59, wherein 0-2 of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl or an optionally substituted heteroaryl. 
     Embodiment 62 
     The compound of any of Embodiments 42-59, wherein 1-2 of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl or an optionally substituted heteroaryl. 
     Embodiment 63 
     The compound of any of Embodiments 42-59, wherein none of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R i , R 18d  and R 3 , R 18d  and R, R 18d  and R 11 , and R 18d  and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl or an optionally substituted heteroaryl. 
     Embodiment 64 
     The compound of any of Embodiments 42-59, wherein one of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl or an optionally substituted heteroaryl. 
     Embodiment 65 
     The compound of any of Embodiments 42-59, wherein two of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl or an optionally substituted heteroaryl. 
     Embodiment 66 
     The compound of any of Embodiments 42-59, wherein 0-3 of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl. 
     Embodiment 67 
     The compound of any of Embodiments 42-59, wherein 0-2 of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl. 
     Embodiment 68 
     The compound of any of Embodiments 42-59, wherein 1-2 of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl. 
     Embodiment 69 
     The compound of any of Embodiments 42-59, wherein none of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl. 
     Embodiment 70 
     The compound of any of Embodiments 42-59, wherein one of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18 , R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl. 
     Embodiment 71 
     The compound of Embodiment 70, wherein said optionally substituted heterocarbocyclyl is a 3-7 membered heterocarbocycl optionally substituted with 1-4 R 79 . 
     Embodiment 72 
     The compound of Embodiment 70, wherein said optionally substituted heterocarbocyclyl is a 5-6 membered heterocarbocycl optionally substituted with 1-4 R 79 . 
     Embodiment 73 
     The compound of any of Embodiments 42-59, wherein two of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl. 
     Embodiment 74 
     The compound of any of Embodiments 42-73, wherein 0-2 of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m , together with the atoms linking them, form an optionally substutituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl. 
     Embodiment 75 
     The compound of any of Embodiments 42-73, wherein 0-1 of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R, R i  and R 4 , R i  and R 5 , R 1  and R n , R m  and R n , R 4  and R m , and R 6  and R m , together with the atoms linking them, form an optionally substutituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl. 
     Embodiment 76 
     The compound of any of Embodiments 42-73, wherein none of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R 1  and R, R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m , together with the atoms linking them, form an optionally substutituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl. 
     Embodiment 77 
     The compound of any of Embodiments 42-73, wherein one of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m , together with the atoms linking them, form an optionally substutituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl. 
     Embodiment 78 
     The compound of any of Embodiments 42-73, wherein 0-2 of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m , together with the atoms linking them, form an optionally substutituted cycloalkyl or optionally substituted heterocycloalkyl. 
     Embodiment 79 
     The compound of any of Embodiments 42-73, wherein 0-1 of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m , together with the atoms linking them, form an optionally substutituted cycloalkyl or optionally substituted heterocycloalkyl. 
     Embodiment 80 
     The compound of any of Embodiments 42-73, wherein none of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m , together with the atoms linking them, form an optionally substutituted cycloalkyl or optionally substituted heterocycloalkyl. 
     Embodiment 81 
     The compound of any of Embodiments 42-73, wherein one of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m , together with the atoms linking them, form an optionally substutituted cycloalkyl or optionally substituted heterocycloalkyl. 
     Embodiment 82 
     The compound of any of Embodiments 42-73, wherein 0-2 of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R 1  and R, R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m , together with the atoms linking them, form an optionally substutituted heterocycloalkyl. 
     Embodiment 83 
     The compound of any of Embodiments 42-73, wherein 0-1 of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m , together with the atoms linking them, form an optionally substutituted heterocycloalkyl. 
     Embodiment 84 
     The compound of any of Embodiments 42-73, wherein none of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m , together with the atoms linking them, form an optionally substutituted heterocycloalkyl. 
     Embodiment 85 
     The compound of any of Embodiments 42-73, wherein one of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m , together with the atoms linking them, form an optionally substutituted heterocycloalkyl. 
     Embodiment 86 
     The compound of Embodiment 85, wherein said optionally substituted heterocarbocyclyl is a 3-7 membered heterocarbocycl optionally substituted with 1-4 R 79 . 
     Embodiment 87 
     The compound of Embodiment 85, wherein said optionally substituted heterocarbocyclyl is a 5-6 membered heterocarbocycl optionally substituted with 1-4 R 79 . 
     Embodiment 88 
     The compound of any of Embodiments 42-87, wherein neither R 4  and R 5  nor R n  and R 5  together form a double bond. 
     Embodiment 89 
     The compound of any of Embodiments 42-88, wherein none of R 3  and R 4 , R 5  and R 6 , R i  and R j , or R m  and R n  together form ═O, ═NR 70 , ═NOR 70 , or ═S. 
     Embodiment 90 
     The compound of Embodiments 42 or 43, wherein R 1 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are H; R 2  is chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are H; R 3  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , and R 18a  and R 11  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3  and R 4 , R 5  and R 6 , R i  and R j , and R m  and R n  can together form ═O. 
     Embodiment 91 
     The compound of Embodiments 42 or 43, wherein R 1 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are H; R 2  is chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are H; R 3  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 1 , R 16  and R 5 , R l  and R 1 , and R 18a  and R 11  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or R 3  and R 4  can together form ═O. 
     Embodiment 92 
     The compound of Embodiments 42 or 43, wherein R 1 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are H; R 2  is chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are H; R 3  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , —CN, —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , and —OR 70 ; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 1 , R 16  and R 5 , R j  and R 11 , and R 18a  and R 11  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or R 3  and R 4  can together form ═O. 
     Embodiment 93 
     The compound of any of Embodiments 42-89, wherein at least five of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are H; and at least four of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are H. 
     Embodiment 94 
     The compound of any of Embodiments 42-89, wherein at least five of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are H; and at least five of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are H. 
     Embodiment 95 
     The compound of any of Embodiments 42-89, wherein at least six of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are H; and at least five of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are H. 
     Embodiment 96 
     The compound of any of Embodiments 42-89, wherein at least six of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are H; and at least six of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are H. 
     Embodiment 97 
     The compound of any of Embodiments 42-89, wherein at least seven of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are H; and at least six of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are H. 
     Embodiment 98 
     The compound of any of Embodiments 42-89, wherein at least seven of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are H; and at least seven of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are H. 
     Embodiment 99 
     The compound of any of Embodiments 42-89, wherein at least eight of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are H; and at least seven of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are H. 
     Embodiment 100 
     The compound of any of Embodiments 42-89, wherein at least eight of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are H; and at least eight of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are H. 
     Embodiment 101 
     The compound of any of Embodiments 42-89, wherein at least nine of R, R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18 , R 18d , and R 18e  are H; and at least eight of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are H. 
     Embodiment 102 
     The compound of any of Embodiments 42-89, wherein at least nine of R, R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18 , R 18d , and R 18e  are H; and at least nine of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are H. 
     Embodiment 103 
     The compound of any of Embodiments 42-89, wherein at least ten of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R e  are H; and at least nine of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are H. 
     Embodiment 104 
     The compound of any of Embodiments 42-89, wherein at least eleven of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are H; and at least nine of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are H. 
     Embodiment 105 
     The compound of any of Embodiments 42-89, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are H; and at least nine of R 3 , R 4 , R 5 , R 6 , R i  R j , R m , R n , R o , and R p  are H. 
     Embodiment 106 
     The compound of any of Embodiments 42-89, wherein at least eleven of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are H; and R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are H. 
     Embodiment 107 
     The compound of any of Embodiments 42-106, wherein R q  is H, —NR 16a R 7a  or —OR 18e . 
     Embodiment 108 
     The compound of any of Embodiments 42-106, wherein R q  is —NR 16a R 7a  or —OR 18e . 
     Embodiment 109 
     The compound of any of Embodiments 42-108, wherein R k  is H, halogen, —CN, —NR 16 R 17 , —OR 18 , —SR 18d , or —CR o R p R q . 
     Embodiment 110 
     The compound of any of Embodiments 42-108, wherein R k  is H, —CN, —NR 16 R 17 , —OR 18c , —SR 18d , or —CR o R p R q . 
     Embodiment 111 
     The compound of any of Embodiments 42-108, wherein R k  is H, —CN, —NR 16 R 17 , —OR 18c , or —CR o R p R q . 
     Embodiment 112 
     The compound of any of Embodiments 42-108, wherein R k  is H, —NR 16 R 17 , —OR 18c , or —CR o R p R q . 
     Embodiment 113 
     The compound of any of Embodiments 42-108, wherein R k  is —NR 16 R 17 , —OR 18c , or —CR o R p R q . 
     Embodiment 114 
     The compound of any of Embodiments 42-106, wherein R k  is H. 
     Embodiment 115 
     The compound of any of Embodiments 42-106, wherein R k  is —NR 16 R 17 . 
     Embodiment 116 
     The compound of any of Embodiments 42-106, wherein R k  is —OR 18c . 
     Embodiment 117 
     The compound of any of Embodiments 42-108, wherein R k  is —CR o R p R q . 
     Embodiment 118 
     The compound of any of Embodiments 42-117, wherein A is —NR 1 R 2 , —CR i R j R k , or —OR 18a . 
     Embodiment 119 
     The compound of any of Embodiments 42-106, wherein A is —NR 1 R 2  or —OR 18a . 
     Embodiment 120 
     The compound of any of Embodiments 42-117, wherein A is —CR i R j R k . 
     Embodiment 121 
     The compound of any of Embodiments 42-106, wherein A is —NR 1 R 2 . 
     Embodiment 122 
     The compound of any of Embodiments 42-106, wherein A is —OR 18a . 
     Embodiment 123 
     The compound of any of Embodiments 42-122, wherein Q is —NR 11 —, —CR m R n —, or —O—. 
     Embodiment 124 
     The compound of any of Embodiments 42-122, wherein Q is —NR 11 —. 
     Embodiment 125 
     The compound of any of Embodiments 42-122, wherein Q is —CR m R n —. 
     Embodiment 126 
     The compound of any of Embodiments 42-122, wherein Q is —O—. 
     Embodiment 127 
     The compound of any of Embodiments 42-106, wherein A is —NR 1 R 2 , —CR i R j R k , or —OR 18a ; Q is —NR 11 —, —CR m R n —, or —O—; and R k  is —NR 16 R 17 , or —OR 18c . 
     Embodiment 128 
     The compound of any of Embodiments 42-106, wherein A is —NR 1 R 2 , —CR i R j R k , or —OR 18a ; Q is —NR 11 —; and R k  is —NR 16 R 17 , or —OR 18c . 
     Embodiment 129 
     The compound of any of Embodiments 42-106, wherein A is —NR 1 R 2 , —CR i R j R k , or —OR 18a ; Q is —NR 11 —; and R k  is —OR 18c . 
     Embodiment 130 
     The compound of any of Embodiments 42-106, wherein A is —NR 1 R 2  or —OR 18a ; and Q is —NR 11 —. 
     Embodiment 131 
     The compound of any of Embodiments 42-106, wherein A is —NR 1 R 2 ; and Q is —NR 11 —. 
     Embodiment 132 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NHR 28  and 3-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 . 
     Embodiment 133 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NHR 28  and 5-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 . 
     Embodiment 134 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NHR 28  and 5-9 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 . 
     Embodiment 135 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NHR 28  and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 . 
     Embodiment 136 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NHR 28  and 5-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 6-11 aryl optionally substituted by 1-3 R 39 , C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 . 
     Embodiment 137 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NHR 28  and 5-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, C 6-11 aryl, C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heterocycloalkyl, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 . 
     Embodiment 138 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NHR 28  and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, C 6-11 aryl, C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heterocycloalkyl, halogen, —CN, —C(═)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 . 
     Embodiment 139 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NHR 28  and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 . 
     Embodiment 140 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NHR 28  and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, and —OH. 
     Embodiment 141 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-6 R 49 ), —NH(3-10 membered heterocycloalkyl optionally substituted by 1-6 R 49 ), —NH(4-11 membered heterocycloalkylalkyl optionally substituted by 1-6 R 49 ), and 3-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 . 
     Embodiment 142 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-6 R 49 ), —NH(3-10 membered heterocycloalkyl), —NH(4-11 membered heterocycloalkylalkyl), and 3-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 . 
     Embodiment 143 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-3 R 49 ), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 . 
     Embodiment 144 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-3 R 49 ), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-9 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 . 
     Embodiment 145 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-3 R 49 ), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 . 
     Embodiment 146 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-3 R 49 ), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 6-11 aryl optionally substituted by 1-3 R 39 , C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)OR 3 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 . 
     Embodiment 147 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-3 R 49 ), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, C 6-11 aryl, C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heterocycloalkyl, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)OR 30 , and —OR 30 . 
     Embodiment 148 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-3 R 49 ), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, C 6-11 aryl, C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heterocycloalkyl, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 . 
     Embodiment 149 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 . 
     Embodiment 150 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 . 
     Embodiment 151 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(5-6 membered heterocycloalkyl), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, and —OH. 
     Embodiment 152 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl), —NH(5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms), —NH(6-10 membered heterocycloalkylalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, C 6-11 aryl, C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heterocycloalkyl, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 3 , and —OR 30 . 
     Embodiment 153 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(benzyl), —NH(5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms), —NH(6-10 membered heterocycloalkylalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 . 
     Embodiment 154 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms), —NH(6-10 membered heterocycloalkylalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 . 
     Embodiment 155 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, and —OH. 
     Embodiment 156 
     The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ) and —NH(5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms). 
     Embodiment 200 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —C(═O)C(═O)R 20 , —C(═NR 25 )R 20 , —C(═NR 25 )NR 22 R 23 , —C(═NOH)NR 22 R 23 , —C(═NOR 26 )R 20 , —C(═NNR 22 R 23 )R 20 , —C(═NNR 24 C(═O)R 21 )R 20 , —C(═NNR 24 C(═O)OR 21 )R 20 , —C(═S)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═NR 25 )NR 22 R 23 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 C(═S)R 20 , —NR 24 C(═S)OR 20 , —NR 24 C(═S)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 4 P(═O)R 78 R 78 , —NR 24 P(═O)(NR 22 R 23 )(N 22 R 23 ), —NR 24 P(═O)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OC(═NR 25 )NR 22 R 23 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 78 R 78 , —OP(═O)(NR 22 R 23 )(NR 22 R 23 ), —OP(═O)(OR 20 )(OR 20 ), —OP(═O)(SR 20 )(SR 20 ), —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —SP(═O)R 78 R 78 , —SP(═O)(NR 22 R 23 )(NR 22 )(NR 23 ), —SP(═O)(OR 20 )(OR 20 ), —SP(═O)(SR 20 )(SR 20 ), —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), —P(═O)(OR 20 )(OR 20 ), and —P(═O)(SR 20 )(SR 20 ); or R and R 8  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 19 . 
     Embodiment 201 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OS(═O) 2 R 20 , —OS(═O) 20 R 20 , —OS(═O) 2 NR 22 R 23 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7  and R 8  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 19 . 
     Embodiment 202 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OS(═) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7  and R 8  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 203 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-4 R 19 , C 2-6 alkenyl optionally substituted by 1-4 R 19 , C 2-6 alkynyl optionally substituted by 1-4 R 19 , C 6-10 aryl optionally substituted by 1-4 R 19 , C 7-11 arylalkyl optionally substituted by 1-4 R 19 , C 3-7 cycloalkyl optionally substituted by 1-4 R 19 , C 4-8 cycloalkylalkyl optionally substituted by 1-4 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-4 R 19 , 4-8 membered heterocycloalkylalkyl optionally substituted by 1-4 R 19 , 5-6 membered heteroaryl optionally substituted by 1-4 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-4 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═)OR 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7  and R 8  can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-4 R 19 , C 3-7 cycloalkyl optionally substituted by 1-4 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-4 R 19  or a 5-6 membered heteroaryl optionally substituted by 1-4 R 19 . 
     Embodiment 204 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , C 4-8 cycloalkylalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 4-8 membered heterocycloalkylalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —S(═) n R 20  and —S(═O) 2 NR 22 R 23 ; or R 7  and R 8  can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19  or a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 205 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , C 4-8 cycloalkylalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 4-8 membered heterocycloalkylalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OS(═O) 2 R 20 , —OS(═O) 2 NR 22 R 23 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7  and R 8  can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19  or a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 206 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , C 4-8 cycloalkylalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 4-8 membered heterocycloalkylalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7  and R 8  can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19  or a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 207 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 7-11 arylalkyl, C 3-7 cycloalkyl, C 4-8 cycloalkylalkyl, 3-7 membered heterocycloalkyl, 4-8 membered heterocycloalkylalkyl, 5-6 membered heteroaryl, 6-21 membered heteroarylalkyl, halogen, —CN, —C(═O)R 20 , —C(═)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 , R 23 ; or R 7  and R 8  can, together with the atoms linking them, form a C 6-10 aryl, C 3-7 cycloalkyl, 3-7 membered heterocycloalkyl or a 5-6 membered heteroaryl. 
     Embodiment 208 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , C 4-8 cycloalkylalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 4-8 membered heterocycloalkylalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7  and R 8  can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19  or a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 209 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7  and R 8  can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19  or a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 210 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7  and R 8  can, together with the atoms linking them, form a C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , or a 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 . 
     Embodiment 211 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)R 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7  and R 8  can, together with the atoms linking them, form a C 3-7 cycloalkyl, or a 3-7 membered heterocycloalkyl. 
     Embodiment 212 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , and —OR 20 ; or R 7  and R 8  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 9 . 
     Embodiment 213 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , and —OR 20 ; or R 7  and R 8  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 19 . 
     Embodiment 214 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)NR 22 R 23 , —NR 22 R 23 , —NR 24 C(═O)R 20 , and —OR 20 ; or R 7  and R 8  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 19 . 
     Embodiment 215 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)NR 22 R 23 , —NR 22 R, —NR 24 C(═O)R 20 , and —OR 20 ; R 8  is chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)NR 22 R 23 , —NR 22 R, —NR 24 C(═O)R 20 , and —OR 20 ; or R 7  and R 8  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 19 . 
     Embodiment 216 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)NR 22 R 23 )(NR)(NR 23 ), —NR 24 P(═)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═)OR 20 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 78 R 78 , —OP(═O)(NR 22 R 23 )(NR 22 R 23 ), —OP(═O)(OR 20 )(OR 20 ), —OP(═O)(SR 20 )(SR 20 ), —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —SP(═O)R 78 R 78 , —SP(═O)(NR 22 R 23 )(NR 22 R 23 ), —SP(═O)(OR 20 )(OR 20 ), —SP(═O)(SR 20 )(SR 20 ), —P(═O)R 78 R 78 , —P(═O)(NR 22 R)(NR 22 R 23 ), —P(═O)(OR 20 )(OR 20 ), and —P(═O)(SR 20 )(SR 20 ); or R and R 8  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 19 . 
     Embodiment 217 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 R 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , and —S(═O)NR 22 R 23 ; or R 7  and R 8  can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 218 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-10 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 2 C(═)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 NR 22 R 23 , —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , and —S(═O)NR 22 R 23 ; or R 7  and R 8  can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 219 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —Si(R 24 ) 3 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7  and R 8  can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 220 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —Si(R 24 ) 3 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 . 
     Embodiment 221 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , halogen, —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 . 
     Embodiment 222 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 . 
     Embodiment 222 
     The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —S(═O) n R 20 . 
     Embodiment 223 
     The compound of any of Embodiments 1-156 or 200-222, wherein R 8  is not phenyl or morpholinyl. 
     Embodiment 224 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , halogen, —CN, —C(═O)R 20 , —C(═)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; R 8  is chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; and R 9  is chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 20 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 . 
     Embodiment 225 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , (═)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; R 8  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; and R 9  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 . 
     Embodiment 226 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —(═)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; R 8  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; and R 9  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 . 
     Embodiment 227 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —OC(═O)R 20 , —S(═) n R 20 , and —S(═O) 2 NR 22 R 23 ; R 8  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , and halogen; and R 9  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 20 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═) n R 20  and —S(═O) 2 NR 22 R 23 . 
     Embodiment 228 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20  and —OC(═O)R 20 ; R 8  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , and halogen; and R 9  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 . 
     Embodiment 229 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 3-10 -cycloalkyl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; R 8  is chosen from H and halogen; and R 9  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —OC(═O)R 20 , and —S(═O) n R 20 . 
     Embodiment 230 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 3-10 -cycloalkyl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; R 8  is chosen from H and halogen; and R 9  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —S(═O) n R 20 . 
     Embodiment 231 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 3-10 -cycloalkyl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; R 8  is chosen from H and halogen; and R 9  is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-10 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —S(═O) n R 20 . 
     Embodiment 232 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 3-6 cycloalkyl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; R 8  is chosen from H and halogen; and R 9  is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —S(═O) n R 20 . 
     Embodiment 233 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 3-6 cycloalkyl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; R 8  is chosen from H and halogen; and R 9  is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5, 6, or 9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —S(═O) n R 20 . 
     Embodiment 234 
     The compound of any of Embodiments 1-156 or 200-233, wherein R 8  is H. 
     Embodiment 235 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 3-10 -cycloalkyl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; R 8  is chosen from H and halogen; and R 9  is chosen from H, C 1-6 alkyl, C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —SR 20 . 
     Embodiment 236 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, C 1-6 alkyl, C 3-6 cycloalkyl, halogen, —NR 22 R 23 , and —OR 20 ; R 8  is chosen from H and halogen; and R 9  is chosen from H, C 2-6 alkynyl, C 6-10 aryl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, halogen, —NR 22 R 23 , —OR 20 , and —SR 20 . 
     Embodiment 237 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, C 3-6 cycloalkyl, and —OR 20 ; R 8  is chosen from H and halogen; and R 9  is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —SR 20 . 
     Embodiment 238 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, C 3-6 cycloalkyl, and —OR 20 ; R 8  is chosen from H and halogen; and R 9  is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5, 6, or 9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —SR 20 . 
     Embodiment 239 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, C 3-6 cycloalkyl, and —O(C 1-6 alkyl); R 8  is chosen from H and halogen; and R 9  is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5, 6, or 9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —SR 20 . 
     Embodiment 240 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, C 3-6 cycloalkyl, and —OR 20 ; R 8  is H; and R 9  is H. 
     Embodiment 241 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, C 3-6 cycloalkyl, and —O(C 1-6 alkyl); R 8  is H; and R 9  is H. 
     Embodiment 242 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, cyclopropyl, and —O(C 1-6 alkyl); R 8  is chosen from H and halogen; and R 9  is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5, 6, or 9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —SR 20 . 
     Embodiment 243 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, cyclopropyl, and —OR 20 ; R 8  is H; and R 9  is H. 
     Embodiment 244 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, cyclopropyl, and —O(C 1-6 alkyl); R 8  is H; and R 9  is H. 
     Embodiment 245 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, cyclopropyl, and —O(CH 3 ); R 8  is H; and R 9  is H. 
     Embodiment 246 
     The compound of any of Embodiments 1-156, wherein R 7  is H; R 8  is H; and R 9  is H. 
     Embodiment 247 
     The compound of any of Embodiments 1-156, wherein R 7  is cyclopropyl; R 8  is H; and R 9  is H. 
     Embodiment 248 
     The compound of any of Embodiments 1-156, wherein R 7  is —O(CH 3 ); R 8  is H; and R 9  is H. 
     Embodiment 249 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, cyclopropyl, and —O(C 1-6 alkyl); R 8  is chosen from H and halogen; and R 9  is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5, 6, or 9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —SR 20 . 
     Embodiment 250 
     The compound of any of Embodiments 1-156, wherein R 7  is chosen from H, C 3-6 cycloalkyl, and —O(CH 3 ); R 8  is chosen from H and halogen; and R 9  is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5, 6, or 9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —SR 20 . 
     Embodiment 300 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 2 , R 13 , R 14 , and R 15  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —C(═O)C(═O)R 20 , —C(═NR 25 )R 20 , —C(═NR 25 )NR 22 R 23 , —C(═NOH)NR 22 R 23 , —C(═NOR 26 )R 20 , —C(═NNR 22 R 23 )R 20 , —C(═NNR 24 C(═O)R 21 )R 20 , —C(═NNR 24 C(═O)OR 21 )R 20 , —C(═S)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 2 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═NR 25 )NR 22 R 23 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 C(═S)R 20 , —NR 24 C(═S)OR 20 , —NR 24 C(═S)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)NR 22 R 23 )(NR 22 R 23 ), —NR 24 P(═)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OC(═NR 25 )NR 22 R 23 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 78 R 78 , —OP(═O)(NR 22 R 23 )(NR 22 R 23 ), —OP(═O)(OR 20 )(OR 20 ), —OP(═O)(SR 20 )(SR 20 ), —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —SP(═O)R 78 R 78 , —SP(═O)(NR 22 R 23 )(NR 22 R 23 ), —SP(═O)(OR 20 )(R 20 ), —SP(═O)(SR 20 )(SR 20 ), —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), —P(═O)(OR 20 )(OR 20 ), and —P(═O)(SR 20 )(SR 20 ); or either or both of R 12  and R 13 , and/or R 14  and R 15 , can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 301 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 13 , R 14 , and R 15  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)(NR 22 R 23 )(NR 22 R 23 ), —NR 24 P(═O)(OR 20 )(OR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 78 R 78 , —OP(═O)(NR 22 R 23 )(NR 22 R 23 ), —OP(═O)(OR 20 )(OR 20 ), —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), and —P(═O)(OR 20 )(OR 20 ); or either or both of R 12  and R 13 , and/or R 14  and R 15 , can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 302 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 13 , R 14 , and R 15  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR, —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)(NR 22 R 23 )(N 22 R 23 ), —NR 24 P(═O)(OR 20 )(OR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 78 R 78 , —OP(═O)(NR 22 R 23 )(NR 22 R 23 ), —OP(═O)(OR 20 )(OR 20 ), —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), and —P(═O)(OR 20 )(OR 20 ); or either or both of R 12  and R 13 , and/or R 14  and R 15 , can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 303 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 13 , R 14 , and R 15  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), and —P(═O)(OR 20 )(OR 20 ); or either or both of R 12  and R 13 , and/or R 14  and R 15 , can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 304 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 13 , R 14 , and R 15  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-11 aryl optionally substituted by 1-3 R 19 , C 7-16 arylalkyl optionally substituted by 1-3 R 19 , C 3-11 cycloalkyl optionally substituted by 1-3 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-15 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 20 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), and —P(═O)(OR 20 )(OR 20 ); or either or both of R 12  and R 13 , and/or R 14  and R 15 , can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-3 R 19 , C 3-11 cycloalkyl optionally substituted by 1-3 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 305 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 13 , R 14 , and R 15  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-10 cycloalkyl optionally substituted by 1-3 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-10 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), and —P(═O)(OR 20 )(OR 20 ); or either or both of R 12  and R 13 , and/or R 14  and R 15 , can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-10 cycloalkyl optionally substituted by 1-3 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 306 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 13 , R 14 , and R 15  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-7  cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , —S(═O) 2 R 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —P(O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), and —P(═O)(OR 20 )(OR 20 ); or either or both of R 12  and R 13 , and/or R 14  and R 15 , can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19  or a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 307 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 13 , R 14 , and R 15  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-10 cycloalkyl optionally substituted by 1-3 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-10 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)N 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or either or both of R 12  and R 13 , and/or R 14  and R 15 , can, together with the atoms linking them, form a C 6-11  aryl optionally substituted by 1-3 R 19 , C 3-11 cycloalkyl optionally substituted by 1-3 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 308 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 13 , R 14 , and R 15  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or either or both of R 12  and R 13 , and/or R 14  and R 15 , can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19  or a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 309 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and halogen; R 13  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 2 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , NR 4 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═NR 25 )NR 22 R 23 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 C(═S)R 20 , —NR 24 C(═S)OR 20 , —NR 24 C(═S)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)(NR 22 R 23 )(NR 22 R 23 ), —NR 24 P(═O)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═)OR 20 , —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , and —S(═O)NR 22 R 23 ; or either or both of R 12  and R 13 , and/or R 14  and R 15 , can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 310 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and halogen; R 13  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═NR 25 )NR 22 R 23 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 C(═S)R 20 , —NR 24 C(═S)OR 20 , —NR 24 C(═S)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)NR 22 R 23 )(NR 22 )(NR 23 ), —NR 24 P(═)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 R 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , and —S(═O)NR 22 R 23 ; or R 12  and R 13  can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 311 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and halogen; R 13  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —SCN, —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12  and R 13  can, together with the atoms linking them, form a C 6 10aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 312 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and halogen; R 13  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 2 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 313 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and halogen; R 13  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 314 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12  and R 14  are H; R 15  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and halogen; R 13  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —SCN, —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12  and R 13  can, together with the atoms linking them, form a C 6 10aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 315 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12  and R 14  are H; R 15  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and halogen; R 13  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 316 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12  and R 14  are H; R 15  is chosen from H and halogen; R 13  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 2 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 317 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14  is H; R 12  and R 15  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and halogen; R 13  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 2 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 318 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14  is H; R 12  and R 15  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and halogen; R 13  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 319 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14  is H; R 12  and R 15  are independently chosen from H and halogen; R 13  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20  and —S(═O) 2 NR 22 R 23 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 320 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14  is H; R 12  and R 15  are independently chosen from H and halogen; R 13  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 2 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 321 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14  is H; R 12  and R 15  are independently chosen from H and halogen; R 13  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , halogen, —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , and —NR 24 S(═O) 2 NR 22 R 23 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 322 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14  is H; R 12  and R 15  are independently chosen from H and halogen; R 13  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , halogen, —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , and —NR 24 S(═O) 2 NR 22 R 23 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19  or a 5-6 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 323 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14  is H; R 12  and R 15  are independently chosen from H and halogen; R 13  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , and —NR 24 S(═O) 2 NR 22 R 23 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19  or a 5-6 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 324 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14  is H; R 12  and R 15  are independently chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , and —NR 24 S(═O) 2 NR 22 R 23 ; or R 12  and R 13  can, together with the atoms linking them, form a 5-6 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 325 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14  is H; R 12  and R 15  are independently chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5-6 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 326 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14  is H; R 12  and R 15  are independently chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 327 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12  and R 14  are H; R 15  is chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 328 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14  and R 15  are H; R 12  is chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 329 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14  is H; R 12  and R 15  are independently chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 330 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12  and R 14  are H; R 15  is chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 331 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14  and R 15  are H; R 12  is chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 332 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14  is H; R 12  and R 15  are independently chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1-2 R 19 . 
     Embodiment 333 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12  and R 14  are H; R 15  is chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1-2 R 19 . 
     Embodiment 334 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14  and R 15  are H; R 12  is chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1-2 R 19 . 
     Embodiment 335 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14  is H; R 12  and R 15  are independently chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1 R 19 . 
     Embodiment 336 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12  and R 14  are H; R 15  is chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1 R 19 . 
     Embodiment 337 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14  and R 15  are H; R 12  is chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1 R 19 . 
     Embodiment 338 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14  is H; R 12  and R 15  are independently chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a pyrrolyl ring optionally substituted by 1 R 19 . 
     Embodiment 339 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12  and R 14  are H; R 15  is chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a pyrrolyl ring optionally substituted by 1 R 19 . 
     Embodiment 340 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14  and R 15  are H; R 12  is chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a pyrrolyl ring optionally substituted by 1 R 19 . 
     Embodiment 341 
     The compound of any of Embodiments 300-340, wherein R 14  is H. 
     Embodiment 342 
     The compound of any of Embodiments 300-341, wherein R 15  is H. 
     Embodiment 343 
     The compound of any of Embodiments 300-342, wherein R 12  is H. 
     Embodiment 344 
     The compound of any of Embodiments 300-343, wherein R 13  is H. 
     Embodiment 345 
     The compound of any of Embodiments 300-340, wherein R 14  and R 15  are H. 
     Embodiment 346 
     The compound of any of Embodiments 300-340, wherein R 12  are R 15  are H. 
     Embodiment 347 
     The compound of any of Embodiments 300-340, wherein R 12 , R 14  and R 15  are H. 
     Embodiment 348 
     The compound of any of Embodiments 300-340, wherein R 12  are R 14  are H. 
     Embodiment 349 
     The compound of any of Embodiments 1, 2, 4-156, 200-250, or 300-340, wherein R 12 , R 13 , R 14 , and R 15  are H. 
     Embodiment 350 
     The compound of any of Embodiments 300-342, wherein R 12  and R 13 , together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1-2 R 19 . 
     Embodiment 351 
     The compound of any of Embodiments 300-342, wherein R 12  and R 13 , together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1 R 19 . 
     Embodiment 352 
     The compound of any of Embodiments 300-342, wherein R 12  and R 13 , together with the atoms linking them, form a pyrrolyl ring optionally substituted by 1 R 19 . 
     Embodiment 353 
     The compound of any of Embodiments 300-342, wherein R 12  and R 13 , together with the atoms linking them, form a pyrrolyl ring. 
     Embodiment 354 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, C 7-16 arylalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 355 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, C 7-16 arylalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 356 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, C 7-16 arylalkyl optionally substituted by 1-3 R 19 , 5-10 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 357 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, halogen, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 358 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, halogen, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19  in which the heterocycloalkyl contains carbon atoms and 1 or 2 nitrogen atoms, or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19  in which the heteroaryl contains carbon atoms and 1 or 2 nitrogen atoms. 
     Embodiment 359 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, halogen, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19  in which the heterocycloalkyl contains carbon atoms and 1 nitrogen atom, or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19  in which the heteroaryl contains carbon atoms and 1 nitrogen atom. 
     Embodiment 360 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 361 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19  in which the heterocycloalkyl contains carbon atoms and 1 or 2 nitrogen atoms, or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19  in which the heteroaryl contains carbon atoms and 1 or 2 nitrogen atoms. 
     Embodiment 362 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, —NR 22 R 23 , and NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19  in which the heterocycloalkyl contains carbon atoms and 1 nitrogen atom, or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19  in which the heteroaryl contains carbon atoms and 1 nitrogen atom. 
     Embodiment 363 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, —NHR 23 , and —NHC(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 364 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, —NHR 23 , and —NHC(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19  in which the heterocycloalkyl contains carbon atoms and 1 or 2 nitrogen atoms, or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19  in which the heteroaryl contains carbon atoms and 1 or 2 nitrogen atoms. 
     Embodiment 365 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, —NHR 23 , and —NHC(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19  in which the heterocycloalkyl contains carbon atoms and 1 nitrogen atom, or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19  in which the heteroaryl contains carbon atoms and 1 nitrogen atom. 
     Embodiment 366 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, —NHR 23 , and —NHC(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 367 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, —NHR 23 , and —NHC(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5-10 membered heteroaryl optionally substituted by 1-3 R 19  in which the heteroaryl contains carbon atoms and 1 or 2 nitrogen atoms. 
     Embodiment 368 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, —NHR 23 , and —NHC(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5-10 membered heteroaryl optionally substituted by 1-3 R 19  in which the heteroaryl contains carbon atoms and 1 nitrogen atom. 
     Embodiment 369 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H and —NHR 23 ; or R 12  and R 13  can, together with the atoms linking them, form a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 370 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H and —NHR 23 ; or R 12  and R 13  can, together with the atoms linking them, form a 5-10 membered heteroaryl optionally substituted by 1-3 R 19  in which the heteroaryl contains carbon atoms and 1 or 2 nitrogen atoms. 
     Embodiment 371 
     The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H and —NHR 23 ; or R 12  and R 13  can, together with the atoms linking them, form a 5-10 membered heteroaryl optionally substituted by 1-3 R 19  in which the heteroaryl contains carbon atoms and 1 nitrogen atom. 
     Embodiment 400 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —C(═O)C(═O)R 20 , —C(═NR 25 )R 20 , —C(═NR 25 )NR 22 R 23 , —C(═NOH)NR 22 R 23 , —C(═NOR 26 )R 20 , —C(═NNR 22 R 23 )R 20 , —C(═NNR 24 C(═O)R 21 )R 20 , —C(═NNR 24 C(═)OR 21 )R 20 , —C(═S)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 240 R 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═NR 25 )NR 22 R 23 , —NR 24 C(═O)C(═O)NR 22 , —NR 24 C(═S)R 20 , —NR 24 C(═S)OR 20 , —NR 24 C(═S)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)(NR 22 R 23 )(NR 22 R 23 ), —NR 24 P(═O)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OC(═NR 25 )NR 22 R 23 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 7 R 7 , —OP(═O)(NR 22 R 23 )(NR 22 R 22 R 23 ), —OP(═O)(OR 20 )(OR 20 ), —OP(═O)(SR 20 )(SR 20 ), —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 R 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —SP(═O)R 78 R 78 , —SP(═O)(NR 22 R 23 )(NR 22 R 23 ), —SP(═O)(OR 20 )(R 20 ), —SP(═O)(SR 20 )(SR 20 ), —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), —P(═O)(OR 20 )(OR 20 ), and —P(═O)(SR 20 )(SR 20 ); or any of R a  and R b , R a  and R c , R a  and R e , R a  and R g , R b  and R d , R b  and R f , R b  and R h , R c  and R d , R c  and R e , R c  and R g , R d  and R f , R d  and R h , R e  and R f , R e  and R g , R f  and R h , and R g  and R h  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 401 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —C(═O)C(═O)R 20 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 2 C(═O)C(═)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)(NR 22 R 23 )(NR 22 R 23 ), —NR 24 P(═O)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OC(═NR 25 )NR 22 R 23 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 78 R 78 , —OP(═O)(NR 22 R 23 )(NR 22 R 23 )(NR 2 ), —OP(═O)(OR 20 )(OR 20 ), —OP(═O)(SR 2 )(SR 20 ), —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —SP(═O)R 78 R 78 , —SP(═O)(NR 22 R 23 )(NR 22 R 23 ), —SP(═O)(OR 20 )(OR 20 ), —SP(═O)(SR 20 )(SR 20 ), —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), —P(═O)(OR 20 )(OR 20 ), and —P(═O)(SR 20 )(SR 20 ); or any of R a  and R b , R a  and R c , R a  and R e , R a  and R g , R b  and R d , R b  and R f , R b  and R h , R c  and R d , R c  and R e , R c  and R g , R d  and R f , R d  and R h , R e  and R f , R e  and R g , R f  and R h , and R g  and R h  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 402 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , and —S(═O) 2 NR 22 R 23 ; or any of R a  and R b , R a  and R e , R a  and R e , R a  and R g , R b  and R d , R b  and R f , R b  and R h , R c  and R d , R c  and R e , R c  and R g , R d  and R f , R d  and R h , R e  and R f , R e  and R f , R f  and R h , and R g  and R h  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 403 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 NR 22 R 23 , —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 R 20 , —SO 3 R 27 , and —S(═O) 2 NR 22 R 23 ; or any of R a  and R b , R a  and R c , R a  and R e , R a  and R g , R b  and R d , R b  and R f , R b  and R h , R c  and R d , R c  and R e , R c  and R g , R d  and R f , R d  and R h , R e  and R f , R e  and R g , R f  and R h , and R g  and R h  can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 404 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or any of R a  and R b , R a  and R e , R a  and R e , R a  and R g , R b  and R d , R b  and R f , R b  and R h , R c  and R d , R c  and R e , R c  and R g , R d  and R f , R d  and R h , R e  and R f , R e  and R g , R f  and R h , and R g  and R h  can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 405 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , C 3-10 cycloalkyl optionally substituted by 1-3 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-10 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or any of R a  and R b , R a  and R e , R a  and R e , R a  and R g , R b  and R d , R b  and R f , R b  and R h , R c  and R d , R c  and R e , R c  and R g , R d  and R f , R d  and R h , R e  and R f , R e  and R g , R f  and R h , and R g  and R h  can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-10 cycloalkyl optionally substituted by 1-3 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 406 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R e , R d , R e , R f , R g , and R h  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , 5-10 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═) n R 20 , and —S(═O) 2 NR 22 R 23 . 
     Embodiment 407 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —OC(═O)R 20 , —OC(═O)OR 20 , —S(═) n R 20 , and —S(═O) 2 NR 22 R 23 . 
     Embodiment 408 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , halogen, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , and —NR 24 S(═O) 2 R 21 . 
     Embodiment 409 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , —NR 22 R 23 , —NR 24 C(═O)R 20 , and —NR 24 S(═O) 2 R 21 . 
     Embodiment 410 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , —NR 22 R 23 , and —NR 24 C(═O)R 20 . 
     Embodiment 411 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and C 7-11 arylalkyl optionally substituted by 1-3 R 19 . 
     Embodiment 412 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and benzyl optionally substituted by 1-3 R 19 . 
     Embodiment 413 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, C 1-6 alkyl optionally substituted by 1 R 19 , and benzyl optionally substituted by 1 R 19 . 
     Embodiment 414 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, C 1-6 alkyl optionally substituted by 1 R 19 , and benzyl. 
     Embodiment 415 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, methyl optionally substituted by 1 R 19 , and benzyl optionally substituted by 1 R 19 . 
     Embodiment 416 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, methyl optionally substituted by 1 R 19 , and benzyl. 
     Embodiment 417 
     The compound of any of Embodiments 400-416, wherein at least three of R a , R b , R c , R d , R e , R f , R g , and R h  are H. 
     Embodiment 418 
     The compound of any of Embodiments 400-416, wherein at least four of R a , R b , R c , R d , R e , R f , R g , and R h  are H. 
     Embodiment 419 
     The compound of any of Embodiments 400-416, wherein at least five of R a , R b , R c , R d , R e , R f , R g , and R h  are H. 
     Embodiment 420 
     The compound of any of Embodiments 400-416, wherein at least six of R a , R b , R c , R d , R e , R f , R g , and R h  are H. 
     Embodiment 421 
     The compound of any of Embodiments 400-416, wherein at least seven of R a , R b , R e , R d , R e , R f , R g , and R h  are H. 
     Embodiment 422 
     The compound of any of Embodiments 400-416, wherein R a , R b  R c , R e , R f , R g , and R h  are H. 
     Embodiment 423 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h  are H; and R d  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —C(═O)C(═O)R 20 , —C(═NR 25 )R 20 , —C(═NR 25 )NR 22 R 23 , —C(═NOH)NR 22 R 23 , —C(═NOR 26 )R 20 , —C(═NNR 22 R 23 )R 20 , —C(═NNR 24 C(═O)R 21 )R 20 , —C(═NNR 24 C(═O)OR 21 )R 20 , —C(═S)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═NR 25 )NR 22 R 23 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 C(═S)R 20 , —NR 24 C(═S)OR 20 , —NR 24 C(═S)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)(NR 22 R 23 )(NR 22 R 23 ), —NR 24 P(═O)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OC(═NR 25 )NR 22 R 23 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 78 R 78 , —OP(═O)(NR 22 R 23 )(NR 22 R 23 ), —OP(═O)(OR 20 )(OR 20 ), —OP(═O)(SR 20 )(SR 20 ), —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 R 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —SP(═O)R 78 R 78 , —SP(═O)(NR 22 R 23 )(NR 22 R 23 ), —SP(═O)(OR 20 )(R 20 ), —SP(═O)(SR 20 )(SR 20 ), —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), —P(═O)(OR 20 )(OR 20 ), and —P(═O)(SR 20 )(SR 20 ); or any of R a  and R b , R a  and R c , R a  and R e , R a  and R g , R b  and R d , R b  and R f , R b  and R h , R c  and R d , R c  and R e , R c  and R g , R d  and R f , R d  and R h , R e  and R f , R e  and R g , R f  and R h , and R g  and R h  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 424 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h  are H; and R d  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —C(═O)C(═O)R 20 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)(NR 22 R 23 )(NR 22 R 23 ), —NR 24 P(═O)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OC(═NR 25 )NR 22 R 23 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 78 R 78 , —OP(═O)(NR 22 R 23 )(NR 22 R 23 ), —OP(═O)(OR 20 )(OR 20 ), —OP(═O)(SR 20 )(SR 20 ), —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —SP(═O)R 78 R 78 , —SP(═O)(NR 22 R 23 )(NR 22 R 23 ), —SP(═O)(OR 20 )(OR 20 ), —SP(═O)(SR 20 )(SR 20 ), —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), —P(═O)(OR 20 )(OR 20 ), and —P(═O)(SR(SR 20 ); or any of R a  and R b , R a  and R e , R a  and R e , R a  and R g , R b  and R d , R b  and R f , R b  and R h , R c  and R d , R c  and R e , R c  and R g , R d  and R f , R d  and R h , R e  and R f , R e  and R g , R f  and R h , and R g  and R h  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 425 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h  are H; and R d  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , and —S(═O) 2 NR 22 R 23 ; or any of R a  and R b , R a  and R c , R a  and R e , R a  and R g , R b  and R d , R b  and R f , R b  and R h , R c  and R d , R c  and R e , R c  and R g , R d  and R f , R d  and R h , R e  and R f , R e  and R g , R f  and R h , and R g  and R h  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 426 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h  are H; and R d  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , and —S(═O) 2 NR 22 R 23 ; or any of R a  and R b , R a  and R e , R a  and R e , R a  and R g , R b  and R d , R b  and R f , R b  and R h , R c  and R d , R c  and R e , R c  and R g , R d  and R f , R d  and R h , R e  and R f , R e  and R g , R f  and R h , and R g  and R h  can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 427 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h  are H; and R d  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or any of R a  and R b , R a  and R c , R a  and R e , R a  and R g , R b  and R d , R b  and R f , R b  and R h , R c  and R d , R c  and R e , R c  and R g , R d  and R f , R d  and R h , R e  and R f , R e  and R g , R f  and R h , and R g  and R h  can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 . 
     Embodiment 428 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h  are H; and R d  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , C 3-10 cycloalkyl optionally substituted by 1-3 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-10 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or any of R a  and R b , R a  and R e , R a  and R e , R a  and R g , R b  and R d , R b  and R f , R b  and R h , R c  and R d , R c  and R e , R c  and R g , R d  and R f , R d  and R h , R e  and R f , R e  and R g , R f  and R h , and R g  and R h  can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-10 cycloalkyl optionally substituted by 1-3 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 . 
     Embodiment 429 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h  are H; and R d  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , 5-10 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 . 
     Embodiment 430 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h  are H; and R d  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —OC(═O)R 20 , —OC(═O)OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 . 
     Embodiment 431 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h  are H; and R d  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , halogen, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , and —NR 24 S(═O) 2 R 21 . 
     Embodiment 432 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h  are H; and R d  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , —NR 22 R 23 , —NR 24 C(═O)R 20 , and —NR 24 S(═O) 2 R 21 . 
     Embodiment 433 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h  are H; and R d  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , —NR 22 R 23 , and —NR 24 C(═O)R 20 . 
     Embodiment 434 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h  are H; and R d  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and C 7-11 arylalkyl optionally substituted by 1-3 R 19 . 
     Embodiment 435 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h  are H; and R d  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and benzyl optionally substituted by 1-3 R 19 . 
     Embodiment 436 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h  are H; and R d  is chosen from H, C 1-6 alkyl optionally substituted by 1 R 19 , and benzyl optionally substituted by 1 R 19 . 
     Embodiment 437 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h  are H; and R d  is chosen from H, C 1-6 alkyl optionally substituted by 1 R 19 , and benzyl. 
     Embodiment 438 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h  are H; and R d  is chosen from H, methyl optionally substituted by 1 R 19 , and benzyl optionally substituted by 1 R 19 . 
     Embodiment 439 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h  are H; and R d  is chosen from H, methyl optionally substituted by 1 R 19 , and benzyl. 
     Embodiment 440 
     The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h  are H. 
     Embodiment 500 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 39 , C 2-6 alkenyl optionally substituted by 1-11 R 39 , C 2-6 alkynyl optionally substituted by 1-9 R 39 , C 6-11 aryl optionally substituted by 1-11 R 39 , C 7-16 arylalkyl optionally substituted by 1-19 R 39 , C 3-11 cycloalkyl optionally substituted by 1-21 R 39 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 39 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 39 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 39 , 5-15 membered heteroaryl optionally substituted by 1-15 R 39 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 39 , halogen, —CN, —C(═O)R 30 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —C(═O)C(═O)R 30 , —C(═NR 35 )R 30 , —C(═NR 35 )NR 32 R 33 , —C(═NOH)NR 32 R 33 , —C(═NOR 36 )R 30 , —C(═NNR 32 R 33 )R 30 , —C(═NNR 34 C(═O)R 31 )R 30 , —C(═NNR 34 C(═O)OR 31 )R 30 , —C(═S)NR 32 R 33 , —NC, —NO 2 , —NR 32 R 33 , —NR 34 NR 32 R 33 , —N═NR 34 , ═NR 30 , ═NOR 30 , —NR 34 OR 36 , —NR 34 C(═O)R 30 , —NR 34 C(═O)C(═O)R 30 , —NR 34 C(═O)OR 31 , —NR 34 C(═O)C(═O)OR 31 , —NR 34 C(═O)NR 32 R 33 , —NR 34 C(═O)NR 34 C(═O)R 30 , —NR 34 C(═O)NR 34 C(═O)OR 30 , —NR 34 C(═NR 35 )NR 32 R 33 , —NR 34 C(═O)C(═O)NR 32 R 33 , —NR 34 C(═S)R 30 , —NR 34 C(═S)OR 30 , —NR 34 C(═S)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —NR 34 P(═O)R 78 R 78 , —NR 34 P(═O)(NR 32 R 33 )(NR 32 R 33 ), —NR 34 P(═O)(OR 30 )(OR 30 ), —NR 34 P(═O)(SR 30 )(SR 3 ), —OR 30 , ═O, —OCN, —OC(═O)R 30 , —OC(═O)NR 32 R 33 , —OC(═O)OR 30 , —OC(═NR 35 )NR 32 R 33 , —OS(═O)R 30 , —OS(═O) 2 R 30 , —OS(═O) 2 OR 30 , —OS(═O) 2 NR 32 R 33 , —OP(═O)R 78 R 78 , —OP(═O)(NR 32 R 33 )(NR 32 R 33 ), —OP(═O)(OR 30 ), —OP(═O)(SR 30 )(SR 30 ), —Si(R 34 ) 3 , —SCN, ═S, —S(═O) n R 30 , —S(═O) 2 OR 30 , —SO 3 R 37 , —S(═O) 2 NR 32 R 33 , —S(═O)NR 32 R 33 , —SP(═O)R 78 R 78 , —SP(═O)(NR 32 R 33 )(NR 32 R 33 ), —SP(═O)(OR 30 )(OR 30 ), —SP(═O)(SR 30 )(SR 30 ), —P(═O)R 78 R 78 , —P(═O)(NR 32 R 33 )(NR 32 R 33 ), —P(═O)(OR 30 )(OR 30 ), and —P(═O)(SR 30 )(SR 30 ). 
     Embodiment 501 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 39 , C 2-6 alkenyl optionally substituted by 1-6 R 39 , C 2-6 alkynyl optionally substituted by 1-6 R 39 , C 6-11 aryl optionally substituted by 1-6 R 39 , C 7-16 arylalkyl optionally substituted by 1-6 R 39 , C 3-11 cycloalkyl optionally substituted by 1-6 R 39 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 39 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 39 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 39 , 5-15 membered heteroaryl optionally substituted by 1-6 R 39 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 39 , halogen, —CN, —C(═O)R 30 , —C(═)OR 30 , —C(═O)NR 32 R 33 , —C(═O)C(═O)R 30 , —C(═NR 35 )R 30 , —C(═NR 35 )NR 32 R 33 , —C(═NOH)NR 32 R 33 , —C(═NOR 36 )R 3 , —C(═NNR 32 R 33 )R 30 , —C(═NNR 34 C(═O)R 31 )R 30 , —C(═NNR 34 C(═O)OR 31 )R 30 , —C(═S)NR 32 R 33 , —NC, —NO 2 , —NR 32 R 33 , —NR 34 NR 32 R 33 , —N═NR 34 , ═NR 30 , ═NOR 30 , —NR 34 OR 36 , —NR 34 C(═O)R 30 , —NR 34 C(═O)C(═O)R 30 , —NR 34 C(═O)OR 31 , —NR 34 C(═O)C(═O)OR 31 , —NR 34 C(═O)NR 32 R 33 , —NR 34 C(═O)NR 34 C(═O)R 30 , —NR 34 C(═O)NR 34 C(═O)OR 30 , —NR 34 C(═NR 35 )NR 32 R 33 , —NR 34 C(═O)C(═O)NR 32 R 30 , —NR 34 C(═S)R 30 , —NR 34 C(═S)OR 30 , —NR 34 C(═S)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —NR 34 P(═O)R 78 R 78 , —NR 34 P(═O)(NR 32 R 33 )(NR 32 R 33 ), —NR 34 P(═O)(OR 30 )(OR 30 ), —NR 34 P(═O)(SR 30 )(SR 3 ), —OR 30 , ═O, —OCN, —OC(═O)R 3 , —OC(═O)NR 32 R 33 , —OC(═O)OR 30 , —OC(═NR 35 )NR 32 R 33 , —OS(═O)R 30 , —OS(═O) 2 R 30 , —OS(═O) 2 OR 30 , —OS(═O) 2 NR 32 R 33 , —OP(═O)R 78 R 78 , —OP(═O)(NR 32 R 33 )(NR 32 R 33 ), —OP(═O)(OR 30 )(OR 30 ), —OP(═O)(SR 30 )(SR 30 ), —Si(R 34 ) 3 , —SCN, ═S, —S(═O) n R 30 , —S(═O) 2 OR 30 , —SO 3 R 37 , —S(═O) 2 NR 32 R 33 , —S(═O)NR 32 R 33 , —SP(═O)R 78 R 78 , —SP(═O)(NR 32 R 33 )(NR 32 R 33 ), —SP(═O)(OR 30 )(OR 30 ), —SP(═O)(SR 30 )(SR 30 ), —P(═O)R 78 R 78 , —P(═O)(NR 32 R 33 )(NR 32 R 33 ), —P(═O)(OR 30 )(OR 30 ), and —P(═O)(SR 30 )(SR 30 )(SR). 
     Embodiment 502 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 39 , C 2-6 alkenyl optionally substituted by 1-6 R 39 , C 2-6 alkynyl optionally substituted by 1-6 R 39 , C 6-11 aryl optionally substituted by 1-6 R 39 , C 7-16 arylalkyl optionally substituted by 1-6 R 39 , C 3-11 cycloalkyl optionally substituted by 1-6 R 39 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 39 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 39 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 39 , 5-15 membered heteroaryl optionally substituted by 1-6 R 39 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 39 , halogen, —CN, —C(═O)R 30 , —C(═)OR 30 , —C(═O)NR 32 R 33 , —C(═)C(═)R 30 , —NC, —NO 2 , —NR 32 R 33 , —NR 34 NR 32 R 33 , —NR 34 OR 36 , —NR 34 C(═O)R 30 , —NR 34 C(═O)C(═O)R 30 , —NR 34 C(═O)OR 31 , —NR 34 C(═O)C(═O)OR 31 , —NR 34 C(═O)NR 32 R 33 , —NR 34 C(═O)NR 34 C(═O)R 30 , —NR 34 C(═O)NR 34 C(═O)OR 30 , —NR 34 C(═NR 35 )NR 32 R 33 , —NR 34 C(═O)C(═O)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —OR 30 , ═O, —OCN, —OC(═O)R 30 , —OC(═O)NR 32 R 33 , —OC(═O)OR 30 , —OC(═NR 35 )NR 32 R 33 , —Si(R 34 ) 3 , —SCN, ═S, —S(═O) n R 30 , —S(═O) 2 OR 30 , —SO 3 R 37 , —S(═O) 2 NR 32 R 33 , —S(═O)NR 32 R 33 , —P(═O)R 78 R 78 , —P(═O)(NR 32 R 33 )(NR 32 R 33 ), —P(═O)(OR 30 )(OR 30 ), and —P(═O)(SR 30 )(SR 30 ). 
     Embodiment 503 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkenyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 6-11 aryl optionally substituted by 1-3 R 39 , C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , C 4-17 cycloalkylalkyl optionally substituted by 1-3 R 39 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-3 R 39 , 5-15 membered heteroaryl optionally substituted by 1-3 R 39 , 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 30 , —C(═)OR 30 , —C(═O)NR 32 R 33 , —C(═O)C(═O)R 30 , —NC, —NO 2 , —NR 32 R 33 , —NR 34 NR 32 R 33 , —NR 34 OR 36 , —NR 34 C(═O)R 30 , —NR 34 C(═O)C(═O)R 30 , —NR 34 C(═O)OR 31 , —NR 34 C(═O)C(═O)OR 31 , —NR 34 C(═O)NR 32 R 33 , —NR 34 C(═O)NR 34 C(═O)R 30 , —NR 34 C(═O)NR 34 C(═O)OR 3 , —NR 34 C(═NR 35 )NR 32 R 33 , —NR 34 C(═O)C(═O)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —OR 30 , ═O, —OCN, —OC(═O)R 30 , —OC(═O)NR 32 R 33 , —OC(═O)OR 30 , —OC(═NR 35 )NR 32 R 33 , —Si(R 34 ) 3 , —SCN, ═S, —S(═O) n R 30 , —S(═O) 2 OR 30 , —SO 3 R 37 , —S(═O) 2 NR 32 R 33 , —S(═O)NR 32 R 33 , —P(═O)R 78 R 78 , —P(═O)(NR 32 R 33 )(NR 32 R 33 ), —P(═O)(OR 30 )(OR 30 ), and —P(═O)(SR 30 )(SR 30 ). 
     Embodiment 504 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkenyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 6-10 aryl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-10 cycloalkyl optionally substituted by 1-3 R 39 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 30 , —C(═)OR 30 , —C(═O)NR 32 R 33 , —C(═O)C(═O)R 30 , —NC, —NO 2 , —NR 32 R 33 , —NR 34 NR 32 R 33 , —NR 34 OR 36 , —NR 34 C(═O)R 30 , —NR 34 C(═O)C(═O)R 30 , —NR 34 C(═O)OR 31 , —NR 34 ═O)C(═O)OR 31 , —NR 34 C(═O)NR 32 R 33 , —NR 34 C(═O)NR 34 C(═O)R 30 , —NR 34 C(═O)NR 34 C(═O)OR 30 , —NR 34 C(═NR 35 )NR 32 R 33 , —NR 34 C(═O)C(═O)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —OR 30 , ═O, —OCN, —OC(═O)R 30 , —OC(═O)NR 32 R 33 , —OC(═O)OR 30 , —OC(═NR 35 )NR 32 R 33 , —Si(R 34 ) 3 , —SCN, ═S, —S(═O) n R 30 , —S(═O) 2 OR 30 , —SO 3 R 37 , —S(═O) 2 NR 32 R 33 , —S(═O)NR 32 R 33 , —P(═O)R 78 R 78 , —P(═O)(NR 32 R 33 )(NR 32 R 33 ), —P(═O)(OR 30 )(OR 30 ), and —P(═O)(SR 30 )(SR 30 ). 
     Embodiment 505 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkenyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 6-10 aryl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-10 cycloalkyl optionally substituted by 1-3 R 39 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 30 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NO 2 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —NR 34 C(═O)OR 31 , —NR 34 C(═O)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —OR 30 , ═O, —OC(═O)R 3 , —OC(═O)NR 32 R 33 , —Si(R 34 ) 3 , ═S, —S(═O) n R 30 , —S(═O) 2 OR 3 , —SO 3 R 37 , —S(═O) 2 NR 32 R 33 , —S(═O)NR 32 R 33 , —P(═O)R 78 R 78 , —P(═O)(NR 32 R 33 )(NR 32 R 33 ), —P(═O)(OR 30 )(OR 30 ), and —P(═O)(SR 30 )(SR 30 ). 
     Embodiment 506 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkenyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 6-10 aryl optionally substituted by 1-3 R 39 , C 2-6 arylalkyl optionally substituted by 1-3 R 39 , C 3-10 cycloalkyl optionally substituted by 1-3 R 39 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 3 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NO 2 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —NR 34 C(═O)OR 31 , —NR 34 C(═O)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —OR 30 , ═O, —OC(═O)R 3 , —OC(═O)NR 32 R 33 , —Si(R 34 ) 3 , ═S, —S(═O) n R 3 , —S(═O) 2 NR 32 R 33 , and —S(═O)NR 32 R 33 . 
     Embodiment 507 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkenyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 6-10 aryl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-10 cycloalkyl optionally substituted by 1-3 R 39 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 30 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NO 2 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —NR 34 C(═O)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —OR, ═O, —OC(═O)R 30 , —OC(═O)NR 32 R 33 , —Si(R 34 ) 3 , ═S, —S(═O) n R 30 , and —S(═O) 2 NR 32 R 33 . 
     Embodiment 508 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkenyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 6-10 aryl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 3 , —C(═O)OR 3 , —C(═O)NR 32 R 33 , —NO 2 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —NR 34 C(═O)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —OR 30 , ═O, —OC(═O)R 30 , —OC(═O)NR 32 R 33 , —Si(R 34 ) 3 , ═S, —S(═O) n R 30 , and —S(═O) 2 NR 32 R 33 . 
     Embodiment 509 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 6-10 aryl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 3 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NO 2 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —NR 34 S(═O) 2 R 31 , —OR 30 , ═O, —OC(═O)R 30 , —OC(═O)NR 32 R 33 , —Si(R 34 ) 3 , —S(═O) n R 30 , and —S(═O) 2 NR 32 R 33 . 
     Embodiment 510 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 6-10 aryl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —NR 34 S(═O) 2 R 31 , —OR 30 , ═O, —S(═O) n R 30 , and —S(═O) 2 NR 32 R 33 . 
     Embodiment 511 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 6-10 aryl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —OR 30 , and ═O. 
     Embodiment 512 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl, C 6-10 aryl, C 7-11 arylalkyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)R 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —OR 30 , and ═O. 
     Embodiment 513 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl, C 6-10 aryl, C 7-11 arylalkyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —C(═O)R 30 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , and OR 30 . 
     Embodiment 514 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 39 , C 2-6 alkenyl optionally substituted by 1-11 R 39 , C 2-6 alkynyl optionally substituted by 1-9 R 39 , C 6-11 aryl optionally substituted by 1-11 R 39 , C 7-16 arylalkyl optionally substituted by 1-19 R 39 , C 3-11 cycloalkyl optionally substituted by 1-21 R 39 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 39 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 39 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 39 , 5-15 membered heteroaryl optionally substituted by 1-15 R 39 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 39 , halogen, —CN, —C(═O)NR 32 R 33 , —NO 2 , —NR 32 R 33 , and —OR 30 . 
     Embodiment 515 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 39 . 
     Embodiment 516 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 6-10 aryl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —C(═O)OR 30 , —NR 32 R 33 , and —OR 30 . 
     Embodiment 517 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , phenyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —C(═O)OR 30 , —NR 32 R 33 , and —OR 3 . 
     Embodiment 518 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl, phenyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl, halogen, —C(═O)OR 30 , —NR 32 R 33 , and —OR 30 . 
     Embodiment 519 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl, phenyl optionally substituted by 1 R 39 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl optionally substituted by 1 R 39 , 5-6 membered heteroaryl, halogen, —C(═O)OR 30 , —NR 32 R 33 , and —OR 30 . 
     Embodiment 520 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl, phenyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —C(═O)OR 30 , —NR 32 R 33 , and —OR 30 . 
     Embodiment 521 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 30 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NO 2 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —NR 34 C(═O)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —OR 30 , ═O, —OC(═O)R 3 , —OC(═O)NR 32 R 33 , —Si(R 34 ) 3 , ═S, —S(═O) n R 30 , and —S(═O) 2 NR 32 R 33 . 
     Embodiment 522 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —NR 34 S(═O) 2 R 31 , —OR 30 , ═O, —OC(═O)R 3 , —S(═O) n R 30 , and —S(═O) 2 NR 32 R 33 . 
     Embodiment 523 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —OR 30 , and ═O. 
     Embodiment 524 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , and —OR 30 . 
     Embodiment 525 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , benzyl optionally substituted by 1-3 R 39 , cyclopropyl optionally substituted by 1-3 R 39 , 6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5 membered heteroaryl optionally substituted by 1-3 R 39 , —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —OR 30 , and ═O. 
     Embodiment 526 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , benzyl optionally substituted by 1-3 R 39 , cyclopropyl optionally substituted by 1-3 R 39 , 6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5 membered heteroaryl optionally substituted by 1-3 R 39 , —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , and —OR 30 . 
     Embodiment 527 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , benzyl optionally substituted by 1-3 R 39 , cyclopropyl optionally substituted by 1-3 R 39 , morpholinyl optionally substituted by 1-3 R 39 , pyrazolyl optionally substituted by 1-3 R 39 , —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —OR 30 , and ═O. 
     Embodiment 528 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , benzyl optionally substituted by 1-3 R 39 , cyclopropyl optionally substituted by 1-3 R 39 , morpholinyl optionally substituted by 1-3 R 39 , pyrazolyl optionally substituted by 1-3 R 39 , —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , and —OR 30 . 
     Embodiment 529 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —OR 30 , and ═O. 
     Embodiment 530 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , and —OR 30 . 
     Embodiment 531 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, benzyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —OR 30 , and ═O. 
     Embodiment 532 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, benzyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , and —OR 30 . 
     Embodiment 533 
     The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, benzyl optionally substituted by 1-3 R 39 , cyclopropyl, morpholinyl, pyrazolyl, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —OR 30 , and ═O. 
     Embodiment 600 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 49 , C 2-6 alkenyl optionally substituted by 1-6 R 49 , C 2-6 alkynyl optionally substituted by 1-6 R 49 , C 6-11 aryl optionally substituted by 1-6 R 49 , C 7-16 arylalkyl optionally substituted by 1-6 R 49 , C 3-11 cycloalkyl optionally substituted by 1-6 R 49 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 49 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 49 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 49 , 5-15 membered heteroaryl optionally substituted by 1-6 R 49 , and 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 49 . 
     Embodiment 601 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 49 , C 2-6 alkenyl optionally substituted by 1-6 R 49 , C 2-6 alkynyl optionally substituted by 1-6 R 49 , C 6-10 aryl optionally substituted by 1-6 R 49 , C 7-11 arylalkyl optionally substituted by 1-6 R 49 , C 3-10 cycloalkyl optionally substituted by 1-6 R 49 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 49 , and 5-10 membered heteroaryl optionally substituted by 1-6 R 49 . 
     Embodiment 602 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , C 2-6 alkenyl optionally substituted by 1-3 R 49 , C 2-6 alkynyl optionally substituted by 1-3 R 49 , C 6-10 aryl optionally substituted by 1-3 R 49 , C 7-11 arylalkyl optionally substituted by 1-3 R 49 , C 3-10 cycloalkyl optionally substituted by 1-3 R 49 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 49 . 
     Embodiment 603 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , C 6-10 aryl optionally substituted by 1-3 R 49 , C 7-11 arylalkyl optionally substituted by 1-3 R 49 , C 3-10 cycloalkyl optionally substituted by 1-3 R 49 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 49 . 
     Embodiment 604 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , C 6-10 aryl optionally substituted by 1-3 R 49 , C 7-11 arylalkyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 . 
     Embodiment 605 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 . 
     Embodiment 606 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , and C 3-6 cycloalkyl optionally substituted by 1-3 R 49 . 
     Embodiment 607 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 . 
     Embodiment 608 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , and C 3-6 cycloalkyl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 609 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is H. 
     Embodiment 610 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 49 . 
     Embodiment 611 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 612 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , C 6-10 aryl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 . 
     Embodiment 613 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 6-10 aryl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 . 
     Embodiment 614 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 . 
     Embodiment 615 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , and cyclopropyl optionally substituted by 1-3 R 49 . 
     Embodiment 616 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , cyclopropyl, thienyl, and pyrazinyl. 
     Embodiment 617 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl optionally substituted by 1-3 R 49 , cyclopropyl, thienyl, and pyrazinyl. 
     Embodiment 618 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl optionally substituted by 1-3 R 49 , cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl. 
     Embodiment 619 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl. 
     Embodiment 620 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl optionally substituted by 1 R 49 , C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 621 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, phenyl optionally substituted by 1 R 49 , C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 622 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 623 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, phenyl, C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 624 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 2 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl. 
     Embodiment 625 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, phenyl, cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl. 
     Embodiment 626 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , C 6-10 aryl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 . 
     Embodiment 627 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 6-10 aryl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , cyclopropyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 . 
     Embodiment 628 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , cyclopropyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 . 
     Embodiment 629 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 3 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 . 
     Embodiment 630 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 . 
     Embodiment 631 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 . 
     Embodiment 632 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl optionally substituted by 1-3 R 49 , cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 . 
     Embodiment 633 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , and cyclopropyl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 . 
     Embodiment 634 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl optionally substituted by 1 R 49 , C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 . 
     Embodiment 635 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl optionally substituted by 1 R 49 , C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 . 
     Embodiment 636 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 . 
     Embodiment 637 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl, C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 3 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 . 
     Embodiment 638 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 . 
     Embodiment 639 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl, cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 . 
     Embodiment 640 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , C 6-10 aryl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 641 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 6-10 aryl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 642 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , and C 3-6 cycloalkyl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 3 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 643 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 3 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 644 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , and C 3-6 cycloalkyl; R 21 , R 24 , R 25 , R 26 , R 27 , R 3 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 645 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 646 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl optionally substituted by 1-3 R 49 , cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 647 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl, and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 648 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 649 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl optionally substituted by 1-3 R 49 , cyclopropyl, thienyl, and pyrazinyl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 650 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 651 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl, C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 652 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 3 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 653 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl, cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 654 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , C 6-10 aryl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is H. 
     Embodiment 655 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 6-10 aryl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is H. 
     Embodiment 656 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is H. 
     Embodiment 657 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 3 , R 31 , R 34 , R 3 , R 36  and R 37  at each occurrence is H. 
     Embodiment 658 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl, benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is H. 
     Embodiment 659 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , cyclopropyl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 3 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is H. 
     Embodiment 660 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , and cyclopropyl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is H. 
     Embodiment 661 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl, benzyl optionally substituted by 1-3 R 49 , cyclopropyl, thienyl, and pyrazinyl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is H. 
     Embodiment 662 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl optionally substituted by 1 R 49 , C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is H. 
     Embodiment 663 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl optionally substituted by 1 R 49 , C 3-6 cycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is H. 
     Embodiment 664 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is H. 
     Embodiment 665 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl, C 3-6 cycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is H. 
     Embodiment 666 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is H. 
     Embodiment 667 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20  at each occurrence is independently chosen from H, phenyl, cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is H. 
     Embodiment 668 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is H. 
     Embodiment 700 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 49 , C 2-6 alkenyl optionally substituted by 1-11 R 49 , C 2-6 alkynyl optionally substituted by 1-9 R 49 , C 6-11 aryl optionally substituted by 1-11 R 49 , C 7-16 arylalkyl optionally substituted by 1-19 R 49 , C 3-11 cycloalkyl optionally substituted by 1-21 R 49 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 49 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 49 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 49 , 5-15 membered heteroaryl optionally substituted by 1-15 R 49 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 49 . 
     Embodiment 701 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49 , C 2-6 alkenyl optionally substituted by 1-3 R 49 , C 2-6 alkynyl optionally substituted by 1-3 R 49 , C 6-11 aryl optionally substituted by 1-3 R 49 , C 7-16 arylalkyl optionally substituted by 1-3 R 49 , C 3-11 cycloalkyl optionally substituted by 1-3 R 49 , C 4-17 cycloalkylalkyl optionally substituted by 1-3 R 49 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 49 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-3 R 49 , 5-15 membered heteroaryl optionally substituted by 1-3 R 49 , and 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 49 . 
     Embodiment 702 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49 , C 2-6 alkenyl optionally substituted by 1-3 R 49 , C 2-6 alkynyl optionally substituted by 1-3 R 49 , C 6-10 aryl optionally substituted by 1-3 R 49 , C 7-11 arylalkyl optionally substituted by 1-3 R 49 , C 3-10 cycloalkyl optionally substituted by 1-3 R 49 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 49 . 
     Embodiment 703 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49 , C 6-10 aryl optionally substituted by 1-3 R 49 , C 7-11 arylalkyl optionally substituted by 1-3 R 49 , C 3-10 cycloalkyl optionally substituted by 1-3 R 49 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 49 . 
     Embodiment 704 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 . 
     Embodiment 705 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 706 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49  and 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 . 
     Embodiment 707 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49  and 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 . 
     Embodiment 708 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49  and 5-6 membered heterocycloalkyl. 
     Embodiment 709 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49  and 5 membered heterocycloalkyl optionally substituted by 1-6 R 49 . 
     Embodiment 710 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49  and 5 membered heterocycloalkyl. 
     Embodiment 711 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49  and pyrrolidinyl. 
     Embodiment 712 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 49  and 5 membered heterocycloalkyl. 
     Embodiment 713 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28  at each occurrence is C 1-6 alkyl optionally substituted by 1-6 R 49 . 
     Embodiment 714 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28  at each occurrence is C 1-6 alkyl optionally substituted by 1-3 R 49 . 
     Embodiment 750 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 59 , C 2-6 alkenyl optionally substituted by 1-11 R 59 , C 2-6 alkynyl optionally substituted by 1-9 R 59 , C 6-11 aryl optionally substituted by 1-11 R 59 , C 7-16 arylalkyl optionally substituted by 1-19 R 59 , C 3-11 cycloalkyl optionally substituted by 1-21 R 59 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 59 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 59 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 59 , 5-15 membered heteroaryl optionally substituted by 1-15 R 59 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 59 ; or any R 22  and R 23  and/or R 32  and R 33  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 69  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 69 . 
     Embodiment 751 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , C 2-6 alkenyl optionally substituted by 1-3 R 59 , C 2-6 alkynyl optionally substituted by 1-3 R 59 , C 6-11 aryl optionally substituted by 1-3 R 59 , C 7-16 arylalkyl optionally substituted by 1-3 R 59 , C 3-11 cycloalkyl optionally substituted by 1-3 R 59 , C 4-17 cycloalkylalkyl optionally substituted by 1-3 R 59 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 59 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-3 R 59 , 5-15 membered heteroaryl optionally substituted by 1-3 R 59 , and 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 59 ; or any R 22  and R 23  and/or R 32  and R 33  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 69  or a 5-15 membered heteroaryl optionally substituted by 1-3 R 69 . 
     Embodiment 752 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , C 2-6 alkenyl optionally substituted by 1-3 R 59 , C 2-6 alkynyl optionally substituted by 1-3 R 59 , C 6-10 aryl optionally substituted by 1-3 R 59 , C 7-11 arylalkyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; or any R 22  and R 23  and/or R 32  and R 33  may form, together with the nitrogen atom to which they are attached, a 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 69  or a 5-10 membered heteroaryl optionally substituted by 1-3 R 69 . 
     Embodiment 753 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , C 2-6 alkenyl optionally substituted by 1-3 R 59 , C 2-6 alkynyl optionally substituted by 1-3 R 59 , C 6-10 aryl optionally substituted by 1-3 R 59 , C 7-11 arylalkyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 . 
     Embodiment 754 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , C 6-10 aryl optionally substituted by 1-3 R 59 , C 7-11 arylalkyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 . 
     Embodiment 755 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , C 6-10 aryl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 . 
     Embodiment 756 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 . 
     Embodiment 757 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 4-5 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-9 membered heteroaryl optionally substituted by 1-3 R 59 . 
     Embodiment 758 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 . 
     Embodiment 759 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl, 4-5 membered heterocycloalkyl, and 5-9 membered heteroaryl optionally substituted by 1-3 R 59 . 
     Embodiment 760 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 59 . 
     Embodiment 761 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , and 6 membered heteroaryl optionally substituted by 1-3 R 59 . 
     Embodiment 762 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1 R 59 , and 6 membered heteroaryl optionally substituted by 1 R 59 . 
     Embodiment 763 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  and R 32  at each occurrence are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 59 , C 2-6 alkenyl optionally substituted by 1-11 R 59 , C 2-6 alkynyl optionally substituted by 1-9 R 59 , C 6-11 aryl optionally substituted by 1-11 R 59 , C 7-16 arylalkyl optionally substituted by 1-19 R 59 , C 3-11  cycloalkyl optionally substituted by 1-21 R 59 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 59 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 59 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 59 , 5-15 membered heteroaryl optionally substituted by 1-15 R 59 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 59 ; R 23  and R 33  at each occurrence is independently chosen from H and C 1-6 alkyl; or any R 22  and R 23  and/or R 32  and R 33  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 69  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 69 . 
     Embodiment 764 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  and R 32  at each occurrence are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , C 2-6 alkenyl optionally substituted by 1-3 R 59 , C 2-6 alkynyl optionally substituted by 1-3 R 59 , C 6-11 aryl optionally substituted by 1-3 R 59 , C 7-16 arylalkyl optionally substituted by 1-3 R 59 , C 3-11 cycloalkyl optionally substituted by 1-3 R 59 , C 4-17 cycloalkylalkyl optionally substituted by 1-3 R 59 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 59 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-3 R 59 , 5-15 membered heteroaryl optionally substituted by 1-3 R 59 , and 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 59 ; R 23  and R 33  at each occurrence is independently chosen from H and C 1-6 alkyl; or any R 22  and R 23  and/or R 32  and R 33  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 69  or a 5-15 membered heteroaryl optionally substituted by 1-3 R 69 . 
     Embodiment 765 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  and R 32  at each occurrence are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , C 6-10 aryl optionally substituted by 1-3 R 59 , bezyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23  and R 33  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 766 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  and R 32  at each occurrence are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23  and R 33  at each occurrence are independently chosen from H and C 1-6 alkyl. 
     Embodiment 767 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  and R 32  at each occurrence are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , benzyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23  and R 33  at each occurrence are independently chosen from H and C 1-6 alkyl. 
     Embodiment 768 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 4-5 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-9 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32  and R 33  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 769 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  and R 32  at each occurrence are independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 23  and R 33  at each occurrence are independently chosen from H and C 1-6 alkyl. 
     Embodiment 770 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32  and R 33  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 59 . 
     Embodiment 771 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  and R 32  at each occurrence are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , benzyl, C 3-10 cycloalkyl, 4-5 membered heterocycloalkyl, and 5-9 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23  and R 33  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 59 . 
     Embodiment 772 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  at each occurrence is independently chosen from H, C 6-10 aryl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32  and R 33  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 773 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 59 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32  and R 33  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 774 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  and R 32  at each occurrence are independently chosen from H, phenyl optionally substituted by 1-3 R 59 , benzyl, and 6 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23  and R 33  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 775 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  at each occurrence is independently chosen from H, phenyl optionally substituted by 1 R 59 , and 6 membered heteroaryl optionally substituted by 1 R 59 ; R 23 , R 32  and R 33  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 776 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 59 , C 2-6 alkenyl optionally substituted by 1-11 R 59 , C 2-6 alkynyl optionally substituted by 1-9 R 59 , C 6-11 aryl optionally substituted by 1-11 R 59 , C 7-16 arylalkyl optionally substituted by 1-19 R 59 , C 3-11 cycloalkyl optionally substituted by 1-21 R 59 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 59 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 59 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 59 , 5-15 membered heteroaryl optionally substituted by 1-15 R 59 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 59 ; R 23 , R 32  and R 33  at each occurrence is H; or any R 22  and R 23  and/or R 32  and R 33  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 69  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 69 . 
     Embodiment 777 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , C 2-6 alkenyl optionally substituted by 1-3 R 59 , C 2-6 alkynyl optionally substituted by 1-3 R 59 , C 6-11 aryl optionally substituted by 1-3 R 59 , C 7-16 arylalkyl optionally substituted by 1-3 R 59 , C 3-11 cycloalkyl optionally substituted by 1-3 R 59 , C 4-17 cycloalkylalkyl optionally substituted by 1-3 R 59 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 59 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-3 R 59 , 5-15 membered heteroaryl optionally substituted by 1-3 R 59 , and 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 59 ; R 23 , R 32  and R 33  at each occurrence is H; or any R 22  and R 23  and/or R 32  and R 33  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 69  or a 5-15 membered heteroaryl optionally substituted by 1-3 R 69 . 
     Embodiment 778 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , C 2-6 alkenyl optionally substituted by 1-3 R 59 , C 2-6 alkynyl optionally substituted by 1-3 R 59 , C 6-10 aryl optionally substituted by 1-3 R 59 , C 7-11 arylalkyl optionally substituted by 1-3 R 59 , C 3-10 -cycloalkyl optionally substituted by 1-3 R 59 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32  and R 33  at each occurrence is H; or any R 22  and R 23  and/or R 32  and R 33  may form, together with the nitrogen atom to which they are attached, a 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 69  or a 5-10 membered heteroaryl optionally substituted by 1-3 R 69 . 
     Embodiment 779 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32  and R 33  at each occurrence is H. 
     Embodiment 780 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32  and R 33  at each occurrence is H; or any R 22  and R 23  and/or R 32  and R 33  may form, together with the nitrogen atom to which they are attached, a 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 69  or a 5-10 membered heteroaryl optionally substituted by 1-3 R 69 . 
     Embodiment 781 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32  and R 33  at each occurrence is H. 
     Embodiment 782 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl, 4-5 membered heterocycloalkyl, and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32  and R 33  at each occurrence is H. 
     Embodiment 783 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl, 4-5 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-9 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32  and R 33  at each occurrence is H. 
     Embodiment 784 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl, 4-5 membered heterocycloalkyl, and 5-9 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32  and R 33  at each occurrence is H. 
     Embodiment 785 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  at each occurrence is independently chosen from H, C 6-10 aryl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32  and R 33  at each occurrence is H. 
     Embodiment 786 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 59 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32  and R 33  at each occurrence is H. 
     Embodiment 787 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 59 , and 6 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32  and R 33  at each occurrence is H. 
     Embodiment 788 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22  at each occurrence is independently chosen from H, phenyl optionally substituted by 1 R 59 , and 6 membered heteroaryl optionally substituted by 1 R 59 ; R 23 , R 32  and R 33  at each occurrence is H. 
     Embodiment 789 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 790 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is H. 
     Embodiment 791 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-13 R 59 ; or any R 22  and R 23  and/or R 32  and R 33  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 69  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 69 . 
     Embodiment 792 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 59 ; or any R 22  and R 23  and/or R 32  and R 33  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 69  or a 5-15 membered heteroaryl optionally substituted by 1-6 R 69 . 
     Embodiment 793 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 59 ; or any R 22  and R 23  and/or R 32  and R 33  may form, together with the nitrogen atom to which they are attached, a 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 69  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 69 . 
     Embodiment 794 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 59 ; or any R 22  and R 23  and/or R 32  and R 33  may form, together with the nitrogen atom to which they are attached, a 3-6 membered heterocycloalkyl optionally substituted by 1-6 R 69  or a 5-6 membered heteroaryl optionally substituted by 1-6 R 69 . 
     Embodiment 795 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H and C 1-6 alkyl optionally; or any R 22  and R 23  and/or R 32  and R 33  may form, together with the nitrogen atom to which they are attached, a 3-6 membered heterocycloalkyl or a 5-6 membered heteroaryl. 
     Embodiment 800 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59  and R 69  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkenyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 6-11 aryl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-11 cycloalkyl optionally substituted by 1-6 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 79 , 5-15 membered heteroaryl optionally substituted by 1-6 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —(═O)C(═O)R 70 , —C(═NR 75 )R 70 , —C(═NR 75 )NR 72 R 73 , —C(═NOH)NR 72 R 73 , —C(═NOR 76 )R 70 , —C(═NNR 72 R 73 )R 70 , —C(═NNR 74 C(═O)R 71 )R 70 , —C(═NNR 74 C(═O)OR 71 )R 70 , —C(═S)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 NR 72 R 73 , —N═NR 74 , ═NR 70 , ═NOR 70 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 C(═O)NR 74 C(═O)OR 70 , —NR 74 C(═NR 75 )NR 72 R 73 , —NR 74 C(═O)C(═O)NR 72 R 73 , —NR 74 C(═S)R 70 , —NR 74 C(═S)OR 70 , —NR 74 C(═S)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —NR 74 P(═O)R 78 R 78 , —NR 74 P(═O)(NR 72 R 73 )(NR 72 R 73 ), —NR 74 P(═)(OR 70 )(OR 70 ), —NR 74 P(═O)(SR 70 )(SR 70 ), —OR 70 , ═O, —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —OC(═NR 75 )NR 72 R 73 , —OS(═O)R 70 , —OS(═O) 2 R 70 , —OS(═O) 2 OR 70 , —OS(═O) 2 NR 72 R 73 , —OP(═O)R 78 R 78 , —OP(═O)(NR 72 R 73 )(NR 72 R 73 ), —OP(═O)(OR 70 )(OR 70 ), —OP(═O)(SR 70 )(SR 70 ), —Si(R 74 ) 3 , —SCN, ═S, —S(═O) n R 70 , —S(═O) 2 OR 70 , —SO 3 R 77 , —S(═O) 2 NR 72 R 73 , —S(═O)NR 72 R 73 , —SP(═O)R 78 R 78 , —SP(═O)(NR 72 R 73 )(NR 72 R 73 ), —SP(═O)(OR 70 )(OR 70 ), —SP(═O)(SR 70 )(SR 70 ), —P(═O)R 78 R 78 , —P(═O)(NR 72 R 73 )(NR 72 R 73 ), —P(═O)(OR 70 )(OR 70 ), and —P(═O)(SR 70 )(SR 70 ). 
     Embodiment 801 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59  and R 69  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 79 , C 6-11 aryl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-11 cycloalkyl optionally substituted by 1-6 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 79 , 5-15 membered heteroaryl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 NR 72 R 73 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —OR 70 , ═O, —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —Si(R 74 ) 3 , —SCN, ═S, —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 . 
     Embodiment 802 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59  and R 69  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 79 , C 6-10 aryl optionally substituted by 1-6 R 79 , C 7-11 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 79 , 5-10 membered heteroaryl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NO 2 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —OR 70 , ═O, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —Si(R 74 ) 3 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 . 
     Embodiment 803 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59  and R 69  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , C 6-10 aryl optionally substituted by 1-3 R 79 , C 7-11 arylalkyl optionally substituted by 1-3 R 79 , C 3-10 cycloalkyl optionally substituted by 1-3 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 79 , 5-10 membered heteroaryl optionally substituted by 1-3 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NO 2 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —OR 70 , ═O, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —Si(R 74 ) 3 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 . 
     Embodiment 804 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59  and R 69  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , phenyl optionally substituted by 1-3 R 79 , benzyl optionally substituted by 1-3 R 79 , C 3-6 cycloalkyl optionally substituted by 1-3 R 79 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 79 , 5-6 membered heteroaryl optionally substituted by 1-3 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NO 2 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 C(═)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —OR 70 , ═O, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —Si(R 74 ) 3 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 . 
     Embodiment 805 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59  and R 69  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , phenyl optionally substituted by 1-3 R 79 , benzyl optionally substituted by 1-3 R 79 , C 3-6 cycloalkyl optionally substituted by 1-3 R 79 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 79 , 5-6 membered heteroaryl optionally substituted by 1-3 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NO 2 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 . 
     Embodiment 806 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59  and R 69  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , phenyl optionally substituted by 1-3 R 79 , benzyl optionally substituted by 1-3 R 79 , C 3-6 cycloalkyl optionally substituted by 1-3 R 79 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 79 , 5-6 membered heteroaryl optionally substituted by 1-3 R 79 , halogen, —CN, —C(═O)NR 72 R 73 , —NR 72 R 73 , —OR 70 , and —S(═O) n R 70 . 
     Embodiment 807 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59  and R 69  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , phenyl optionally substituted by 1-3 R 79 , benzyl optionally substituted by 1-3 R 79 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)NR 72 R 73 , —NR 72 R 73 , —OR 70 , and —S(═O) n R 70 . 
     Embodiment 808 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59  and R 69  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , phenyl optionally substituted by 1-3 R 79 , benzyl optionally substituted by 1-3 R 79 , cyclopropyl, 5-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)NR 72 R 73 , —NR 72 R 73 , —OR 70 , and —S(═O) n R 70 . 
     Embodiment 809 
     The compound of any of Embodiments 800-808, wherein R 39  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , benzyl optionally substituted by 1-3 R 79 , and 5-6 membered heteroaryl. 
     Embodiment 810 
     The compound of any of Embodiments 800-808, wherein R 39  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , benzyl optionally substituted by 1-3 R 79 , and 6 membered heteroaryl. 
     Embodiment 811 
     The compound of any of Embodiments 800-810, wherein R 49  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , phenyl optionally substituted by 1-3 R 79 , 5-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —C(═O)NR 72 R 73 , and —NR 72 R 73 . 
     Embodiment 812 
     The compound of any of Embodiments 800-810, wherein R 49  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , phenyl optionally substituted by 1-3 R 79 , 5-6 membered heterocycloalkyl, 6 membered heteroaryl, halogen, —C(═O)NR 72 R 73 , and —NR 72 R 73 . 
     Embodiment 813 
     The compound of any of Embodiments 800-812, wherein R 59  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , phenyl optionally substituted by 1-3 R 79 , cyclopropyl, 5-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —NR 72 R 73 , —OR 70 , and —S(═O)R 70 . 
     Embodiment 814 
     The compound of any of Embodiments 800-812, wherein R 59  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , phenyl optionally substituted by 1-3 R 79 , cyclopropyl, 6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —NR 72 R 73 , —OR 70 , and —S(═O) n R 70 . 
     Embodiment 815 
     The compound of any of Embodiments 800-814, wherein R 69  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 . 
     Embodiment 816 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59  and R 69  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 . 
     Embodiment 817 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59  and R 69  at each occurrence is independently C 1-6 alkyl. 
     Embodiment 850 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76  and R 77  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 89 , C 2-6 alkenyl optionally substituted by 1-11 R 89 , C 2-6 alkynyl optionally substituted by 1-9 R 89 , C 6-11 aryl optionally substituted by 1-11 R 89 , C 7-16 arylalkyl optionally substituted by 1-19 R 89 , C 3-11 cycloalkyl optionally substituted by 1-21 R 89 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 89 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 89 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 89 , 5-15 membered heteroaryl optionally substituted by 1-15 R 89 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 89 . 
     Embodiment 851 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76  and R 77  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 89 , C 2-6 alkenyl optionally substituted by 1-6 R 89 , C 2-6 alkynyl optionally substituted by 1-6 R 89 , C 6-10 aryl optionally substituted by 1-6 R 89 , C 7-11 arylalkyl optionally substituted by 1-6 R 89 , C 3-10 cycloalkyl optionally substituted by 1-6 R 89 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 89 , and 5-10 membered heteroaryl optionally substituted by 1-6 R 89 . 
     Embodiment 852 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76  and R 77  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 89 , C 2-6 alkenyl optionally substituted by 1-3 R 89 , C 2-6 alkynyl optionally substituted by 1-3 R 89 , C 6-10 aryl optionally substituted by 1-3 R 89 , C 7-11 arylalkyl optionally substituted by 1-3 R 89 , C 3-10 cycloalkyl optionally substituted by 1-3 R 89 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 89 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 89 . 
     Embodiment 853 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76  and R 77  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 89 , phenyl optionally substituted by 1-3 R 89 , benzyl optionally substituted by 1-3 R 89 , C 3-10 cycloalkyl optionally substituted by 1-3 R 89 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 89 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 89 . 
     Embodiment 854 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76  and R 77  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, and 5-10 membered heteroaryl. 
     Embodiment 855 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76  and R 77  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 89 , phenyl optionally substituted by 1-3 R 89 , benzyl optionally substituted by 1-3 R 89 , C 5-6 cycloalkyl optionally substituted by 1-3 R 89 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 89 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 89 . 
     Embodiment 856 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76  and R 77  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 857 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76  and R 77  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 858 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76  and R 77  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl optionally substituted by 1 R 89 , and 5-6 membered heteroaryl. 
     Embodiment 859 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76  and R 77  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 89 . 
     Embodiment 860 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76  and R 77  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 861 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76  and R 77  at each occurrence is H. 
     Embodiment 862 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72  and R 73  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 99 , C 2-6 alkenyl optionally substituted by 1-11 R 99 , C 2-6 alkynyl optionally substituted by 1-9 R 99 , C 6-11 aryl optionally substituted by 1-11 R 99 , C 7-16 arylalkyl optionally substituted by 1-19 R 99 , C 3-11 cycloalkyl optionally substituted by 1-21 R 99 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 99 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 99 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 99 , 5-15 membered heteroaryl optionally substituted by 1-15 R 99 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 99 ; or any R 72  and R 73  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 109  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 109 . 
     Embodiment 863 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72  and R 73  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 99 , C 2-6 alkenyl optionally substituted by 1-6 R 99 , C 2-6 alkynyl optionally substituted by 1-6 R 99 , C 6-11 aryl optionally substituted by 1-6 R 99 , C 7-16 arylalkyl optionally substituted by 1-6 R 99 , C 3-11 cycloalkyl optionally substituted by 1-6 R 99 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 99 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 99 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 99 , 5-15 membered heteroaryl optionally substituted by 1-6 R 99 , and 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 99 ; or any R 72  and R 73  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 109  or a 5-15 membered heteroaryl optionally substituted by 1-6 R 109 . 
     Embodiment 864 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72  and R 73  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 99 , phenyl optionally substituted by 1-3 R 99 , benzyl optionally substituted by 1-3 R 99 , C 3-10 cycloalkyl optionally substituted by 1-3 R 99 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 99 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 99 ; or any R 72  and R 73  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 109  or a 5-15 membered heteroaryl optionally substituted by 1-3 R 109 . 
     Embodiment 865 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72  and R 73  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 99 , phenyl optionally substituted by 1-3 R 99 , benzyl optionally substituted by 1-3 R 99 , C 3-10 cycloalkyl optionally substituted by 1-3 R 99 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 99 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 99 . 
     Embodiment 866 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72  and R 73  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 99 , phenyl optionally substituted by 1-3 R 99 , benzyl optionally substituted by 1-3 R 99 , C 3-6 cycloalkyl optionally substituted by 1-3 R 99 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 99 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 99 ; or any R 72  and R 73  may form, together with the nitrogen atom to which they are attached, a 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 109  or a 5-10 membered heteroaryl optionally substituted by 1-3 R 109 . 
     Embodiment 867 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72  and R 73  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 99 , phenyl optionally substituted by 1-3 R 99 , benzyl optionally substituted by 1-3 R 99 , C 5-6 cycloalkyl optionally substituted by 1-3 R 99 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 99 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 99 . 
     Embodiment 868 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72  and R 73  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 99 , phenyl optionally substituted by 1-3 R 99 , benzyl optionally substituted by 1-3 R 99 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 99 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 99 . 
     Embodiment 869 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72  and R 73  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; or any R 72  and R 73  may form, together with the nitrogen atom to which they are attached, a 5-6 membered heterocycloalkyl or a 5-6 membered heteroaryl. 
     Embodiment 870 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72  and R 73  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 871 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72  and R 73  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 99 , phenyl optionally substituted by 1-3 R 99 , and benzyl optionally substituted by 1-3 R 99 . 
     Embodiment 872 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72  and R 73  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 99 . 
     Embodiment 873 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72  and R 73  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, and benzyl. 
     Embodiment 874 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72  and R 73  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 875 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72  and R 73  at each occurrence is H. 
     Embodiment 876 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 89 , C 2-6 alkenyl optionally substituted by 1-11 R 89 , C 2-6 alkynyl optionally substituted by 1-9 R 89 , C 6-11 aryl optionally substituted by 1-11 R 89 , C 7-16 arylalkyl optionally substituted by 1-19 R 89 , C 3-11 cycloalkyl optionally substituted by 1-21 R 89 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 89 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 89 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 89 , 5-15 membered heteroaryl optionally substituted by 1-15 R 89 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 89 ; or any two R 78  attached to the same phosphorus atom can, together with the phosphorus atom linking them, form a 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 89 . 
     Embodiment 877 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 89 , C 2-6 alkenyl optionally substituted by 1-3 R 89 , C 2-6 alkynyl optionally substituted by 1-3 R 89 , C 6-11 aryl optionally substituted by 1-3 R 89 , C 7-16 arylalkyl optionally substituted by 1-3 R 89 , C 3-11 cycloalkyl optionally substituted by 1-3 R 89 , C 4-17 cycloalkylalkyl optionally substituted by 1-3 R 89 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 89 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-3 R 89 , 5-15 membered heteroaryl optionally substituted by 1-3 R 89 , and 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 89 ; or any two R 78  attached to the same phosphorus atom can, together with the phosphorus atom linking them, form a 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 89 . 
     Embodiment 878 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 89 , C 2-6 alkenyl optionally substituted by 1-3 R 89 , C 2-6 alkynyl optionally substituted by 1-3 R 89 , C 6-10 aryl optionally substituted by 1-3 R 89 , C 7-11 arylalkyl optionally substituted by 1-3 R 89 , C 3-10 cycloalkyl optionally substituted by 1-3 R 89 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 89 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 89 ; or any two R 78  attached to the same phosphorus atom can, together with the phosphorus atom linking them, form a 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 89 . 
     Embodiment 879 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 89 , C 6-10 aryl optionally substituted by 1-3 R 89 , C 7-11 arylalkyl optionally substituted by 1-3 R 89 , C 3-10 cycloalkyl optionally substituted by 1-3 R 89 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 89 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 89 ; or any two R 78  attached to the same phosphorus atom can, together with the phosphorus atom linking them, form a 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 89 . 
     Embodiment 880 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 89 , phenyl optionally substituted by 1-3 R 89 , benzyl optionally substituted by 1-3 R 89 , C 3-6 cycloalkyl optionally substituted by 1-3 R 89 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 89 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 89 ; or any two R 78  attached to the same phosphorus atom can, together with the phosphorus atom linking them, form a 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 89 . 
     Embodiment 881 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78  at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; or any two R 78  attached to the same phosphorus atom can, together with the phosphorus atom linking them, form a 6 membered heterocycloalkyl optionally substituted by 1-3 R 89 . 
     Embodiment 882 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 89 , phenyl, and benzyl. 
     Embodiment 883 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 89 , phenyl optionally substituted by 1-3 R 89 , and benzyl optionally substituted by 1-3 R 89 ; or any two R 78  attached to the same phosphorus atom can, together with the phosphorus atom linking them, form a 6 membered heterocycloalkyl optionally substituted by 1-3 R 89 . 
     Embodiment 884 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78  at each occurrence is independently chosen from C 1-6 alkyl, phenyl, and benzyl; or any two R 78  attached to the same phosphorus atom can, together with the phosphorus atom linking them, form an azaphosphinane ring optionally substituted by 1-3 C 1-6 alkyl. 
     Embodiment 885 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78  at each occurrence is C 1-6 alkyl optionally substituted by 1-3 R 89 ; or any two R 78  attached to the same phosphorus atom can, together with the phosphorus atom linking them, form an azaphosphinane ring optionally substituted by 1-3 R 89 . 
     Embodiment 886 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78  at each occurrence is C 1-6 alkyl. 
     Embodiment 900 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99  and R 109  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 119 , C 2-6 alkenyl optionally substituted by 1-6 R 119 , C 2-6 alkynyl optionally substituted by 1-6 R 119 , C 6-11 aryl optionally substituted by 1-6 R 119 , C 7-16 arylalkyl optionally substituted by 1-6 R 119 , C 3-11 cycloalkyl optionally substituted by 1-6 R 119 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 119 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 119 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 119 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 119 , halogen, —CN, —C(═O)R 110 , —C(═O)OR 110 , —C(═O)NR 112 R 113 , —C(═O)C(═O)R 110 , —C(═NR 115 )R 110 , —C(═NR 115 )NR 112 R 113 , —C(═NOH)NR 112 R 113 , —C(═NOR 116 )R 110 , —C(═NNR 112 R 113 )R 110 , —C(═NNR 114 C(═O)R 111 )R 110 , —C(═NNR 114 C(═O)OR 111 )R 110 , —C(═S)NR 112 R 113 , —NC, —NO 2 , —NR 112 R 113 , —NR 114 NR 112 R 113 , —N═NR 114 , ═NR 110 , ═NOR 110 , —NR 114 OR 116 , —NR 114 C(═O)R 110 , —NR 114 C(═O)C(═O)R 110 , —NR 114 C(═O)OR 111 , —NR 114 C(═O)C(═O)OR 111 , —NR 114 C(═O)NR 112 R 113 , —NR 114 C(═O)NR 114 C(═O)R 110 , —NR 14 C(═O)NR 114 C(═O)OR 110 , —NR 14 C(═NR 115 )NR 112 R 113 , —NR 114 C(═O)C(═O)NR 112 R 113 , —NR 114 C(═S)R 110 , —NR 114 C(═S)OR 110 , —NR 114 C(═S)NR 112 R 113 , —NR 114 S(═O) 2 R 11 , —NR 114 S(═O) 2 NR 112 R 113 , —NR 114 P(═O)R 118 R 118 , —NR 114 P(═O)(NR 112 R 113 )(NR 112 R 113 ), —NR 114 P(═O)(OR 110 )(OR 110 )—NR 114 P(═O)(SR 110 )(SR 110 ), —OR 110 , ═O, —OCN, —OC(═O)R 110 , —OC(═O)NR 112 R 113 , —OC(═O)OR 110 , —OC(═NR 115 )NR 112 R 113 , —OS(═O)R 110 , —OS(═O) 2 R, —OS(═O) 2 OR 110 , —OS(═O) 2 NR 112 R 113 , —OP(═O)R 118 R 118 , —OP(═O)(NR 112 R 113 )(NR 112 R 113 ), —OP(═O)(OR 110 )(OR 110 ), —OP(═O)(SR 110 )(SR 110 ), —Si(R 114 ) 3 , —SCN, ═S, —S(═O) n R 110 , —S(═O) 2 OR 110 , —SO 3 R 1111 , —S(═O) 2 NR 112 R 113 , —S(═O)NR 112 R 113 , —SP(═O)R 118 R 118 , —SP(═O)(NR 112 R 113 )(NR 112 R 113 ), —SP(═O)(OR 110 )(OR 110 ), —SP(═O)(SR 110 )(SR 110 ), —P(═O)R 118 R 118 , —P(═O)(NR 112 R 113 )(NR 112 R 113 ), —P(═O)(OR 110 )(OR 110 ), and —P(═O)(SR 110 )(SR 110 ). 
     Embodiment 901 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99  and R 109  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 119 , C 6-11 aryl optionally substituted by 1-6 R 119 , C 7-16 arylalkyl optionally substituted by 1-6 R 119 , C 3-11 cycloalkyl optionally substituted by 1-6 R 119 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 119 , 5-15 membered heteroaryl optionally substituted by 1-6 R 119 , halogen, —CN, —C(═O)R 110 , —C(═O)OR 110 , —C(═O)NR 112 R 113 , —NC, —NO 2 , —NR 112 R 113 , —NR 114 NR 112 R 113 , —NR 114 OR 116 , —NR 114 C(═O)R 110 , —NR 114 C(═O)OR 111 , —NR 114 C(═O)NR 112 R 113 , —NR 114 C(═O)NR 114 C(═O)R 110 , —NR 114 S(═O) 2 R 111 , —NR 114 S(═O) 2 NR 112 R 113 , —OR 110 , ═O, —OCN, —OC(═O)R 110 , —OC(═O)NR 112 R 113 , —OC(═O)OR 110 , —Si(R 114 ) 3 , —SCN, ═S, —S(═O) n R 110 , and —S(═O) 2 NR 112 R 113 . 
     Embodiment 902 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99  and R 109  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 119 , C 6-10 aryl optionally substituted by 1-6 R 119 , C 7-11 arylalkyl optionally substituted by 1-6 R 119 , C 3-10 cycloalkyl optionally substituted by 1-6 R 119 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 119 , 5-10 membered heteroaryl optionally substituted by 1-6 R 119 , halogen, —CN, —C(═O)R 110 , —C(═O)OR 110 , —C(═O)NR 112 R 113 , —NO 2 , —NR 112 R 113 , —NR 114 C(═O)R 110 , —NR 114 C(═O)OR 111 , —NR 114 C(═O)NR 112 R 113 , —NR 114 C(═O)NR 114 C(═O)R 110 , —NR 114 S(═O) 2 R 111 , —NR 114 S(═O) 2 NR 112 R 113 , —OR 110 , ═O, —OC(═O)R 110 , —OC(═O)NR 112 R 113 , —OC(═O)OR 110 , —Si(R 114 ) 3 , —S(═O) n R 110 , and —S(═O) 2 NR 112 R 113 . 
     Embodiment 903 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99  and R 109  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 119 , C 6-10 aryl optionally substituted by 1-3 R 119 , C 7-11 arylalkyl optionally substituted by 1-3 R 119 , C 3-10 cycloalkyl optionally substituted by 1-3 R 119 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 119 , 5-10 membered heteroaryl optionally substituted by 1-3 R 119 , halogen, —CN, —C(═O)R 110 , —C(═O)OR 110 , —C(═O)NR 112 R 113 , —NO 2 , —NR 112 R 113 , —NR 114 C(═O)R 110 , —NR 114 C(═O)OR 111 , —NR 114 C(═O)NR 112 R 113 , —NR 114 C(═O)NR 114 C(═O)R 110 , —NR 114 S(═O) 2 R 111 , —NR 114 S(═O) 2 NR 112 R 113 , —OR 110 , ═O, —OC(═O)R 110 , —OC(═O)NR 112 R 113 , —OC(═)OR 110 , —Si(R 114 ) 3 , —S(═O) n R 110 , and —S(═O) 2 NR 112 R 113 . 
     Embodiment 904 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99  and R 109  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 119 , phenyl optionally substituted by 1-3 R 119 , benzyl optionally substituted by 1-3 R 119 , C 3-6 cycloalkyl optionally substituted by 1-3 R 119 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 119 , 5-6 membered heteroaryl optionally substituted by 1-3 R 119 , halogen, —CN, —C(═O)R 11 , —C(═O)OR 110 , —C(═O)NR 112 R 113 , —NO 2 , —NR 112 R 113 , —NR 114 C(═O)R 110 , —NR 114 C(═O)OR 111 , —NR 114 C(═O)NR 112 R 113 , —NR 114 C(═O)NR 114 C(═O)R 110 , —NR 114 S(═O) 2 R 111 , —NR 114 S(═O) 2 NR 112 R 113 , —OR 10 , ═O, —OC(═O)R 110 , —OC(═O)NR 112 R 113 , —OC(═O)OR 110 , —Si(R 114 ) 3 , —S(═) n R 110 , and —S(═O) 2 NR 112 R 113 . 
     Embodiment 905 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99  and R 109  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 119 , phenyl optionally substituted by 1-3 R 119 , benzyl optionally substituted by 1-3 R 119 , C 3-6 cycloalkyl optionally substituted by 1-3 R 119 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 119 , 5-6 membered heteroaryl optionally substituted by 1-3 R 119 , halogen, —CN, —C(═O)R 11 , —C(═O)OR 110 , —C(═O)NR 112 R 113 , —NO 2 , —NR 112 R 113 , —NR 114 C(═O)R 111 , —NR 114 S(═O) 2 R 111 , —OR 110 , —OC(═O)R 110 , —OC(═O)NR 112 R 113 , —S(═O) n R 110 , and —S(═O) 2 NR 112 R 113 . 
     Embodiment 906 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99  and R 109  at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)R 110 , —C(═O)OR 110 , —C(═O)NR 112 R 113 , —NO 2 , —NR 112 R 113 , —NR 114 C(═O)R 110 , —NR 114 S(═O) 2 R 111 , —OR 110 , —OC(═O)R 110 , —OC(═O)NR 112 R 113 , —S(═O) n R 110 , and —S(═O) 2 NR 112 R 113 . 
     Embodiment 907 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99  and R 109  at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, halogen, —CN, —C(═O)OR 110 , —C(═O)NR 112 R 113 , —NO 2 , —NR 112 R 113 , —OR 110 , and —S(═O) n R 110 . 
     Embodiment 908 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99  and R 109  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 119 , phenyl optionally substituted by 1-3 R 119 , benzyl optionally substituted by 1-3 R 119 , halogen, —CN, —C(═O)OR 110 , —C(═O)NR 112 R 113 , —NO 2 , —NR 112 R 113 , —OR 110 , and —S(═O) n R 110 . 
     Embodiment 909 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99  and R 109  at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, halogen, —NR 112 R 113  and —OR 110 . 
     Embodiment 910 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99  and R 109  at each occurrence is independently chosen from C 1-6 alkyl, halogen, —NR 12 R 113 , and —OR 110 . 
     Embodiment 911 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99  and R 109  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 119  and halogen. 
     Embodiment 912 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99  and R 109  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 119 . 
     Embodiment 913 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99  and R 109  at each occurrence is independently C 1-6 alkyl. 
     Embodiment 914 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 114 , R 115 , R 116  and R 117  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 129 , C 2-6 alkenyl optionally substituted by 1-11 R 129 , C 2-6 alkynyl optionally substituted by 1-9 R 129 , C 6-11 aryl optionally substituted by 1-11 R 129 , C 7-16 arylalkyl optionally substituted by 1-19 R 129 , C 3-11 cycloalkyl optionally substituted by 1-21 R 129 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 129 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 129 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 129 , 5-15 membered heteroaryl optionally substituted by 1-15 R 129 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 129 . 
     Embodiment 915 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 4 , R 115 , R 116  and R 117  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 129 , C 2-6 alkenyl optionally substituted by 1-6 R 129 , C 2-6 alkynyl optionally substituted by 1-6 R 129 , C 6-10 aryl optionally substituted by 1-6 R 129 , C 7-11 arylalkyl optionally substituted by 1-6 R 129 , C 3-10 cycloalkyl optionally substituted by 1-6 R 129 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 129 , and 5-10 membered heteroaryl optionally substituted by 1-6 R 129 . 
     Embodiment 916 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 114 , R 115 , R 116  and R 117  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 129 , C 2-6 alkenyl optionally substituted by 1-3 R 129 , C 2-6 alkynyl optionally substituted by 1-3 R 129 , C 6-10 aryl optionally substituted by 1-3 R 129 , C 7-11 arylalkyl optionally substituted by 1-3 R 129 , C 3-10 cycloalkyl optionally substituted by 1-3 R 129 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 129 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 129 . 
     Embodiment 917 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 4 , R 115 , R 116  and R 117  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 129 , phenyl optionally substituted by 1-3 R 129 , benzyl optionally substituted by 1-3 R 129 , C 3-10 cycloalkyl optionally substituted by 1-3 R 129 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 129 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 129 . 
     Embodiment 918 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 114 , R 115 , R 116  and R 117  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, and 5-10 membered heteroaryl. 
     Embodiment 919 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 114 , R 115 , R 116  and R 117  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 129 , phenyl optionally substituted by 1-3 R 129 , benzyl optionally substituted by 1-3 R 129 , C 5-6 cycloalkyl optionally substituted by 1-3 R 129 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 129 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 129 . 
     Embodiment 920 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 114 , R 115 , R 116  and R 117  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 921 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 4 , R 115 , R 116  and R 117  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 922 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 4 , R 115 , R 116  and R 117  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl optionally substituted by 1 R 129 , and 5-6 membered heteroaryl. 
     Embodiment 923 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 4 , R 115 , R 116  and R 117  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 129 . 
     Embodiment 924 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 114 , R 115 , R 116  and R 117  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 925 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 4 , R 115 , R 116  and R 117  at each occurrence is H. 
     Embodiment 926 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12  and R 113  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 139 , C 2-6 alkenyl optionally substituted by 1-11 R 139 , C 2-6 alkynyl optionally substituted by 1-9 R 139 , C 6-11 aryl optionally substituted by 1-11 R 139 , C 7-16 arylalkyl optionally substituted by 1-19 R 139 , C 3-11  optionally substituted by 1-21 R 139 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 139 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 139 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 139 , 5-15 membered heteroaryl optionally substituted by 1-15 R 139 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 139 ; or any R 112  and R 113  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 149  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 149 . 
     Embodiment 927 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12  and R 113  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 139 , C 2-6 alkenyl optionally substituted by 1-6 R 139 , C 2-6 alkynyl optionally substituted by 1-6 R 39 , C 6-11 aryl optionally substituted by 1-6 R 139 , C 7-16 arylalkyl optionally substituted by 1-6 R 139 , C 3-11 cycloalkyl optionally substituted by 1-6 R 139 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 139 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 139 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 139 , 5-15 membered heteroaryl optionally substituted by 1-6 R 139 , and 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 139 ; or any R 2  and R 113  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 149  or a 5-15 membered heteroaryl optionally substituted by 1-6 R 149 . 
     Embodiment 928 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12  and R 113  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 139 , phenyl optionally substituted by 1-3 R 139 , benzyl optionally substituted by 1-3 R 139 , C 3-10 cycloalkyl optionally substituted by 1-3 R 139 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 139 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 139 ; or any R 112  and R 113  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 149  or a 5-15 membered heteroaryl optionally substituted by 1-3 R 149 . 
     Embodiment 929 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12  and R 113  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 139 , phenyl optionally substituted by 1-3 R 139 , benzyl optionally substituted by 1-3 R 139 , C 3-10 cycloalkyl optionally substituted by 1-3 R 139 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 139 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 139 . 
     Embodiment 930 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12  and R 113  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 139 , phenyl optionally substituted by 1-3 R 139 , benzyl optionally substituted by 1-3 R 139 , C 3-6 cycloalkyl optionally substituted by 1-3 R 139 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 139 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 139 ; or any R 112  and R 113  may form, together with the nitrogen atom to which they are attached, a 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 149  or a 5-10 membered heteroaryl optionally substituted by 1-3 R 149 . 
     Embodiment 931 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12  and R 113  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 139 , phenyl optionally substituted by 1-3 R 139 , benzyl optionally substituted by 1-3 R 139 , C 5-6 cycloalkyl optionally substituted by 1-3 R 139 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 139 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 139 . 
     Embodiment 932 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12  and R 113  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 139 , phenyl optionally substituted by 1-3 R 139 , benzyl optionally substituted by 1-3 R 139 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 139 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 139 . 
     Embodiment 933 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 112  and R 113  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; or any R 112  and R 113  may form, together with the nitrogen atom to which they are attached, a 5-6 membered heterocycloalkyl or a 5-6 membered heteroaryl. 
     Embodiment 934 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12  and R 113  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 935 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12  and R 113  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 139 , phenyl optionally substituted by 1-3 R 139 , and benzyl optionally substituted by 1-3 R 139 . 
     Embodiment 936 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12  and R 113  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 139 . 
     Embodiment 937 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 112  and R 113  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, and benzyl. 
     Embodiment 938 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12  and R 113  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 939 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 112  and R 113  at each occurrence is H. 
     Embodiment 940 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 129 , C 2-6 alkenyl optionally substituted by 1-11 R 129 , C 2-6 alkynyl optionally substituted by 1-9 R 129 , C 6-11 aryl optionally substituted by 1-11 R 129 , C 7-16 arylalkyl optionally substituted by 1-19 R 129 , C 3-11 cycloalkyl optionally substituted by 1-21 R 129 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 129 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 129 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 129 , 5-15 membered heteroaryl optionally substituted by 1-15 R 129 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 129 . 
     Embodiment 941 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 129 , C 2-6 alkenyl optionally substituted by 1-3 R 129 , C 2-6 alkynyl optionally substituted by 1-3 R 129 , C 6-11 aryl optionally substituted by 1-3 R 129 , C 7-16 arylalkyl optionally substituted by 1-3 R 129 , C 3-11  cycloalkyl optionally substituted by 1-3 R 129 , C 4-17 cycloalkylalkyl optionally substituted by 1-3 R 129 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 129 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-3 R 129 , 5-15 membered heteroaryl optionally substituted by 1-3 R 129 , and 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 129 . 
     Embodiment 942 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 129 , C 2-6 alkenyl optionally substituted by 1-3 R 129 , C 2-6 alkynyl optionally substituted by 1-3 R 129 , C 6-10 aryl optionally substituted by 1-3 R 129 , C 7-11 arylalkyl optionally substituted by 1-3 R 129 , C 3-10 cycloalkyl optionally substituted by 1-3 R 129 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 129 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 129 . 
     Embodiment 943 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 129 , C 6-10 aryl optionally substituted by 1-3 R 129 , C 7-11 arylalkyl optionally substituted by 1-3 R 129 , C 3-10 cycloalkyl optionally substituted by 1-3 R 129 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 129 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 129 . 
     Embodiment 944 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 129 , phenyl optionally substituted by 1-3 R 129 , benzyl optionally substituted by 1-3 R 129 , C 3-6 cycloalkyl optionally substituted by 1-3 R 129 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 129 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 129 . 
     Embodiment 945 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118  at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 946 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 129 , phenyl, and benzyl. 
     Embodiment 947 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 129 , phenyl optionally substituted by 1-3 R 129 , and benzyl optionally substituted by 1-3 R 129 . 
     Embodiment 948 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118  at each occurrence is independently chosen from C 1-6 alkyl, phenyl, and benzyl. 
     Embodiment 949 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118  at each occurrence is C 1-6 alkyl optionally substituted by 1-3 R 129 . 
     Embodiment 950 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118  at each occurrence is C 1-6 alkyl. 
     Embodiment 951 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , —R 139  and R 149  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 159 , C 2-6 alkenyl optionally substituted by 1-6 R 159 , C 2-6 alkynyl optionally substituted by 1-6 R 159 , C 6-11 aryl optionally substituted by 1-6 R 159 , C 7-16 arylalkyl optionally substituted by 1-6 R 159 , C 3-11 cycloalkyl optionally substituted by 1-6 R 159 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 159 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 159 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 159 , 5-15 membered heteroaryl optionally substituted by 1-6 R 159 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 159 , halogen, —CN, —C(═O)R 150 , —C(═O)OR 150 , —C(═O)NR 152 R 153 , —(═O)C(═O)R 150 , —C(═NR 155 )R 150 , —C(═NR 155 )NR 152 R 153 , —C(═NOH)NR 152 R 153 , —C(═NOR 156 )R 150 , —C(═NNR 152 R 153 )R 150 , —C(═NNR 154 C(═O)R 151 )R 150 , —C(═NNR 154 C(═O)OR 151 )R 150 , —C(═S)NR 152 R 153 , —NC, —NO 2 , —NR 152 R 153 , —NR 154 NR 152 R 153 , —N═NR 154 , ═NR 150 , ═NOR 150 , —NR 154 OR 156 , —NR 154 C(═O)R 150 , —NR 154 C(═O)C(═O)R 150 , —NR 154 C(═O)OR 151 , —NR 154 C(═O)C(═O)OR 151 , —NR 154 C(═O)NR 152 R 153 , —NR 154 C(═O)NR 154 C(═O)R 150 , —NR 154 C(═O)NR 154 C(═O)OR 150 , —NR 154 C(═NR 155 )NR 152 R 153 , —NR 154 C(═O)C(═O)NR 152 R 153 , —NR 154 C(═S)R 150 , —NR 154 C(═S)OR 150 , —NR 154 C(═S)NR 152 R 153 , —NR 154 S(═O) 2 R 151 , —NR 154 S(═O) 2 NR 152 R 15 , —NR 154 P(═O)R 158 R 15 , —NR 154 P(═O)(NR 152 R 153 )(NR 152 R 153 ), —NR 154 P(═)(OR 150 )(OR 150 ), —NR 154 P(═O)(SR 150 )(SR 150 ), —OR 150 , ═O, —OCN, —OC(═O)R 150 , —OC(═O)NR 152 R 153 , —OC(═O)OR 150 , —OC(═NR 155 )NR 152 R 153 , —OS(═O)R 150 , —OS(═O) 2 R 150 , —OS(═O) 2 OR 150 , —OS(═O) 2 NR 152 R 153 , —OP(═O)R 158 R 158 , —OP(═O)(NR 152 R 153 )(NR 152 R 153 ), —OP(═O)(OR 150 )(OR 150 ), —OP(═O)(SR 150 )(SR 150 ), —Si(R 154 ) 3 , —SCN, ═S, —S(═O) n R, —S(═O) 2 OR 150 , —SO 3 R 1515 , —S(═O) 2 NR 152 R 153 , —S(═O)NR 152 R 153 , —SP(═O)R 158 R 158 , —SP(═O)(NR 152 R 153 )(NR 152 R 153 ), —SP(═O)(OR 150 )(OR 150 ), —SP(═O)(SR 150 )(SR 150 ), —P(═O)R 158 R 158 , —P(═O)(NR 152 R 153 )(NR 152 R 153 ), —P(═O)(OR 150 )(OR 150 ), and —P(═O)(SR 150 )(SR 150 ). 
     Embodiment 952 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , —R 139  and R 149  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 159 , C 6-11 aryl optionally substituted by 1-6 R 159 , C 7-16 arylalkyl optionally substituted by 1-6 R 159 , C 3-11 cycloalkyl optionally substituted by 1-6 R 159 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 159 , 5-15 membered heteroaryl optionally substituted by 1-6 R 159 , halogen, —CN, —C(═O)R 150 , —C(═O)OR 150 , —C(═O)NR 152 R 153 , —NC, —NO 2 , —NR 152 R 153 , —NR 154 NR 152 R 153 , —NR 154 OR 156 , —NR 154 C(═O)R 150 , —NR 154 C(═O)OR 151 , —NR 154 C(═O)NR 152 R 153 , —NR 154 C(═O)NR 154 C(═O)R 150 , —NR 154 S(═O) 2 R 151 , —NR 154 S(═O)NR 152 R 153 , —OR 150 , ═O, —OCN, —OC(═O)R 150 , —OC(═O)NR 152 R 153 , —OC(═O)OR 150 , —Si(R 154 ) 3 , —SCN, ═S, —S(═) n R 150 , and —S(═O) 2 NR 152 R 153 . 
     Embodiment 953 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , —R 139  and R 149  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 159 , C 6-10 aryl optionally substituted by 1-6 R 159 , C 7-11 arylalkyl optionally substituted by 1-6 R 159 , C 3-10 cycloalkyl optionally substituted by 1-6 R 159 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 159 , 5-10 membered heteroaryl optionally substituted by 1-6 R 159 , halogen, —CN, —C(═O)R 150 , —C(═O)OR 150 , —C(═O)NR 152 R 153 , —NO 2 , —NR 152 R 153 , —NR 154 C(═O)R 150 , —NR 154 C(═O)OR 151 , —NR 154 C(═O)NR 152 R 153 , —NR 154C (═O)NR 154 C(═O)R 150 , —NR 154 S(═O) 2 R 151 , —NR 154 S(═O) 2 NR 152 R 153 , —OR 150 , ═O, —OC(═O)R 150 , —OC(═O)NR 152 R 153 , —OC(═O)OR 150 , —Si(R 154 ) 3 , —S(═O) n R 150 , and —S(═O) 2 NR 152 R 153 . 
     Embodiment 954 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139  and R 149  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 159 , C 6-10 aryl optionally substituted by 1-3 R 159 , C 7-11 arylalkyl optionally substituted by 1-3 R 159 , C 3-10 cycloalkyl optionally substituted by 1-3 R 159 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 159 , 5-10 membered heteroaryl optionally substituted by 1-3 R 159 , halogen, —CN, —C(═O)R 150 , —C(═O)OR 150 , —C(═O)NR 152 R 153 , —NO 2 , —NR 152 R 153 , —NR 154 C(═O)R 150 , —NR 154 C(═O)OR 151 , —NR 154 C(═O)NR 152 R 153 , —NR 154 C(═O)NR 154 C(═O)R 150 , —NR 154 S(═O) 2 R 151 , —NR 154 S(═O) 2 NR 152 R 153 , —OR 150 , ═O, —OC(═O)R 150 , —OC(═O)NR 152 R 153 , —OC(═O)OR, —Si(R 154 ) 3 , —S(═O) n R 150 , and —S(═O) 2 NR 152 R 153 . 
     Embodiment 955 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139  and R 149  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 159 , phenyl optionally substituted by 1-3 R 159 , benzyl optionally substituted by 1-3 R 159 , C 3-6 cycloalkyl optionally substituted by 1-3 R 159 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 159 , 5-6 membered heteroaryl optionally substituted by 1-3 R 159 , halogen, —CN, —C(═O)R 150 , —C(═O)OR 150 , —C(═O)NR 152 R 153 , —NO 2 , —NR 152 R 153 , —NR 154 C(═O)R 150 , —NR 154 C(═O)OR 151 , —NR 154 C(═O)NR 152 R 153 , —NR 154 C(═O)NR 154 C(═O)R 150 , —NR 154 S(═O) 2 R 151 , —NR 154 S(═O) 2 NR 152 R 153 , —OR 150 , ═O, —OC(═O)R 150 , —OC(═O)NR 152 R 153 , —OC(═O)OR 150 , —Si(R 154 ) 3 , —S(═O) n R 150 , and —S(═O) 2 NR 152 R 153 . 
     Embodiment 956 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139  and R 149  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 159 , phenyl optionally substituted by 1-3 R 159 , benzyl optionally substituted by 1-3 R 159 , C 3-6 cycloalkyl optionally substituted by 1-3 R 159 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 159 , 5-6 membered heteroaryl optionally substituted by 1-3 R 159 , halogen, —CN, —C(═O)R 150 , —C(═)OR 150 , —C(═O)NR 152 R 153 , —NO 2 , —NR 152 R 153 , —NR 154 C(═O)R 150 , —NR 154 S(═O) 2 R 151 , —OR 150 , —OC(═O)R 150 , —OC(═O)NR 152 R 153 , —S(═O) n R 150 , and —S(═O) 2 NR 152 R 153 . 
     Embodiment 957 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139  and R 149  at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)R 50 , —C(═O)OR 150 , —C(═O)NR 152 R 153 , —NO 2 , —NR 152 R 15 , —NR 154 C(═O)R 150 , —NR 154 S(═O) 2 R 151 , —OR 150 , —OC(═O)R 150 , —OC(═O)NR 152 R 153 , —S(═O) n R 150 , and —S(═O) 2 NR 152 R 153 . 
     Embodiment 958 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139  and R 149  at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, halogen, —CN, —C(═O)OR 5 , —C(═O)NR 152 R 153 , —NO 2 , —NR 152 R 153 , —OR 150 , and —S(═O) n R 15 . 
     Embodiment 959 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139  and R 149  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 159 , phenyl optionally substituted by 1-3 R 159 , benzyl optionally substituted by 1-3 R 159 , halogen, —CN, —C(═O)OR 150 , —C(═O)NR 152 R 153 , —NO 2 , —NR 152 R 153 , —OR 150 , and —S(═O) n R 150 . 
     Embodiment 960 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139  and R 149  at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, halogen, —NR 152 R 153 , and —OR 150 . 
     Embodiment 961 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139  and R 149  at each occurrence is independently chosen from C 1-6 alkyl, halogen, —NR 152 R 153 , and —OR 150 . 
     Embodiment 962 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139  and R 149  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 159  and halogen. 
     Embodiment 963 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139  and R 149  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 159 . 
     Embodiment 964 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139  and R 149  at each occurrence is independently C 1-6 alkyl. 
     Embodiment 965 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 5 , R 156  and R 157  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 169 , C 2-6 alkenyl optionally substituted by 1-11 R 169 , C 2-6 alkynyl optionally substituted by 1-9 R 169 , C 6-11 aryl optionally substituted by 1-11 R 169 , C 7-16 arylalkyl optionally substituted by 1-19 R 169 , C 3-11 cycloalkyl optionally substituted by 1-21 R 169 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 169 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 169 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 169 , 5-15 membered heteroaryl optionally substituted by 1-15 R 169 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 169 . 
     Embodiment 966 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 , R 156  and R 157  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 169 , C 2-6 alkenyl optionally substituted by 1-6 R 169 , C 2-6 alkynyl optionally substituted by 1-6 R 169 , C 6-10 aryl optionally substituted by 1-6 R 169 , C 7-11 arylalkyl optionally substituted by 1-6 R 169 , C 3-10 cycloalkyl optionally substituted by 1-6 R 169 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 169 , and 5-10 membered heteroaryl optionally substituted by 1-6 R 169 . 
     Embodiment 967 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 , R 156  and R 157  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 169 , C 2-6 alkenyl optionally substituted by 1-3 R 169 , C 2-6 alkynyl optionally substituted by 1-3 R 169 , C 6-10 aryl optionally substituted by 1-3 R 169 , C 7-11 arylalkyl optionally substituted by 1-3 R 169 , C 3-10 cycloalkyl optionally substituted by 1-3 R 169 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 169 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 169 . 
     Embodiment 968 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 , R 156  and R 157  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 169 , phenyl optionally substituted by 1-3 R 169 , benzyl optionally substituted by 1-3 R 169 , C 3-10 cycloalkyl optionally substituted by 1-3 R 169 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 169 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 69 . 
     Embodiment 969 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 R 156  and R 157  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, and 5-10 membered heteroaryl. 
     Embodiment 970 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 54 , R 15 , R 156  and R 157  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 169 , phenyl optionally substituted by 1-3 R 169 , benzyl optionally substituted by 1-3 R 169 , C 5-6 cycloalkyl optionally substituted by 1-3 R 169 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 169 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 169 . 
     Embodiment 971 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 , R 156  and R 157  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 972 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 , R 156  and R 157  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 973 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 , R 156  and R 157  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl optionally substituted by 1 R 169 , and 5-6 membered heteroaryl. 
     Embodiment 974 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 , R 156  and R 157  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 169 . 
     Embodiment 975 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 R 156  and R 157  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 976 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 , R 156  and R 157  at each occurrence is H. 
     Embodiment 977 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152  and R 153  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 179 , C 2-6 alkenyl optionally substituted by 1-11 R 179 , C 2-6 alkynyl optionally substituted by 1-9 R 179 , C 6-11 aryl optionally substituted by 1-11 R 179 , C 7-16 arylalkyl optionally substituted by 1-19 R 179 , C 3-11 cycloalkyl optionally substituted by 1-21 R 179 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 179 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 179 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 179 , 5-15 membered heteroaryl optionally substituted by 1-15 R 179 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 179 ; or any R 152  and R 153  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 189  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 189 . 
     Embodiment 978 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152  and R 153  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 179 , C 2-6 alkenyl optionally substituted by 1-6 R 179 , C 2-6 alkynyl optionally substituted by 1-6 R 179 , C 6-11 aryl optionally substituted by 1-6 R 179 , C 7-16 arylalkyl optionally substituted by 1-6 R 179 , C 3-11 cycloalkyl optionally substituted by 1-6 R 179 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 179 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 179 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 179 , 5-15 membered heteroaryl optionally substituted by 1-6 R 179 , and 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 179 ; or any R 152  and R 153  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 189  or a 5-15 membered heteroaryl optionally substituted by 1-6 R 189 . 
     Embodiment 979 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152  and R 153  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 179 , phenyl optionally substituted by 1-3 R 179 , benzyl optionally substituted by 1-3 R 179 , C 3-10 cycloalkyl optionally substituted by 1-3 R 179 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 179 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 179 ; or any R 152  and R 153  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 189  or a 5-15 membered heteroaryl optionally substituted by 1-3 R 189 . 
     Embodiment 980 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152  and R 153  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 179 , phenyl optionally substituted by 1-3 R 179 , benzyl optionally substituted by 1-3 R 179 , C 3-10 cycloalkyl optionally substituted by 1-3 R 179 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 179 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 179 . 
     Embodiment 981 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152  and R 153  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 179 , phenyl optionally substituted by 1-3 R 179 , benzyl optionally substituted by 1-3 R 179 , C 3-6 cycloalkyl optionally substituted by 1-3 R 179 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 179 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 179 ; or any R 152  and R 153  may form, together with the nitrogen atom to which they are attached, a 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 189  or a 5-10 membered heteroaryl optionally substituted by 1-3 R 189 . 
     Embodiment 982 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152  and R 153  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 179 , phenyl optionally substituted by 1-3 R 179 , benzyl optionally substituted by 1-3 R 179 , C 5-6 cycloalkyl optionally substituted by 1-3 R 179 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 179 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 179 . 
     Embodiment 983 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152  and R 153  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 179 , phenyl optionally substituted by 1-3 R 179 , benzyl optionally substituted by 1-3 R 179 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 179 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 179 . 
     Embodiment 984 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152  and R 153  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; or any R 152  and R 153  may form, together with the nitrogen atom to which they are attached, a 5-6 membered heterocycloalkyl or a 5-6 membered heteroaryl. 
     Embodiment 985 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152  and R 153  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 986 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152  and R 153  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 179 , phenyl optionally substituted by 1-3 R 179 , and benzyl optionally substituted by 1-3 R 179 . 
     Embodiment 987 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152  and R 153  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 179 . 
     Embodiment 988 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152  and R 153  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, and benzyl. 
     Embodiment 989 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152  and R 153  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 990 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152  and R 153  at each occurrence is H. 
     Embodiment 991 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 169 , C 2-6 alkenyl optionally substituted by 1-11 R 169 , C 2-6 alkynyl optionally substituted by 1-9 R 169 , C 6-11 aryl optionally substituted by 1-11 R 169 , C 7-16 arylalkyl optionally substituted by 1-19 R 169 , C 3-11 cycloalkyl optionally substituted by 1-21 R 169 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 169 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 169 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 169 , 5-15 membered heteroaryl optionally substituted by 1-15 R 169 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 169 . 
     Embodiment 992 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 169 , C 2-6 alkenyl optionally substituted by 1-3 R 169 , C 2-6 alkynyl optionally substituted by 1-3 R 169 , C 6-11 aryl optionally substituted by 1-3 R 169 , C 7-16 arylalkyl optionally substituted by 1-3 R 169 , C 3-11 cycloalkyl optionally substituted by 1-3 R 169 , C 4-17 cycloalkylalkyl optionally substituted by 1-3 R 169 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 169 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-3 R 169 , 5-15 membered heteroaryl optionally substituted by 1-3 R 169 , and 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 169 . 
     Embodiment 993 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 169 , C 2-6 alkenyl optionally substituted by 1-3 R 169 , C 2-6 alkynyl optionally substituted by 1-3 R 169 , C 6-10 aryl optionally substituted by 1-3 R 169 , C 7-11 arylalkyl optionally substituted by 1-3 R 169 , C 3-10 cycloalkyl optionally substituted by 1-3 R 169 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 169 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 169 . 
     Embodiment 994 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 169 , C 6-10 aryl optionally substituted by 1-3 R 169 , C 7-11 arylalkyl optionally substituted by 1-3 R 169 , C 3-10 cycloalkyl optionally substituted by 1-3 R 169 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 169 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 169 . 
     Embodiment 995 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 169 , phenyl optionally substituted by 1-3 R 169 , benzyl optionally substituted by 1-3 R 169 , C 3-6 cycloalkyl optionally substituted by 1-3 R 169 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 169 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 169 . 
     Embodiment 996 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158  at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 997 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 169 , phenyl, and benzyl. 
     Embodiment 998 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 169 , phenyl optionally substituted by 1-3 R 169 , and benzyl optionally substituted by 1-3 R 169 . 
     Embodiment 999 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158  at each occurrence is independently chosen from C 1-6 alkyl, phenyl, and benzyl. 
     Embodiment 1000 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158  at each occurrence is C 1-6 alkyl optionally substituted by 1-3 R 169 . 
     Embodiment 1001 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158  at each occurrence is C 1-6 alkyl. 
     Embodiment 1002 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179  and R 189  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 199 , C 2-6 alkenyl optionally substituted by 1-6 R 199 , C 2-6 alkynyl optionally substituted by 1-6 R 199 , C 6-11 aryl optionally substituted by 1-6 R 199 , C 7-16 arylalkyl optionally substituted by 1-6 R 199 , C 3-11 cycloalkyl optionally substituted by 1-6 R 199 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 199 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 199 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 199 , 5-15 membered heteroaryl optionally substituted by 1-6 R 199 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 199 , halogen, —CN, —C(═O)R 190 , —C(═)OR 190 , —C(═O)NR 192 R 193 , —(═O)C(═O)R 190 , —C(═NR 195 )R 190 , —C(═NR 195 )NR 192 R 193 , —C(═NOH)NR 192 R 193 , —C(═NOR 196 )R 190 , —C(═NNR 192 R 193 )R 190 , —C(═NNR 194 C(═O)R 191 )R 190 , —C(═NNR 194 C(═O)OR 191 )R 190 , —C(═S)NR 192 R 193 , —NC, —NO 2 , —NR 192 R 193 , —NR 194 NR 192 R 193 , —N═NR 194 , ═NR 190 , ═NOR 190 , —NR 194 OR 196 , —NR 194 C(═O)R 190 , —NR 194 C(═O)C(═O)R 190 , —NR 194 C(═O)OR, —NR 194 C(═O)C(═O)OR 191 , —NR 194 C(═O)NR 192 R 193 , —NR 194 C(═O)NR 194 C(═O)R 190 , —NR 194 C(═O)NR 194 C(═O)OR 190 , —NR 194 C(═NR 195 )NR 192 R 193 , —NR 194 C(═O)C(═O)NR 192 R 193 , —NR 194 C(═S)R 190 , —NR 194 C(═S)OR 190 , —NR 194 C(═S)NR 192 R 193 , —NR 194 S(═O) 2 R 19 , —NR 194 S(═O) 2 NR 192 R 193 , —NR 194 P(═O)R 198 R 198 , —NR 194 P(═O)(NR 192 R 193 )(NR 192 R 193 ), —NR 194 P(═)(OR 190 )(OR 190 ), —NR 194 P(═O)(SR 190 )(SR 190 ), —OR 190 , ═O, —OCN, —OC(═O)R 190 , —OC(═O)NR 192 R 193 , —OC(═O)OR 190 , —OC(═NR 195 )NR 192 R 193 , —OS(═O)R 190 , —OS(═O) 2 R 190 , —OS(═O) 2 OR 190 , —OS(═O) 2 NR 192 R 193 , —OP(═O)R 198 R 198 , —OP(═O)(NR 192 R 193 )(NR 192 R 193 ), —OP(═O)(OR 190 )(OR 190 ), —OP(═O)(SR 190 )(SR 190 ), —Si(R 194 ) 3 , —SCN, ═S, —S(═O) n R 190 , —S(═O) 2 OR 190 , —SO 3 R, —S(═O) 2 NR 192 R 193 , —S(═O)NR 192 R 193 , —SP(═O)R 198 R 198 , —SP(═O)(NR 192 R 193 )(NR 192 R 193 ), —SP(═O)(OR 190 )(OR 190 ), —SP(═O)(SR 190 )(SR 190 ), —P(═O)R 198 R 198 , —P(═O)(NR 192 R 193 )(NR 192 R 193 ), —P(═O)(OR 190 )(OR 190 ), and —P(═O)(SR 190 )(SR 190 ). 
     Embodiment 1003 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179  and R 189  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 199 , C 6-11 aryl optionally substituted by 1-6 R 199 , C 7-16 arylalkyl optionally substituted by 1-6 R 199 , C 3-11 cycloalkyl optionally substituted by 1-6 R 199 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 199 , 5-15 membered heteroaryl optionally substituted by 1-6 R 199 , halogen, —CN, —C(═O)R 190 , —C(═O)OR 190 , —C(═O)NR 192 R 193 , —NC, —NO 2 , —NR 192 R 193 , —NR 194 NR 192 R 193 , —NR 194 OR 196 , —NR 194 C(═O)R 190 , —NR 194 C(═O)OR 191 , —NR 194 C(═O)NR 192 R 193 , —NR 194 C(═O)NR 194 C(═O)R 190 , —NR 194 S(═O) 2 R 191 , —NR 194 S(═O) 2 NR 192 R 193 , —OR 190 , ═O, —OCN, —OC(═O)R 190 , —OC(═O)NR 192 R 193 , —OC(═O)OR 190 , —Si(R 194 ) 3 , —SCN, ═S, —S(═O) n R 190 , and —S(═O) 2 NR 192 R 193 . 
     Embodiment 1004 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 159 , R 169 , R 179  and R 189  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 199 , C 6-10 aryl optionally substituted by 1-6 R 199 , C 7-11 arylalkyl optionally substituted by 1-6 R 199 , C 3-10 cycloalkyl optionally substituted by 1-6 R 199 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 199 , 5-10 membered heteroaryl optionally substituted by 1-6 R 199 , halogen, —CN, —C(═O)R 190 , —C(═O)OR 190 , —C(═O)NR 192 R 193 , —NO 2 , —NR 192 R 193 , —NR 194 C(═O)R 190 , —NR 194 C(═O)OR, —NR 194 C(═O)NR 192 R 193 , —NR 194 C(═O)NR 194 C(═O)R 190 , —NR 194 S(═O) 2 R 191 , —NR 194 S(═O) 2 NR 192 R 193 , —OR 190 , ═O, —OC(═O)R 190 , —OC(═O)NR 192 R 193 , —OC(═O)OR 190 , —Si(R 194 ) 3 , —S(═O) n R 190 , and —S(═O) 2 NR 192 R 193 . 
     Embodiment 1005 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179  and R 189  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 199 , C 6-10 aryl optionally substituted by 1-3 R 199 , C 7-11 arylalkyl optionally substituted by 1-3 R 199 , C 3-10 cycloalkyl optionally substituted by 1-3 R 199 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 199 , 5-10 membered heteroaryl optionally substituted by 1-3 R 199 , halogen, —CN, —C(═O)R 190 , —C(═O)OR 190 , —C(═O)NR 192 R 193 , —NO 2 , —NR 192 R 193 , —NR 194 C(═O)R 190 , —NR 194 C(═O)OR 191 , —NR 194 C(═O)NR 192 R 193 , —NR 194 C(═O)NR 194 C(═O)R 190 , —NR 194 S(═O) 2 R 191 , —NR 194 S(═O) 2 NR 192 R 193 , —OR 190 , ═O, —OC(═O)R 190 , —OC(═O)NR 192 R 193 , —OC(═O)OR 190 , —Si(R 194 ) 3 , —S(═O) n R 190 , and —S(═O) 2 NR 192 R 193 . 
     Embodiment 1006 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179  and R 189  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 199 , phenyl optionally substituted by 1-3 R 199 , benzyl optionally substituted by 1-3 R 199 , C 3-6 cycloalkyl optionally substituted by 1-3 R 199 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 199 , 5-6 membered heteroaryl optionally substituted by 1-3 R 199 , halogen, —CN, —C(═O)R 190 , —C(═O)OR 190 , —C(═O)NR 192 R 193 , —NO 2 , —NR 192 R 193 , —NR 194 C(═O)R 190 , —NR 194 C(═O)OR 191 , —NR 194 C(═O)NR 192 R 193 , —NR 194 C(═O)NR 194 C(═O)R 190 , —NR 194 S(═O) 2 R 191 , —NR 194 S(═O) 2 NR 192 R 193 , —OR 190 , ═O, —OC(═O)R 190 , —OC(═O)NR 192 R, —OC(═O)OR 190 , —Si(R 194 ) 3 , —S(═O) n R 190 , and —S(═O) 2 NR 192 R 193 . 
     Embodiment 1007 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179  and R 189  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 199 , phenyl optionally substituted by 1-3 R 199 , benzyl optionally substituted by 1-3 R 199 , C 3-6 cycloalkyl optionally substituted by 1-3 R 199 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 199 , 5-6 membered heteroaryl optionally substituted by 1-3 R 199 , halogen, —CN, —C(═O)R 190 , —C(═O)OR 190 , —C(═O)NR 192 R 193 , —NO 2 , —NR 192 R 193 , —NR 194 C(═O)R 190 , —NR 194 S(═O) 2 R 191 , —OR 190 , —OC(═O)R 190 , —OC(═O)NR 192 R 193 , —S(═O) n R 190 , and —S(═O) 2 NR 192 R 193 . 
     Embodiment 1008 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179  and R 189  at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)R 190 , —C(═O)OR 190 , —C(═O)NR 192 R 9 , —NO 2 , —NR 192 R 193 , —NR 194 C(═O)R 190 , —NR 194 S(═O) 2 R 191 , —OR 190 , —OC(═O)R 190 , —OC(═O)NR 192 R 193 , —S(═O) n R 190 , and —S(═O) 2 NR 192 R 193 . 
     Embodiment 1009 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179  and R 189  at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, halogen, —CN, —C(═O)OR 190 , —C(═O)NR 192 R 193 , —NO 2 , —NR 192 R 193 , —OR 190 , and —S(═O) n R 190 . 
     Embodiment 1010 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179  and R 189  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 199 , phenyl optionally substituted by 1-3 R 199 , benzyl optionally substituted by 1-3 R 199 , halogen, —CN, —C(═O)OR 190 , —C(═O)NR 192 R 193 , —NO 2 , —NR 192 R 193 , —OR 190 , and —S(═O) n R 190 . 
     Embodiment 1011 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 159 , R 169 , R 179  and R 189  at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, halogen, —NR 192 R 193 , and —OR 190 . 
     Embodiment 1012 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179  and R 189  at each occurrence is independently chosen from C 1-6 alkyl, halogen, —NR 192 R 193 , and —OR 190 . 
     Embodiment 1013 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179  and R 189  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 199  and halogen. 
     Embodiment 1014 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179  and R 189  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 199 . 
     Embodiment 1015 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179  and R 189  at each occurrence is independently C 1-6 alkyl. 
     Embodiment 1016 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196  and R 197  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 209 , C 2-6 alkenyl optionally substituted by 1-11 R 209 , C 2-6 alkynyl optionally substituted by 1-9 R 209 , C 6-11 aryl optionally substituted by 1-11 R 209 , C 7-16 arylalkyl optionally substituted by 1-19 R 209 , C 3-11 cycloalkyl optionally substituted by 1-21 R 209 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 209 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 209 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 209 , 5-15 membered heteroaryl optionally substituted by 1-15 R 209 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 209 . 
     Embodiment 1017 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196  and R 197  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 209 , C 2-6 alkenyl optionally substituted by 1-6 R 209 , C 2-6 alkynyl optionally substituted by 1-6 R 209 , C 6-10 aryl optionally substituted by 1-6 R 209 , C 7-11 arylalkyl optionally substituted by 1-6 R 209 , C 3-10 cycloalkyl optionally substituted by 1-6 R 209 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 209 , and 5-10 membered heteroaryl optionally substituted by 1-6 R 209 . 
     Embodiment 1018 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196  and R 197  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 209 , C 2-6 alkenyl optionally substituted by 1-3 R 209 , C 2-6 alkynyl optionally substituted by 1-3 R 209 , C 6-10 aryl optionally substituted by 1-3 R 209 , C 7-11 -arylalkyl optionally substituted by 1-3 R 209 , C 3-10 cycloalkyl optionally substituted by 1-3 R 209 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 209 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 209 . 
     Embodiment 1019 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196  and R 197  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 209 , phenyl optionally substituted by 1-3 R 209 , benzyl optionally substituted by 1-3 R 209 , C 3-10 cycloalkyl optionally substituted by 1-3 R 209 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 209 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 209 . 
     Embodiment 1020 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196  and R 197  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, and 5-10 membered heteroaryl. 
     Embodiment 1021 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196  and R 197  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 209 , phenyl optionally substituted by 1-3 R 209 , benzyl optionally substituted by 1-3 R 209 , C 5-6 cycloalkyl optionally substituted by 1-3 R 209 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 209 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 209 . 
     Embodiment 1022 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196  and R 197  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 1023 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196  and R 197  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 1024 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196  and R 197  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl optionally substituted by 1 R 209 , and 5-6 membered heteroaryl. 
     Embodiment 1025 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196  and R 197  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 209 . 
     Embodiment 1026 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196  and R 197  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 1027 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196  and R 197  at each occurrence is H. 
     Embodiment 1028 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192  and R 193  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 219 , C 2-6 alkenyl optionally substituted by 1-11 R 219 , C 2-6 alkynyl optionally substituted by 1-9 R 219 , C 6-11 aryl optionally substituted by 1-11 R 219 , C 7-16 arylalkyl optionally substituted by 1-19 R 219 , C 3-11 cycloalkyl optionally substituted by 1-21 R 219 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 219 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 219 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 219 , 5-15 membered heteroaryl optionally substituted by 1-15 R 219 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 219 ; or any R 192  and R 193  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 229  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 229 . 
     Embodiment 1029 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192  and R 193  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 219 , C 2-6 alkenyl optionally substituted by 1-6 R 219 , C 2-6 alkynyl optionally substituted by 1-6 R 219 , C 6-11 aryl optionally substituted by 1-6 R 219 , C 7-16 arylalkyl optionally substituted by 1-6 R 219 , C 3-11 cycloalkyl optionally substituted by 1-6 R 219 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 219 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 219 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 219 , 5-15 membered heteroaryl optionally substituted by 1-6 R 219 , and 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 219 ; or any R 192  and R 193  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 229  or a 5-15 membered heteroaryl optionally substituted by 1-6 R 229 . 
     Embodiment 1030 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192  and R 193  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 219 , phenyl optionally substituted by 1-3 R 219 , benzyl optionally substituted by 1-3 R 219 , C 3-10 cycloalkyl optionally substituted by 1-3 R 219 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 219 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 219 ; or any R 192  and R 193  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 229  or a 5-15 membered heteroaryl optionally substituted by 1-3 R 229 . 
     Embodiment 1031 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192  and R 193  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 219 , phenyl optionally substituted by 1-3 R 219 , benzyl optionally substituted by 1-3 R 219 , C 3-10 cycloalkyl optionally substituted by 1-3 R 219 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 219 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 219 . 
     Embodiment 1032 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192  and R 193  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 219 , phenyl optionally substituted by 1-3 R 219 , benzyl optionally substituted by 1-3 R 219 , C 3-6 cycloalkyl optionally substituted by 1-3 R 219 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 219 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 219 ; or any R 192  and R 193  may form, together with the nitrogen atom to which they are attached, a 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 229  or a 5-10 membered heteroaryl optionally substituted by 1-3 R 229 . 
     Embodiment 1033 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192  and R 193  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 219 , phenyl optionally substituted by 1-3 R 219 , benzyl optionally substituted by 1-3 R 219 , C 5-6 cycloalkyl optionally substituted by 1-3 R 219 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 219 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 219 . 
     Embodiment 1034 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192  and R 193  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 219 , phenyl optionally substituted by 1-3 R 219 , benzyl optionally substituted by 1-3 R 219 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 219 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 219 . 
     Embodiment 1035 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192  and R 193  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; or any R 192  and R 193  may form, together with the nitrogen atom to which they are attached, a 5-6 membered heterocycloalkyl or a 5-6 membered heteroaryl. 
     Embodiment 1036 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192  and R 193  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 1037 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192  and R 193  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 219 , phenyl optionally substituted by 1-3 R 219 , and benzyl optionally substituted by 1-3 R 219 . 
     Embodiment 1038 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192  and R 193  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 219 . 
     Embodiment 1039 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192  and R 193  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, and benzyl. 
     Embodiment 1040 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192  and R 193  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 1041 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192  and R 193  at each occurrence is H. 
     Embodiment 1042 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 209 , C 2-6 alkenyl optionally substituted by 1-11 R 209 , C 2-6 alkynyl optionally substituted by 1-9 R 209 , C 6-11 aryl optionally substituted by 1-11 R 209 , C 7-16 arylalkyl optionally substituted by 1-19 R 209 , C 3-11 cycloalkyl optionally substituted by 1-21 R 209 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 209 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 209 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 209 , 5-15 membered heteroaryl optionally substituted by 1-15 R 209 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 209 . 
     Embodiment 1043 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 209 , C 2-6 alkenyl optionally substituted by 1-3 R 209 , C 2-6 alkynyl optionally substituted by 1-3 R 209 , C 6-11 aryl optionally substituted by 1-3 R 209 , C 7-16 arylalkyl optionally substituted by 1-3 R 209 , C 3-11 cycloalkyl optionally substituted by 1-3 R 209 , C 4-17 cycloalkylalkyl optionally substituted by 1-3 R 209 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 209 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-3 R 209 , 5-15 membered heteroaryl optionally substituted by 1-3 R 209 , and 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 209 . 
     Embodiment 1044 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 209 , C 2-6 alkenyl optionally substituted by 1-3 R 209 , C 2-6 alkynyl optionally substituted by 1-3 R 209 , C 6-10 aryl optionally substituted by 1-3 R 209 , C 7-11 arylalkyl optionally substituted by 1-3 R 209 , C 3-10 cycloalkyl optionally substituted by 1-3 R 209 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 209 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 209 . 
     Embodiment 1045 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 209 , C 6-10 aryl optionally substituted by 1-3 R 209 , C 7-11 arylalkyl optionally substituted by 1-3 R 209 , C 3-10  cycloalkyl optionally substituted by 1-3 R 209 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 209 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 209 . 
     Embodiment 1046 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 209 , phenyl optionally substituted by 1-3 R 209 , benzyl optionally substituted by 1-3 R 209 , C 3-6 cycloalkyl optionally substituted by 1-3 R 209 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 209 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 209 . 
     Embodiment 1047 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198  at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-6 membered heteroaryl. 
     Embodiment 1048 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 209 , phenyl, and benzyl. 
     Embodiment 1049 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 209 , phenyl optionally substituted by 1-3 R 209 , and benzyl optionally substituted by 1-3 R 209 . 
     Embodiment 1050 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198  at each occurrence is independently chosen from C 1-6 alkyl, phenyl, and benzyl. 
     Embodiment 1051 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198  at each occurrence is C 1-6 alkyl optionally substituted by 1-3 R 209 . 
     Embodiment 1052 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198  at each occurrence is C 1-6 alkyl. 
     Embodiment 1053 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219  and R 229  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 halogen, C 2-6 alkenyl, C 2-6 alkynyl, C 6-11 aryl, C 7-16 arylalkyl, C 3-11 cycloalkyl, C 4-17 cycloalkylalkyl, 3-15 membered heterocycloalkyl, 4-21 membered heterocycloalkylalkyl, 5-15 membered heteroaryl, 6-21 membered heteroarylalkyl, halogen, —CN, —C(═O)R 230 , —C(═O)OR 230 , —C(═O)NR 230 R 230 , —C(═O)C(═O)R 230 , —C(═NR 230 )R 230 , —C(═NR 230 )NR 230 R 230 , —C(═NOH)NR 230 R 230 , —C(═NOR 230 )R 230 , —C(═NNR 230 R 230 )R 230 , —C(═NNR 230 C(═O)R 230 )R 230 , —C(═NNR 230 C(═O)OR 230 )R 230 , —C(═S)NR 230 R 230 , —NC, —NO 2 , —NR 230 R 230 , —NR 230 NR 230 R 230 , —N═NR 230 , ═NR 230 , ═NOR 230 , —NR 230 OR 230 , —NR 230 C(═O)R 230 , —NR 230 C(═O)C(═O)R 230 , —NR 230 C(═O)OR 230 , —NR 230 C(═O)C(═O)OR 230 , —NR 230 C(═O)NR 230 R 230 , —NR 230 C(═O)NR 230 C(═O)R 230 , —NR 230 C(═O)NR 230 C(═O)OR 230 , —NR 230 C(═NR 230 )NR 230 R 230 , —NR 230 C(O)C(═O)NR 230 R 230 , —NR 230 C(═S)R 230 , —NR 230 C(═S)OR 230 , —NR 230 C(═S)NR 230 R 230 , —NR 230 S(═O) 2 R 230 , —NR 230 S(═O) 2 N 230 R 230 , —NR 230 P(═O)R 231 R 231 , —NR 230 P(═O)(NR 230 R 230 )(NR 230 R 230 ), —NR 230 P(═O)(OR 230 )(OR 230 ), —NR 230 P(═)(SR 230 )(SR 230 ), —OR 230 , ═O, —OCN, —OC(═O)R 230 , —OC(═O)NR 230 R 230 , —OC(═)OR 230 , —OC(═NR 230 )NR 230 R 230 , —OS(═O)R 230 , —OS(═O) 2 R 230 , —OS(═O) 2 OR 230 , —OS(═O) 2 NR 230 R 230 , —OP(═O)R 231 R 231 , —OP(═O)(NR 230 R 230 )(NR 230 R 230 ), —OP(═)(OR 230 )(OR 230 ), —OP(═O)(SR 230 )(SR 230 ), —Si(R 230 ) 3 , —SCN, ═S, —S(═O) n R 230 , —S(═O) 2 R 230 , —SO 3 R 230 , —S(═O) 2 NR 230 R 230 , —S(═O)NR 230 R 230 , —SP(═O)R 231 R 231 , —SP(═O)(NR 230 R 230 )(NR 230 R 230 ), —SP(═O)(OR 230 )(OR 230 ), —SP(═O)(SR 230 )(SR 230 ), —P(═O)R 231 R 231 , —P(═O)(NR 230 R 230 )(NR 230 R 230 ), —P(═O)(OR 230 )(OR 230 ), and —P(═O)(SR 230 )(SR 230 ). 
     Embodiment 1054 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219  and R 229  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, C 2-6 alkenyl, C 2-6 alkynyl, C 6-11 aryl, C 7-16 arylalkyl, C 3-11 cycloalkyl, C 4-17 cycloalkylalkyl, 3-15 membered heterocycloalkyl, 4-15 membered heterocycloalkylalkyl, 5-15 membered heteroaryl, 6-15 membered heteroarylalkyl, halogen, —CN, —C(═O)R 230 , —C(═O)OR 230 , —C(═O)NR 230 R 230 , —C(═O)C(═O)R 230 , —NC, —NO 2 , —NR 230 R 230 , —NR 230 NR 230 R 230 , —NR 230 OR 230 , —NR 230 C(═O)R 230 , —NR 230 C(═O)C(═O)R 230 , —NR 230 C(═O)OR 230 , —NR 230 C(═O)C(═O)OR 230 , —NR 230 C(═O)NR 230 R 230 , —NR 230 C(═O)NR 230 C(═O)R 230 , —NR 230 C(═O)NR 230 C(═O)OR 230 , —NR 230 C(═O)C(═O)NR 230 R 230 , —NR 230 S(═O) 2 R 230 , —NR 230 S(═O) 2 NR 230 R 230 , —NR 230 P(═O)R 231 R 231 , —NR 230 P(═O)(NR 230 R 230 )(NR 230 R 230 ), —NR 230 P(═O)(OR 230 )(OR 230 ), —OR 230 , ═O, —OCN, —OC(═O)R 230 , —OC(═O)NR 230 R 230 , —OC(═O)OR 230 , —OS(═O)R 230 , —OS(═O) 2 R 230 , —OS(═O) 2 R 230 , —OS(═O) 2 NR 230 R 230 , —OP(═O)R 231 R 231 , —OP(═O)(NR 230 R 230 )(NR 230 R 230 ), —OP(═O)(OR 230 )(OR 230 ), —Si(R 230 ) 3 , —SCN, ═S, —S(═O) n R 230 , —S(═O) 2 OR 230 , —SO 3 R 230 , —S(═O) 2 NR 230 R 230 , —S(═O)NR 230 R 230 , —P(═O)R 231 R 231 , —P(═O)(NR 230 R 230 )(NR 230 R 230 ), and —P(═O)(OR 230 )(OR 230 ). 
     Embodiment 1055 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219  and R 229  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 halogen, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 7-11 arylalkyl, C 3-10 cycloalkyl, C 4-17 cycloalkylalkyl, 3-10 membered heterocycloalkyl, 4-10 membered heterocycloalkylalkyl, 5-10 membered heteroaryl, 6-10 membered heteroarylalkyl, halogen, —CN, —C(═O)R 230 , —C(═O)OR 230 , —C(═O)NR 230 R 230 , —NC, —NO 2 , —NR 230 R 230 , —NR 230 OR 230 , —NR 230 C(═O)R 230 , —NR 230 C(═O)OR 230 , —NR 230 C(═O)NR 230 R 230 , —NR 230 C(═O)NR 230 C(═O)R 230 , —NR 230 S(═O) 2 R 230 , —NR 230 S(═O) 2 NR 230 R 230 , —NR 230 P(═O)R 231 R 231 , —NR 230 P(═O)(NR 230 R 230 )(NR 230 R 230 ), —NR 230 P(═O)(OR 230 )(OR 230 ), —OR 230 , ═O, —OCN, —OC(═O)R 230 , —OC(═O)NR 230 R 230 , —OS(═O) 2 NR 230 R 230 , —OP(═O)R 231 R 231 , —OP(═O)(NR 230 R 230 )(NR 230 R 230 ), —SCN, ═S, —S(═O) n R 230 , —S(═O) 2 NR 230230 , —S(═O)NR 230 R 230 , —P(═O)R 231 R 231 , and —P(═O)(NR 230 R 230 )(NR 230 R 230 ). 
     Embodiment 1056 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219  and R 229  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 halogen, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 7-11 arylalkyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, halogen, —CN, —C(═O)R 230 , —C(═O)OR 230 , —C(═O)NR 230 R 230 , —NO 2 , —NR 230 R 230 , —NR 230 OR 230 , —NR 230 C(═O)R 230 , —NR 230 C(═O)NR 230 R 230 , —NR 230 S(═O) 2 R 230 , —NR 230 S(═O) 2 NR 230 R 230 , —OR 230 , ═O, —OCN, —OC(═O)R 230 , —S(═O) n R 230 , —S(═O) 2 NR 230 R 230 , and —S(═O)NR 230 R 230 . 
     Embodiment 1057 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219  and R 229  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 halogen, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)R 230 , —C(═O)OR 230 , —C(═O)NR 230 R 230 , —NO 2 , —NR 230 R 230 , —NR 230 C(═O)R 230 , —NR 230 C(═O)NR 230 R 230 , —NR 230 S(═O) 2 R 230 , —NR 230 S(═O) 2 NR 230 R 230 , —OR 230 , ═O, —S(═O) n R 230 , and —S(═O) 2 NR 230 R 230 . 
     Embodiment 1058 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219  and R 229  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 halogen, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)R 230 , —C(═O)OR 230 , —C(═O)NR 230 R 230 , —NR 230 R 230 , —NR 230 C(═O)R 230 , —NR 230 S(═O) 2 R 230 , —OR 230 , ═O, —S(═O) n R 230 , and —S(═O) 2 NR 230 R 230 . 
     Embodiment 1059 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219  and R 229  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 halogen, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)R 230 , —C(═O)OR 230 , —C(═O)NR 230 R 230 , —NR 230 R 230 , —OR 230 , ═O, —S(═O) n R 230 , and —S(═O) 2 NR 230 R 230 . 
     Embodiment 1060 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219  and R 229  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 halogen, halogen, and —NR 2 30R 230 . 
     Embodiment 1061 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219  and R 229  at each occurrence is independently chosen from C 1-6 alkyl, halogen, and —NR 230 R 230 . 
     Embodiment 1062 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219  and R 229  at each occurrence is independently chosen from C 1-6 alkyl and —NR 230 R 230 . 
     Embodiment 1063 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219  and R 229  at each occurrence is —NR 230 R 230 . 
     Embodiment 1064 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219  and R 229  at each occurrence is C 1-6 alkyl. 
     Embodiment 1065 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199  at each occurrence is independently chosen from C 1-6 alkyl and —NR 230 R 230 ; R 209 , R 219  and R 229  at each occurrence is C 1-6 alkyl. 
     Embodiment 1066 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199  at each occurrence is independently chosen from C 1-6 alkyl and —NR 230 R 230 ; R 209 , R 219  and R 229  at each occurrence is —NR 230 R 230 . 
     Embodiment 1067 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199  at each occurrence is —NR 230 R 230 ; R 209 , R 219  and R 229  at each occurrence is C 1-6 alkyl. 
     Embodiment 1068 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1067, wherein R 230  at each occurrence is independently chosen from H, C 1-6 alkyl and C 1-6 -haloalkyl. 
     Embodiment 1069 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1067, wherein R 230  at each occurrence is independently chosen from H and C 1-6 alkyl. 
     Embodiment 1070 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1067, wherein R 230  at each occurrence is C 1-6 alkyl. 
     Embodiment 1071 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1067, wherein R 230  at each occurrence is H. 
     Embodiment 1072 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1071, wherein R 231  at each occurrence is independently chosen from C 1-6 alkyl and C 1-6 -haloalkyl. 
     Embodiment 1073 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1071, wherein R 231  at each occurrence is C 1-6 alkyl. 
     Embodiment 1074 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1071, wherein R 231  at each occurrence is C 1-6 -haloalkyl. 
     Embodiment 1075 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1074, wherein n at each occurrence is independently chosen from 0, 1, and 2. 
     Embodiment 1076 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1074, wherein n at each occurrence is independently chosen from 0 and 2. 
     Embodiment 1077 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1074, wherein n at each occurrence is independently chosen from 1 and 2. 
     Embodiment 1078 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1074, wherein n at each occurrence is independently chosen from 0 and 1. 
     Embodiment 1079 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1074, wherein n at each occurrence is 0. 
     Embodiment 1080 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1074, wherein n at each occurrence is 1. 
     Embodiment 1081 
     The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1074, wherein n at each occurrence is 2. 
     The above Embodiments include salts of acidic and basic compounds of formula (I). Preferably, the salts are pharmaceutically acceptable. Pharmaceutically acceptable acid addition salts of basic compounds of formula (I) include, but are not limited to, salts derived from inorganic acids such as hydrochloric, nitric, phosphoric, sulfuric, hydrobromic, hydriodic, and phosphorus, as well as the salts derived from organic acids, such as aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxy alkanoic acids, alkanedioic acids, aromatic acids, and aliphatic and aromatic sulfonic acids. Such salts thus include, but are not limited to, sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, propionate, caprylate, isobutyrate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, mandelate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, phthalate, benzenesulfonate, toluenesulfonate, phenylacetate, citrate, lactate, maleate, tartrate, and methanesulfonate. See, for example, Berge et al., “Pharmaceutical Salts,” J. of Pharmaceutical Science, 1977; 66:1-19. 
     Acid addition salts may be prepared by contacting a compound of formula (I) with a sufficient amount of the desired acid to produce the salt in the conventional manner. The free base form of the compound of formula (I) may be regenerated by contacting the salt form with a base and isolating the free base in the conventional manner. 
     Pharmaceutically acceptable base salts of acidic compounds of formula (I) are formed with metals or amines, such as alkali and alkaline earth metal hydroxides, or of organic amines. Examples of metals used as cations include, but are not limited to, sodium, potassium, magnesium, and calcium. Examples of suitable amines include, but are not limited to, N,N′-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine (ethane-1,2-diamine), N-methylglucamine, and procaine. See, for example, Berge et al., “Pharmaceutical Salts,” J. of Pharmaceutical Science, 1977; 66:1-19. 
     Base salts may be prepared by contacting a compound of formula (I) with a sufficient amount of the desired base to produce the salt in the conventional manner. The acid form of the compound of formula (I) may be regenerated by contacting the salt form with an acid and isolating the acid in a conventional manner. 
     Some compounds of the present application may exist as stereoisomers, including enantiomers, diastereomers, and geometric isomers. Geometric isomers include compounds of the present application that have alkenyl groups, which may exist as entgegen or zusammen conformations, in which case all geometric forms thereof, both entgegen and zusammen, cis and trans, and mixtures thereof, are within the scope of the present application. Some compounds of the present application have cycloalkyl groups, which may be substituted at more than one carbon atom, in which case all geometric forms thereof, both cis and trans, and mixtures thereof, are within the scope of the present application. All of these forms, including (R), (S), epimers, diastereomers, cis, trans, syn, anti, (E), (Z), tautomers, and mixtures thereof, are included in the compounds of the present application. 
     The compounds of the present application may be in any physical form, including amorphous or crystalline solids in any polymorphic form, in any state of purity. Crystalline polymorphic forms include unsolvated forms as well as solvated forms, such as hydrated forms. 
     III. Pharmaceutical Compositions 
     The present application further provides pharmaceutical compositions comprising a compound of any of the above Embodiments (e.g., a compound of formula (I) or a pharmaceutically acceptable salt thereof), together with a pharmaceutically acceptable excipient. For preparing a pharmaceutical composition from a compound of the present application, pharmaceutically acceptable excipients can be either solid or liquid. An excipient can be one or more substances which may act as, e.g., a carrier, diluent, flavoring agent, binder, preservative, tablet disintegrating agent, or an encapsulating material. The pharmaceutical composition may contain two or more compounds of the present application (e.g., two different salt forms of a compound of formula (I), may be used together in the same pharmaceutical composition). Preferably, the pharmaceutical composition contains a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt form thereof. In one embodiment, the composition contains an amount of a compound of formula (I) or a pharmaceutically acceptable salt form thereof effective to treat an atypical protein kinase C (aPKC)-dependent disorder or condition. Preferably, a compound of the present application will cause a decrease in symptoms or disease indicia associated with an aPKC-dependent disorder as measured quantitatively or qualitatively. The composition may also contain, in addition to a compound of formula (I) or a pharmaceutically acceptable salt form thereof and a pharmaceutically acceptable excipient, another therapeutic compound, such as a compound useful in the treatment of cancer. 
     A compound of the present application can be formulated as a pharmaceutical composition in any delivery form, such as a syrup, an elixir, a suspension, a powder, a granule, a tablet, a capsule, a lozenge, a troche, an aqueous solution, a cream, an ointment, a lotion, a gel, an emulsion, etc. Solid form preparations include powders, tablets, pills, capsules, cachets, suppositories, and dispersible granules. Preferably, the pharmaceutical composition is a tablet or capsule. In one embodiment, the pharmaceutical composition is a tablet. In another embodiment, the pharmaceutical composition is a capsule. 
     In powders, the excipient may be a finely divided solid in a mixture with a finely divided active component (i.e., compound of the present application). In tablets, the active component may be mixed with an excipient having the necessary binding properties in suitable proportions and compacted in the shape and size desired. Suitable excipients include magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, low melting wax, cocoa butter, and the like. 
     The pharmaceutical composition preferably contains from 1% to 95% (w/w) of the active compound (i.e., compound of the present application). More preferably, the pharmaceutical composition contains from 5% to 70% (w/w) of the active compound. 
     For preparing suppositories, a low melting wax, such as a mixture of fatty acid glycerides or cocoa butter, may be melted and the active component dispersed homogeneously therein, as by stirring. The molten homogeneous mixture may then be poured into convenient sized molds, allowed to cool, and thereby to solidify. 
     Liquid form preparations include solutions, suspensions, and emulsions. Formulations suitable for parenteral administration, such as, for example, by intravenous, intramuscular, intradermal, and subcutaneous routes, include aqueous and non-aqueous, isotonic sterile injection solutions, which can contain antioxidants, buffers, bacteriostats, and solutes that render the formulation isotonic with the blood of the intended recipient, and aqueous and nonaqueous sterile suspensions that can include suspending agents, solubilizers, thickening agents, stabilizers, and preservatives. In practice, compositions can be administered, for example, by intravenous infusion, orally, topically, intraperitoneally, intravesically or intrathecally. The formulations of compounds can be presented in unit-dose or multi-dose sealed containers, such as ampoules and vials. Injection solutions and suspensions can be prepared from sterile powders, granules, and tablets of the kind previously described. 
     A compound of the present application, alone or in combination with other suitable components, can be made into aerosol formulations (e.g., they can be “nebulized”) to be administered via inhalation. Aerosol formulations can be placed into pressurized acceptable propellants, such as dichlorodifluoromethane, propane, nitrogen, and the like. 
     Pharmaceutically acceptable excipients are determined in part by the particular composition being administered, as well as by the particular method used to administer the composition. Accordingly, there is a wide variety of suitable formulations of pharmaceutical compositions of the present application (see, e.g.,  Remington: The Science and Practice of Pharmacy,  20th ed., Gennaro et al. Eds., Lippincott Williams and Wilkins, 2000). 
     The quantity of active component in a pharmaceutical composition may be varied or adjusted from, e.g., 1 mg to 1,000 mg, 5 mg to 500 mg, 10 mg to 300 mg, or 25 mg to 250 mg, according to the particular application and the desired size of the dosage form. 
     The dose administered to a subject is preferably sufficient to induce a beneficial therapeutic response in the subject over time. The beneficial dose can vary from subject to subject depending upon, e.g., the subject&#39;s condition, body weight, surface area, and side effect susceptibility. Administration can be accomplished via single or divided doses. 
     IV. Method of Treatment 
     In another aspect, the present application provides a method of treating an aPKC-dependent disorder or condition in a subject comprising: administering to the subject a compound of formula (I) as defined in any of the above Embodiments or a pharmaceutically acceptable salt form thereof. In another aspect, the present application provides a compound of formula (I) as defined in any of the above Embodiments or a pharmaceutically acceptable salt form thereof for use in treating an aPKC-dependent disorder or condition in a subject. In another aspect, the present application provides a compound of formula (I) as defined in any of the above Embodiments or a pharmaceutically acceptable salt form thereof for use in the preparation of a medicament for treating an aPKC-dependent disorder or condition in a subject. Preferably, the compound is administered to the subject as a pharmaceutical composition comprising a pharmaceutically acceptable excipient. Preferably, the compound is administered to the subject in a pharmaceutically acceptable amount. In one embodiment, the aPKC-dependent condition or disorder is cancer. In another embodiment, the aPKC-dependent condition is selected from non-small cell lung cancer (NSCLC), squamous cell carcinoma (e.g., oesophageal squamous cell carcinoma), leukaemia, prostate cancer, non-Hodgkin&#39;s lymphoma (e.g., follicular lymphoma), endometrial cancer, lung cancer and breast cancer. 
     The aPKC-dependent disorder or condition can be treated prophylactically, acutely, or chronically using compounds of the present application, depending on the nature of the disorder or condition. Typically, the subject in each of these methods is human, although other mammals can also benefit from the administration of a compound of the present application. 
     In another embodiment, the present application provides a method of treating a proliferative disorder in a subject, comprising administering to the subject a compound of formula (I) as defined in any of the above Embodiments or a pharmaceutically acceptable salt form thereof. 
     In another aspect, the present application provides a compound of formula (I) as defined in any of the above Embodiments or a pharmaceutically acceptable salt form thereof for use in treating a proliferative disorder in a subject. In another aspect, the present application provides a compound of formula (I) as defined in any of the above Embodiments or a pharmaceutically acceptable salt form thereof for use in the preparation of a medicament for treating a proliferative disorder in a subject. Preferably, the compound is administered to the subject in a pharmaceutical composition comprising a pharmaceutically acceptable excipient. Preferably, the compound is administered to the subject in a pharmaceutically acceptable amount. In certain embodiments, the proliferative disorder is aPKC-dependent. In certain embodiments, the proliferative disorder is cancer. In certain embodiments, the proliferative disorder is selected from non-small cell lung cancer (NSCLC), squamous cell carcinoma (e.g., oesophageal squamous cell carcinoma), leukaemia, prostate cancer, non-Hodgkin&#39;s lymphoma (e.g., follicular lymphoma), endometrial cancer, lung cancer and breast cancer. 
     The proliferative disorder can be treated prophylactically, acutely, or chronically using a compound of the present application, depending on the nature of the disorder or condition. Typically, the subject in each of these methods is human, although other mammals can also benefit from the administration of a compound of the present application. 
     In therapeutic applications, the compounds of the present application can be prepared and administered in a wide variety of oral and parenteral dosage forms. Thus, the compounds of the present application can be administered by injection, that is, intravenously, intramuscularly, intracutaneously, subcutaneously, intraduodenally, or intraperitoneally. Also, the compounds described herein can be administered by inhalation, for example, intranasally. Additionally, the compounds of the present application can be administered transdermally. In another embodiment, the compounds of the present application are delivered orally. The compounds can also be delivered rectally, bucally or by insufflation. 
     Determination of the proper dosage for a particular situation is within the skill of the practitioner. Generally, treatment is initiated with smaller dosages which are less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under the circumstances is reached. For convenience, the total daily dosage may be divided and administered in portions during the day, if desired. A typical dose is about 1 mg to about 1,000 mg per day, such as about 5 mg to about 500 mg per day. In certain embodiments, the dose is about 10 mg to about 300 mg per day, such as about 25 mg to about 250 mg per day. 
     V. Chemistry 
     Abbreviations 
     For convenience, the following common abbreviations are used herein: 
     LCMS for Liquid Chromatography-Mass Spectrometry. 
     HPLC for High Pressure Liquid Chromatography. 
     NMR for Nuclear Magnetic Resonance. 
     RT for Retention Time. 
     MI for Molecular Ion 
     h for hours 
     min for minutes 
     AlCl 3  for aluminium chloride 
     BBr 3  for boron tribromide 
     Boc for tert-butoxycarbonyl 
     cataCXium C for trans-Bis(acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II). 
     Cs 2 CO 3  for cesium carbonate 
     CuI for copper(I)iodide 
     DAST for diethylaminosulfur trifluoride 
     DBU for 1,8-diazabicyclo(5.4.0)undec-7-ene 
     DMAP for 4-(dimethylamino) pyridine 
     DCE for 1,1-dichloroethane or ethylidene chloride 
     DCM for dichloromethane or methylene chloride 
     DEA for diethanolamine 
     DIPEA for N,N,-di-isopropyethylamine, Hunig&#39;s base 
     DMA for N,N-dimethylacetamide 
     DMF for N,N-dimethylformamide 
     DMSO for dimethylsulfoxide. 
     Et 3 N for triethylamine 
     EtOH for ethyl alcohol, ethanol 
     Ex for example 
     HCl for hydrochloric acid 
     H 2 SO 4  for sulfuric acid 
     Int for intermediate 
     KOH for potassium hydroxide 
     MW for microwave 
     mCPBA for meta-Chloroperoxybenzoic acid 
     MeOH for methyl alcohol, methanol 
     Mo(CO) 6  for Molybdenum hexacarbonyl 
     MP-BH 4  for macroporous triethylammonium methyl polystyrene borohydride 
     NaOH for sodium hydroxide 
     Na 2 CO 3  for sodium carbonate 
     Na 2 SO 4  for sodium sulphate 
     NaOAc for sodium acetate 
     NaOtBu for sodium t-butoxide 
     NMP for 1-methyl-2-pyrrolidinone 
     NMM for N-methylmorpholine 
     Pd(dba) 2  for Bis(dibenzylideneacetone)palladium 
     Pd(OAc) 2  for Palladium diacetate 
     Pd(Ph 3 ) 4  for tetrakis(triphenylphosphine)palladium 
     Pd(PPh 3 ) 2 Cl 2  for Bis(triphenylphosphine)palladium(II) dichloride 
     POCl 3  for phosphorus oxychloride 
     PPh 3  for triphenylphosphine 
     PS-TsCl for polystyrene sulfonyl chloride 
     PS-PPh 3 -Pd for polystyrene triphenylphosphine-Pd(0) 
     SCX-2 for a silica-based sorbent with a chemically bonded propylsulfonic acid functional group 
     TBAF for Tetra-n-butylammonium fluoride 
     TBDMS for tert-butyldimethylsilyl 
     TCA for trichloroacetic acid 
     TFA for trifluoroacetic acid 
     THF for tetrahydrofuran 
     TMS azide for trimethylsilyl azide 
     Xantphos for 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene 
     XPhos for 2-Dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl 
     LCMS Methods 
     Samples analysed by High Performance Liquid Chromatography-Mass Spectrometry employed the following conditions. Unless otherwise noted, Method X was utilized. 
     Method 1 
     Method 1 employed Gilson 306 pumps, Gilson 811C mixer, Gilson 806 manometric module, and Gilson UV/VIS 152 detector at 254 nm wavelength. The mass spectrometer was a Finnigan AQA and the column used was a Waters SunFire, 5 μm pore size, C18 of dimensions 50×4.60 mm. The injection volume was 10 μl. The mobile phase consisted of a mixture of water and acetonitrile containing 0.1% formic acid. The eluent flow rate was 1.5 mL/min, using 95% water: 5% acetonitrile, changed linearly to 5% water: 95% acetonitrile over 5.5 minutes and then maintained at this mixture for 2 minutes. 
     Method 2 
     Method 2 employed Waters 515 pumps, a Waters 2525 mixer and a Waters 2996 diode array detector. The detection was performed between 210 nm and 650 nm. The mass spectrometer was a Waters micromass ZQ and the column used was a Waters SunFire, 5 μm pore size, C18 of dimensions 50×4.60 mm. The injection volume was 10 μl. The mobile phase consisted of a mixture of water and acetonitrile containing 0.1% formic acid. The eluent flow rate was 1.5 mL/min, using 95% water: 5% acetonitrile, changed linearly to 5% water: 95% acetonitrile over 5.5 minutes and then maintained at this mixture for 2 minutes. 
     Method 3 
     Method 3 employed Waters 515 pumps, a Waters 2525 mixer and a Waters 2487 UV detector (single wavelength 254 nm). The mass spectrometer was a Waters micromass ZQ and the column used was a Waters SunFire, 5 μm pore size, C18 of dimensions 50×4.60 mm. The injection volume was 10 μl. The mobile phase consisted of a mixture of water and acetonitrile containing 0.1% formic acid. The eluent flow rate was 1.5 mL/min, using 95% water: 5% acetonitrile, changed linearly to 5% water: 95% acetonitrile over 5.5 minutes and then maintained at this mixture for 2 minutes. 
     Method 4 
     Method 4 employed Waters 515 pumps, a Waters 2545 mixer with valves directing to the different columns and a Waters 2996 diode array detector. The detection was performed between 210 nm and 650 nm. The mass spectrometer used was a Waters 3100 which detected masses between 100 and 700 g/mol. The column used was a XBridge, 5 micron pore size, C18, 50×4.60 mm. The injection volume was 10 μl of a solution (around 1 mg/ml). The flow rate was 1.5 mL/min and the mobile phases of water pH 10 0.03% ammonium hydroxide) (3 ml/101) and acetonitrile 0.03% ammonium hydroxide (3 ml/101). The elution was started at 95% water: 5% acetonitrile ramping up to 5% water:95% acetonitrile over 5.50 minutes. The eluent level was returned to the starting conditions of 95% water: 5% acetonitrile over 6 seconds. These conditions were held for 1.4 minutes to allow equilibration of the column before the next sample was injected. The run lasted 7 minutes in total. 
     Method 5 
     Method 5 employed Waters 515 pumps, a Waters 2525 mixer with valves directing to the different columns and a Waters 2487 UV detector. The detection was done between at 254 nm. The mass spectrometer used was a Waters micromass ZQ which detected masses between 100 and 700 g/mol. The column used was a SunFire, 5 micron pore size, C18 column of dimensions 50×4.60 mm was used. The injection volume was 10 μL of a solution (around 1 mg/mL). The flow rate was 1.5 mL/min and the mobile phases of water and methanol contained 0.1% formic acid. The elution was started at 85% water:15% methanol ramping up to 15% water:85% methanol over 4.5 minutes, these conditions were held for 1 minute before the eluent level was returned to the starting conditions of 85% water:15% methanol over 6 seconds. These conditions were held for 1.4 minutes to allow equilibration of the column before the next sample was injected. The run lasted 7 minutes in total. 
     Method 6 
     Method 6 employed Waters 515 pumps, a Waters 2545 mixer with valves directing to the different columns and a Waters 2996 diode array detector. The detection was done between 210 nm and 650 nm. The mass spectrometer used was a Waters 3100 which detected masses between 100 and 700 g/mol. The column used was a XBridge, 5 micron pore size, C18, 50×4.60 mm. The injection volume was 10 μL of a solution (around 1 mg/mL). The flow rate was 1.5 mL/min and the mobile phases of water pH 10 0.03% ammonium hydroxide) (3 ml/101) and methanol 0.03% ammonium hydroxide (3 ml/101). The elution was started at 85% water: 15% methanol ramping up to 15% water:85% methanol over 4.5 minutes. These conditions were held for 1 minute before the eluent level was returned to the starting conditions of 85% water:15% methanol over 6 seconds. These conditions were held for 1.4 minutes to allow equilibration of the column before the next sample was injected. The run lasted 7 minutes in total. 
     Method 7 
     Method 7 employed Waters 515 pumps, a Waters 2545 mixer with valves directing to the different columns and a Waters 2487 UV detector. The detection was done between at 254 nm. The mass spectrometer used was a Waters micromass ZQ which detected masses between 100 and 700 g/mol. The column used was a SunFire, 5 micron pore size, C18 column of dimensions 50×4.60 mm was used. The injection volume was 10 μL of a solution (around 1 mg/mL). The flow rate was 1.5 mL/min and the mobile phases of water and methanol contained 0.1% formic acid. The elution was started at 85% water:15% methanol ramping up to 15% water:85% methanol over 4.5 minutes., these conditions were held for 1 minute before the eluent level was returned to the starting conditions of 85% water:15% methanol over 6 seconds. These conditions were held for 1.4 minutes to allow equilibration of the column before the next sample was injected. The run lasted 7 minutes in total. 
     Method 8 
     Method 8 employed Waters 515 pumps, a Waters 2525 mixer with valves directing to the different columns and a Waters 2487 UV detector. The detection was done between at 254 nm. The mass spectrometer used was a Waters micromass ZQ which detected masses between 100 and 700 g/mol. The column used was a SunFire, 5 micron pore size, C18 column of dimensions 50×4.60 mm was used. The injection volume was 10 μL of a solution (around 1 mg/mL). The flow rate was 1.5 mL/min and the mobile phases of water and methanol contained 0.1% formic acid. The elution was started at 85% water:15% methanol ramping up to 15% water:85% methanol over 3 minutes., these conditions were held for 2.5 minute before the eluent level was returned to the starting conditions of 85% water:15% methanol over 6 seconds. These conditions were held for 1.4 minutes to allow equilibration of the column before the next sample was injected. The run lasted 7 minutes in total. 
     Method 9 
     Method 9 employed Waters 515 pumps, a Waters 2545 mixer with valves directing to the different columns and a Waters 2487 UV detector. The detection was done between at 254 nm. The mass spectrometer used was a Waters micromass ZQ which detected masses between 100 and 700 g/mol. The column used was a XBridge, 5 micron pore size, C18, 50×4.60 mm. The injection volume was 10 μL of a solution (around 1 mg/mL). The flow rate was 1.5 mL/min and the mobile phases of water pH 10 0.03% ammonium hydroxide) (3 ml/101) and methanol 0.03% ammonium hydroxide (3 ml/101). The elution was started at 85% water:15% methanol ramping up to 15% water:85% methanol over 4.5 minutes. These conditions were held for 1 minute before the eluent level was returned to the starting conditions of 85% water: 15% methanol over 6 seconds. These conditions were held for 1.4 minutes to allow equilibration of the column before the next sample was injected. The run lasted 7 minutes in total. 
     Method 10 
     LCMS results were obtained on either of two instruments. LCMS analysis was performed on a Waters Aquity Ultra Performance LC with a 2.1 mm×50 mm Waters Aquity UPLC BEH C18 1.7 μm column. The target column temperature was 45° C., with a run time of two (2) minutes, a flow rate of 0.600 mL/min, and a solvent mixture of 5% (0.1% formic acid/water):95% (acetonitrile/0.1% formic acid). The mass spectrometry data was acquired on a Micromass LC-ZQ 2000 quadrupole mass spectrometer. Alternatively, LCMS analysis was performed on a Bruker Esquire 200 ion trap. 
     Preparative HPLC Methods 
     Samples purified by Mass Spectrometry directed High Performance Liquid Chromatography employed the following conditions. 
     Method A 
     Method A employed Waters 515 pumps, a Waters 2525 mixer and a Waters 2487 UV detector (single wavelength 254 nm). The mass spectrometer was a Waters micromass ZQ and the column used was a Waters SunFire, 5 μm pore size, C18 of dimensions 50×19 mm. The injection volume was up to 500 μL of solution at a maximum concentration of 50 mg/mL. The mobile phase consisted of a mixture of water and acetonitrile containing 0.1% formic acid. The eluent flow rate was 25 mL/min using 95% water, 5% acetonitrile, changing linearly over 5.3 minutes to 95% acetonitrile, 5% water, and maintaining for 0.5 minutes. 
     Method B 
     Method B employed Waters 515 pumps a Waters 2545 mixer with valves directing to the different columns and a Waters 2996 diode array detector. The detection was performed between 210 nm and 650 nm. The mass spectrometer used was a Waters 3100 which detected masses between 100 and 700 g/mol. The column used was a XBridge, 5 micron pore size, C18, 50×19 mm. The injection volume was chosen by the user and can be up to 500 L of the solution (max 50 mg/mL). The flow rate was 25 mL/min and the mobile phases of water pH 10 0.03% ammonium hydroxide (3 ml/101) and acetonitrile 0.03% ammonium hydroxide (3 ml/101). The elution was started at 95% water:5% acetonitrile ramping up to 5% water:95% acetonitrile over 5.30 minutes. The eluent level was returned to the starting conditions of 95% water: 5% acetonitrile over 0.6 minutes. These conditions were held for 1.4 minutes to allow equilibration of the column before the next sample was injected. The run lasted 7 minutes in total. 
     Analytical HPLC Methods 
     Method X 
     Method X employs gradient elution (0 to 100%) acetonitrile (containing 0.1% trifluoroacetic acid):water (containing 0.1% trifluoroacetic acid) over five minutes on a 4.6×75 mm (2.5 micron) Zorbax XDB-C8 column at 2.5 ml/min on an Agilent 1100 series HPLC. 
     Synthesis 
     Several methods for the chemical synthesis of 4-substituted-2-(pyridin-4-yl)-azaquinazoline compounds (for convenience, collectively referred to herein as “4PAZ compounds”) of the present application are described herein. These and/or other well known methods may be modified and/or adapted in known ways in order to facilitate the synthesis of additional compounds within the scope of the present application. 
     
       
         
         
             
             
         
       
     
     In one approach, 4PAZ compounds of general formula [F-001](where A=NH or N alkyl) are prepared by reacting a compound of formula [F-002](where X is a halogen such as chlorine or a sulfonate) with a compound of formula [F-003](where A is NH or NH2 and Z on the terminal nitrogen is H, alkyl or a suitable nitrogen protecting group, such as Boc, Alloc, Cbz or Fmoc) in a suitable solvent such as DMF in the presence of a suitable base such as triethylamine. The reaction is suitably conducted at an elevated temperature for example 40° C. Where Z is a suitable nitrogen protecting group, such as Boc, Alloc, Cbz or Fmoc, compounds of formula [F-001] are prepared by a suitable deprotection reaction. For example: where Z is a Boc protecting group reaction with an acid such as TFA in a suitable solvent such as DCM. The reaction is suitably conducted at ambient temperature. In one approach, compounds of formula [F-001](where A=O) are prepared by reacting a compound of formula [F-002](where X is a halogen such as chlorine or sulfonate) with a compound of formula [F-003](where A is OH and Z on the terminal nitrogen is H, alkyl or a suitable nitrogen protecting group, such as Boc, Alloc, Cbz or Fmoc) in a suitable solvent such as DMA in the presence of a suitable base such as sodium hydride. The reaction is suitably conducted at ambient temperature. Where Z is a suitable nitrogen protecting group, such as Boc, Alloc, Cbz or Fmoc, compounds of formula [F-001] are prepared by a suitable deprotection reaction. For example: where Z is a Boc protecting group reaction with an acid such as TFA in a suitable solvent such as DCM. The reaction is suitably conducted at ambient temperature. 
     
       
         
         
             
             
         
       
     
     In one approach, compounds of formula [F-002](where X is a halogen such as chlorine) are prepared by reacting a compound of formula [F-004] with a suitable halogenating agent such as phosphorous oxychloride. The reaction is suitably conducted at elevated temperature such as 125° C. Compounds of formula [F-002](where X is a sulfonate) are prepared by reacting a compound of formula [F-004] with a suitably substituted sulfonyl chloride in a suitable solvent such as DMA in the presence of a suitable base such as triethylamine and a catalytic amount of DMAP. The reaction is suitably conducted at ambient temperature. 
     
       
         
         
             
             
         
       
     
     In one approach, compounds of formula [F-004] are prepared by reacting a compound of formula [F-005](where Rx is an alkyl group such as methyl or ethyl) with a compound of formula [F-006] in a suitable solvent in a dry non-aprotic solvent such as dioxane or THF in the presence of a hindered alkoxide base such as potassium-tert-pentylate 1.7M in toluene or potassium-tert-butoxide. The reaction is suitably conducted at ambient temperature. 
     In one approach, compounds of formula [F-004] are prepared by reacting a compound of formula [F-007] with a compound of formula [F-006] in a suitable solvent in a protic solvent such as methanol in the presence of a base such as sodium methoxide. The reaction is suitably conducted first at ambient temperature then at reflux overnight. 
     
       
         
         
             
             
         
       
     
     An example of a method as described above is illustrated in the following scheme. 
     
       
         
         
             
             
         
       
     
     General Synthesis of 4-substituted-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine Derivatives of General Formula [F-001] Scheme A1 
     Substituted 2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol derivatives of general formula [F-001] were prepared by the reaction of a 2-amino-pyridyl derivative of general formula [F-005] with a 4-cyanopyridyl derivative of general formula [F-006] in the presence of a base such as sodium methoxide in a polar aprotic solvent such as methanol. The reaction is suitably conducted at elevated temperature to yield the cyclised 2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol product of general formula [F-004]. 4-substituted-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine derivatives of general formula [F-001] were prepared by the reaction of a 2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol derivatives of general formula [F-004] with a chlorinatation agent such as phosphorous oxychloride to yield 4-chloro-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine derivatives of general formula [F-008] which were reacted with primary or secondary amino derivative of general formula [F-003], in a polar aprotic solvent such as DMA, DMF, NMP in the presence of a tertiary amine base such as Et3N, DIPEA or NMM at ambient temperature [method A]. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, TCA, methanesulfonic acid, HCl or H 2 SO 4  in a solvent such as DCM, DCE, THF, EtOH or MeOH and the crude reaction product was purified by normal phase silica gel chromatography or reverse phase preparative HPLC. 4-substituted-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine derivatives of general formula [F-001] were prepared by the reaction of a 2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol derivatives of general formula [F-004] with 2,4,6-triisopropylbenzenesulfonyl chloride in a polar aprotic solvent such as DMA, DMF, NMP with a tertiary alkylamine base such as Et 3 N, DIPEA or NMM and a catalytic amount of DMAP [method B]. The intermediate 6,7-substituted-(2,4,6-triisopropyl-benzenesulfonic acid)-2-pyridin-4-yl-thieno[3,2-d]pyrimidin-4-yl ester was then reacted with a primary or secondary amino derivative, of general formula [F-003], in a polar aprotic solvent such as DMA, DMF, NMP in the presence of a tertiary amine base such as Et 3 N, DIPEA or NMM at ambient temperature. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, TCA, methanesulfonic acid, HCl or H 2 SO 4  in a solvent such as DCM, DCE, THF, EtOH or MeOH and the crude reaction product was purified by reverse phase preparative HPLC 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Synthesis of 4-Piperazin-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine [1] Method A 
     
       
         
         
             
             
         
       
     
     Synthesis of 2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol [A001] 
     A mixture of 4-Cyanopyridine (8.25 g, 79.2 mmol), sodium methoxide (891 mg, 16.5 mmol) and methanol (400 mL) was stirred at room temperature for 60 minutes. 3-Amino-isonicotinic acid (9.12 g, 66.0 mmol) was added and the mixture heated to reflux for 3 days. After cooling to room temperature the solid precipitate was collected by filtration then dried in the vacuum oven to yield the title compound as an off-white solid (6.02 g): (1H, 300 MHz, d6-dmso) 13.10 (1H, br s), 9.16 (1H, s), 8.80 (2H, dd), 8.70 (1H, d), 8.10 (2H, dd), 8.00 (1H, dd) 
     Synthesis of 4-Chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine [A002] 
     2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol [A001](4 g, 17.8 mmol) in POCl 3  (50 mL, 538 mmol) was heated to 110° C. for 3 hours. The reaction mixture was concentrated under vacuum, quenched with saturated NaHCO 3  solution, extracted into DCM, washed with water then brine, passed through a phase separator cartridge and evaporated to yield the title compound [A002] (2.6 g) as a yellow/brown solid which was used without further purification: LCMS method: 1, RT: 4.09 min, MI 243 [M+H]. 
     Synthesis of 1-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine [1] 
     A solution of 4-Chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine [A002](100 mg, 0.43 mmol), piperazine (172 mg, 2 mmol) in anhydrous DMA (5 mL) was stirred at room temperature for 3 days. The reaction mixture was partitioned between NaOH (2M aqueous solution) and ethyl acetate. The organic layer was further washed with water then brine, dried (MgSO 4 ), passed through a phase separator cartridge and evaporated to yield the crude material, which was purified by preparative HPLC (method A) to yield the title compound (1.87 mg). LCMS method: 1, RT: 3.49 min, MI 293 [M+H]; 1H-NMR (300 MHz; DMSO-d6): 9.26 (1H, s), 8.76 (2H, d), 8.58 (1H, d), 8.32 (2H, d), 8.24 (1H, s), 7.92 (1H, d), 3.96 (4H, br tr), 2.99 (4H, br tr) 
     Synthesis of (5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-(R)-pyrrolidin-3-yl-amine [2]method B 
     
       
         
         
             
             
         
       
     
     Synthesis of 5-Methoxy-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A003] 
     To a stirred solution of 2-chloro-4-pyridinecarbonitrile (1 g, 9.6 mmol) in MeOH (20 mL) was added 0.5 M NaOMe (2 mmol, 4 mL) followed by 3-Amino-5-methoxy-isonicotinic acid (1.35 g, 8 mmol). The RM was heated at 75° C. over night. The RM was left to cool and a solid ppt formed which was collected by filtration, washed with cold MeOH and dried in a vac oven to give the title compound as a pale brown solid (610 mg, 30% yield). LCMS method: 1, RT: 3.82 min, MI 255.09 [M+H]. 
     
       
         
         
             
             
         
       
     
     Synthesis of (5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-(R)-pyrrolidin-3-yl-amine [2] 
     5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-[A003](0.157 mmol, 0.04 g), 2,4,6-triisopropylbenzenesulfonyl chloride (0.173 mmol, 0.052 g), were dissolved in anhydrous DMA (2 mL), and Et 3 N (0.314 mmol, 0.045 mL), and DMAP (5 mg) were added sequentially. The mixture was stirred at room temperature for 1 hour and (R)-3-amino-pyrrolidine-1-carboxylic acid tert-butyl ester (0.236 mmol, 0.044 g) was added. The mixture was stirred at room temperature overnight. The solvent was then removed under reduced pressure and the residue was stirred in trifluoroacetic acid (1 mL) at room temperature for 3 h. The solution was poured on to an SCX-2 cartridge (5 g), washed with methanol (10 mL) and then washed with ammonia (2N in methanol, 20 mL). The ammonia washes were concentrated in vacuo to a brown residue that was purified by preparative HPLC (method A) to yield the title compound (0.016 g). LCMS method: 1, RT: 1.47 min, MI 323 [M+H]; 1H-NMR 300 MHz (1H d6-dmso) 8.81 (1H, s), 8.76 (2H, dd), 8.35 (1H, s), 8.32 (2H, dd), 8.23 (1H, d), 6.42 (1H, s), 4.98 (1H, m), 4.14 (3H, s), 3.19-3.07 (2H, m), 2.41-2.29 (2H, m), 2.07-1.95 (2H, m). 
     Synthesis of 2-(3-Fluoro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol [A004] 
     
       
         
         
             
             
         
       
     
     2-(3-Fluoro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol [A004] 
     3-Amino-2-chloro-isonicotinamide (0.5 g, 3.64 mmol), 3-Fluoroisonicotinaldehyde (0.54 g, 4.37 mmol), NaHSO3 (0.75 g, 7.29 mmol) and DMA (5 mL) were added successively to a microwave vial. The vial was sealed then heated at 160° C. for 6 min. Water (10 mL) was added and the resulting solid was filtered and used without further purification. LCMS method: 1, RT: 3.07 min, MI 243 [M+H] 
     Synthesis of 8-Chloro-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A005] 
     
       
         
         
             
             
         
       
     
     8-Chloro-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A005] 
     A solution of 3-Amino-2-chloro-isonicotinamide (0.5 g, 2.91 mmol) and 4-Pyridinecarboxaldehyde (0.35 g, 3.32 mmol) in DMA (10 mL) was heated under microwave (100° C., 2 h). Sodium hydrogen sulfite (0.606 g, 5.83 mmol) was then added and the mixture was heated under microwave (150° C., 1 h). Water was then added to the mixture and the resulting solid (0.34 g, 45%) was collected, washed with water and then by MeOH. LCMS method: 1, RT: 3.89 min, MI 258 [M+H] 
     Synthesis of 8-Chloro-2-Pyridin-4-Yl-3H-Pyrido[3,4-d]Pyrimidin-4-One [A005] 
     
       
         
         
             
             
         
       
     
     Synthesis of 2-Chloro-3-[(pyridine-4-carbonyl)-amino]-isonicotinamide [A006] 
     To a suspension of 3-Amino-2-chloro-isonicotinamide (0.5 g, 2.913 mmol) and K 2 CO 3  (1 g, 7.28 mmol) in refluxing Et 2 O (25 mL), Isonicotinoyl chloride hydrochloride (0.622 g, 3.5 mmol) was added portionwise. The mixture was stirred under reflux for 4 h. The solvent was removed under reduced pressure and water (50 mL) was added. The resulting solid was filtered, washed with H 2 O and then collected, dried with an azeotrope with toluene, to yield the title compound (0.78 g, 96%) which was used without further purification. LCMS method: 1, RT: 2.55 min, MI 277 [M+H] 
     
       
         
         
             
             
         
       
     
     Synthesis of 8-Chloro-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A004] 
     To a solution of 2-Chloro-3-[(pyridine-4-carbonyl)-amino]-isonicotinamide [A006](0.2 g, 0.723 mmol) in MeOH (20 mL) was added a solution of cesium carbonate (0.47 g, 1.44 mmol) in H 2 O (2 mL). The mixture was stirred at room temperature overnight. The MeOH was removed under reduced pressure and water (10 mL) was added. Acetic acid was added slowly and the resulting solid was collected, dried with a toluene azeotrope to yield the title compound which was used without further purification. LCMS method: 1, RT: 3.43 min, MI 259 [M+H] 
     Synthesis of 6-Chloro-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A007] 
     
       
         
         
             
             
         
       
     
     6-Chloro-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A007] 
     A solution of potassium pentoxide (2.6 mL, 5.1 mmol, 25% soln in Toluene) was added dropwise (˜0.5 mL/min) to a solution of 5-Amino-2-chloro-isonicotinic acid ethyl ester (0.4 g, 2 mmol) and 4-cyanopyridine (0.25 g, 2.4 mmol) in anhydrous THF (5 mL) cooled in an ice bath. The reaction was allowed to warm to RT and left to stir at room temperature overnight. Water (9 mL) was added and the mixture was stirred at RT for 20 mins. Acetic acid (˜1 mL) was then added and the mixture was left to stir at RT and the resulting yellow precipitate was filtered and the siolid washed with deionised water (2×3 mL). To give the title compound (0.43 g, 83% yield). LCMS method: 1, RT: 2.21 min, MI 259 [M+H] 
     Synthesis of 2-(3-Fluoro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol [A008] 
     
       
         
         
             
             
         
       
     
     2-(3-Fluoro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol [A008] 
     To a stirred solution of 3-Fluoroisonicotinonitrile (0.088 g, 0.71 mmol) in MeOH (5 mL) was added NaOMe (0.008 g, 0.15 mmol). After 1 hr 3-amino-5-methoxy-isonicotinic acid (0.1 g, 0.54 mmol) was added and the RM heated to 85° C. for 18 hr. The solution became yellow in colour. The reaction mixture was allowed to cool to RT and the white solid was collected by filtration and washed with MeOH to yield the title compound (0.07 g, 43% yield). LCMS method: 1, RT: 1.19 min, MI 271.24 [M+H] 
     The following compounds were synthesised according to the general synthesis shown in scheme [A1]: 
     
       
         
           
               
               
               
               
               
               
            
               
                   
               
               
                   
                 Pre- 
                 Meth- 
                 Amine 
                 Analysis 
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Ex 
                 cursor 
                 od 
                 [F-003] 
                 LCMS 
                 NMR 
                 Name 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 3 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.2 min, MI: 267 [M + H] 
                   
                 N-(2-aminoethyl)-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4-amine 
               
               
                   
               
               
                 4 
                 [A001 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.45 min, MI, 281 [M + H] 
                   
                 N-[(2R)-2- aminopropyl]-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4-amine 
               
               
                   
               
               
                 5 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.52 min, MI, 281 [M + H] 
                   
                 N-[(2S)-2- aminopropyl]-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4-amine 
               
               
                   
               
               
                 6 
                 [A001] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.51 min, MI, 357 [M + H] 
                 (1H, 300 MHz, d6-dmso); 9.15 ppm (1H, d), 8.70 ppm (2H, d), 8.62 ppm (2H, d), 8.20 ppm (1H, d), 8.12 ppm (2H, d), 7.35-7.26 ppm (5H, m), 3.86 ppm, (1H, d), 3.35 ppm (2H, m), 2.27 ppm (2H, m) 
                 N-[(2S)-2-amino-3- phenylpropyl]-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4-amine 
               
               
                   
               
               
                 7 
                 [A001] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 0.88 min, MI, 293 [M + H] 
                 (1H, 300 MHz, d6-dmso), 9.18 (1H, s), 8.94-8.90 (1H, m), 8.76 (2H, dd), 8.65 (1H, d), 8.35 (2H, dd), 4.94-4.85 (1H, m), 3.87-3.74 (3H, m), 3.19-3.07 (2H, m), 2.30-2.18  (2H, m), 2.02-1.92 (2H, m) 
                 (3R)-N-[2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]pyrrolidin-3-amine 
               
               
                   
               
               
                 8 
                 [A004] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 0.5 min, MI, 311 [M + H] 
                 (1H, 300 MHz, d6-dmso), 9.47 (1H, brd), 9.15 (1H, s), 8.71 (1H, d), 8.66 (1H, d), 8.57 (1H, d), 8.47 (1H, s), 8.39 (1H, d), 8.08 (1H, dd), 4.92 (1H, br s), 3.46 (1H, dd), 3.34-3.22 (2H, m), 2.30-2.20 (1H, m), 2.18-2.08 (1H, m) 
                 (3R)-N-[2-(3- fluoropyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]pyrrolidin-3-amine 
               
               
                   
               
               
                 9 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.92 min, MI, 387 [M + H] 
                 (1H, 300 MHz, d6-dmso); 8.72 (1H, s), 8.68 (2H, d), 8.28 (1H, s), 8.00 (2H, d), 7.39-7.30 (5H, m), 4.00 (3H, s), 3.96-3.91 (1H, m), 3.59 (2H, br s), 3.00 (1H, dd), 2.79 (1H, dd) 
                 N-[(2S)-2-amino-3- phenylpropyl]-5- methoxy-2-(pyridin- 4-yl)pyrido[3,4- d]pyrimidin-4-amine 
               
               
                   
               
               
                 10 
                 [A004] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: ,2.95 min MI, 375 [M + H] 
                 (1H, 300 MHz, d6-dmso), 9.12 (1H, s), 8.69 (1H, d), 8.53 (1H, d), 8.46 (1H, S), 8.21 (1H, d), 7.83 (1H, dd), 7.28-7.19 (5H, m), 3.81 (1H, dd), 3.66-3.49 (2H, m), 2.90 (1H, dd), 2.80 (1H, dd), 
                 N-[(2S)-2-amino-3- phenylpropyl]-2-(3- fluoropyridin-4- yl)pyrido[3,4- d]pyrimidin-4-amine 
               
               
                   
               
               
                 11 
                 [A005] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.98 min, MI: 392 [M + H] 
                 (1H, 300 MHz, d6-dmso), 8.70 (2H, d), 8.40 (1H, d), 8.36 (1H, br s), 7.98 (2H, d), 7.43-7.32 (5H, m), 3.97 (1H, d), 3.69-3.54 (2H, m), 3.06 (1H, dd), 2.84 (1H, dd) 
                 N-[(2S)-2-amino-3- phenylpropyl]-8- chloro-2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4-amine 
               
               
                   
               
               
                 12 
                 [A007] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 6.51 min, MI: 391 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.06 s), 8.69 (2H, dd), 7.98 (2H, dd), 7.87 (1H, s), 7.42-7.27 (5H, m), 4.54 (1H, dd), 4.37 (1H, d), 3.58- 3.48 (1H, m), 3.04-2.93 (3H, m), 2.85-2.59 (3H, m) 
                 N-[(2S)-2-amino-3- phenylpropyl]-6- chloro-2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4-amine 
               
               
                   
               
               
                 13 
                 [A007] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 4.35 min, MI: 327 [M + H] 
                 (300 MHz, 1H, d6-dmso) 9.20 (1H, s), 8.79 (2H, d), 8.35 (2H, d), 8.13 (1H, s), 6.61 (1H, s), 4.15 (4H, br s), 3.33 (4H, br s) 
                 1-[6-chloro-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 14 
                 [A007] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.91 min, MI: 443.9 [M + H] 
                 (300 MHz, 1H, d6-dmso) 9.06 (1H, s), 8.69 (2H, dd), 7.98 (2H, dd), 7.87 (1H, s), 7.41-7.29 (5H, m), 4.54 (1H, dd), 4.37 (1H, d), 3.53 (1H, dt), 3.03-2.93 (3H, m), 2.85- 2.57 (3H, m) 
                 (3S)-3-benzyl-1-[6- chloro-2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 15 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 4.30 min, MI: 358 [M + H] 
                 (300 MHz, 1H, d4-MeOH) 8.55 (d, 1H), 8.22 (dd, 2H), 8.03 (dd, 1H), 7.76 (m, 5H), 4.28 (m, 1H), 4.09 (1H, dd), 3.58 (1H, dd), 2.96 (1H, dd), 2.88 (1H, dd) 
                 (2S)-1-phenyl-3-{[2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]amino}propan-2- ol 
               
               
                   
               
               
                 16 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.44 min, MI: 383 [M + H] 
                 (1H, 300 MHz, CDCl 3 ): 9.34 (s, 1H), 8.73 (d, 2H), 8.46 (d, 1H), 8.21 (d, 2H), 7.49 (d, 1H), 7.33 (m, 3H), 7.25 (d, 2H), 4.58 (d, 1H), 4.48 (d, 1H), 3.46 (t, 1H), 3.02 (m, 4H), 2.76 (m, 2H) 
                 (3S)-3-benzyl-1-[2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 17 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.45 min, MI: 383 [M + H] 
                 (1H, 300 MHz, CDCl 3 ): 9.34 (s, 1H), 8.73 (d, 2H), 8.46 (d, 1H), 8.21 (d, 2H), 7.49 (d, 1H), 7.33 (m, 3H), 7.25 (d, 2H), 4.58 (d, 1H), 4.48 (d, 1H), 3.46 (t, 1H), 3.02 (m, 4H), 2.76 (m, 2H) 
                 (3R)-3-benzyl-1-[2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 18 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.99 min, MI: 307 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.26 (1H, s), 8.75 (2H, dd), 8.58 (1H, d), 8.31 (2H, dd), 7.91 (1H, d), 3.98-3.96 (4H, m), 2.55-2.52 (4H, m), 2.25 (3H, s) 
                 1-methyl-4-[2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 19 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 4.00 min, MI: 321 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.19 (1H, s), 8.75 (2H, dd), 8.52 (1H, d), 8.29 (2H, dd), 7.98 (1H, d), 4.13-4.06 (4H, m), 2.85-2.83 (2H, m), 2.55-2.51 (2H, m), 2.26 (3H, s), 2.10-2.03 (2H, m) 
                 1-methyl-4-[2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4-yl]- 1,4-diazepane 
               
               
                   
               
               
                 20 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 4.29 min, MI: 473 [M + H] 
                 (1H, 300 MHz, CDCl 3 ): 9.31 (s, 1H), 8.75 (d, 2H), 8.47 (d, 1H), 8.30 (d, 2H), 7.49 (d, 1H), 7.36 (m, 5H), 7.02 (m, 5H), 5.02 (s, 1H), 4.30 (d, 1H), 3.90 (td, 1H), 3.62 (d, 1H), 3.45 (d, 1H), 3.26 (m, 2H), 3.04 (d, 1H), 2.92 (d, 1H), 2.35 (m, 2H) 
                 (2S)-2,4-dibenzyl-1- [2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 21 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.86 min, MI: 294 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.28 (1H, s), 8.76 (2H, d), 8.59 (1H, d), 8.33 (2H, d), 7.97 (1H, d), 4.02-3.99 (4H, t), 3.83-3.80 (4H, t) 
                 4-[2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]morpholine 
               
               
                   
               
               
                 22 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 4.76 min, MI: 349 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.28 (1H, s), 8.77 (2H, dd), 8.60 (1H, d), 8.34 (2H, dd), 7.97 (1H, d), 4.03-4.00 (4H, m), 3.61 (4H, br s), 1.43 (9H, s) 
                 tert-butyl 4-[2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine-1- carboxylate 
               
               
                   
               
               
                 23 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 4.18 min, MI: 407 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.22 (1H, s), 8.76 (2H, dd), 8.56 (1H, d), 8.30 (2H, dd), 8.08-8.03 (1H, m), 4.28- 4.22 (2H, m), 4.15-4.10 (2H, m), 3.72-3.65 (2H, m), 3.42 (2H, br s), 2.09-1.97 (2H, m), 1.11 (4H, s), 0.93 (5H, s) 
                 tert-butyl 4-[2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4-yl]- 1,4-diazepane-1- carboxylate 
               
               
                   
               
               
                 24 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.8 min, MI: 310 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.29 (1H, s), 8.76 (2H, dd), 8.60 (1H, d), 8.32 (2H, dd), 7.87 (1H, d), 4.23-4.20 (4H, m), 2.93-2.89 (4H, m) 
                 4-[2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]thiomorpholine 
               
               
                   
               
               
                 25 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.34 min, MI: 385 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.13 (1H, s), 8.67 (2H, dd), 8.61 (1H, d), 8.15 (1H, d), 7.99 (2H, d), 7.37-7.26 (5H, m), 3.76 (2H, br s), 3.33-3.13 (1H, m), 3.07-2.88 (2H, m), 2.35 (6H, br s) 
                 N,N-Dimethyl[(2S)- 1-phenyl-3-{[2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]amino}propan-2- yl]amine 
               
               
                   
               
               
                 26 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.44 min, MI: 371 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.15 (1H, s), 8.77-8.75 (2H, m), 8.64 (1H, d), 8.30-8.28 (2H, m), 8.24 (1H, d), 7.32-7.29 (2H, m), 7.20-7.15 (2H, m), 7.09-7.04 (1H, m), 5.08- 4.99 (1H, m), 3.11-2.87 (4H, m), 2.38 (3H, s). 
                 N-[(2S)-2-amino-3- phenylpropyl]-N- methyl-2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4-amine 
               
               
                   
               
               
                 27 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.21 min, MI: 307 [M + H] 
                 1H NMR (d6-DMSO, 300 MHz) 9.28 (1H, s), 8.77 (2H, d), 8.61 (1H, d), 8.34 (2H, d), 8.31 (1H, s), 8.03 (1H, d), 4.51 (2H, s), 4.18 (2H, t), 3.53-3.43 (2H, m). 
                 4-[2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazin-2-one 
               
               
                   
               
               
                 28 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.44 min, MI: 357 [M + H] 
                 — 
                 N-[(2S)-1-amino-3- phenylpropan-2-yl]- 2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4-amine 
               
               
                   
               
               
                 29 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.12 min, MI: 383.18 [M + H] 
                 (1H, 300 MHz, CDCl 3 ): 9.27 (s, 1H), 8.75 (d, 2H), 8.47 (d, 1H), 8.29 (d, 2H), 7.45 (d, 1H), 7.11 (m, 5H), 5.05 (m, 1H), 4.28 (d, 1H), 3.83 (dt, 1H), 3.23 (m, 3H), 3.09 (m, 2H), 3.01 (dt, 1H). 
                 (2R)-2-benzyl-1-[2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 30 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.71 min, MI: 413.17 [M + H] 
                 (1H, 500 MHz, d6-dmso) 8.77 (s, 1H), 8.69 (d, 2H), 8.22 (s, 1H), 8.03 (d, 2H), 7.34 (m, 3H), 7.27 (d, 2H), 4.27 (m, 1H), 4.02 (m, 1H), 3.90 (s, 3H), 3.22 (t, 1H), 2.99 (m, 2H), 2.83 (t, 1H), 2.72 (dd, 1H), 2.63 (t, 1H), 2.62 (dd, 1H). 
                 (3S)-3-benzyl-1-[5- methoxy-2-(pyridin- 4-yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 31 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 1.261 min, MI: 323.07 [M + H] 
                 (1H, 300 MHz, d6-dmso) 8.86 (1H, t), 8.78-8.76 (2H, m), 8.36 (1H, s), 8.32-8.30 (2H, m), 4.08 (3H, s), 3.75 (4H, m), 3.03 (4H, m). 
                 1-[5-methoxy-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 32 
                 [A005] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 1.39 min, MI: 327 [M + H] 
                 (1H, 300 MHz, d6-dmso): 8.79 (d, 2H), 8.32-8.37 (m, 3H), 7.92 (d, 1H), 3.94 (brs, 4H), 2.95 (brs, 4H). 
                 1-[8-chloro-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 33 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.92 min, MI: 307 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.21 (1H, s), 8.77-8.75 (2H, m), 8.54 (1H, d), 8.32-8.30 (2H, m), 8.00 (1H, d), 4.14-4.07 (4H, m), 3.15-3.12 (2H, m), 2.85-2.81 (2H, m), 2.04-1.97 (2H, m). 
                 1-[2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4-yl]- 1,4-diazepane 
               
               
                   
               
               
                 34 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 4.04 min, MI: 337 [M + H]  
                 (1H, 300 MHz, d6-dmso) 9.27 (1H, s), 8.78-8.76 (2H, m), 8.60 (1H, d), 8.34-8.32 (2H, m), 7.94 (1H, d), 4.50 (1H, br m), 4.00 (4H, br m), 3.60-3.54 (2H, m), 2.67 (4H, br m), 2.49-2.46 (2H, m). 
                 2-{4-[2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazin-1- yl}ethan-1-ol 
               
               
                   
               
               
                 35 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.35 min, MI: 294 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.19 (1H, s), 8.77-8.74 (2H, m), 8.56 (1H, d), 8.34-8.32 (2H, m), 8.17 (1H, br m), 5.18 (1H, d), 4.49 (1H, br m), 4.08 (3H, br m), 3.88 (1H, br d), 2.05 (2H, br m). 
                 (3S)-1-[2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]pyrrolidin-3-ol 
               
               
                   
               
               
                 36 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.39 min, MI: 294 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.19 (1H, s), 8.77-8.74 (2H, m), 8.56 (1H, d), 8.34-8.32 (2H, m), 8.17 (1H, br m), 5.18 (1H, d), 4.49 (1H, br m), 4.08 (3H, br m), 3.88 (1H, br d), 2.05 (2H, br m). 
                 (3R)-1-[2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]pyrrolidin-3-ol 
               
               
                   
               
               
                 37 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.74 min, MI: 413.17 [M + H] 
                 (1H, 500 MHz, d6-dmso): 8.79 (s, 1H), 8.70 (d, 2H), 8.23 (s, 1H), 8.05 (d, 2H), 7.33 (m, 3H), 7.27 (d, 2H), 3.21 (t, 1H), 3.17 (d, 2H), 3.00 (d, 1H), 2.92 (m, 1H), 2.82 (t, 1H), 2.76 (dd, 1H), 2.68 (d, 1H), 2.61 (dd, 1H). 
                 (3R)-3-benzyl-1-[5- methoxy-2-(pyridin- 4-yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 38 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.06 min, MI: 383.17 [M + H] 
                 (1H, 500 MHz, CDCl 3 ): 9.29 (s, 1H), 8.75 (d, 2H), 8.47 (d, 1H), 8.28 (d, 2H), 7.45 (d, 1H), 7.09 (m, 5H), 5.04 (m, 1H), 4.25 (d, 1H), 3.83 (t, 1H), 3.28 (m, 2H), 3.22 (d, 1H), 3.09 (m, 2H), 3.02 (t, 1H). 
                 (2S)-2-benzyl-1-[2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 39 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 1.04 min, MI: 351.25 [M + H] 
                 (1H, 300 MHz, d4-MeOH): 9.20 (s, 1H), 8.71 (dd, 2H), 8.59 (d, 1H), 8.48 (dd, 2H), 8.08 (d, 1H), 4.98 (m, 1H), 4.99 (m, 1H), 4.02 (dd, 1H), 3.74 (s, 3H), 3.42 (dd, 1H), 3.25 (dd, 1H), 2.78 (m, 2H), 2.21 (m, 1H). 
                 methyl (2S,4S)-4- {[2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]amino}pyrrolidine- 2-carboxylate 
               
               
                   
               
               
                 40 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 0.52 min, MI: 463 [M + H] 
                 (1H, 300 MHz, d4-MeOH): 9.21 (s, 1H), 8.71 (ss, 2H), 8.60 (d, 1H), 8.50 (dd, 2H), 8.09 (d, 1H), 4.99 (m, 1H), 4.29 (m, 1H), 3.86 (m, 2H), 3.73 (s, 3H), 3.47 (dd, 1H), 3.14 (m, 2H), 2.89 (dd, 1H), 2.74 (m, 1H), 2.49 (m, 1H), 2.12 (m, 1H), 1.88 (m, 1H). 
                 methyl (2S,4S)-4- [(2S,4S)-4-{[2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]amino}pyrrolidine- 2-amido]pyrrolidine- 2-carboxylate 
               
               
                   
               
               
                 41 
                 [A003] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 5.14 min, MI: 401 [M + H] 
                 (1H, 300 MHz, d6-dmso) 8.77 (s, 1H), 8.72-8.70 (2H, m), 8.33 (1H, s), 8.20 (1H, s), 8.12- 8.10 (2H, m), 7.33-7.23 (5H, m), 4.12 (3H, s), 3.86-3.78 (1H, m), 3.62-3.53 (1H, m), 3.18-3.11 (1H, m), 2.98-2.92 (1H, m)2.71- 2.64 (1H, m), 2.45 (3H, s). 
                 [(2S)-1-{[5-methoxy- 2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]amino}-3- phenylpropan-2- yl](methyl)amine 
               
               
                   
               
               
                 42 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.0 min, MI: 294 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.21 (1H, s), 8.81-8.77 (3H, m), 8.67 (1H, d), 8.37-8.33 (3H, m), 6.57 (2H, s), 5.00-4.90 (1H, m), 4.14-4.09 (1H, m), 4.01-3.94 (1H, m), 3.86-3.79 (2H, m), 2.42- 2.33 (1H, m), 2.20-2.09 (1H, m). 
                 N-[(3R)-oxolan-3- yl]-2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4-amine 
               
               
                   
               
               
                 43 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.41 min, MI: 391.13 [M + H] 
                 (1H, 300 MHz, CDCl 3 ): 9.01 (s, 1H), 8.76 (d, 2H), 8.31 (d, 2H), 8.22 (s, 1H), 4.42 (d, 1H), 4.15-4.04 (m, 1H), 4.07 (s, 3H), 3.62 (br m, 1H), 3.33-3.12 (m, 3H), 3.00 (t, 1H). 
                 1-[5-methoxy-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4-yl]-3- (trifluoromethyl)piper- azine 
               
               
                   
               
               
                 44 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3jdf138qc, 96%, 337.23, 1.37 min, + [M + H] LC- MS17QC 
                 (1H, 300 MHz, CDCl 3 ): 8.95 (s, 1H), 8.74 (d, 2H), 8.31 (d, 2H), 8.16 (s, 1H), 4.20 (t, 2H), 4.05 (s, 3H), 3.16 (m, 2H), 2.99 (m, 2H), 2.81 (t, 1H), 1.14 (d, 3H). 
                 (3S)-1-[5-methoxy-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4-yl]-3- methylpiperazine 
               
               
                   
               
               
                 45 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method RT: 1.52 min, MI: 323 [M + H] 
                 (1H, 300 MHz, d6-dmso) 8.80 (1H, s), 8.78-8.75 (2H, m), 8.34 (1H, s), 8.32-8.30 (2H, m), 4.07 (3H, s), 3.94 (2H, br s), 3.82 (1H, br s), 3.72 (1H, br s), 2.15 (1H, br s), 1.10 (1H, br s). 
                 (3R)-1-[5-methoxy- 2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]pyrrolidin-3-amine 
               
               
                   
               
               
                 46 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 1.32 min, MI: 353.2 [M + H] 
                 (1H, 300 MHz, d6-dmso): 8.84 (s, 1H), 8.76 (d, 2H), 8.34 (s, 1H), 8.29 (d, 2H), 4.87 (bs, 1H), 4.28 (dd, 2H), 4.06 (s, 3H), 3.43 (m, 1H), 3.07 (m, 3H), 2.82 (m, 3H). 
                 [(2R)-4-[5-methoxy- 2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazin-2- yl]methanol 
               
               
                   
               
               
                 47 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.79 min, MI: 405.22 [M + H] 
                 (1H, 300 MHz, CDCl 3 ): 8.90 (s, 1H), 8.72 (d, 2H), 8.22 (d, 2H), 8.14 (s, 1H), 7.40 (m, 5H), 5.43 (dd, 1H), 4.18 (m, 1H), 4.10 (s, 3H), 3.53 (m, 2H). 
                 N-[(2R,3R)-2-amino- 3-fluoro-3- phenylpropyl]-5- methoxy-2-(pyridin- 4-yl)pyrido[3,4- d]pyrimidin-4-amine 
               
               
                   
               
               
                 48 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.76 min, MI: 470.24 [M + H] 
                 (1H, 300 MHz, CDCl 3 ): 8.94 (s, 1H), 8.70 (d, 2H), 8.12 (d, 2H), 8.05 (s, 1H), 7.28 (m, 2H), 7.08 (m, 3H), 4.04 (d, 1H), 3.84 (m, 4H), 3.65 (m, 1H), 3.56 (d, 1H), 3.29 (m, 1H), 3.06 (m, 3H), 2.89 (m, 1H), 2.66 (dt, 1H), 2.53 (dd, 1H). 
                 2-[(2S)-2-benzyl-4- [5-methoxy-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazin-1- yl]acetamide 
               
               
                   
               
               
                 49 
                 [A003] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 5.71 min, MI: 415 [M + H] 
                 (1H, 300 MHz, d4-MeOH) 8.63 (1H, s), 8.58-8.56 (2H, m), 8.10 (1H, s), 8.06-8.04 (2H, m), 7.31-7.19 (5H, m), 4.06 (3H, m), 3.98-3.91 (1H, m), 3.71-3.63 (1H, m), 3.59-3.47 (1H, m), 3.20- 3.14 (1H, m), 2.67-2.60 (7H, m). 
                 [(2S)-1-{[5-methoxy- 2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]amino}-3- phenylpropan-2- yl]dimethylamine 
               
               
                   
               
               
                 50 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.69 min, MI: 324.19 [M + H] 
                 (1H, 300 MHz, CDCl 3 ) 8.92 (1H, s), 8.74-8.72 (2H, m), 8.36-8.34 (2H, m), 8.16 (1H, m), 4.62 (1H, br s), 4.26-4.16 (1H, m), 4.07 (3H, m), 3.82-3.75 (1H, m), 3.63 (1H, d), 2.12-2.20 (1H, m), 1.22-1.21 (2H, m). 
                 (3S)-1-[5-methoxy-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]pyrrolidin-3-ol 
               
               
                   
               
               
                 51 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 0.63 min, MI: 351 [M + H] 
                 (1H, 300 MHz, CDCl 3 ): 8.97 (s, 1H), 8.78 (d, 2H), 8.31 (d, 2H), 8.19 (s, 1H), 4.23 (m, 2H), 4.07 (s, 3H), 3.08 (m, 2H), 2.75 (t, 2H), 1.16 (m, 6H). 
                 1-[5-methoxy-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4-yl]- 3,5-cis- dimethylpiperazine 
               
               
                   
               
               
                 52 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 4.03 min, MI: 337.37 [M + H] 
                 (1H, 300 MHz, CDCl 3 ): 8.98 (s, 1H), 8.77 (d, 2H), 8.32 (d, 2H), 8.19 (s, 1H), 4.22 (t, 2H), 4.07 (s, 3H), 3.19 (m, 2H), 3.05 (m, 2H), 2.82 (m, 1H), 1.15 (d, 3H). 
                 (3R)-1-[5-methoxy- 2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4-yl]-3- methylpiperazine 
               
               
                   
               
               
                 53 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 1H NMR (300 MHz, d 6 -DMSO) 8.78-8.73 (3H, m), 8.30-8.28 (3H, m), 4.05 (3H, s), 3.92 (4H, m), 3.36 (3H, m) 
                 (3S)-1-[5-methoxy-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]pyrrolidin-3-amine 
               
               
                   
               
               
                 54 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 1.48 min, MI: 355.15 [M + H] 
                 (1H, 300 MHz, CDCl 3 ) 9.02 (1H, s), 8.80-8.78 (2H, m), 8.35-8.33 (2H, m), 8.22 (1H, m), 4.59-4.57 (1H, m), 4.44-4.41 (1H, m), 4.28 (1H, d), 4.22-4.16 (1H, m), 4.10 (3H, s), 3.25-3.20 (1H, m), 3.12- 3.03 (1H, m). 
                 3-(fluoromethyl)-1- [5-methoxy-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 55 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 4.22 min, MI: 377.43 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.25 (1H, s), 8.75 (2H, dd), 8.58 (1H, d), 8.31 (2H, dd), 7.89 (1H, d), 7.74 (1H, d), 4.58 (2H, d), 3.86- 3.79 (1H, m), 3.33 (3H, m), 1.94- 1.78 (4H, m), 1.03 (6H, d). 
                 N-(propan-2-yl)-1-[2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperidine-4- carboxamide 
               
               
                   
               
               
                 56 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.42 min, MI: 336.18 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.27 (1H, s), 8.76 (2H, dd), 8.60 (1H, d), 8.33 (2H, dd), 7.98 (1H, d), 6.11 (2H, s), 4.02-3.99 (4H, m), 3.60-3.56 (4H, m). 
                 4-[2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine-1- carboxamide 
               
               
                   
               
               
                 57 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 4.8 min, MI: 418.47 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.25 (1H, s), 8.76 (2H, d), 8.58 (1H, d), 8.31 (2H, d), 7.96 (1H, d), 6.27 (1H, d), 4.00 (4H, m), 3.57 (4H, m), 3.47-3.38 (1H, m), 1.77- 1.66 (4H, m), 1.56 (1H, d, br), 1.25-1.04 (5H, m). 
                 N-cyclohexyl-4-[2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine-1- carboxamide 
               
               
                   
               
               
                 58 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 0.64 min, MI: 362.18 [M + H] 
                 (1H, 300 MHz, CDCl 3 ) 9.03 (1H, s), 8.81-7.79 (2H, m), 8.36-8.34 (1H, m), 8.24 (1H, s), 4.38-4.34 (1H, m), 4.16-4.12 (4H, m), 3.42-3.33 (1H, m), 3.28- 3.19 (2H, m), 3.09-3.02 (2H, m), 2.60-2.58 (2H, m). 
                 2-{4-[5-methoxy-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazin-2- yl}acetonitrile 
               
               
                   
               
               
                 59 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.3 min, MI: 361 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.31 (1H, s), 8.80-8.78 (2H, m), 8.63 (1H, d), 8.32-8.30 (2H, m), 7.97 (1H, d), 4.54 (1H, d), 4.25 (1H, d), 3.78-3.56 (3H, m), 3.18- 3.06 (2H, m), 2.96-2.90 (2H, m). 
                 1-[2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4-yl]-3- (trifluoromethyl)piper- azine 
               
               
                   
               
               
                 60 
                 [A005] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 4.43 min, MI: 395 [M + H] 
                   
                 1-[8-chloro-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4-yl]-3- (trifluoromethyl)piper- azine 
               
               
                   
               
               
                 61 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 1.30 min, MI: 321 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.33 (s, 1H), 8.78 (d, 2H), 8.65 (d, 1H), 8.33 (d, 2H), 8.01 (d, 1H), 4.55-4.66 (m, 1H), 3.73 (t, 1H), 3.28-3.47 (m, 4H), 1.66-1.75 (m, 2H), 1.04 (t, 3H). 
                 (3S)-3-ethyl-1-[2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 62 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 1.76 min, MI: 335 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.21-9.25 (m, 1H), 8.71-8.77 (m, 2H), 8.54-8.60 (m, 1H), 8.22-8.29 (m, 2H), 7.82-7.89 (m, 1H), 4.44- 4.62 (m, 2H), 3.31-3.44 (m, 2H), 3.01-3.15 (m, 2H), 2.90 (t, 1H), 2.73 (brs, 1H), 1.68-1.79 (m, 1H), 1.00 (d, 6H). 
                 (3S)-3-(propan-2-yl)- 1-[2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 63 
                 [A008] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.19 min, MI: 341.14 [M + H] 
                 (1H, 300 MHz, d4-MeOH) 8.89 (1H, s), 8.61 (1H, d), 8.54 (1H, d), 8.43 (1H, s), 8.35 (1H, s), 8.20 (1H, dd), 4.16 (3H, s), 3.94 (4H, m), 3.36 (4H, m). 
                 1-[2-(3- fluoropyridin-4-yl)-5- methoxypyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 64 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 0.66 min, MI: 333 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.27 (1H, s), 8.78-8.76 (2H, m), 8.59 (1H, d), 8.33-8.31 (2H, m), 7.94 (1H, d), 4.67 (2H, dd), 3.47- 3.39 (1H, m), 3.18-3.10 (2H, m), 3.08-3.04 (1H, m), 2.41-2.33 (1H, m), 2.21-2.09 (2H, m), 1.94- 1.83 (1H, m), 1.80-1.65 (2H, m), 1.48-1.35 (1H, m). 
                 4-{4-[(8aR)- octahydropyrrolo[1,2- a]piperazin-2- yl]pyrido[3,4- d]pyrimidin-2- yl}pyridine 
               
               
                   
               
               
                 65 
                 [A004] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 1.89 min, MI: 311.15 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.28 (1H, s), 8.73 (1H, d), 8.65 (1H, d), 8.60 (1H, d), 8.13 (1H, dd), 8.00 (1H, d), 4.06 (4H, m), 3.22 (4H, m), 2.97 (1H, s, br). 
                 1-[2-(3- fluoropyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 66 
                 [A004] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 4.02 min, MI: 379.15 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.27 (1H, s), 8.73 (1H, d), 8.64 (1H, d), 8.60 (1H, d), 8.11 (1H, dd), 7.97 (1H, dd), 4.53 (1H, dd), 4.21 (1H, d), 3.75 (1H, m), 3.66 (1H, td), 3.51 (1H, dd), 3.15 (1H, d), 3.03 (1H, d), 2.88 (1H, t). 
                 1-[2-(3- fluoropyridin-4- yl)pyrido[3,4- d]pyrimidin-4-yl]-3- (trifluoromethyl)piper- azine 
               
               
                   
               
               
                 67 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 4.32 min, MI: 333.18 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.27 (1H, s), 8.78-8.76 (2H, m), 8.59 (1H, d), 8.33-8.31 (2H, m), 7.94 (1H, d), 4.64 (1H, dd), 3.46 (1H, br t), 3.20-3.03 (3H, m), 2.41 (1H, br m), 2.18 (2H, br m), 1.94-1.04 (1H, br m), 1.78-1.68 (2H, br m), 1.49-1.36 (1H, m). 
                 4-{4-[(3aS)- octahydo-1H- pyrrolo[3,2- c]pyridin-5- yl]pyrido[3,4- d]pyrimidin-2- yl}pyridine 
               
               
                   
               
               
                 68 
                 [A005] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.05 min, MI: 417 [M + H] 
                 (1H, 300 MHz, d6-dmso) 7.79 (d, 2H), 7.53 (brs, 1H), 7.39 (d, 1H), 7.26 (d, 2H), 6.83 (d, 1H), 6.57-6.67 (m, 5H), 3.83 (dd, 1H), 3.04 (t, 1H), 2.82-2.93 (m, 1H), 2.68 (d, 1H), 2.59 (d, 1H), 2.35 (dd, 1H), 2.14 (dd, 1H). 
                 (3S)-3-benzyl-1-[8- chloro-2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 69 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.32 min, MI: 369 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.23 (s, 1H), 8.74 (d, 2H), 8.56 (d, 1H), 8.26 (d, 2H), 7.89 (d, 1H), 7.51 (d, 2H), 7.25-7.40 (m, 3H), 4.51 (dd, 2H), 3.95 (d, 1H), 3.34- 3.46 (m, 1H), 3.13-3.24 (m, 2H), 2.97-3.03 (m, 1H). 
                 3-phenyl-1-[2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 70 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.47 min, MI: 324.18 [M + H]; 
                 (1H, 300 MHz, CDCl 3 ) 9.00 (1H, s), 8.76 (2H, d), 8.33 (2H, d), 8.20 (1H, s), 4.08 (3H, s), 3.89 (4H, t), 3.77 (4H, t). 
                 4-[5-methoxy-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]morpholine 
               
               
                   
               
               
                 71 
                 [A001] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.72 min, MI: 317.26 [M + H] 
                 (1H, 300 MHz, d4-MeOH) 9.24 (1H, s), 8.69 (2H, dd), 8.54 (1H, d), 8.42 (2H, dd), 7.97 (1H, dd), 4.20 (1H, dd), 4.07-3.92 (4H, m), 3.36-3.29 (1H, m), 3.00-2.94 (1H, m), 2.80 (1H, d), 2.65 (1H, s, br). 
                 3-ethynyl-1-[2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 72 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 5.36 min, MI: 414.22 [M + H] 
                 (1H, 300 MHz, d6-dmso) 8.82 (1H, s), 8.71 (2H, dd), 8.27 (1H, s), 8.10 (2H, dd), 7.34-7.28 (5H, m), 4.27 (1H, d), 4.04 (1H, d), 3.95-3.91 (1H, m), 3.91 (3H, s), 3.81-3.73 (1H, m), 3.59-3.52 (1H, m), 3.38-3.33 (1H, m), 3.04-2.96 (1H, dd), 2.91-2.75 (2H, m). 
                 2-benzyl-4-[5- methoxy-2-(pyridin- 4-yl)pyrido[3,4- d]pyrimidin-4- yl]morpholine 
               
               
                   
               
               
                 73 
                 [A005] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.33 min, MI: 330 [M + H] 
                   
                 {1-[8-chloro-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]azetidin-3- yl}methanol 
               
               
                   
               
               
                 74 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 1.88 min, MI: 431.18 [M + H] 
                   
                 (3R)-3- [fluoro(phenyl)methyl]- 1-[5-methoxy-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 75 
                 [A005] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.73 min, MI: 342 [M + H] 
                 (1H, 300 MHz, d6-dmso) 8.78 (d, 2H), 8.35 (d, 1H), 8.33 (d, 2H), 7.89 (d, 1H), 4.88 (d, 1H), 4.21-4.27 (m, 2H), 3.85-3.91 (m, 1H), 3.64-3.72 (m, 2H), 1.93-1.99 (m, 2H), 1.57-1.65 (m, 2H). 
                 1-[8-chloro-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperidin-4-ol 
               
               
                   
               
               
                 76 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.08 min, MI: 431.14 [M + H] 
                 (1H, 500 MHz, d6-dmso) 8.81 (1H, s), 8.71 (2H, d), 8.28 (1H, s), 8.10 (2H, d), 7.46-7.45 (5H, m), 5.51 (1H, dd), 4.41 (1H, d, br), 4.02 (1H, m, br), 3.98 (3H, s), 3.20 (2H, t, br), 3.08 (1H, d), 2.99 (1H, d), 2.68 (1H, t). 
                 (3R)-3- [fluoro(phenyl)methyl]- 1-[5-methoxy-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 77 
                 [A003] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.08 min, MI: 447.08 [M + H] (3:1 mixture of diastereomers) 
                 (1H, 500 MHz, d6-dmso) 8.79 (0.25H, s), 8.77 (0.75H, s), 8.70 (2H, dd), 8.27 (0.25H, s), 8.22 (0.75H, s), 8.11 (0.75H, d), 8.08 (0.25H, d), 7.99 (1H, d, br), 7.43 (2H, t, br), 7.23 (1.5H, t), 7.20 (0.5H, t), 5.65 (0.75H, d), 5.54 (0.25H, d), 4.54 (0.25H, t), 4.43 (0.75H, t), 3.99 (0.75H, s), 3.93 (2.25H, s), 3.22 (0.75H, t), 3.14 (0.25H, t), 3.94-2.92 (2H, m), 2.85 (1H, t), 2.74 (1H, m), 2.65 (1H, t). 
                 (4- fluorophenyl)[(2R)- 4-[5-methoxy-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazin-2- yl]methanol 
               
               
                   
               
            
           
         
       
     
     Synthesis of (S)—N 2 ,N 2 -Dimethyl-3-phenyl-propane-1,2-diamine [A009] 
     
       
         
         
             
             
         
       
     
     Synthesis of [(S)-1-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester [A010] 
     A mixture of Boc-L-phenylalaninol (25 g, 99.5 mmol), triphenylphosphine (31.3 g, 119.4 mmol), phthalimide (16.1 mg, 109.5 mmol) and THF (300 mL) was chilled to 0° C. A solution of diisopropyl azodicarboxylate (19.5 mL, 99.5 mmol) in THF (100 mL) was added over 15 mins. The resulting pale yellow solution was allowed to return to room temperature over night. The reaction mixture was concentrated to approximately 100 mL then partitioned between ethyl acetate and water. A white precipitate formed which was collected by filtration. The organic layer was washed with more water (×1) then brine (×1), dried (MgSO 4 ), filtered and evaporated to yield the title compound as a second white solid and this was material was used in further reactions, without further analysis. 
     Synthesis of ((S)-1-Aminomethyl-2-phenyl-ethyl)-carbamic acid tert-butyl ester [A011] 
     A mixture of [(S)-1-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester [A010](2 g, 5.25 mmol), 4M HCl in dioxane (5 mL, 20 mmol) and methanol (50 mL) was stirred at room temperature. The reaction mixture was loaded straight on to a methanol conditioned SCX-2 cartridge. The cartridge was washed with methanol (2col cols) and then eluted with 2N ammonia in methanol (2CV). LCMS analysis showed the target material to be predominantly in the methanol wash but also partially in the NH3 elution. The collected fractions were left to stand for a 3 days. After this time, needle like crystals started to form in the methanol fraction. The crystals were collected by filtration and dried in the vac oven to yield the title compound [A011] (400 mg): NMR: (1H, 300 MHz, d6-DMSO) 8.08 (2H, br s), 7.04 (4H, s), 7.35-7.29 (4H, m), 7.26-7.17 (1H, m), 3.83-3.66 (2H, m), 3.61 (1H, dd), 3.06 (1H, dd), 2.86 (1H, dd); LCMS method: 1, RT: 2.50 min, MI 281 [M+H] 
     Synthesis of 2-((S)-2-Dimethylamino-3-phenyl-propyl)-isoindole-1,3-dione [A012] 
     A mixture of 2-((S)-2-Amino-3-phenyl-propyl)-isoindole-1,3-dione [A011](200 mg, 0.71 mmol), formaldehyde (2 mL, xs) and formic acid (2 mL, xs) was heated to 100° C. for 2 hours. The reaction mixture was concentrated under vacuum then partioned between 2M K 2 CO 3  and DCM. The organic layer was washed with water then brine, passed through a phase separator and evaporated to yield the title compound [A012] (200 mg) which was used without further purification: LCMS method: 1, RT: 2.42 min, MI 309 [M+H] 
     Synthesis of (S)—N 2 ,N 2 -Dimethyl-3-phenyl-propane-1,2-diamine [A009] 
     A solution of 2-((S)-2-Dimethylamino-3-phenyl-propyl)-isoindole-1,3-dione [A012] (350 mg), hydrazine monohydrate (66.1 ul, 1.36 mmol) and methanol (50 mL) was stirred at room temperature for 20 hours. The solvent was removed under vacuum to yield a white solid. This was then partitioned between 10% citric acid and isopropanol. The aqueous layer was filtered, basified with 2M NaOH, extracted into isoropanol, washed with brine, passed through a phase separator and evaporated to yield title compound [A009] (93 mg): LCMS method: 1, RT: 0.53 min, MI 179 [M+H] 
     Synthesis of ((S)-1-Methylaminomethyl-2-phenyl-ethyl)-carbamic acid tert-butyl ester [A013] 
     
       
         
         
             
             
         
       
     
     Synthesis of Synthesis of Toluene-4-sulfonicacid(S)-2-tert-butoxycarbonylamino-3-phenyl-propyl ester [A014] 
     To a solution of Boc-L-phenylalaninol (0.5 g, 1.989 mmol) in DCM (10 mL) at 0° C. was added triethylamine (0.83 mL, 5.968 mmol). The reaction mixture was stirred at this temperature for 5 minutes. para-Toluenesufonyl chloride (2.188 mmol, 0.42 g) was added dropwise as a solution in DCM (5 mL), and the reaction mixture was allowed to warm up to room temperature slowly. The reaction mixture stirred at room temperature for 4 hours. The reaction mixture was diluted with DCM (20 mL) and washed with water. Layers separated and the organic layer dried over anhydrous magnesium sulphate. The DCM was evaporated to dryness under reduced pressure to afford the title compound [A014] as a clear oil (0.8 g). No further purification was carried out and the crude product was used immediately in the next step. 
     Synthesis of ((S)-1-Methylaminomethyl-2-phenyl-ethyl)-carbamic acid tert-butyl ester [A013] 
     Toluene-4-sulfonicacid(S)-2-tert-butoxycarbonylamino-3-phenyl-propyl ester [A014](0.80 g, 1.973 mmol) was dissolved in THF (10 mL) and methyl amine (2N in THF, 10 mL) was added in one portion. The reaction mixture was stirred at 60° C. overnight. The mixture was diluted with ethyl acetate and washed with brine. The layers were separated and the ethyl acetate dried over anhydrous magnesium sulphate. The solvent was removed under reduced pressure to afford the title compound [A013] as a clear oil. No further purification was carried out at this stage. Crude material was used directly in subsequent reactions without further purification. 
     Synthesis of (2S,4S)-4-Amino-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester [A015] 
     
       
         
         
             
             
         
       
     
     Synthesis of (2S,4R)-4-Methanesulfonyloxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester [A016] 
     N-Boc-trans-4-hydroxy-L-proline methyl ester (12.28 mmol, 3 g), was dissolved in DCM (30 mL) and triethylamine (13.45 mmol, 1.87 mL) was added. The reaction was cooled to 0° C. and methanesulfonyl chloride (24.46 mmol, 1.89 mL) was added dropwise over 5 minutes. The reaction mixture was allowed to stir at this temperature for 45 minutes and then warmed to room temperature for 2 hours. Brine was added and the layers were separated, the aqueous was extracted with dichloromethane (×2). The organics were washed with brine (×1), dried with MgSO 4 , filtered and evaporated to yield the title compound as a clear oil (3.95 g): NMR (1H, 300 MHz, CDCl 3 ): 5.22 (m, 1H), 4.39 (m, 1H), 3.74 (s, 3H), 3.73 (m, 2H), 3.65 (s, 3H), 3.07 (s, 3H), 2.51 (m, 1H), 2.22 (m, 2H), 1.41 (d, 9H) 
     Step 2: Synthesis of (2S,4S)-4-Azido-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester [A017] 
     (2S,4R)-4-Methanesulfonyloxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester [A016](12.28 mmol, 3.95 g), was dissolved in anhydrous DMF (20 mL) and sodium azide (61.14 mmol, 3.97 g) was added in one portion. The reaction was heated to 80° C. for 3 hours. Upon cooling the reaction mixture was quenched with water and extracted with ethyl acetate (×3). The organics were washed with brine, dried with MgSO 4 , filtered and evaporated to a colourless oil. Purified by flash column chromatography using 0 to 40% EtOAc/cyclohexane to yield the title compound [A017] (2.24 g): NMR (1H, 300 MHz, CDCl 3 ): 4.36 (m, 1H), 4.13 (m, 1H), 3.74 (s, 3H), 3.67 (m, 1H), 3.48 (dt, 1H), 2.47 (m, 1H), 2.14 (m, 2H), 1.43 (d, 9H) 
     Synthesis of (2S,4S)-4-Amino-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester [A015] 
     Water (5 mL) was added to a stirred solution of (2S,4S)-4-azido-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester [A017](4.44 mmol, 1.2 g) and triphenylphosphine (9.32 mmol 2.45 g), in toluene (40 mL) and the reaction was heated to 60° C. overnight. Upon cooling water was added and the layers separated. The aqueous was basified with 2M NaOH added and extracted twice with ethyl acetate, the organics combined, dried over anhydrous MgSO 4 , filtered and concentrated in vacuo to give the title compound (200 mg): NMR (1H, 300 MHz, CDCl 3 ): 4.20 (m, 1H), 3.71 (s, 3H), 3.62 (m, 1H), 3.50 (m, 1H), 3.22 (m, 1H), 2.43 (m, 1H), 1.78 (m, 1H), 1.43 (d, 9H) 
     Synthesis of ((1R,2R)-1-Aminomethyl-2-fluoro-2-phenyl-ethyl)-carbamic acid tert-butyl ester [A018] 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Synthesis of ((1R,2R)-2-Hydroxy-1-hydroxymethyl-2-phenyl-ethyl)-carbamic acid tert-butyl ester [A019] 
     (1R,2R)-(−)-2-Amino-1-phenyl-propane-1,3-diol (5.98 mmol, 1.0 g) was dissolved in methanol (10 mL) and cooled to 0° C. A solution of di-tert-butyl dicarbonate in methanol (4 mL) was added and the reaction was warmed to room temperature and stirred for 2 hours. The solvent was removed in vacuo and the product was purified by flash chromatography eluting with 0 to 70% EtOAc/cyclohexane to yield the title compound [A019] (1.20 g): NMR (1H, 300 MHz, CDCl 3 ): 7.29 (m, 5H), 5.19 (m, 1H), 4.96 (m, 1H), 3.35 (m, 1H), 2.66 (m, 1H), 1.33 (s, 9H); LCMS method: 1, RT: 4.35 min, MI: no trace. 
     Synthesis of ((1R,2R)-2-Hydroxy-1-hydroxymethyl-2-phenyl-ethyl)-carbamic acid tert-butyl ester [A020] 
     
       
         
         
             
             
         
       
     
     Allyl chloroformate (11.222 mmol, 1.35 g) was added dropwise to a stirred solution of ((1R,2R)-2-Hydroxy-1-hydroxymethyl-2-phenyl-ethyl)-carbamic acid tert-butyl ester [A019](1.20 g, 4.48 mmol) and pyridine (15.711 mmol, 1.27 mL) in DCM (50 mL) at 0° C. The reaction was allowed to warm to room temperature and stirred for an hour. Water was added and the layers separated. The aqueous was extracted twice with DCM. The organics were combined, washed with brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography using 0 to 100% EtOAc/cyclohexane to yield the title compound [A020] (0.93 g): NMR (1H, 300 MHz, CDCl 3 ): 7.28 (m, 5H), 5.91 (m, 1H), 5.34 (d, 1H), 5.27 (d, 1H), 4.99 (m, 1H), 4.84 (t, 1H), 4.61 (d, 2H), 4.27 (dd, 1H), 4.07 (dd, 1H), 4.01 (m, 1H), 3.09 (bs, 1H), 1.33 (s, 9H); LCMS: LC-MS17QC 94% 352+[M+H]5.17 min 
     Synthesis of Carbonic acid allyl ester (2R,3R)-2-tert-butoxycarbonylamino-3-phenyl-3-(tetrahydro-pyran-2-yloxy)-propyl ester [A021] 
     
       
         
         
             
             
         
       
     
     A solution of ((1R,2R)-2-Hydroxy-1-hydroxymethyl-2-phenyl-ethyl)-carbamic acid tert-butyl ester [A020](1.42 mmol, 0.50 g) and DIPEA (4.97 mmol 0.865 mL) in DCM (20 mL) was added dropwise to a solution of (diethylamino)sulfur trifluoride (DAST) (4.97 mmol, 0.610 mL) at −78° C. under nitrogen. The reaction was slowly warmed to room temperature and stirred for 2 hours. Water was added then extracted twice with DCM. The organics were combined, washed with brine, dried over anhydrous MgSO 4 , filtered and concentrated in vacuo to yield the title compound [A021] which was used directly in the next step without further purification: LCMS method: 1, RT: 3.27 min, MI not seen. 
     Synthesis of ((1R,2R)-2-Fluoro-1-hydroxymethyl-2-phenyl-ethyl)-carbamic acid tert-butyl ester [A022] 
     
       
         
         
             
             
         
       
     
     To a solution of carbonic acid allyl ester (2R,3R)-2-tert-butoxycarbonylamino-3-fluoro-3-phenyl-propyl ester [A021](2.0 mmol, 0.71 g) in anhydrous THF (15 mL) under nitrogen, was added tetrakis(triphenylphosphine)palladium(0) (0.08 mmol 0.093 g) and morpholine (3.014 mmol, 0.26 mL). The reaction was stirred at rt for 1 h under a nitrogen atmosphere. Brine was added and the mixture extracted twice with ethyl acetate. The organics were combined, dried over MgSO 4 , filtered and concentrated in vacuo. The product was purified by flash chromatography using 0 to 10% MeOH/DCM to yield the title compound [A022] (0.19 g): NMR (1H, 300 MHz, CDCl 3 ): 7.32 (m, 5H), 5.68 (d, 1H), 5.11 (m, 1H), 3.99 (m, 1H), 3.86 (m, 1H), 3.67 (m, 1H), 1.39 (s, 9H) 
     Synthesis of [(1R,2R)-1-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-2-fluoro-2-phenyl-ethyl]-carbamic acid tert-butyl ester [A023] 
     
       
         
         
             
             
         
       
     
     A solution of ((1R,2R)-2-Fluoro-1-hydroxymethyl-2-phenyl-ethyl)-carbamic acid tert-butyl ester [A022](0.705 mmol, 0.19 g), triphenylphosphine (0.988 mmol, 0.259 g) and phthalimide (0.988 mmol, 0.145 g) was cooled to 0° C. and diisopropyl azodicarboxylate (DIAD) (0.988 mmol, 0.193 mL) was added dropwise. The reaction was allowed to warm to room temperature and stirred for 1 hour. The solvent was removed in vacuo and the residue was dissolved in DCM. 2M NaOH (aqueous solution) was added and the layers separated using a phase separator. The organic was concentrated in vacuo. The product was purified by flash chromatography using 0 to 30% EtOAc/cyclohexane to yield the title compound [A023] (0.28 g): 1LCMS1; 98%, 399.15+[M+H]+, 5.45 min; NMR (1H, 300 MHz, CDCl 3 ): 7.80 (m, 2H), 7.65 (m, 2H), 7.40 (m, 4H), 7.31 (m, 1H), 5.72 (dd, 1H), 5.06 (d, 1 h), 4.47 (m, 1H), 3.83 (dd, 1H), 3.57 (dd, 1H), 1.20 (s, 9H) 
     Synthesis of ((1R,2R)-1-Aminomethyl-2-fluoro-2-phenyl-ethyl)-carbamic acid tert-butyl ester [A018] 
     
       
         
         
             
             
         
       
     
     [(1R,2R)-1-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-2-fluoro-2-phenyl-ethyl]-carbamic acid tert-butyl ester [A023](0.705 mmol, 0.28 g) was dissolved in methanol (5 mL) and Hydrazine monohydrate (0.916 mmol, 0.045 mL) was added. The reaction was stirred at room temperature for 1 hour then at 60° C. overnight. Upon cooling the solvent was removed in vacuo and the residue dissolved in DCM. 2M NaOH (aqueous solution) was added and the mixture extracted twice. The organics were combined, dried over anhydrous MgSO 4 , filtered and concentrated in vacuo. The product was purified using an SCX-2 cartridge, applying the crude material as a DCM solution and washing with methanol and DCM. The material was then washed off the SCX-2 cartridge by washing with ammonia (2N in methanol) and the ammonia washes concentrated in vacuo to yield the title compound [A018] (0.12 g): NMR (1H, 300 MHz, CDCl 3 ): 7.34 (m, 5H), 5.62 (d, 1H), 5.19 (d, 1H), 3.89 (m, 1H), 2.83 (m, 2H), 1.40 (s, 9H) Synthesis of 2-Fluoromethyl-piperazine [A024] 
     
       
         
         
             
             
         
       
     
     (1,4-Dibenzyl-piperazin-2-yl)-methanol [A026] 
     A solution of 1,4-Dibenzyl-piperazine-2-carboxylic acid ethyl ester [A025](3.7 g, 10.9 mmol) in THF (10 mL) was added dropwise to a suspension of LiAlH 4  (2.24 g, 59 mmol) in THF (20 mL) at 0° C. The reaction was warmed to room temperature and stirred overnight. The reaction was diluted with ether, cooled to 0° C. and quenched with water (2.25 mL) and 2M NaOH (4.5 ml) and water (4.5 mL). The suspension was stirred for 15 mins and anhydrous MgSO4 was added and stirred for a further 15 mins. The white solid was filtered off (celite) and the solvent removed in vacuo. The product was purified by flash chromatography using 0 to 100% EtOAc/cyclohexane to give the title compound [A026](3.03 g, 94% yield). LCMS method: 1, RT: 2.16 min, MI 297.23 [M+H]; NMR (1H, 300 MHz, CDCl 3 ): 3.43 (m, 3H), 2.63 (m, 3H), 2.95 (m, 1H), 3.49 (m, 3H), 3.61 (d, 1H), 4.04 (dd, 2H), 7.31 (m, 10H) 
     1,4-Dibenzyl-2-fluoromethyl-piperazine [A027] 
     (1,4-Dibenzyl-piperazin-2-yl)-methanol [A026](1.09 g, 3.6 mmol) in DCM (5 mL) was added dropwise to a stirred solution of DAST (0.9 mL, 7.35 mmol) in DCM (10 mL) at 0° C. The reaction was warmed to room temperature and stirred overnight. Aqueous 2M NaOH (10 mL) was added the layers separated by phase seperator. The solvent was removed in vacuo and the product was purified by flash chromatography using 0 to 30% EtOAc/cyclohexane to give the title compound [A027](0.42 g, 38% yield). LCMS method: 1, RT: 5.88 min, MI 299.38 [M+H]; NMR (1H, 300 MHz, CDCl 3 ): 2.28 (m, 3H), 2.50 (m, 2H), 2.70 (m, 2H), 2.83 (m, 1H), 3.49 (m, 3H), 4.11 (d, 1H), 4.53 (ddd, 1H), 4.68 (ddd, 1H), 7.25 (m, 10H) 
     2-Fluoromethyl-piperazine [A024] 
     1,4-Dibenzyl-2-fluoromethyl-piperazine [A027](0.32 g, 1.07 mmol) was dissolved in DCE (10 mL) and 1-Chloroethyl chloroformate (0.35 mL, 3.21 mmol) was added. The reaction was heated to reflux overnight. Upon cooling the solvent was removed in vacuo and the intermediate dicarabamate was purified by flash chromatography eluting with 0 to 50% EtOAc/cyclohexane. The residue was dissolved in methanol (10 mL) and heated to reflux for 1 hour. The solvent was removed in vacuo to give the title compound [A024] which was used in the next step and used without further purification 
     Synthesis of Piperazin-2-yl-acetonitrile [A028] 
     
       
         
         
             
             
         
       
     
     (1,4-Dibenzyl-piperazin-2-yl)-acetonitrile [A029] 
     A solution of (1,4-Dibenzyl-piperazin-2-yl)-methanol [A026](1 g, 3.37 mmol) in DCM (10 mL) was added dropwise to a solution of thionyl chloride (0.32 mL, 4.4 mmol) in DCM (5 mL) and the reaction was stirred at room temperature overnight. The solvent was removed in vacuo and water was added. The aqueous was extracted with ether then bascified with saturated Na2CO3. This was extracted twice with DCM, dried over anhydrous MgSO4, filtered and concentrated in vacuo and used crude in the next step and used without further purification. 
     To a refluxing solution of KCN (0.244 g, 3.7 mmol) in water (10 mL) was added 1,4-Dibenzyl-2-chloromethyl-piperazine (0.91 g, 2.9 mmol) in ethanol (10 mL) dropwise. The reaction was heated to reflux for 3 hours. Upon cooling the solvent was removed in vacuo and the residue was taken up in DCM, washed with water, dried over MgSO4, filtered and concentrated in vacuo. The product was purified by flash chromatography using 0 to 40% EtOAc/cyclohexane, to give the title compound [A029](0.52 g, 59% yield). LCMS method: 1, RT: 2.87 min, MI 306.26 [M+H]; NMR (1H, 300 MHz, CDCl 3 ): 2.43 (m, 3H), 2.58 (m, 4H), 2.87 (dd, 1H), 3.00 (m, 1H), 3.48 (m, 3H), 3.80 (d, 1H), 7.28 (m, 10H). 
     Piperazin-2-yl-acetonitrile [A028] 
     (1,4-Dibenzyl-piperazin-2-yl)-acetonitrile [A029](0.52 g, 1.7 mmol) was dissolved in DCE (10 mL) and 1-Chloroethyl chloroformate (0.55 mL, 5.1 mmol) was added. The reaction was heated to reflux for 2 days. Upon cooling the solvent was removed in vacuo and the intermediate dicarabamate was purified by flash chromatography eluting with 0 to 40% EtOAc/cyclohexane. The residue was dissolved in methanol (10 ml) and heated to reflux for an hour. The solvent was removed in vacuo to give clean product. NMR (1H, 300 MHz, d6-dmso): 3.16 (m, 3H), 3.03 (t, 1H), 3.49 (m, 4H), 3.89 (m, 1H), 10.06 (m, 2H) 
     Synthesis of 2-Ethynyl-piperazine [A030] 
     
       
         
         
             
             
         
       
     
     Synthesis of (R)-2-Hydroxymethyl-piperazine-1,4-dicarboxylic acid di-tert-butyl ester [A031] 
     To a stirred solution of (R)-1-Boc-2-Hydroxymethyl-piperazine (1 g, 4.62 mmol) and Na 2 CO 3  (990 mg, 9.25 mmol) in a mixture of dioxane (8 ml) and water (2 ml) at 0 OC was added Di-tert-butyl dicarbonate and the reaction mixture warmed to room temperature. After 18 hours all solvents were removed in vacuo and the resulting residue partitioned between DCM and water. The DCM phase was passed through phase separation cartridge and evaporated to provide a white solid. Purification by column chromatography (0-50% EtOAc:cyclohexane) gave the title compound [A031] as a white solid (1.26 g, 86%). 1H-NMR (1H, 300 MHz, CDCl 3 ): 4.17 (2H, s, br), 3.93 (1H, s, br), 3.84 (1H, d, br), 3.59 (2H, s, br), 2.95 (3H, s, br), 1.46 (18H, s). 
     Synthesis of 2-Formyl-piperazine-1,4-dicarboxylic acid di-tert-butyl ester [A032] 
     A solution of oxalyl chloride (165 μl, 1.90 mmol) in DCM (5 ml) was cooled to −78° C. DMSO (270 μl, 3.79 mmol) was added dropwise and the reaction mixture stirred for 15 mins. A solution of (R)-2-Hydroxymethyl-piperazine-1,4-dicarboxylic acid di-tert-butyl ester [A031](500 mg, 0.58 mmol) in DCM (1 ml) was added dropwise and the reaction mixture stirred for 1 hour. Triethylamine (1.1 ml, 7.90 mmol) was added and the reaction mixture warmed to room temperature. Saturated NaHCO 3  was added, the layers separated and the organic phase collected and evaporated to give the title compound [A032] as a white powder (480 mg, 97%). 1H-NMR (1H, 300 MHz, CDCl 3 ): 9.58 (1H, s), 4.63-4.45 (2H, m, br), 3.95-3.79 (2H, m, br), 3.15-3.11 (2H, m, br), 2.88 (1H, d, br), 1.44 (18H, s). 
     Synthesis of 2-Ethynyl-piperazine-1,4-dicarboxylic acid di-tert-butyl ester [A033] 
     To a stirred solution of 2-Formyl-piperazine-1,4-dicarboxylic acid di-tert-butyl ester [A032](480 mg, 0.530 mmol) and K 2 CO 3  (425 mg, 3.06 mmol) in MeOH (20 ml) was added Dimethyl (1-diazo-2-oxopropyl)phosphonate (350 mg, 1.83 mmol). After 18 hours the solvent was removed in vacuo and the resulting residue partitioned (DCM:water). The organic phase was separated and concentrated to provide the title compound [A033] as a white solid (430 mg, 91%). 1H-NMR (1H, 300 MHz, CDCl 3 ): 4.88 (1H, s, br), 4.25-4.01 (2H, m, br), 3.80 (1H, d, br), 3.18 (1H, t, br), 3.02-2.74 (2H, m), 2.23 (1H, d), 1.47 (18H, s). 
     Synthesis of 2-Ethynyl-piperazine [A030] 
     2-Ethynyl-piperazine-1,4-dicarboxylic acid di-tert-butyl ester [A033](430 mg, 1.39 mmol) was stirred in 4N HCl:dioxane (1 ml) for 4 hours. A pale yellow solid (226 mg, 89%) was collected by filtration and washed with Et 2 O then dried in a vacuum oven at 40 OC to yield the title compound [A030]: 1H-NMR (1H, 300 MHz, d6-dmso): 4.57 (1H, dt), 4.04 (1H, d), 3.63 (1H, dd), 3.42-3.23 (5H, m). 
     Synthesis of 2-Benzyl-morpholine [A034] 
     
       
         
         
             
             
         
       
     
     Synthesis of 1-Chloro-3-phenyl-propan-2-ol [A035] 
     To a stirred solution of Phenyl magnesium bromide (3M in Et 2 O, 4.4 ml, 13 mmol) in Et 2 O (14 ml) at 0° C. was added CuI (210 mg, 1.08 mmol). Epichlorohydrin (1 g, 10.8 mmol) in Et 2 O (14 ml) was then added and the reaction mixture allowed to warm to room temperature then stirred for 2 hours. Sat. NH 4 Cl was added and the solution diluted with water then extracted with EtOAc (×2). The combined organics were washed with brine, dried over MgSO 4  and concentrated. Purification by column chromatography (0-20% Et 2 O:cyclohexane) provided the title compound [A035] as a colourless oil (1.66 g, 90%). 1H-NMR (1H, 300 MHz, CDCl 3 ): 7.36-7.22 (5H, m), 4.11-4.01 (1H, m), 3.59 (1H, dd), 3.50 (1H, dd), 2.90 (2H, d), 2.18 (1H, d). 
     Synthesis of 2-Benzyl-morpholine [A034] 
     To a stirred solution of NaOH (1.63 g, 40.8 mmol) in water 3.5 ml) was added 1-Chloro-3-phenyl-propan-2-ol [A035](1.16 g, 6.8 mmol) in MeOH (7 ml). After 5 min 2-Aminoethane hydrogen sulphate (3.84 g, 27.2 mmol) was added and the reaction mixture stirred at 40 OC for 2 hours. NaOH (powdered, 1.63 g, 40.8 mmol) and PhMe (18 ml) were then added and the reaction heated to 65° C. for 18 hours. Dilution with water (10 ml), was followed by extraction with PhMe (×2). The combined organics were washed (water then brine), dried and concentrated. Purification by column chromatography (0-10% MeOH:DCM) provided the title compound as a colourless oil (360 mg, 30%). 1H-NMR (1H, 300 MHz, CDCl 3 ): 7.31-7.19 (5H, m), 3.86 (1H, dd), 3.70-3.54 (2H, m), 2.92-2.77 (4H, m), 2.67-2.55 (2H, m). 
     Synthesis of (R)-2-(Fluoro-phenyl-methyl)-piperazine [A036] 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Synthesis of (R)-Piperazine-1,2,4-tricarboxylic acid 1,4-di-tert-butyl ester 2-methyl ester [A037] 
     To a stirred suspension of (R)-1-N-Boc-piperazine-2-carboxylic acid methyl ester hydrochloride (2 g, 7.12 mmol) and Na 2 CO 3  (2.26 g, 21.4 mmol) in dioxane (16 ml) and water (4 ml) at 0° C. was added Di-tert-butyl-dicarbonate (1.55 g, 7.12 mmol). After 18 hours all solvents were removed in vacuo and the resulting residue partitioned between DCM and water. The organic phase was collected and evaporated to give a colourless oil. Purification by column chromatography (0-30% EtOAc:cyclohexane) gave the title compound [A037] as a white powder (2.33 g, 95%). 1H-NMR (1H, 300 MHz, CDCl 3 ): 5.30 (1H, s), 4.72 (1H, s, br), 4.54 (1H, t, br), 4.08-3.80 (1H, m), 3.73 (3H, s), 3.27-2.73 (3H, m), 1.44 (18H, s). 
     Synthesis of (R)-Piperazine-1,2,4-tricarboxylic acid 1,4-di-tert-butyl ester [A038] 
     (R)-Piperazine-1,2,4-tricarboxylic acid 1,4-di-tert-butyl ester 2-methyl ester [A037](2.33 g, 6.77 mmol) and KOH (1.14 g, 20.3 mmol) were heated to reflux in EtOH (50 ml) for 18 hours. Having cooled to room temperature, solvents were removed in vacuo and the residue purified by column chromatography (0-10% MeOH:DCM; 0.1% TEA) to provide the title compound [A038] as a pale orange foam (2.1 g, 94%). 1H-NMR (1H, 300 MHz, CDCl 3 ): 4.66-4.50 (2H, m, br), 3.96-3.74 (2H, m, br), 3.47 (1H, s), 3.23 (1H, s, br), 2.85 (1H, s, br), 1.42 (18H, s). 
     Synthesis of (R)-2-(Methoxy-methyl-carbamoyl)-piperazine-1,4-dicarboxylic acid di-tert-butyl ester [A039] 
     (R)-Piperazine-1,2,4-tricarboxylic acid 1,4-di-tert-butyl ester [A038](2.10 g, 6.36 mmol), O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (2.9 g, 7.63 mmol), N,O-Dimethylhydroxylamine hydrochloride (750 mg, 7.63 mmol) and TEA (2.2 ml, 15.3 mmol) were stirred in DMA for 18 hours. The reaction mixture was then partitioned between EtOAc and NaOH (1M), and the aqueous phase re-extracted with EtOAc. The combined organics were dried over MgSO 4  and concentrated. Purification by column chromatography (0-50% EtOAc:cyclohexane) gave the title compound [A039] as a viscous pale yellow oil (2.15 g, 91%). 1H-NMR (1H, 300 MHz, CDCl 3 ): 5.30 (1H, s), 4.86-4.71 (1H, m), 4.47-4.32 (1H, m), 4.06-3.75 (2H, m), 3.85 (3H, s), 3.18 (3H, s), 3.18-2.85 (2H, m), 1.45 (9H, s), 1.42 (9H, s). LCMS method: 1, RT: 3.46 min, MI 374.26 [M+H]. 
     Synthesis of (R)-2-Benzoyl-Piperazine-1,4-Dicarboxylic Acid Di-Tert-Butyl Ester [A040] 
     To a stirred solution of (R)-2-(Methoxy-methyl-carbamoyl)-piperazine-1,4-dicarboxylic acid di-tert-butyl ester [A039](500 mg, 1.34 mmol) in THF at 0° C. was added Phenylmagnesium chloride solution (3.4 ml, 6.7 mmol, 2.0 M in THF) and the reaction mixture allowed to warm to room temperature. Having stirred for 4 hours the solution was quenched (1N NaOH) and solvents removed in vacuo. The residue was partitioned between DCM and Rochelles salt (10% aq.) and the organic phase separated and aqueous re-extracted with DCM. The combined organics were then dried (MgSO 4 ) and concentrated. Purification by column chromatography (0-50% EtOAc:cyclohexane) provided the title compound [A040] as a white solid (416 mg, 80%). 1H-NMR (1H, 300 MHz, CDCl 3 ): 7.89 (2H, s, br), 7.57 (1H, s, br), 7.47 (2H, s, br), 5.53 (0.6H, s, br), 5.35 (0.4H, s, br), 4.53-4.38 (1H, m, br), 4.06 (0.6H, m, br), 3.87-3.80 (1.4H, m, br), 3.67-3.53 (1H, m, br), 3.41-3.29 (1H, m, br), 2.94-2.81 (1H, m, br), 1.55-1.12 (19H, m, br); LCMS method: 1, RT: 3.75 min, MI 391.32 [M+H] 
     Synthesis of (R)-2-(Hydroxy-phenyl-methyl)-piperazine-1,4-dicarboxylic acid di-tert-butyl ester [A041] 
     To a stirred suspension of (R)-2-Benzoyl-piperazine-1,4-dicarboxylic acid di-tert-butyl ester [A040](220 mg, 0.553 mmol) in MeOH (4 ml) was added sodium borohydride (41 mg, 1.11 mmol). After 2 hours the reaction mixture was partitioned between EtOAc and water, the organic phase separated and concentrated in vacuo to give the title compound [A041] as a white crystalline solid (210 mg, 97%). 1H-NMR (1H, 300 MHz, CDCl 3 ): 7.43-7.26 (5H, m), 4.74 (1H, s, br), 4.31-3.65 (4H, m), 3.25-2.81 (3H, m), 1.55-1.46 (18H, m), 1.13 (1H, s, br); LCMS method: 1, RT: 3.86 min, MI 393.32 [M+H] 
     Synthesis of (R)-2-(Fluoro-phenyl-methyl)-piperazine-1,4-dicarboxylic acid di-tert-butyl ester [A042] 
     To a stirred solution of (R)-2-(Hydroxy-phenyl-methyl)-piperazine-1,4-dicarboxylic acid di-tert-butyl ester [A041](210 mg, 0.535 mmol) in CHCl 3  (3 ml) at 0 OC was added (Diethylamino)sulfur trifluoride (330 μl, 2.68 mmol). After 2 hours the reaction mixture was quenched with ice, basified with NaHCO 3  (to pH8), then the product extracted into DCM, which was evaporated to give a colourless oil. Purification was achieved by column chromatography (0-50% EtOAc:cyclohexane) to provide the title compound [A042] as a white solid (85 mg, 40%). 1H-NMR (1H, 300 MHz, CDCl 3 ): 7.34 (5H, m, br), 5.53 (1H, d, br), 4.38-3.84 (4H, m, br), 3.08-2.84 (3H, m, br), 1.49 (9H, s, br), 1.25 (9H, s, br); LCMS method: 1, RT: 3.68 min, MI 295.21 [M+H] 
     Synthesis of (R)-2-(Fluoro-phenyl-methyl)-piperazine [A036] 
     (R)-2-(Fluoro-phenyl-methyl)-piperazine-1,4-dicarboxylic acid di-tert-butyl ester [A042](85 mg, 0.215 mmol) was stirred in 4N HCl:dioxane (2 ml). After 2 hours the solution was dissolved in MeOH and loaded onto an SCX cartridge which was washed with MeOH followed by 2N NH 3 :MeOH. Evaporation provided the title compound [A036] as a yellow gum (35 mg, 83%). 1H-NMR (1H, 300 MHz, d4-MeOH): 7.49-7.43 (5H, m), 5.25 (1H, d), 3.85 (1H, dd), 3.79-3.726 (1H, m), 3.20-3.14 (2H, m), 3.00-2.82 (3H, m). 
     Synthesis of (4-Fluoro-phenyl)-(R)-piperazin-2-yl-methanol [A043] 
     
       
         
         
             
             
         
       
     
     Synthesis of (R)-2-(4-Fluoro-benzoyl)-piperazine-1,4-dicarboxylic acid di-tert-butyl ester [A044] 
     To a stirred solution of (R)-2-(Methoxy-methyl-carbamoyl)-piperazine-1,4-dicarboxylic acid di-tert-butyl ester [A043](1.15 g, 3.08 mmol) in THF (24 ml) was added 4-Fluorophenylmagnesium bromide solution (2.0M in Et 2 O, 7.7 ml, 15.4 mmol) and the reaction mixture allowed to warm to room temperature. Having stirred for 4 hours the reaction was quenched (1N NaOH) and solvents removed in vacuo. The residue was partitioned between DCM and Rochelles salt (10% aq). The organic phase was separated and aqueous phase re-extracted with DCM. Evaporation of the combined organics followed by purification by column chromatography (0-50% EtOAc:cyclohexane) gave the title compound [A044] as a pale yellow oil (800 mg, 64%). 1H-NMR (1H, 300 MHz, CDCl 3 ): 7.94 (2H, s, br), 7.15 (2H, s, br), 5.47 (1H, m, br), 4.48-4.32 (1H, m, br), 4.07-4.03 (1H, m, br), 3.91-3.76 (1H, m, br), 3.61-3.51 (1H, m, br), 3.43-3.31 (1H, m, br), 3.18-3.24 (1H, m, br), 1.56-1.17 (18H, m, br); LCMS method: 1, RT: 3.79 min, MI 409.32 [M+H] 
     Synthesis of (R)-2-[(4-Fluoro-phenyl)-hydroxy-methyl]-piperazine-1,4-dicarboxylic acid di-tert-butyl ester [A045] 
     To a stirred solution of (R)-2-(4-Fluoro-benzoyl)-piperazine-1,4-dicarboxylic acid di-tert-butyl ester [A044](520 mg, 1.28 mmol) in MeOH (8 ml) was added sodium borohydride at 0 OC and the reaction mixture allowed to warm to room temperature. After 2 hours the reaction mixture was partitioned between EtOAc and water, the organic phase separated and concentrated in vacuo to give a pale yellow oil. Purification by column chromatography (0-50% EtOAc:cyclohexane) provided the title compound [A045] as a white crystalline solid (330 mg, 63%). 1H-NMR (1H, 300 MHz, CDCl 3 ): 7.41-7.08 (5H, m), 4.74 (1H, m), 4.27-3.93 (3H, m), 3.64 (1H, m), 3.23-2.84 (1H, m), 1.45 (18H, m), 1.18 (1H, s, br). 
     Synthesis of (4-Fluoro-phenyl)-(R)-piperazin-2-yl-methanol [A043] 
     (R)-2-[(4-Fluoro-phenyl)-hydroxy-methyl]-piperazine-1,4-dicarboxylic acid di-tert-butyl ester [A045](330 mg, 0.808 mmol) was stirred in 4N HCl:dioxane (2 ml). After 2 hours the solution was dissolved in MeOH and loaded onto an SCX cartridge which was washed with MeOH followed by 2N NH 3 :MeOH. Evaporation provided the title compound [A043] as a yellow gum which was used without further purification (170 mg, 100%). 
     Synthesis of N—[(S)-1-Benzyl-2-(2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ylamino)-ethyl]-formamide [78] 
     
       
         
         
             
             
         
       
     
     A mixture of (S)-3-Phenyl-N 1 -(2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-propane-1,2-diamine [6](70 mg, 0.21 mmol) and ethylformate (1.5 mL, 18.6 mmol) was heated in the microwave at 100° C. for 1 hour. The reaction mixture was concentrated under vacuum, redissolved in methanol then loaded onto a methanol conditioned SCX-2 cartridge (5 g). The cartridge was washed with methanol (2ColVols) then eluted with 2N NH3 in methanol (2CV). The ammonia washes were evaporated to yield the title compound [78]: LCMS method: 1, RT: 3.87 min, MI 385 [M+H]; NMR: (1H, 300 MHz, d6-dmso) 9.17 (1H, s), 8.90-8.87 (1H, br t), 8.73 (2H, d), 8.63 (1H, d), 8.25 (2H, dd), 8.14 (1H, d), 8.04 (1H, br d), 7.97 (1H, br s), 7.327.20 (5H, m), 4.55-4.46 (1H, m), 3.98-3.90 (1H, m), 3.70-3.62 (1H, m), 3.00-2.93 (1H, dd), 2.85-2.77 (1H, dd) 
     Synthesis of N—[(S)-1-Benzyl-2-(2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ylamino)-ethyl]-acetamide [79] 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (S)-3-Phenyl-N 1 -(2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-propane-1,2-diamine [6](70 mg, 0.21 mmol), DIPEA (73 ul, 0.42 mmol) and anhydrous DCM (5 mL) at room temperature was added acetic anhydride (29 μl, 0.31 mmol). The reaction mixture was concentrated under vacuum then redissolved in methanol plus formic acid (2 drops) and loaded onto a methanol conditioned SCX-2 cartridge (5 g). The cartridge was washed with methanol (2CV) then eluted with 2N NH 3  in methanol (2CV). The ammonia washes were evaporated to yield the title compound [79]: LCMS method: 1, RT: 3.92 min, MI 399 [M+H]; NMR: (1H, 300 MHz, d6-dmso) 9.17 (1H, s), 8.85 (1H, br t), 8.72 (2H, dd), 8.63 (1H, d), 7.85 (1H, dd), 7.30-7.17 (5H, m), 4.43-4.33 (1H, m), 4.01-3.92 (1H, m), 3.63-3.55 (1H, m), 2.90 (1H, dd), 2.80 (1H, dd), 1.70 (3H, s) 
     Synthesis of methyl[(2S)-1-phenyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-2-yl]amine [80] 
     
       
         
         
             
             
         
       
     
     A stirred suspension of lithium aluminium hydride (19 mg, 0.5 mmol) in anhydrous THF (2.5 mL) was chilled to 0° C. N—[(S)-1-Benzyl-2-(2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ylamino)-ethyl]-formamide [78](40 mg, 0.1 mmol) in THF (2.5 mL) was added over five minutes. The reaction mixture was allowed to warm to room temperature and stirred for 18 h. A further portion of lithium aluminium hydride (10.5 mg, 0.28 mmol) was added to the reaction mixture and stirring continued at room temperature for 18 hours. Another portion of lithium aluminium hydride (30 mg, 0.79 mmol) was added to the reaction mixture and stirring continued at room temperature for a further 18 hours. This procedure was repeated on a second batch of N—[(S)-1-Benzyl-2-(2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ylamino)-ethyl]-formamide [78](40 mg, 0.234 mmol) and the crude reaction mixture combined and diluted with ether (20 mL), cooled to 0° C. and quenched by drop-wise addition of water (approx 150 μL), NaOH (approx 300 μL of a 2M solution) and water (approx 300 μL of a 2M solution) again. MgSO 4  was added and the mixture filtered and concentrated by rotary evaporation. The crude residue was purified by preparative HPLC (method A). The appropriate fractions were combined, the solvent evaporated and the residue was dissolved in MeOD resulting in precipitation of an impurity which was removed by filtration to give the title compound [80] (2.5 mg). LCMS method: 1, RT: 2.39 min, MI 371 [M+H].  1 H NMR (1H, 300 MHz, d6-dmso) 9.13 (1H, s), 8.64-8.62 (2H, m), 8.54 (1H, d), 8.21-8.19 (2H, m), 7.99 (1H, d), 7.32-7.21 (5H, m), 3.97-3.91 (1H, m), 3.78-3.71 (1H, m), 3.29-3.22 (1H, m), 3.05-2.99 (1H, m), 2.77-2.70 (1H, m). 
     Synthesis of (2S)-2-benzyl-4-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]-1-methylpiperazine; formic acid [81] 
     
       
         
         
             
             
         
       
     
     A stirred solution of 4-((S)-3-Benzyl-piperazin-1-yl)-5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine [30] in CH 2 Cl 2  (2 mL) was prepared. Paraformaldehyde (55 mg), acetic acid (6 mL, 0.121 mmol) and CNBH 3  (180 mg of MP-CNBH 3  with 2 mmol/g loading, 0.360 mmol) were added and the reaction was shaken at room temperature overnight. The resin was filtered off and the product was loaded onto a CSX cartridge, washing with methanol and eluting with ammonia in methanol. The ammonia fraction was concentrated and the residue purified then by prep LCMS. The appropriate fractions were combined and concentrated to give the title compound [81]. LCMS method: 1, RT: 2.74 min, MI 427.22 [M+H];  1 H NMR (1H, 300 MHz, CDCl 3 ) 8.95 (s, 1H), 8.73-8.71 (d, 2H), 8.29 (s, 1H), 8.13-8.11 (d, 2H), 8.06 (s, 1H), 7.37-7.35 (m, 3H), 7.22-7.19 (m, 2H), 4.28 (d, 1H), 4.07 (d, 1H), 3.82 (s, 3H), 3.72-3.63 (m, 1H), 3.34 (dd, 1H), 3.23-3.15 (m, 2H), 2.76-2.69 (m, 1H), 2.63 (s, 3H), 2.60-2.51 (m, 2H). 
     Synthesis of 2-{[(2S)-1-phenyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-2-yl]amino}acetamide [82] 
     
       
         
         
             
             
         
       
     
     A mixture of N-[(2S)-2-amino-3-phenylpropyl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine [6](100 mg, 0.28 mmol), 2-Bromoacetamide (38.5 mg, 0.28 mmol), and potassium carbonate (77.5 mg, 0.56 mmol) in DMF (5 mL) was stirred at room temperature for 3 days. A further portion of 2-Bromoacetamide (38.5 mg, 0.28 mmol) was added and the reaction mixture stirred for a further 24 h. The solvent was removed by rotary evaporation and the residue dissolved in methanol (2 mL), filtered then purified by preparative HPLC (method B). The appropriate fractions were combined, evaporated, triturated with diethyl ether and dried in the vac oven to give the title compound [82]: LCMS method: 1, RT: 4.49 min, MI 414 [M+H];  1 H NMR (1H, 300 MHz, d6-dmso) 9.16 (1H, s), 9.00 (1H, br m), 8.72-8.70 (2H, m), 8.64-8.62 (1H, m), 8.23-8.21 (1H, m), 8.10-8.08 (2H, m), 7.32-7.26 (5H, m), 7.03 (1H, br s), 3.89-3.81 (1H, m), 3.53-3.45 (1H, m). 
     Synthesis of N-(1-phenyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-2-yl)methanesulfonamide [83] 
     
       
         
         
             
             
         
       
     
     To a solution of N-[(2S)-2-amino-3-phenylpropyl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine [6](100 mg, 0.28 mmol) and DIPEA (98 mL, 0.56 mmol) in CH 2 Cl 2  (10 mL) at room temperature was added methane sulfonyl chloride (22 mL, 0.28 mmol). The reaction mixture was stirred at room temperature for 30 min, diluted with water and the organic phase separated, dried over MgSO 4  and purified by column chromatography on silica, eluting with CH 2 Cl 2  containing 0-10% Methanol. The appropriate fractions were combined and concentrated to give the title compound [83]: LCMS method: 1, RT: 4.04 min, MI 435 [M+H];  1 H NMR (1H, 300 MHz, d6-dmso) 9.18 (1H, s), 8.92 (1H, br t), 8.73-8.71 (2H, m), 8.65 (1H, d), 8.22-8.20 (2H, m), 8.16 (1H, d), 7.39 (1H, br s), 7.33-7.31 (4H, m), 7.30-7.24 (1H, m), 3.93-3.88 (2H, m), 3.69-3.61 (1H, m), 2.99-2.92 (1H, m), 2.83-2.76 (1H, m), 2.35 (3H, s). 
     Synthesis of (1-phenyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-2-yl)urea [84] 
     
       
         
         
             
             
         
       
     
     A mixture of N-[(2S)-2-amino-3-phenylpropyl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine [6](100 mg, 0.28 mmol), potassium cyanate (227 mg, 2.8 mmol), and acetic acid (4 mL) in water (4 mL) was stirred at 50° C. for 3 hours. A further portion of potassium cyanate (227 mg, 2.8 mmol) was added and the reaction mixture heated in a sealed tube in the microwave at 100° C. for 30 min. The reaction mixture was concentrated under vacuum then partitioned between ethyl acetate and water. The target material was found to partially precipitate on the internal surface of the separating funnel. This solid was collected and combined with the organic layer which was evaporated to dryness then dissolved in DMSO/Methanol (1 mL), the target material started to precipitate, water (2 mL) was added and the solid was collected by filtration then dried in the vac oven to give (the title compound [84]: LCMS method: 1, RT: 4.54 min, MI 398 [M+H];  1 H NMR (1H, 300 MHz, d6-dmso) 9.18 (1H, s), 8.99 (1H, br t), 8.74-8.72 (2H, m), 8.64 (1H, d), 8.28-8.25 (2H, m), 8.12 (1H, d), 7.32-7.19 (5H, m), 6.05 (1H, d), 5.48 (2H, s), 4.29-4.23 (1H, m), 3.88-3.80 (1H, m), 3.69-3.60 (1H, m), 2.94-2.88 (1H, m), 2.83-2.76 (1H, m). 
     Synthesis of 3-ethyl-1-(1-phenyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-2-yl)urea [85] 
     
       
         
         
             
             
         
       
     
     A solution of N-[(2S)-2-amino-3-phenylpropyl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine [6](100 mg, 0.28 mmol) and ethyl isocyanate (19 mg, 0.27 mmol) in CH 2 Cl 2  (5 mL) was stirred at room temperature for 1 h. The reaction mixture was concentrated by rotary evaporation and the residue purified by column chromatography on silica, eluting with CH 2 Cl 2  containing 0-10% MeOH. The appropriate fractions were combined, evaporated and the residue triturated with diethyl ether then dried in the vacuum oven to give the title compound [85]. LCMS method: 1, RT: 4.20 min, MI 428 [M+H];  1 H NMR (1H, 300 MHz, d6-dmso) 9.17 (1H, s), 8.94 (1H, br t), 8.74-8.72 (2H, m), 8.64 (1H, d), 8.28-8.24 (2H, m), 8.13 (1H, d), 7.32-7.20 (5H, m), 5.86 (1H, d), 5.79 (1H, t), 4.29-4.22 (1H, m), 3.90-3.83 (1H, m), 3.70-3.61 (1H, m), 2.94-2.77 (2H, m), 0.84 (3H, t). 
     Synthesis of (3aR)-5-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]-hexahydro-1H-[1,3]oxazolo[3,4-a]piperazin-1-one [86] 
     
       
         
         
             
             
         
       
     
     (R)-2-Benzyl-4-(5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A046] 
     To a solution of 2-Pyridin-4-yl-pyrido[2,3-d]pyrimidin-4-ol [A003](0.2 g, 0.78 mmol) in DMA 93 mL), 2,4,6-Triisopropylbenzenesulfonyl chloride (0.26 g, 0.86 mmol), Et 3 N (0.22 mL, 1.57 mmol) and DMAP (10 mg) were added successively. The mixture was stirred at rt for 2 h and (R)-2-Hydroxymethyl-piperazine-1-carboxylic acid tert-butyl ester (0.2 g, 0.94 mmol) was added. The reaction was stirred overnight and the solvent was removed under reduced pressure. The product was purified by flash chromatography using 0 to 8% MeOH/DCM to give the title compound [A046](0.14 g, 39% yield). LCMS method: 1, RT: 4.41 min, MI 453.27 [M+H]. 
     (3aR)-5-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]-hexahydro-1H-[1,3]oxazolo[3,4-a]piperazin-1-one [86] 
     A solution of (R)-2-Hydroxymethyl-4-(5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A046](20 mg, 0.044 mmol) in CH 2 Cl 2  was added drop-wise to a stirred solution of DAST (11 mL, 0.088 mmol) in CH 2 Cl 2  (3 mL) at 0° C. The reaction mixture was warmed to room temperature and stirred overnight. Aqueous NaHCO 3  was added the organic phase separated, loaded onto a SCX cartridge, washed with MeOH and eluted with ammonia in methanol. The product was purified purified by preparative HPLC (method A). The appropriate fractions were combined and concentrated to give the title compound [86]: LCMS method: 1, RT: 2.95 min, MI 379 [M+H];  1 H, NMR (1H, 300 MHz, CDCl 3 ): 9.03 (s, 1H), 8.60 (d, 2H), 8.29 (d, 2H), 8.24 (s, 1H), 4.50 (m, 2H), 4.18 (d, 1H), 4.09 (m, 4H), 3.97 (dd, 1H), 3.31 (td, 1H), 3.16 (td, 1H), 3.10 (dd, 1H). 
     Example [87]: Synthesis of 2-{4-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazin-1-yl}acetonitrile [87] 
     
       
         
         
             
             
         
       
     
     To a stirred mixture of 1-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine [31](90 mg, 0.28 mmol) and NEt 3  (78 mL, 0.56 mmol) in DMA (2 mL) was added Chloroacetonitrile (26 mL, 0.42 mmol) and the mixture was stirred at room temperature overnight. The crude reaction mixture was diluted with water and extracted with CH 2 Cl 2  (2×5 mL), the organic extracts were combined washed with sat NaHCO 3  (2×10 mL) brine (10 mL) dried MgSO 4  filtered and evaporated to give a brown oil which was purified by SXC-2 ion exchange (1 g) to give the title compound [87] as a pale yellow solid (0.085 g, 90% yield). LCMS method: 1, RT: 4.90 min, MI 362 [M+H];  1 H NMR (1H, 300 MHz, CDCl 3 ): 9.02 (1H, s), 8.97-8.77 (2H, m), 8.36-8.34 (2H, m), 8.22 (s, 1H), 4.11 (3H, s), 3.81 (4H, br t), 3.65 (2H, s), 2.83 (4H, br t). 
     General Synthesis of 2-Substituted-Piperazine Derivatives of General Formula [F-008b] Scheme A2 
     2-substituted piperazine derivatives of general formula [F-008b] were prepared by the reaction of (R)-1,1-Dioxo-tetrahydro-2-oxa-1λ 6 -thia-5,7a-diaza-indene-5-carboxylic acid tert-butyl ester [A049] with a phenol in the presence of a strong base such as sodium hydride or potassium cyanide in a polar aprotic solvent such as DMF to give the 2-substituted piperazine derivatives of general formula [F-008a]. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release resin, followed by chromatographic purification. The N-Boc derivatives of general formula [F-008a] were deprotected under acidic conditions with a strong acid such as TFA, TCA, methanesulfonic acid, HCl or H 2 SO 4  in a solvent such as DCM, DCE, THF, EtOH or MeOH and the crude reaction product was purified by normal phase silica gel chromatography or reverse phase preparative HPLC to give the 2-substituted-piperazine derivatives of general formula [F-008b]. 
     
       
         
         
             
             
         
       
     
     Synthesis of (R)-2-Phenoxymethyl-piperazine [A047] 
     
       
         
         
             
             
         
       
     
     (R)-1-Oxo-tetrahydro-2-oxa-1λ 4 -thia-5,7a-diaza-indene-5-carboxylic acid tert-butyl ester [A048] 
     A solution of (R)-3-Hydroxymethyl-piperazine-1-carboxylic acid tert-butyl ester (5.00 g, 23.118 mmol) in CH 2 Cl 2  (330 mL) was prepared and cooled to 0° C. Imidazole (6.295 g, 92.472 mmol) and triethylamine (7.06 mL, 50.860 mmol) were added followed drop-wise addition of thionyl chloride (1.94 mL, 26.586 mmol) as a solution in CH 2 Cl 2  (20 mL) over 20 min. The reaction mixture was allowed to warm to room temperature (ice bath not removed) and the reaction mixture stirred at room temperature for 3 days. The reaction mixture was diluted with water (250 mL) and the organic phase separated. The aqueous phase was extracted with CH 2 Cl 2  (3×50 mL) and the combined organic portions dried over MgSO 4 , filtered and concentrated by rotary evaporation. The residue was purified by chromatography on silica, eluting with cyclohexane containing 0-50% EtOAc. The appropriate fractions were combined and concentrated to give the title compound [A048](5.196 g, 86%) as a pale yellow oil that solidified on standing.  1 H NMR (1H, 400 MHz, d6-dmso) 4.81 (1H, dd), 4.58 (1H, dd), 4.44 (1H, dd), 4.28 (1H, br d), 4.12 (1H, br d), 4.02 (1H, br d), 3.93-3.87 (2H, m), 3.67-3.56 (2H, m), 3.46-3.34 (2H, m), 3.14-3.06 (1H, d), 3.01-2.69 (4H, br m), 2.55 (1H, dt), 1.42 (s, 9H), 1.41 (s, 9H). 
     (R)-1,1-Dioxo-tetrahydro-2-oxa-1λ 6 -thia-5,7a-diaza-indene-5-carboxylic acid tert-butyl ester [A049] 
     A stirred solution of (R)-1-Oxo-tetrahydro-2-oxa-1λ 4 -thia-5,7a-diaza-indene-5-carboxylic acid tert-butyl ester [A048](2.99 g, 11.409 mmol) in anhydrous MeCN (25 mL) was prepared under nitrogen and cooled to 0° C. Sodium (meta)periodate (2.464 g, 11.523 mmol) was added followed by ruthenium (III) chloride hydrate (24 mg, 0.114 mmol) (reaction mixture turns brown) and water (25 mL). The reaction mixture was stirred at 0° C. for 10 min and then removed from ice bath and stirred at room temperature for 10 min. TLC shows complete conversion to a new, slightly more polar spot. The reaction mixture was diluted with sat. NaHCO 3  (aq) (100 mL) and extracted with CH 2 Cl 2  (3×40 mL). The combined organic extracts were dried and concentrated by rotary evaporation. The residue was purified by chromatography on silica, eluting with cyclohexane containing 0-50% EtOAc to give the title compound [A049](1.72 g, 54%) as a pale yellow solid.  1 H NMR (1H, 500 MHz, CDCl 3 ) 4.63 (1H, dd), 4.25-4.07 (3H, overlapping t and broad m), 3.67-3.61 (1H, m), 3.45 (1H, br. d, J=11.2 Hz), 3.13 (1H, br. s), 2.98-2.94 (2H, br. m), 1.47 (9H, s). 
     (R)-3-Phenoxymethyl-piperazine-1-carboxylic acid tert-butyl ester [A050] 
     A solution of (R)-1,1-Dioxo-tetrahydro-2-oxa-1λ 6 -thia-5,7a-diaza-indene-5-carboxylic acid tert-butyl ester [A049](200 mg, 0.719 mmol) in anhydrous DMF (5 mL) was prepared under nitrogen. Sodium phenolate (88 mg, 0.754 mmol) was added and the reaction mixture heated to 50° C. overnight. A further 0.25 equivalents of sodium phenolate was added and heating continued for a further 5 hours. The reaction mixture was cooled to room temperature and 2 mL of 2M HCl (aq) was added. The mixture was stirred at room temperature for 1 hour. The reaction mixture was loaded onto a 10 g SCX cartridge, washing with methanol and eluting with 7N ammonia in MeOH. The ammonia fractions were combined and concentrated under reduced pressure. The residue was purified by chromatography on silica, eluting with CH 2 Cl 2  containing 0-10% MeOH. The appropriate fractions were combined and concentrated to give the title compound [A00?](75 mg, 36%) as a colourless oil. LCMS method: 1, RT: 2.85 min, MI 293 [M+H];  1 H NMR (1H, 500 MHz, CDCl 3 ) 7.31-7.24 (2H, m), 6.97 (1H, t), 6.91 (2H, d), 4.05 (1H, br s), 3.97-3.95 (2H, m), 3.88-3.85 (1H, m), 3.09 (1H, br s), 3.04-3.01 (1H, br m), 2.96-2.91 (1H, br m), 2.83-2.74 (1H, br m), 2.74 (1H, br s), 2.14 (1H, br s) 1.48 (9H, s). 
     (R)-2-Phenoxymethyl-piperazine [A047] 
     A solution of (R)-3-Phenoxymethyl-piperazine-1-carboxylic acid tert-butyl ester [A050](98 mg, 0.332 mmol) in anhydrous dioxane (1 mL) was prepared and 4M HCl in dioxane (5 mL) was added. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated by rotary evaporation to give a pale pink solid. The product was dissolved in MeOH and loaded onto a SCX cartridge, washing with MeOH and eluting with 7N ammonia in MeOH. The ammonia fraction was concentrated by rotary evaporation to give the title compound [A047](58 mg, 91%) as a pale oil that crystalised on standing. LCMS method: 1, RT: 0.56 min, MI 193 [M+H];  1 H NMR (1H, 500 MHz, CDCl 3 ) 7.30-7.27 (2H, m), 6.97-6.94 (1H, m), 6.91-6.90 (2H, m), 3.92-3.90 (1H, m), 3.83-3.83 (1H, m), 3.17-3.12 (1H, m), 3.07-3.03 (2H, m), 2.99-2.96 (1H, m), 2.92-2.87 (1H, m), 2.84-2.79 (1H, m) 2.63 (1H, dd). 
     Synthesis of (R)-2-(2-Fluoro-phenoxymethyl)-piperazine [A051] 
     
       
         
         
             
             
         
       
     
     (R)-3-(2-Fluoro-phenoxymethyl)-piperazine-1-carboxylic acid tert-butyl ester [A052] 
     A suspension of sodium hydride (69 mg, 1.726 mmol) in anhydrous DMF (5 mL) was prepared and 2-fluorophenol (0.15 mL, 1.726 mmol) added dropwise. The reaction mixture was stirred at room temperature for 10 min then (R)-1,1-Dioxo-tetrahydro-2-oxa-1λ 6 -thia-5,7a-diaza-indene-5-carboxylic acid tert-butyl ester [A051](400 mg, 1.438 mmol) was added. The reaction mixture was heated to 50° C. overnight. The reaction mixture was cooled to room temperature and 2M HCl (aq) (1.4 mL, 2.875 mmol) was added. The reaction mixture was stirred at room temperature for 1.5 h. The reaction mixture was loaded onto a SCX cartridge, washing with methanol and eluting with 7N ammonia in MeOH. The ammonia fractions were combined and concentrated by rotary evaporation. The residue was purified by chromatography on silica, eluting with CH 2 Cl 2  containing 0-10% MeOH. The appropriate fractions were combined and concentrated to give the title compound [A052](318 mg, 71%) as a colourless oil. LCMS method: 1, RT: 2.92 min, MI 311 [M+H];  1 H NMR (1H, 500 MHz, CDCl 3 ) 7.10-7.04 (2H, m), 6.99-6.91 (2H, m), 4.04-3.89 (4H, m and overlapping br s), 3.14-3.11 (1H, m), 3.03 (1H, br d), 2.96 (1H, br t), 2.83-2.79 (1H, m), 2.75 (1H, br s), 2.23 (1H, br s), 1.48 (9H, s). 
     (R)-2-(2-Fluoro-phenoxymethyl)-piperazine [A051] 
     Following the procedure described in scheme A2, (R)-3-(2-Fluoro-phenoxymethyl)-piperazine-1-carboxylic acid tert-butyl ester [A052](310 mg, 1.00 mmol) was treated with 4M HCl in dioxane (2 mL) to give the title compound [A051](196 mg, 93%) as a pale yellow oil. LCMS method: 1, RT: 0.75 min, MI 211 [M+H]; LCMS method 1LCMS5, RT: 0.75 min, MI: 211 [M+1].  1 H NMR (1H, 500 MHz, CDCl 3 ) 7.10-7.03 (2H, m), 6.98-6.89 (2H, m), 4.00-3.97 (1H, m), 3.91-3.88 (1H, m), 3.23-3.18 (1H, m), 3.08-3.03 (2H, m), 3.00-2.98 (1H, m), 2.94-2.89 (1H, m), 2.85-2.80 (1H, m), 2.66-2.61 (1H, m). 
     Synthesis of (R)-2-(4-Fluoro-phenoxymethyl)-piperazine [A053] 
     
       
         
         
             
             
         
       
     
     (R)-3-(4-Fluoro-phenoxymethyl)-piperazine-1-carboxylic acid tert-butyl ester [A054] 
     Following the procedure described in Scheme A2 step 1, (R)-1,1-Dioxo-tetrahydro-2-oxa-1λ 6 -thia-5,7a-diaza-indene-5-carboxylic acid tert-butyl ester [A048](400 mg, 1.438 mmol) was reacted with 4-fluorophenol (193 mg, 1.726 mmol) to give the title compound [A054](100 mg, 22%) as a colourless oil. LCMS method: 1, RT: 3.00 min, MI 311 [M+H].  1 H NMR (1H, 500 MHz, CDCl 3 ) 6.99-6.96 (2H, m), 6.85-6.83 (2H, m), 4.06 (1H, br s), 3.95 (1H, br s), 3.95-3.90 (1H, m), 3.84-3.80 (1H, m), 3.10-3.05 (1H, m), 3.03 (1H, br d), 2.93 (1H, br t), 2.83-2.78 (1H, m), 2.72 (1H, br s), 2.10 (1H, br s), 1.48 (9H, s). 
     (R)-2-(4-Fluoro-phenoxymethyl)-piperazine [A053] 
     Following the procedure described in example Scheme A2, step 4, (R)-3-(4-Fluoro-phenoxymethyl)-piperazine-1-carboxylic acid tert-butyl ester [A054](100 mg, 0.322 mmol) was treated with 4M HCl in dioxane (2 mL) to give the title compound [A053](68 mg, 100%) as a colourless oil that solidified on standing. LCMS method: 1, RT: 0.59 min, MI 211 [M+H];  1 H NMR (1H, 500 MHz, CDCl 3 ) 6.99-6.95 (2H, m), 6.85-6.82 (2H, m), 3.88-3.86 (1H, m), 3.81-3.78 (1H, m), 3.15-3.10 (1H, m), 3.05-3.02 (2H, m), 2.98-2.96 (1H, m), 2.91-2.86 (1H, m), 2.83-2.78 (1H, m), 2.63-2.58 (1H, m). 
     Synthesis of (S)-Piperazin-2-yl-acetonitrile [A055] 
     
       
         
         
             
             
         
       
     
     (S)-3-Cyanomethyl-piperazine-1-carboxylic acid tert-butyl ester [A056] 
     Following the procedure described in Scheme A1, step 3, (R)-1,1-Dioxo-tetrahydro-2-oxa-1λ 6 -thia-5,7a-diaza-indene-5-carboxylic acid tert-butyl ester [A048](1.52 g, 5.46 mmol) was reacted with KCN (356 mg, 5.46 mmol) to give the title compound [A056](850 mg, 69%).  1 H NMR (1H, 500 MHz, CDCl 3 ) 3.95 (1H, br s), 3.84 (1H, br d), 3.03-2.92 (3H, m), 2.82-2.75 (1H, m), 2.70 (1H, br s), 2.51-2.41 (2H, m), 1.49 (9H, s). LCMS method: 1, RT: 1.39 min, MI 226 [M+H]. 
     (S)-Piperazin-2-yl-acetonitrile [A055] 
     Following the procedure described in example Scheme A2, step 4, (S)-3-Cyanomethyl-piperazine-1-carboxylic acid tert-butyl ester [A056](800 mg, 3.55 mmol) was treated with 4M HCl in dioxane to give the title compound [A055](434 mg, 98%) as a pale orange solid. LCMS method: 1, RT: 0.49 min, MI 126 [M+H];  1 H NMR (1H, 500 MHz, CDCl 3 ) 3.06-2.99 (3H, m), 2.93-2.90 (1H, m), 2.87-2.82 (1H, m), 2.77-2.72 (1H, m), 2.56-2.51 (1H, m), 2.44-2.42 (2H, m). 
     Synthesis of Phenyl-(S)-piperidin-3-yl-amine [A057] 
     
       
         
         
             
             
         
       
     
     (S)-3-Phenylamino-piperidine-1-carboxylic acid tert-butyl ester [A058] 
     A solution of (S)-3-Amino-piperidine-1-carboxylic acid tert-butyl ester (500 mg, 2.497 mmol), Pd2(dba)3 (95 mg, 0.104 mmol) and 2-Dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (61 mg, 0.156 mmol) in toluene (5 mL) was prepared under nitrogen. The solvent was degasses and sodium tert-butoxide (280 mg, 2.912 mmol) was added followed by bromobenzene (0.22 mL, 2.080 mmol). The reaction mixture was heated to 100° C. for 24 h. The reaction mixture was cooled to room temperature and concentrated by rotary evaporation. The residue was filtered through a plug of silica, eluting with CH 2 Cl 2 . The eluent was concentrated by rotary evaporation. The crude residue was purified by chromatography on silica, eluting with cyclohexane containing 5-50% EtOAc. The appropriate fractions were combined and concentrated to give the title compound [A058](535 mg, 78%) as a pale yellow oil that solidified on standing. LCMS method: 1, RT: 5.51 min, MI 227 [M+H];  1 H NMR (1H, 500 MHz, CDCl 3 ) 7.20-7.17 (2H, m), 6.71 (1H, t), 6.64 (2H, d), 4.02 (1H, br s), 3.74-3.70 (1H, m), 3.63 (1H, br s), 3.39 (1H, br m), 3.09 (1H, br m), 2.89 (1H, br s), 2.02-1.99 (1H, m), 1.78-1.73 (1H, m), 1.59-1.51 (2H, m), 1.46 (9H, s). 
     Phenyl-(S)-piperidin-3-yl-amine [A057] 
     Following the procedure described in Scheme A2, step 4, (S)-3-phenylamino-piperidine-1-carboxylic acid tert-butyl ester [A058](138 mg, 0.5 mmol) was treated with 4 HCl in dioxane (2 mL) to give the title compound [A057](85 mg, 97%) as a pale yellow oil. LCMS method: 1, RT: 0.96 min, MI 177 [M+H]. 
     General Synthesis of 8-Substituted-1-Yl-2-Pyridin-4-Yl-Pyrido[3,4-d]Pyrimidine Derivatives of General Formula [F-011] Scheme A3 
     4-Substituted 8-Chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin derivatives of general formula [F-010] were prepared by the reaction of a 8-Chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol derivative of general formula [F-009] with 2,4,6-triisopropylbenzenesulfonyl chloride in a polar aprotic solvent such as DMA, DMF, NMP with a tertiary alkylamine base such as Et 3 N, DIPEA or NMM and a catalytic amount of DMAP. The intermediate 6,7-substituted-(2,4,6-triisopropyl-benzenesulfonic acid)-8-Chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidini-4-yl ester was then reacted with a primary or secondary amino derivative, of general formula [F-003], in a polar aprotic solvent such as DMA, DMF, NMP in the presence of a tertiary amine base such as Et 3 N, DIPEA or NMM at ambient temperature. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the crude reaction product was purified by normal phase chromatography or reverse phase preparative HPLC. The 4-Substituted 8-Chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin derivatives of general formula [F-010] were reacted in a Suzuki type reaction utilising a suitable boronic acid or boronic ester, of general formula [F-012], a palladium catalyst such as Pd(PPh 3 ) 4  or Pd(PPh 3 ) 2 Cl 2 a base such as Et 3 N, KOH, Na 2 CO 3  or NaOH in a polar solvent such as EtOH, THF, DMA or dioxane at high temperature either by heating thermally or using a microwave reactor. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, TCA, methanesulfonic acid, HCl or H 2 SO 4  in a solvent such as DCM, DCE, THF, EtOH or MeOH and the crude reaction product was purified by normal phase chromatography or reverse phase preparative HPLC. 
     
       
         
         
             
             
         
       
     
     Synthesis of N-{3-[4-((S)-2-Amino-3-phenyl-propylamino)-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-8-yl]-phenyl}-methanesulfonamide [88] 
     
       
         
         
             
             
         
       
     
     [(S)-1-Benzyl-2-(8-chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ylamino)-ethyl]-carbamic acid tert-butyl ester [A059] 
     To a solution of 2-Pyridin-4-yl-pyrido[2,3-d]pyrimidin-4-ol [A005](1 g, 3.8 mmol) in DMA (15 mL), 2,4,6-Triisopropylbenzenesulfonyl chloride (1.3 g, 4.25 mmol), Et 3 N (1.1 mL, 7.73 mmol) and DMAP (0.1 g) were added successively. The mixture was stirred at rt for 1 h then ((S)-2-Amino-1-benzyl-ethyl)-carbamic acid tert-butyl ester (1.16 g, 4.64 mmol) was added. The reaction was stirred overnight and the solvent was removed under reduced pressure and the crude mixture was purified by flash chromatography (SP1 [eluent: DCM/MeOH: 1/0 then 95/5 then 9/1]) to give the title compound: LCMS method: 1, RT: 5.76 min, MI 492 [M+H] 
     N-{3-[4-((S)-2-Amino-3-phenyl-propylamino)-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-8-yl]-phenyl}-methanesulfonamide [88] 
     A microwave vial was charged with [(S)-1-Benzyl-2-(8-chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ylamino)-ethyl]-carbamic acid tert-butyl ester [A059](0.07 g, 0.142 mmol), 3-(methanesulfonylamino)phenylboronic acid pinacol ester (0.06 g, 0.2 mmol), Pd(Ph3P) 4  (0.017 g, 0.014 mmol), aq K3PO4 (0.5M, 0.57 mL, 0.28 mmol) and DMA (1 mL). The vial was heated under microwave irradiations (150° C., 10 min). The solvent was removed under reduced pressure. The crude was purified by Column chromatography (Eluent: DCM/MeOH: 1:0 to 9/1). The purified compound was solubilised in DCM (2 mL) and TFA (0.5 mL) was added. The solution was stirred 3 h and then was poured onto SCX2 column, washed with MeOH and the expected product was released using a solution MeOH/NH3 2M which was used without further purification to give the title compound [88]: LCMS method: 1, RT: 3.01 min, MI 526 [M+H]; NMR 1H (1H, 300 MHz, d6-dmso) 8.70 (d, 2H), 8.68 (d, 1H), 8.25 (d, 2H), 8.14 (d, 1H), 8.04 (d, 2H), 7.37-7.24 (m, 7H), 3.91-3.86 (m, 1H), 3.46-3.33 (m, 2H), 3.10 (s, 3H), 2.77-2.69 (m, 2H). 
     The following compounds were synthesised according to the general synthesis shown in scheme [A3]: 
     
       
         
           
               
               
               
               
               
             
               
                   
               
               
                 Ex 
                 SM 
                 Boronic acid 
                 Analysis 
                 Name 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 89 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.01 min, MI: 423 [M + H] 
                 (1H, 300 MHz, d6-dmso) 8.76 ppm (2H, dd), 8.67 ppm (1H, d), 8.29 ppm (1H, s), 8.15 ppm (1H, d), 8.08 ppm (2H, dd), 7.71 ppm (1H, d), 7.61 ppm (1H, d), 7.41-7.30 ppm (5H, m), 3.97 ppm, (1H, d), 3.58 ppm (2H, br s), 3.35 ppm (2H, m), 2.97- 2.80 ppm (2H, m) 
                 N-[(2S)-2-amino-3- phenylpropyl]-8- (1H-pyrazol-5-yl)- 2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 90 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.62 min, MI: 433 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.47 ppm (1H, br s), 8.70 ppm (1H, d), 8.67 ppm (2H, dd), 8.42 ppm (1H, br s), 8.18-8.14 ppm (3H, m), 7.90 ppm (2H, dd), 7.57-7.46 ppm (3H, m), 7.42-7.31 ppm (5H, m), 3.99 ppm (1H, d), 3.67-3.51 ppm (2H, m), 3.01 ppm (1H, dd), 2.83 ppm (1H, dd) 
                 N-[(2S)-2-amino-3- phenylpropyl]-8- phenyl-2-(pyridin- 4-yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 91 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.93 min, MI: 449 [M + H] 
                 (1H, 300 MHz, d6-dmso), 8.85-8.85 ppm (1H, br s), 8.70 ppm (2H, d), 8.62 ppm (1H, d), 8.12 ppm (2H, d), 8.04 ppm (1H, d), 8.00 ppm (2H, d), 7.39- 7.27 ppm (5H, m), 6.91 ppm (2H, d), 3.97-3.86 ppm (1H, m), 3.54- 3.44 ppm (2H, m), 2.83 ppm (2H, br s) 
                 4-(4-{[(2S)-2- amino-3- phenylpropyl]- amino}-2-(pyridin- 4-yl)pyrido[3,4- d]pyrimidin-8- yl)phenol 
               
               
                   
               
               
                 92 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.00 min, MI: 449 [M + H] 
                 (1H, 300 MHz, d6-dmso), 8.73-8.69 ppm (3H, t), 8.16 ppm (1H, d), 8.04 ppm (2H, d), 7.64- 7.62 ppm (2H, m), 7.36-7.23 ppm (5H, m), 6.88 ppm (1H, dd), 3.88 ppm (1H, d), 3.46-3.30 ppm (2H, m), 2.77-2.74 ppm (2H, m) 
                 3-(4-{[(2S)-2- amino-3- phenylpropyl]- amino}-2-(pyridin- 4-yl)pyrido[3,4- d]pyrimidin-8- yl)phenol 
               
               
                   
               
               
                 93 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.16 min, MI: 463 [M + H] 
                 (1H, 300 MHz, d6-dmso), 8.65-8.63 ppm (3H, t), 8.19 ppm (1H, d), 7.87 ppm (2H, d), 7.48 ppm (1H, dt), 7.36-7.24 ppm (5H, m), 7.17 ppm (1H, d), 7.07 ppm (1H, t), 3.92-3.84 ppm (1H, dd), 3.61 ppm (3H, s), 3.44- 3.29 ppm (2H, m), 2.77-2.75 ppm (2H, m) 
                 N-[(2S)-2-amino-3- phenylpropyl]-8-(2- methoxyphenyl)-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 94 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.54 min, MI: 463 [M + H] 
                 (1H, 300 MHz, d6-dmso), 8.70 ppm (3H, d), 8.18 ppm (1H, d), 8.02 ppm (2H, d), 7.80- 7.76 ppm (2H, m), 7.45 ppm (1H, t), 7.34-7.24 ppm (5H, m), 7.07 ppm (1H, dd), 3.88 ppm (1H, d), 3.83 ppm (3H, s), 3.43- 3.33 ppm (2H, m), 2.77-2.73 ppm (2H, m) 
                 N-[(2S)-2-amino-3- phenylpropyl]-8-(3- methoxyphenyl)-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 95 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.56 min, MI: 463 [M + H] 
                 (1H, 300 MHz, d6-dmso), 8.70 ppm (2H, d), 8.65 ppm (1H, d), 8.24 (2H, d), 8.10 ppm (1H, d), 8.04 ppm (2H, d), 7.36-7.23 ppm (5H, m), 7.09 ppm (2H, d), 3.89- 3.84 ppm (1H, m), 3.85 ppm (3H, s), 3.44-3.30 ppm (2H, m), 2.74 ppm (2H, t) 
                 N-[(2S)-2-amino-3- phenylpropyl]-8-(4- methoxyphenyl)-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 96 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.46 min, MI: 467 [M + H] 
                 (1H, 300 MHz, d6-dmso) 8.69 ppm (2H, d), 8.63 ppm (2H, dd), 8.28 ppm (1H, d), 8.19- 8.16 ppm (1H, m), 8.01 ppm (1H, d), 7.84 ppm (2H, dd), 7.64- 7.60 ppm (1H, m), 7.36-7.23 ppm (5H, m), 3.92-3.84 ppm (1H, m), 3.44-3.25 ppm (2H, m), 2.76- 2.74 ppm (2H, m) 
                 N-[(2S)-2-amino-3- phenylpropyl]-8-(2- chlorophenyl)-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 97 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.69 min, MI: 473 [M + H] 
                 (1H, 300 MHz, d6-dmso): 8.68 (d, 3H), 8.48 (d, 1H), 8.18- 8.15 (m, 2H), 8.06 (d. 1H), 8.01 (d, 1H), 7.73 (d, 1H), 7.36-7.26 (m, 5H), 7.10 (d, 1H), 3.88 (d, 1H), 3.45-3.37 (m, 2H), 2.77-2.73 (m, 2H). 
                 N-[(2S)-2-amino-3- phenylpropyl]-8-(1- benzofuran-5-yl)-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 98 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.98 min, MI: 437 [M + H] 
                 (1H, 300 MHz, d6-dmso) 8.77 (s, 1H), 8.75 (d, 2H), 8.54 (d, 1H), 8.44 (s, 1H), 8.12 (d, 2H), 7.97 (d, 1H), 7.36-7.27 (m, 5H), 3.99 (s, 3H), 3.87 (d, 1H), 3.43-3.35 (m, 2H), 2.77-2.74 (m, 2H). 
                 N-[(2S)-2-amino-3- phenylpropyl]-8-(1- methyl-1H-pyrazol- 4-yl)-2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 99 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.58 min, MI: 434 [M + H] 
                 (1H, 300 MHz, d6-dmso): 9.33 (d, 1H), 8.73-8.66 (m, 3H), 8.51 (td, 1H), 8.21 (d, 1H), 7.98 (d, 2H), 7.57 (dd, 1H), 7.37-7.27 (m, 5H), 3.92-3.84 (m, 1H), 3.47- 3.38 (m, 2H), 2.78-2.76 (m, 2H). 
                 N-[(2S)-2-amino-3- phenylpropyl]-8- (pyridin-3-yl)-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 100 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.41 min, MI: 434 [M + H] 
                 (1H, 300 MHz, d6-dmso): 8.77-2.75 (m, 3H), 8.71 (d, 2H), 8.28 (d, 1H), 8.15 (d, 2H), 8.02 (d, 2H), 7.36-7.26 (m, 5H), 3.91- 3.86 (m, 1H), 3.46-3.36 (m, 2H), 2.78-2.73 (m, 2H). 
                 N-[(2S)-2-amino-3- phenylpropyl]-2,8- bis(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 101 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.90 min, MI: 479 [M + H] 
                 (1H, 300 MHz, d6-dmso): 8.75-8.73 (m, 3H), 8.54 (d, 1H), 8.49 (s, 1H), 8.11 (d, 2H), 7.98 (d, 1H), 7.35-7.25 (m, 5H), 4.07 (d, 2H), 3.88-3.84 (m, 1H), 3.43- 3.36 (m, 2H), 2.74-2.70 (m, 2H), 2.23-2.14 (m, 1H), 0.91 (d, 6H). 
                 N-[(2S)-2-amino-3- phenylpropyl]-8-[1- (2-methylpropyl)- 1H-pyrazol-4-yl]-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 102 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 4.05 min, MI: 466 [M + H] 
                   
                 N-[(2S)-2-amino-3- phenylpropyl]-8-(3- chlorophenyl)-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 103 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 4.08 min, MI: 467 [M + H] 
                 (1H, 300 MHz, d6-dmso) 8.72-8.62 (m, 3H), 8.35 (s, 1H), 8.23 (d, 2H), 8.19 (d, 1H), 7.94 (d, 2H), 7.62 (d, 2H), 7.39-7.32 (m, 5H), 4.02-3.94 (m, 1H), 3.59- 3.50 (m, 2H), 3.00-2.92 (m, 1H), 2.85-2.80 (m, 1H). 
                 N-[(2S)-2-amino-3- phenylpropyl]-8-(4- chlorophenyl)-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 104 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.72 min, MI: 437 [M + H] 
                 (1H, 300 MHz, d6-dmso): 8.72 (d, 2H), 8.72 (d, 1H), 8.22 (d, 1H), 8.04 (d, 2H), 7.61 (d, 1H), 7.35-7.23 (m, 5H), 7.09 (d, 1H), 4.02 (s, 3H), 3.90-3.85 (m, 1H), 3.44-3.33 (m, 2H), 2.75-2.71 (m, 2H). 
                 N-[(2S)-2-amino-3- phenylpropyl]-8-(1- methyl-1H-pyrazol- 5-yl)-2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 105 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 (1H, 300 MHz, d6-dmso): 8.68-8.74 (m, 3H), 8.38 (d, 1H), 8.35 (s, 1H), 8.22 (d, 1H), 7.96 (d, 2H), 7.32-7.40 (m, 6H), 6.98- 7.04 (m, 2H), 3.98 (d, 1H), 3.50- 3.58 (m, 2H), 2.95 (dd, 1H), 2.85 (dd, 1H). 
                 2-(4-{[(2S)-2- amino-3- phenylpropyl]amino}- 2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-8- yl)phenol 
               
               
                   
               
               
                 106 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 4.74 min, MI: 543 [M + H] 
                 (1H, 300 MHz, d6-dmso): 8.75 (d, 1H), 8.66 (d, 2H), 8.52 (s, 1H), 8.26-8.18 (m, 2H), 7.99 (d, 2H), 7.83 (d, 1H), 7.80 (s, 1H), 7.72 (d, 1H), 7.67 (t, 1H), 7.52 (t, 1H), 7.46 (d, 1H), 7.38- 7.30 (m, 5H), 4.00-3.92 (m, 1H), 3.58-3.52 (m, 2H), 2.91-2.86 (m, 2H). 
                 N-[(2S)-2-amino-3- phenylpropyl]-8-[3- (3-chlorophenyl)- phenyl]-2-(pyridin- 4-yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 107 
                 [A059] 
                   
                 Method 
                 (1H, 300 MHz, d6-dmso): 
                 N-[(2S)-2-amino-3- 
               
               
                   
                   
                   
                 1: RT: 
                 8.74 (d, 1H), 8.70 (d, 2H), 8.34 
                 phenylpropyl]-8-[4- 
               
               
                   
                   
                   
                 4.73 
                 )d, 2H), 8.27 (d, 2H), 8.18 (d, 
                 (4-chlorophenyl)- 
               
               
                   
                   
                   
                 min, 
                 1H), 8.01 (d, 2H), 7.88 (d, 2H), 
                 phenyl]-2-(pyridin- 
               
               
                   
                   
                   
                 MI: 543 
                 7.83 (d, 2H), 7.57 (d, 2H), 7.40- 
                 4-yl)pyrido[3,4- 
               
               
                   
                   
                   
                 [M + H] 
                 7.31 (m, 5H), 3.99-3.93 (m, 1H), 
                 d]pyrimidin-4- 
               
               
                   
                   
                   
                   
                 3.60-3.53 (m, 2H), 2.89-2.82 (m, 
                 amine 
               
               
                   
                   
                   
                   
                 2H). 
                   
               
               
                   
               
               
                 108 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.83 min, MI: 435 [M + H] 
                 (1H, 300 MHz, d6-dmso): 9.50 (s, 2H), 9.27 (s, 1H), 8.71 (d, 1H), 8.69 (d, 2H), 8.22 (d, 1H), 7.93 (d, 2H), 7.37-7.28 (m, 5H), 3.92-3.85 (m, 1H), 3.47-3.38 (m, 2H), 2.79-2.76 (m, 2H). 
                 N-[(2S)-2-amino-3- phenylpropyl]-2- (pyridin-4-yl)-8- (pyrimidin-5- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 109 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.43 min, MI: 448 [M + H] 
                 (1H, 300 MHz, d6-dmso): 8.69 (d, 2H), 8.65 (d, 1H), 8.13 (d, 1H), 8.04 (d, 2H), 7.38-7.26 (m, 7H), 7.17 (t, 1H), 6.68 (d, 1H), 5.16 (brs, 2H), 3.91-3.85 (m, 1H), 3.45-3.35 (m, 2H), 2.77-2.75 (m, 2H). 
                 N-[(2S)-2-amino-3- phenylpropyl]-8-(3- aminophenyl)-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 110 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 4.07 min, MI: 473 [M + H] 
                 (1H, 300 MHz, d6-dmso): 8.78 (d, 2H), 8.72 (d, 1H), 8.53 (s, 1H), 8.16 (d, 3H), 7.90 (d, 1H), 7.71 (d, 1H), 7.43 (t, 1H), 7.36-7.26 (m, 6H), 3.92-3.84 (m, 1H), 3.52-3.45 (m, 2H), 2.83-2.79 (m, 2H). 
                 N-[(2S)-2-amino-3- phenylpropyl]-8-(1- benzofuran-7-yl)-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 111 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 1.81 min, MI: 453 [M + H] 
                 (1H, d6-DMSO, 500 MHz) 8.67 (d, 2H), 8.30-8.16 (m, 1H), 8.01 (d, 2H), 7.36-7.24 (m, 7H), 6.82 (d, 1H), 3.86-3.73 (m, 1H), 2.75- 2.72 (m, 2H). 
                 N-[(2S)-2-amino-3- phenylpropyl]-8-(5- methylthiophen-2- yl)-2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 112 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.02 min, MI: 452 [M + H] 
                   
                 N-[(2S)-2-amino-3- phenylpropyl]-8- (dimethyl-1,2- oxazol-4-yl)-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 113 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.42 min, MI: 426 [M + H] C 
                 (1H, 300 MHz, d6-dmso): 8.99 (d, 1H), 8.71 (d, 2H), 8.58 (d, 1H), 8.44 (s, 1H), 8.03 (d, 1H), 7.96 (d, 2H), 7.82 (t, 1H), 7.39-7.29 (m, 5H), 4.00-3.94 (m, 1H), 3.68-3.48 (m, 2H), 303 (dd, 1H), 2.84 (dd, 1H). 
                 N-[(2S)-2-amino-3- phenylpropyl]-8- (furan-3-yl)-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 114 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.55 min, MI: 439 [M + H] 
                 (1H, 300 MHz, d6-dmso): 8.96 (d, 1H), 8.74 (d, 2H), 8.63 (d, 1H), 8.13-8.09 (m, 4H), 7.64 (d, (dd, 1H), 7.36-7.25 (m, 5H), 3.92- 3.85 (m, 1H), 3.45-3.36 (m, 2H), 2.76-2.71 (m, 2H). 
                 N-[(2S)-2-amino-3- phenylpropyl]-2- (pyridin-4-yl)-8- (thiophen-3- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 115 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.26 min, MI: 423 [M + H] 
                 (1H, 300 MHz, d6-dmso): 8.76 (d, 2H), 8.61 (d, 1H), 8.12- 8.06 (m, 3H), 7.95 (s, 1H), 7.36- 7.26 (m, 5H), 6.80-6.78 (m, 1H), 3.92-3.85 (m, 1H), 3.46-3.39 (m, 2H), 2.78-2.75 (m, 2H). 
                 N-[(2S)-2-amino-3- phenylpropyl]-8- (furan-2-yl)-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 116 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.23 min, MI: 473 [M + H] 
                   
                 N-[(2S)-2-amino-3- phenylpropyl]-8- (1H-1,3- benzodiazol-5-yl)- 2-(pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 117 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.72 min, MI: 477 [M + H] 
                   
                 N-[(2S)-2-amino-3- phenylpropyl]-8-(3- ethoxyphenyl)-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 118 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                   
                 N-[(2S)-2-amino-3- phenylpropyl]-8-(2- methylphenyl)-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 119 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                   
                 N-[(2S)-2-amino-3- phenylpropyl]-8-(3- methylphenyl)-2- (pyridin-4- yl)pyrirido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 120 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.55 min, MI: 499 [M + H] 
                 (1H, 300 MHz, d6-dmso): 8.87 (brs, 1H), 8.70 (d, 1H), 8.67 (d, 2H), 8.18 (d, 1H), 8.14- 8.09 (m, 3H), 7.91 (d, 1H), 7.77 (brs, 1H), 7.56 (t, 1H), 7.36-7.26 (m, 5H), 6.74 (d, 1H), 3.94-3.85 (m, 1H), 3.44-3.39 (m, 2H), 2.77- 2.74 (m, 2H). 
                 N-[(2S)-2-amino-3- phenylpropyl]-8-[3- (1H-pyrazol-5- yl)phenyl]-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 121 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                   
                 N-[(2S)-2-amino-3- phenylpropyl]-8-[5- (aminomethyl)- furan-2-yl]-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
            
           
         
       
     
     General synthesis of 8-substituted-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine derivatives of General Formula [F011] Scheme A4 
     8-substituted-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine derivatives of general formula [F011] were prepared by reaction of a 4-Substituted 8-Chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin derivatives of general formula [F-010] in a Stille type reaction utilising a suitable stannane of general formula [F013], a palladium catalyst such as Pd(PPh 3 ) 4  or Pd(PPh 3 ) 2 Cl 2  a base such as K 3 PO 4 , in a polar solvent such as DMA or dioxane at high temperature either by heating thermally or using a microwave reactor. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, TCA, methanesulfonic acid, HCl or H 2 SO 4  in a solvent such as DCM, DCE, THF, EtOH or MeOH and the crude reaction product was purified by normal phase chromatography or reverse phase preparative HPLC. 
     
       
         
         
             
             
         
       
     
     Synthesis of (R)-3-Phenyl-N 1 -(2-pyridin-4-yl-8-pyridin-2-yl-pyrido[3,4-d]pyrimidin-4-yl)-propane-1,2-diamine [122] 
     
       
         
         
             
             
         
       
     
     (R)-3-Phenyl-N 1 -(2-pyridin-4-yl-8-pyridin-2-yl-pyrido[3,4-d]pyrimidin-4-yl)-propane-1,2-diamine [122] 
     A microwave vial was charged with [(S)-1-Benzyl-2-(8-chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ylamino)-ethyl]-carbamic acid tert-butyl ester [A059](0.07 g, 0.142 mmol), 2-(Tributylstannyl)pyridine (0.068 g, 0.185 mmol), Pd(Ph 3 P) 4  (0.016 g, 0.014 mmol), LiCl (0.018 g, 0.428 mmol) and DMA (1.5 mL). The mixture was heated under microwave irradiation (150° C., 10 min) and the solvent was removed under reduced pressure. The crude was purified by Column chromatography (Eluent: DCM/MeOH: 1:0 to 9:1). The purified compound was solubilised in DCM and 0.5 mL of TFA was added. The solution was stirred 3 h and then was poured on a SCX column, washed with MeOH and the expected product was released using a solution MeOH/NH3 2M, the basic solvent was concentrated under reduced pressure to yield the title compound as a yellow solid which was used without further purification: LCMS method: 1, RT: 2.34 min, MI 434 [M+H];  1 H NMR (1H, 500 MHz, CDCl 3 ); 8.70-8.76 (m, 2H), 8.63 (d, 2H), 8.42 (brs, 1H), 8.27 (d, 1H), 7.96 (dd, 1H), 7.93 (m, 1H), 7.81 (d, 2H), 7.50 (td, 1H), 7.32-7.52 (m, 5H), 4.00 (d, 1H), 3.51-3.60 (m, 2H), 3.01 (dd, 1H), 2.83 (dd, 1H). 
     General synthesis of 8-substituted-1-yl-2-pyridin-4-yl-pyrido[3,4-d]Pyrimidine Derivatives of General Formula [F-014] Scheme A5 
     8-substituted-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine derivatives of general formula [F-014] were prepared by reaction of a 4-Substituted 8-Chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin derivatives of general formula [F-010] in a Buchwald type reaction utilising a suitable amine, of general formula [F-015], a palladium catalyst such as Pd(dba) 2  or Pd(OAc) 2 , a ligand such as Xantphos and a base such as NaOtBu or Cs 2 CO 3  in a polar solvent such as dioxane or a combination of dioxane and DMA at high temperature either by heating thermally or using a microwave reactor. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the intermediate was purified by column chromatography and the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, HCl in a solvent such as DCM, DCE or 1,4-dioxane or by catch and release sulfonic acidic resins such as polymer supported toluene sulfonic acid and the crude reaction product was purified by normal phase chromatography or reverse phase preparative HPLC. 
     
       
         
         
             
             
         
       
     
     Synthesis of N 4 —((R)-2-Amino-3-phenyl-propyl)-N 8 -phenyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine-4,8-diamine [123] 
     
       
         
         
             
             
         
       
     
     N 4 —((R)-2-Amino-3-phenyl-propyl)-N 8 -phenyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine-4,8-diamine [123] 
     In a microwave vial, [(S)-1-Benzyl-2-(8-chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ylamino)-ethyl]-carbamic acid tert-butyl ester [A059](0.05 g 0.1 mmol) Aniline (0.015 g, 0.15 mmol), Pd(dba) 2  (0.003 g, 0.005 mmol), Xantphos (0.006 g, 0.01 mmol), Sodium tert butoxide (0.02 g, 0.2 mmol) and dioxane (1.3 mL) were added successively. The microwave vial was heated under microwaves (150° C., 10 min). The solvent was then removed under reduced pressure, DCM (2 mL) and TFA (0.5 mL) were added successively and the solution was stirred 3 h. The solution was poured on a SCX2 column and was washed with MeOH. The compound was released using a 2M NH3/MeOH solution, and then was concentrated under reduce pressure. The crude was purified by preparative HPLC (method A) to yield the title compound [123]: LCMS method: 1, RT: 3.53 min, MI 448 [M+H]; NMR (1H, 300 MHz, d6-dmso): peaks might be underneath solvent peaks at 2.5 and 3.3 ppm. 9.35 (s, 1H), 8.71 (d, 2H), 8.35 (d, 2H), 8.03-8.08 (m, 3H), 7.46 (d, 1H), 7.27-7.38 (m, 7H), 7.02 (t, 1H), 3.86 (d, 1H), 2.70-2.78 (m, 2H). 
     The following compounds were synthesised according to the general synthesis shown in scheme [A5]: 
     
       
         
           
               
               
               
               
               
             
               
                   
               
               
                 Ex 
                 SM 
                 Amine 
                 Analysis 
                 Name 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 1124 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.16 min, MI: 450 [M + H] 
                 (1H, 300 MHz, d6-dmso): 8.70 (d, 2H), 8.64 (d, 2H), 8.34 (s, 1H), 8.25 (d, 1H), 8.04 (d, 2H),  7.70 (d, 1H), 7.40-7.33 (m, 5H), 7.10 (t, 1H), 3.97-3.92 (m, 1H), 3.58-3.50 (m, 2H), 2.99-2.93 (m, 1H), 2.87-2.80 (m, 1H). 
                 4-N-[(2S)-2-amino-3- phenylpropyl]-2-(pyridin- 4-yl)-8-N-(pyrimidin-2- yl)pyrido[3,4- d]pyrimidine-4,8-diamine 
               
               
                   
               
               
                 125 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT:  2.16 min, MI: 482 [M + H] 
                   
                 4-N-[(2S)-2-amino-3- phenylpropyl]-8-N-(3- chlorophenyl)-2-(pyridin- 4-yl)pyrido[3,4- d]pyrimidine-4,8-diamine 
               
               
                   
               
               
                 126 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.69 min, MI: 439 [M + H] 
                   
                 4-N-[(2S)-2-amino-3- phenylpropyl]-2-(pyridin- 4-yl)-8-N-(1H-1,2,4- triazol-3-yl)pyrido[3,4- d]pyrimidine-4,8-diamine 
               
               
                   
               
            
           
         
       
     
     General synthesis of 8-substituted-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine derivatives of General Formula [F-014] Scheme A6 
     8-substituted-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine derivatives of general formula [F-014] were prepared by reaction of a 4-Substituted 8-Chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin derivative of general formula [F-010] in a nucleophilic aromatic substitution type reaction utilising a suitable amine [method A], thiol [method B] or phenol [method C] of general formula [F-015], and a base such as NaH in a polar aprotic solvent such as DMA or DMF at high temperature either by heating thermally or using a microwave reactor. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the intermediate was purified by column chromatography and the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, HCl in a solvent such as DCM, DCE or 1,4-dioxane or by catch and release sulfonic acidic resins such as polymer supported toluene sulfonic acid and the crude reaction product was purified by normal phase chromatography or reverse phase preparative HPLC. 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Synthesis of (R)—N-[8-(4-Methyl-piperazin-1-yl)-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl]-3-phenyl-propane-1,2-diamine [127] 
     
       
         
         
             
             
         
       
     
     (R)—N 1 -[8-(4-Methyl-piperazin-1-yl)-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl]-3-phenyl-propane-1,2-diamine [127] 
     A microwave vial was charged with [(S)-1-Benzyl-2-(8-chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ylamino)-ethyl]-carbamic acid tert-butyl ester [A059](0.07 g, 0.142 mmol), N-methylpiperazine (0.031 mL, 0.285 mmol) and DMA (2 mL). The solution was heated under microwaves (150° C., 10 min). 2 other equivalent of N-methylpiperazine (0.031 mL, 0.285 mmol) was added and the vial was heated again under microwaves (150° C., 10 min). The solvent was removed under reduced pressure and DCM (2 mL) and TFA (0.5 mL) were added successively. The solution was stirred 3 h and then was poured on a SCX-2 column, washed with MeOH and the expected product was released using a solution MeOH/NH3 2M. The crude was then purified by preparative HPLC (method A) to yield the title compound [127]: LCMS method: 1, RT: 1.55 min, MI 455 [M+H]; NMR (1H, 300 MHz, d6-dmso): 9.17 (brs, 1H), 8.86 (d, 2H), 8.30 (s, 3H), 8.10 (d, 1H), 7.86 (d, 2H), 7.48 (d, 1H), 7.35-7.41 (m, 5H), 3.83-4.04 (m, 5H), 3.66-3.76 (m, 1H), 3.54-3.64 (m, 1H), 3.12 (dd, 1H), 2.86 (dd, 1H), 2.67-2.72 (m, 4H), 2.53 (s, 3H). 
     Synthesis of (R)-3-Phenyl-N 1 -(8-phenylsulfanyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-propane-1,2-diamine [128] 
     
       
         
         
             
             
         
       
     
     (R)-3-Phenyl-N 1 -(8-phenylsulfanyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-propane-1,2-diamine [128] 
     To a suspension of NaH (60% in mineral oil, 0.008 g, 0.2 mmol) in DMF (2 mL), Thiophenol (0.02 g, 0.185 mmol) was added. The mixture was stirred 1 h and [(S)-1-Benzyl-2-(8-chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ylamino)-ethyl]-carbamic acid tert-butyl ester [A059](0.07 g, 0.142 mmol) was added. The mixture was stirred overnight and water (0.3 mL) was added. The solvent were removed under reduced pressure and DCM (2 mL) and TFA (0.5 mL) were added successively. The solution was stirred 3 h and then was poured on a SCX-2 column, washed with MeOH and the expected product was released using a solution MeOH/NH3 2M. The crude was then purified by preparative HPLC (method A). To yield the title compound [128]: LCMS method: 1, RT: 4.06 min, MI 465 [M+H]; NMR (1H, 300 MHz, d6-dmso): 9.38 (brs, 1H), 8.72 (d, 2H), 8.23 (s, 3H), 8.03 (d, 2H), 7.89 (d, 1H), 7.58-7.61 (m, 2H), 7.36-7.47 (m, 6H), 3.98 (d, 1H), 3.56-3.73 (m, 2H), 3.05 (dd, 1H), 2.87 (dd, 1H). 
     The following compounds were synthesised according to the general synthesis shown in scheme [A6]: 
     
       
         
           
               
               
               
               
               
               
             
               
                   
               
               
                   
                 Meth- 
                   
                   
                   
                   
               
               
                 Ex 
                 od 
                 SM 
                 Nuc 
                 Analysis 
                 Name 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 129 
                 B 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.39 min, MI: 449 [M + H] 
                 (1H, 300 MHz, d6-dmso): 9.43 (brs, 1H), 8.68 (d, 2H), 8.29 (s, 2H), 8.03  (d, 1H), 7.99 (d, 2H), 7.85 (d, 1H), 7.36-7.48 (m, 6H), 7.21-7.28 (m, 3H), 4.00 (d, 1H), 3.58-3.55 (m, 2H), 3.06 (dd, 1H), 2.81-2.93 (m, 1H), 
                 N-[(2S)-2-amino-3- phenylpropyl]-8- phenoxy-2-(pyridin- 4-yl)pyrido[3,4- d]pyrimidin-4-amine 
               
               
                   
               
               
                 130 
                 C 
                 [A059] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.43 min, MI: 403 [M + H] 
                 (1H, 300 MHz, d6-dmso): 9.58 (brs, 1H), 8.69 (d, 2H), 8.42 (d, 1H), 8.32 (s, 2H), 7.94 (d, 2H), 7.81 (d, 1H), 7.36-7.45 (m, 5H), 3.99 (d, 1H), 3.59-3.70 (m, 2H), 3.07 (dd, 1H), 2.81 (dd, 1H), 2.53 (s, 3H). 
                 N-[(2S)-2-amino-3- phenylpropyl]-8- (methylsulfanyl)-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4-amine 
               
               
                   
               
            
           
         
       
     
     Synthesis of 4-(4-{[(2S)-2-amino-3-phenylpropyl]amino}-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-8-yl)-2-methylbut-3-yn-2-ol [131] 
     
       
         
         
             
             
         
       
     
     4-(4-{[(2S)-2-amino-3-phenylpropyl]amino}-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-8-yl)-2-methylbut-3-yn-2-ol [131] 
     A microwave vial was charged with [(S)-1-Benzyl-2-(8-chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ylamino)-ethyl]-carbamic acid tert-butyl ester [A059](0.05 g, 0.1 mmol), Pd(PPh 3 ) 2 Cl 2  (0.007 g, 0.01 mmol), CuI (0.002 g, 0.1 mmol), 2-methyl-3-butyn-2-ol (0.035 g, 0.037 mmol), Triphenylphosphine (0.005 g, 0.02 mmol), Triethylamine (0.2 mL) and DMF (0.8 mL). The vial was heated under microwave (150° C., 10 min). The solvent was removed under reduced pressure and DCM (2 mL) and TFA (1 mL) were added and the mixture was stirred 3 h. The solution was poured on a SCX2 column and was washed with MeOH. The compound was released using a 2M NH3/MeOH solution, and then was concentrated under reduce pressure. The crude was purified by preparative HPLC (method A) to yield the title compound [131]: LCMS method: 1, RT: 3.12 min, MI 439 [M+H]; NMR (1H, 300 MHz, d6-dmso): 8.71 (d, 2H), 8.56 (d, 1H), 8.31 (brs, 1H), 8.15 (d, 1H), 8.08 (d, 2H), 7.41-7.31 (m, 5H), 3.97-3.92 (m, 1H), 3.59-3.50 (m, 2H), 2.99-2.90 (m, 1H), 2.86-2.79 (m, 1H), 1.59 (s, 6H). 
     General Synthesis of Substituted 5-Substituted-1-Yl-2-Pyridin-4-Yl-Pyrido[3,4-d]Pyrimidine Derivatives of General Formula [F-001] Scheme A7 
     2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol derivatives of general formula [F-004] were prepared by coupling of a ortho-halo-isonicotinic acid derivative of general formula [F-016] with an appropriately substituted 4-carbamimidoyl-pyridines of general formula [F-018] with a suitable coupling agent such as O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) in a polar aprotic solvent such as DMA or DMF. The isonicotinoyl-amidine derivative of general formula [F-017] were then cyclised to displace the relevant halogen group to yield the desired 2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol derivatives of general formula [F-004]. 4-substituted-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine derivatives of general formula [F-001] were prepared by the reaction of a 2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol derivatives of general formula [F-004] with a chlorinatation agent such as phosphorous oxychloride and the intermediate 4-chloro derivative was then reacted with primary or secondary amino derivative of general formula [F-015], in a polar aprotic solvent such as DMA, DMF, NMP in the presence of a tertiary amine base such as Et 3 N, DIPEA or NMM at ambient temperature [method A]. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, TCA, methanesulfonic acid, HCl or H 2 SO 4  in a solvent such as DCM, DCE, THF, EtOH or MeOH and the crude reaction product was purified by normal phase silica gel chromatography or reverse phase preparative HPLC. 4-substituted-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine derivatives of general formula [F-001] were prepared by the reaction of a 2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol derivatives of general formula [F-004] with 2,4,6-triisopropylbenzenesulfonyl chloride in a polar aprotic solvent such as DMA, DMF, NMP with a tertiary alkylamine base such as Et 3 N, DIPEA or NMM and a catalytic amount of DMAP [method B]. The intermediate 6,7-substituted-(2,4,6-triisopropyl-benzenesulfonic acid)-2-pyridin-4-yl-thieno[3,2-d]pyrimidin-4-yl ester was then reacted with a primary or secondary amino derivative, of general formula [F-015], in a polar aprotic solvent such as DMA, DMF, NMP in the presence of a tertiary amine base such as Et 3 N, DIPEA or NMM at ambient temperature. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, TCA, methanesulfonic acid, HCl or H 2 SO 4  in a solvent such as DCM, DCE, THF, EtOH or MeOH and the crude reaction product was purified by reverse phase preparative HPLC. 
     
       
         
         
             
             
         
       
     
     Synthesis of 5-Chloro-4-piperazin-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine [132] 
     
       
         
         
             
             
         
       
     
     Synthesis of 3,5-Dichloro-N-(imino-pyridin-4-yl-methyl)-isonicotinamide [A060] 
     3,5-Dichloro-isonicotinic acid (10.4 mmol, 1.997 g), was dissolved in anhydrous DMF (50 mL) at room temperature and HATU (10.4 mmol, 3.95 g), added in one portion and the mixture stirred for 5 mins. Then DIPEA (28.6 mmol, 5.0 mL) was added in one portion and reaction stirred for 40 minutes. Pyridine-4-carboximidamide hydrochloride (9.52 mmol, 1.5 g) was added in one portion and reaction stirred at room temperature for 18 hours. 
     The reaction mixture was then poured into water (˜250 mL in total including rinses of reaction vessel) in a conical flask. The resultant mixture was stirred at room temperature for 90 minutes and the precipitate formed was filtered, washed with water (×2) and ether (×2). Then the solid was dried in vac oven for 4 hrs to yield the title compound [A060] (2.359 g), as a pale brown powder. LCMS method: 1, RT: 3.31 min, MI 295 [M+H]. 
     Synthesis of 5-Chloro-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A061] 
     In a 25 mL Biotage microwave vessel, under nitrogen, was added 3,5-Dichloro-N-(imino-pyridin-4-yl-methyl)-isonicotinamide [A060](1.5 mmol, 0.443 g), cesium carbonate (3.0 mmol, 0.978 g) and N,N′-Dibenzylethylenediamine (0.3 mmol, 0.071 mL). The mixture was stirred in anhydrous DMA (10 mL), vigorously and iron (III) chloride (0.15 mmol, 0.024 g) added in one portion. Then the mixture was heated in the microwave at 120° C. for 90 mins. The reaction was allowed to cool to room temperature and acetic acid (12.0 mmol, 0.69 mL), added dropwise over about 5 minutes and the resulting mixture diluted with MeOH (10 mL) and stirred at RT for 30 mins. The mixture was added to a 10 g SCX-2 cartridge and washed with methanol (˜25-30 mL). The cartridge was then washed with ammonia (2N in MeOH, 40 mL) and the ammonia washes concentrated in vacuo to yield 5-Chloro-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one (130 mg). The non-basic methanol washes of the SCX-2 cartridge were left standing overnight, forming a precipitate. This was filtered, washed with methanol (×1), and dried in a vacuum oven overnight to yield the title compound [A061] (13 mg) as an off-white solid. LCMS method: 1, RT: 2.12 min, MI 259 [M+H]. 
     Synthesis of 4-(5-Chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A062] 
     5-Chloro-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A061](0.553 mmol, 0.143 g), was suspended in anhydrous DCM (14 mL) at RT under nitrogen and triethylamine (1.38 mmol, 0.193 mL), DMAP (approximately 0.005 g) and 2,4,6-triisopropylbenzene sulfonyl chloride (0.663 mmol, 0.201 g) were added sequentially. The reaction was stirred at room temperature as an off-white suspension for 2 hrs. Slowly the mixture becomes a pale green suspension, that was left stirring overnight. Then pyridine (4 mL) was added and the reaction vessel sonicated for 5 minutes to try to improve the dissolution causing the reaction to change colour from green to brown suspension. The resultant mixture was stirred at room temperature for 1 hour. Boc-piperazine (0.608 mmol, 0.113 g) was added in one portion and the mixture left stirring for 18 hours. 
     The reaction was diluted with water and extracted with DCM (×3). Combined organics washed with brine (×1), dried (MgSO 4 ), filtered and concentrated in vacuo. To yield the title compound [A062] which was used in the next reaction without further purification: LCMS method: 1, RT: 5.69 min, MI 427 [M+H]. 
     Synthesis of 5-Chloro-4-piperazin-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine [132] 
     To a solution of 4-(5-Chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A062](0.47 mmol, 0.201 g), in anhydrous DCM (8 mL), at room temperature was added HCl (4.0N in dioxane, 2 mL) to yield an orange suspension that was stirred at room temperature for 3 hours. The mixture was then concentrated in vacuo, redissolved in DCM/MeOH (1:1, 6 mL total) and added to an SCX-2 10 g cartridge. The cartridge was washed with DCM and MeOH (˜35 mL total ˜2:3 ratio respectively). Then the cartridge was washed with ammonia in methanol (2N, 40 mL) and the ammonia washes were concentrated in vacuo to yield 92 mg brown oil. The crude material was purified by column chromatography (SP1 4 g VWR column with 0-20% MeOH/DCM 15 volumes) to yield the title compound [138] (0.044 g) as an orangey-yellow foam. LCMS method: 1, RT: 1.60 min, MI 327 [M+H]; NMR: (1H, 300 MHz, d6-dmso); 9.15 (1H, s), 8.77 (2H, d), 8.61 (1H, s), 8.29 (2H, d), 3.69 (4H, br s), 2.85 (4H, br s) 
     Synthesis of 5,8-Dichloro-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A063] 
     
       
         
         
             
             
         
       
     
     2,3,5-Trichloro-N-(imino-pyridin-4-yl-methyl)-isonicotinamide [A064] was prepared by reaction of 2,3,5-Trichloro-isonicotinic acid, pyridine-4-carboximidamide hydrochloride, HATU, DIPEA and DMF at room temperature to give the title compound. LCMS method: 1, RT: 4.37 min, MI 330 [M+H]; NMR: (1H, 300 MHz, d6-dmso); 10.24 (1H, br s), 10.14 (1H, br s), 8.75 (2H, d), 8.60 (1H, s), 7.89 (2H, d). 
     
       
         
         
             
             
         
       
     
     5,8-Dichloro-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A063] was prepared by reaction of 2,3,5-Trichloro-N-(imino-pyridin-4-yl-methyl)-isonicotinamide [A064], FeCl 3 , Ce 2 CO 3 , HCl (4N in dioxane) and DMA in a in wave for 2 hrs at 120° C. The reaction mixture was cooled and water (0.5 mL) was added followed by MeOH (2 mL) and HCl (4 eq wrt carbonate, 2.4 mmol, 0.6 mL 4N HCl in dioxane) and the mixture was stirred for 10 mins. The yellow precipitate was collected by filtration and the solid was washed with MeOH (2×, 2 mL) then dried in vac oven to give the title compound as a yellow solid (51 mg, 56% yield): LCMS method: 1, RT: 4.80 min, MI 293 [M+H]; NMR: (1H, 300 MHz, d6-dmso); 13.36 (1H, br s), 8.92 (2H, d), 8.49 (1H, s), 8.14 (2H, br d). 
     Synthesis of 3-Bromo-5-fluoro-N-(imino-pyridin-4-yl-methyl)-isonicotinamide [A065] 
     
       
         
         
             
             
         
       
     
     2-Bromo-5-fluoro-N-(imino-pyridin-4-yl-methyl)-isonicotinamide [A066] was prepare by reaction of 3-Bromo-4-carboxy-5-fluoro-pyridinium; chloride, pyridine-4-carboximidamide hydrochloride, HATU, DIPEA and DMF at room temperature to give the title compound. LCMS method: 1, RT: 3.20 min, MI 325 [M+H]. 
     
       
         
         
             
             
         
       
     
     2-Bromo-5-fluoro-N-(imino-pyridin-4-yl-methyl)-isonicotinamide [A066](0.05 g, 0.155 mmol), DMA (0.5 mL), K 2 CO 3  (0.022 g, 0.16 mmol), DIPEA (0.28 mL, 0.16 mmol) and DBA (0.024 mL, 0.16 mmol) was heated at 150° C. in wave for 45 mins. The crude reaction mixture was evapourated under reduced pressure and the crude material was purified by column chromatography (SP1 4 g VWR column in 0.5% Et3N/DCM/0-20% MeOH) to yield the title compound [A065](0.044 g, 80% yield) as an orangey-yellow foam: LCMS method: 1, RT: 11.57 min, MI 304 [M+H]. 
     The following compounds were synthesised according to the general synthesis shown in scheme [A7]: 
     
       
         
           
               
               
               
               
               
               
             
               
                   
               
               
                   
                   
                 Me- 
                 Amine 
                   
                   
               
               
                 Ex 
                 SM 
                 thod 
                 [F-015] 
                 Analysis 
                 Name 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 133 
                 [A065] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 1.77 min, MI: 373 [M + H] 
                 (1H, 500 MHz, d6-dmso), d6- dmso) 9.17 (1H, s), 8.77 (2H, dd), 8.72 (1H, s), 8.29 (2H, dd), 3.78-3.61 (4H, m), 2.94 (2H, br s), 2.82-2.71 (2H, m) 
                 1-[5-bromo-2-(pyridin- 4-yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 134 
                 [A063] 
                 A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 5.02 min, MI: 361 [M + H] 
                 (1H, 500 MHz, d6-dmso) 8.79 (2H, dd), 8.41 (1H, s), 8.30 (2H, dd), 3.74 (4H, br s), 2.98-2.75 (4H, m) 
                 1-[5,8-dichloro-2- (pyridin-4-yl)pyrido [3,4-d]pyrimidin-4- yl]piperazine 
               
               
                   
               
            
           
         
       
     
     General Synthesis of Substituted 5-Substituted-1-Yl-2-Pyridin-4-Yl-Pyrido[3,4-d]Pyrimidine Derivatives of General Formula [F-001] Scheme A8 
     Ortho-halo-isonicotinic acid derivatives of general formula [F-020] were prepared by reaction of a dihalo isoinicotinic acid derivative of general formula [F-019] with a grindard reagent of general formula [F-021] in a polar aprotic solvent such as THF or Et 2 O. 2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol derivatives of general formula [F-004] were prepared by coupling of a ortho-halo-isonicotinic acid derivative of general formula [F-020] with an appropriately substituted 4-carbamimidoyl-pyridines of general formula [F-018] with a suitable coupling agent such as 0-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) in a polar aprotic solvent such as DMA or DMF. The isonicotinoyl-amidine derivative of general formula [F-022] were cyclised to displace the relevant halogen group to yield the desired-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol derivatives of general formula [F-004]. 4-substituted-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine derivatives of general formula [F-001] were prepared by the reaction of a 2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol derivative of general formula [F-004] with a chlorinatation agent such as phosphorous oxychloride and the intermediate 4-chloro derivative was then reacted with primary or secondary amino derivative of general formula [F-015], in a polar aprotic solvent such as DMA, DMF, NMP in the presence of a tertiary amine base such as Et 3 N, DIPEA or NMM at ambient temperature [method A]. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, TCA, methanesulfonic acid, HCl or H 2 SO 4  in a solvent such as DCM, DCE, THF, EtOH or MeOH and the crude reaction product was purified by normal phase silica gel chromatography or reverse phase preparative HPLC. 4-substituted-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine derivatives of general formula [F-001] were prepared by the reaction of a 2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol derivatives of general formula [F-004] with 2,4,6-triisopropylbenzenesulfonyl chloride in a polar aprotic solvent such as DMA, DMF, NMP with a tertiary alkylamine base such as Et 3 N, DIPEA or NMM and a catalytic amount of DMAP [method B]. The intermediate 6,7-substituted-(2,4,6-triisopropyl-benzenesulfonic acid)-2-pyridin-4-yl-thieno[3,2-d]pyrimidin-4-yl ester was then reacted with a primary or secondary amino derivative, of general formula [F-015], in a polar aprotic solvent such as DMA, DMF, NMP in the presence of a tertiary amine base such as Et 3 N, DIPEA or NMM at ambient temperature. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, TCA, methanesulfonic acid, HCl or H 2 SO 4  in a solvent such as DCM, DCE, THF, EtOH or MeOH and the crude reaction product was purified by reverse phase preparative HPLC. 
     
       
         
         
             
             
         
       
     
     Synthesis of 5-Butyl-4-piperazin-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine [135] 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Synthesis of 3-Butyl-5-fluoro-isonicotinic acid [A067] 
     3,5-Difluoro-isonicotinic acid (0.557 g, 3.5 mmol) was suspended in anhydrous THF (8 mL) at 0° C., under an atmosphere of nitrogen. To this was added butyl magnesium chloride (2.0 M in diethyl ether, 5.25 mL, 10.5 mmol) dropwise over 10 minutes. The suspension slowly changed form during the slow addition with preliminary agglomeration of solid then the solid started to dissolve slowly, achieving full solution around completion of addition of reagent. The reaction mixture was allowed to warm to room temperature and stirred over 72 hours to form a thick yellow suspension. Diluted with water and transferred into a single neck flask and concentrated in vacuo. The yellow solid was diluted with water (10 mL) and EtOAc (10 mL). The pH was adjusted pH-2, by dropwise addition of HCl (conc.) and extracted with EtOAc (×3—some of the yellow colour goes into organics). Combined organics were washed with brine (×1), dried (MgSO 4 ) and concentrated in vacuo to yield the title compound [A067] as an orange gum/solid (0.402 g) that solidifies slowly: NMR: (1H, 300 MHz, d6-dmso); 8.52 (1H, s), 8.42 (1H, s), 2.67 (2H, t), 1.58-1.48 (2H, m), 1.35-1.22 (2H, m), 0.87 (3H, t); LCMS method: 1, RT: 1.22 min, MI 198 [M+H]. 
     Synthesis of 3-Butyl-5-fluoro-N-(imino-pyridin-4-yl-methyl)-isonicotinamide [A068] 
     3-Butyl-5-fluoro-isonicotinic acid [A067](2.05 mmol, 0.402 g) was dissolved in anhydrous DMF (8 mL) and diisopropylethylamine (DIPEA) (5.95 mmol, 1.04 mL) was added and the mixture stirred at room temperature for 5 minutes. Then O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (2.05 mmol, 0.78 g) was added in one portion and the resultant mixture stirred for 1 hour. pyridine-4-carboximidamide hydrochloride (1.95 mmol, 0.307 g) was then added portionwise over 5 minutes to the reaction. The resultant solution was stirred at room temperature for 18 hours. The reaction mixture was poured into water (85 mL) and stirred for 30 minutes and then extracted with EtOAc (×3). The combined organics washed with water (×4), brine (×1), dried (MgSO 4 ), filtered and concentrated in vacuo to yield the title compound [A068] (480 mg) as a brown solid. The material was used crude in next reaction: NMR: (1H, 300 MHz, d6-dmso); 10.28 (1H, br s), 9.93 (1H, br s), 8.74 (2H, d), 8.45 (1H, s), 8.37 (1H, s), 7.90 (2H, d), 2.72-2.66 (2H, m), 1.58-1.48 (2H, m), 1.28-1.15 (2H, m), 0.79 (3H, t); LCMS method: 1, RT: 3.90 min, MI 301 [M+H]. 
     Synthesis of 5-Butyl-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A069] 
     3-butyl-5-fluoro-N-(imino-pyridin-4-yl-methyl)-isonicotinamide [A068] was placed into 25 mL Biotage microwave vessel in solution in anhydrous DMA (5 mL) and heated at 150° C. in the microwave for 45 mins. The reaction mixture was filtered material through an SCX-2 25 g cartridge. The cartridge was washed with methanol (50 mL). Then the cartridge was washed with ammonia (2N, 40 mL) and the ammonia washes concentrated in vacuo to yield the title compound [A069] (390 mg) as a pale brown solid: NMR: (1H, 300 MHz, d6-dmso); 8.95 (1H, s), 8.79 (2H, dd), 8.46 (1H, s), 8.10 (2H, dd), 3.21 (2H, t), 1.63-1.50 (2H, m), 1.43-1.27 (2H, m), 0.91 (3H, t)—also shows one equivalent of DMA; LCMS method: 1, RT: 3.29 min, MI 281 [M+H]. 
     Synthesis of 5-Butyl-4-chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine [A070] 
     5-Butyl-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A069](1.35 mmol, 0.378 g) was suspended in anhydrous 1,2-dichloroethane (DCE) (10 mL) and phosphorus oxychloride (POCl 3 ) (1.4 mmol, 0.131 mL) was added dropwise over 2-3 minutes. Finally DIPEA (2.0 mmol, 0.348 mL) was added and the mixture stirred at RT under nitrogen overnight. The brown solid slowly to change appearance after POCl 3  addition, then darkens further on addition of DIPEA to become a dark brown apparent solution. The reaction was left stirring at room temperature overnight under nitrogen. After 20 hours POCl 3  (65 μL) was added and stirred at room temperature overnight. The crude mixture was concentrated in vacuo, then azeotroped with toluene (×2) to dryness. The residue was diluted with sodium carbonate (aq. soln., 2N, 20 mL) and extracted with DCM (×2), EtOAc (×1). Combined organics washed with brine (×1), dried (MgSO 4 ), filtered through a pad of silica and concentrated in vacuo to yield the title compound [A070] (180 mg) as a of a pale brown solid which was used in the next reaction without further purification: LCMS method: 1, RT: 5.66 min, MI 299 [M+H]. 
     Synthesis of 4-(5-Butyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A071] 
     5-Butyl-4-chloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine [A070](0.615 mmol, 0.180 g), was dissolved in anhydrous DCM (5 mL), under nitrogen at room temperature and treated with triethylamine (0.868 mmol, 0.121 mL) and N-Boc-piperazine (0.682 mmol, 0.127 g) in one portion. The resulting mixture was stirred at room temperature for 2 hours. Then sodium carbonate (1N aq. soln, 20 mL) was added and extracted with DCM (×2) and EtOAc (×1). Combined organics washed with brine (×1), dried (MgSO 4 ), filtered and concentrated in vacuo to a dark brown solid, which was purified by column chromatography (SP1 on 25 g VWR cartridge in 0-10% MeOH/DCM, 15 col vols) to yield the title compound [A071] as a brown gum (0.092 g) which was used in the next reaction without further purification: NMR: (1H, 300 MHz, d6-dmso); 9.24 (1H, s), 8.79 (2H, d), 8.49 (1H, s), 8.36 (2H, d), 3.77-3.48 (8H, m), 3.19-3.07 (2H, m), 1.64-1.23 (4H, m), 1.48 (9H, s), 0.96-0.87 (3H, t) 
     Synthesis of 5-Butyl-4-piperazin-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine [135] 
     4-(5-Butyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A071](0.20 mmol, 0.09 g) was dissolved in anhydrous DCM (4 mL) and treated with hydrogen chloride (4N in dioxane, 4 mL) at room temperature and stirred for 2 hours. The reaction was diluted with methanol and poured onto SCX-2 cartridge (5 g), washing with MeOH/DCM (20 mL). The cartridge was then washed with ammonia (2N, 20 mL) and the ammonia washes concentrated in vacuo to yield a brown gum (0.059 g). The residue was purified by column chromatography (SP1 4 g column, in a gradient 5-20% MeOH/DCM 15col vols) to yield the title compound [133] as an orangey-brown gum (0.020 g); NMR: (1H, 300 MHz, d6-dmso); 9.09 (1H, s), 8.76 (2H, d), 8.51 (1H, s), 8.31 (2H, d), 3.73-3.58 (2H, br s), 3.50-3.37 (2H, br s), 3.07 (2H, t), 2.90-2.79 (4H, br s), 1.51-1.38 (2H, m), 1.28-1.15 μm (2H, m), 0.84 (3H, t); LCMS method: 1, RT: 2.58 min, MI 349 [M+H]. 
     The following compounds were synthesised according to the general synthesis shown in scheme [A8]: 
     
       
         
           
               
               
               
               
               
               
             
               
                   
               
               
                   
                   
                 Grig- 
                   
                   
                   
               
               
                   
                 SM 
                 nard 
                 Amine 
                   
                   
               
               
                 Ex 
                 [F-019] 
                 [F-021] 
                 [F-015] 
                 Analysis 
                 Name 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 136 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 EtMgBr 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 1.64 min, MI: 321 [M + H] 
                 (1H, 300 MHz, d6-dmso), 9.08 (1H, s), 8.76 (2H, dd), 8.54 (1H, s), 8.30  (2H, dd), 3.72-3.58 (2H, br s), 3.55-3.45 (2H,  br s), 3.10 (2H, dd),  2.89-2.77 (4H, br s),  1.17 (3H, t) 
                 1-[5-ethyl-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
               
                 137 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 EtMgBr 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.90 min, MI: 385 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.02 (1H, s), 8.72 (2H, dd), 8.42 (1H, s), 8.16 (2H, dd), 7.35-7.24 (5H, m), 3.91 (1H, dd), 3.43 (1H, dd), 3.37-3.29 (1H, m), 3.21 (2H, dd), 2.83-2.70 (2H, m), 1.33 (3H, t) 
                 N-[(2S)-2- amino-3- phenylpropyl]- 5-ethyl-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- amine 
               
               
                   
               
               
                 138 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 MeMgBr 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.93 min, MI: 307 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.06 (1H, s), 8.76 (2H, dd), 8.43 (1H, s), 8.30 (2H, dd), 3.57 (4H, br s), 2.84  (4H, br s), 2.65 (3H, s) 
                 1-[5-methyl-2- (pyridin-4- yl)pyrido[3,4- d]pyrimidin-4- yl]piperazine 
               
               
                   
               
            
           
         
       
     
     General synthesis of substituted 5-substituted-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine derivatives of general formula [F-001] Scheme A9 
     5-Substituted 2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol derivatives of general formula [F-004] were prepared by reaction of a 5-halo substituted 2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol derivatives of general formula [F-024](prepared in scheme A7) in a palladium catalysed cross coupling reaction with a boronic acid or boronate ester derivative of general formula [F-023] in the presence of a palladium catalyst such as Pd(PPh 3 ) 4  or Pd(OAc) 2 , and a base such as K 2 CO 3  or Cs 2 CO 3  in a polar solvent such as dioxane or a combination of dioxane and DMA at high temperature either by heating thermally or using a microwave reactor, or a palladium catalysed cross coupling reaction of a 5-halo substituted 2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol derivatives of general formula [F-024](prepared in scheme A7) with a fluoroborate derivative of general formula [F-025] in the presence of a catalyst such as Pd(PPh 3 ) 4  or Pd(OAc) 2 , a ligand such as RuPhos and a base such as K 2 CO 3  or Cs 2 CO 3  in a polar solvent such as dioxane or a combination of dioxane and DMA at high temperature either by heating thermally or using a microwave reactor. 5-substituted-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine derivatives of general formula [F-001] were prepared by the reaction of a 5-substituted 2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol derivatives of general formula [F-004] with a chlorinatation agent such as phosphorous oxychloride and the intermediated 4-chloro derivative was then reacted with primary or secondary amino derivative of general formula [F-015], in a polar aprotic solvent such as DMA, DMF, NMP in the presence of a tertiary amine base such as Et 3 N, DIPEA or NMM at ambient temperature [method A]. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, TCA, methanesulfonic acid, HCl or H 2 SO 4  in a solvent such as DCM, DCE, THF, EtOH or MeOH and the crude reaction product was purified by normal phase silica gel chromatography or reverse phase preparative HPLC. 4-substituted-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine derivatives of general formula [F-001] were prepared by the reaction of a 2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol derivatives of general formula [F-004] with 2,4,6-triisopropylbenzenesulfonyl chloride in a polar aprotic solvent such as DMA, DMF, NMP with a tertiary alkylamine base such as Et 3 N, DIPEA or NMM and a catalytic amount of DMAP [method B]. The intermediate 6,7-substituted-(2,4,6-triisopropyl-benzenesulfonic acid)-2-pyridin-4-yl-thieno[3,2-d]pyrimidin-4-yl ester was then reacted with a primary or secondary amino derivative, of general formula [F-015], in a polar aprotic solvent such as DMA, DMF, NMP in the presence of a tertiary amine base such as Et 3 N, DIPEA or NMM at ambient temperature. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, TCA, methanesulfonic acid, HCl or H 2 SO 4  in a solvent such as DCM, DCE, THF, EtOH or MeOH and the crude reaction product was purified by reverse phase preparative HPLC 
     
       
         
         
             
             
         
       
     
     Synthesis of 1-[5-cyclopropyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine [139] 
     
       
         
         
             
             
         
       
     
     5-Cyclopropyl-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A060] 
     5-Chloro-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A061](0.670 mmol, 0.173 g), potassium carbonate (2.01 mmol, 0.278 g) and cyclopropyl boronic acid (1.34 mmol, 0.115 g) was suspended in anhydrous DMA (3 mL) and then subjected to vacuum/argon balloon sparge (×3). Then tetrakis(triphenylphosphine)palladium (0.067 mmol, 0.077 g) was added in one portion and the reaction vessel sealed and heated in a microwave at 150° C. for 1 hr. The reaction was cooled to room temperature, under nitrogen. Potassium carbonate (2.0 mmol, 0.278 g) and cyclopropyl boronic acid (1.34 mmol, 0.115 g) were added and the reaction mixture subjected to vacuum/argon balloon sparge (×3). Then tetrakis(triphenylphosphine)palladium (0.067 mmol, 0.077 g) was added in one portion and the reaction vessel sealed and heated in a microwave at 180° C. for 1 hr. The reaction was cooled to room temperature under air and left standing over 48 hours. The reaction mixture was then poured on to an SCX-2 cartridge (10 g) and washed with methanol (˜40 mL total). Then the cartridge was washed with ammonia (2N in MeOH, ˜40 mL) and the ammonia washes concentrated in vacuo to yield the title compound [A072] (78 mg) as a yellow solid which was taken through to next reaction without purification. 
     
       
         
         
             
             
         
       
     
     4-(5-Cyclopropyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A073] 
     A mixture of 5-Cyclopropyl-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A072](0.08 g, 0.3 mmol), DIPEA (0.16 mL, 0.9 mmol), 2,4,6-triisopropylbenzene sulfonyl chloride (0.11 g, 0.36 mmol), DMAP (3 mg) and DMA (2 mL) was stirred at room temperature under nitrogen and left to stir at at RT for 2 hrs. Boc-piperazine (0.062 g, 0.33 mmol) was added and the mixture was left to stir at RT overnight. Water was added and the mixture was extracted with EtOAc (×4). The extracts were combined washed with water (×4), brine, dried (MgSO4) and concentrated in vacuo. The crude reaction product was purified by flash column chromatography (SP1, EtOAc:cyclohexane elution) to yield the title compound [A073]: method: 1, RT: 5.57 min, MI 433 [M+H]. 
     1-[5-cyclopropyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine [139] 
     A mixture of 4-(5-Cyclopropyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A073](0.9 g, 0.2 mmol) in DCM (3 mL) and 4N HCl dioxane (1 mL) was stirred at RT overnight. The crude reaction mixture was evapourated under reduced pressure then dissolved in MeOH and washed onto SCX-2 (5 g) cartridge and washed with MeOH/DCM (1:1, ˜4 mL) then MeOH (10 mL). Then eluted with ammonia (2N in MeOH, 15 mL). The Ammonia eluent was concentrated in vacuo and the crude product was purified by normal phase chromatography (SiO2, SP1 in MeOH (0-15%)/CHCl3) to give the title compound [139](30 mg, 43% yield): LCMS method: 1, RT: 1.65 min, MI 333 [M+H]; NMR: (1H, 300 MHz, d6-dmso); 8.99 (1H, s), 8.76 (2H, dd), 8.30 (2H, dd), 8.09 (1H, s), 3.87-3.54 (4H, m), 2.87 (4H, br s), 2.63-2.57 (1H, m), 1.24 (2H, ddd), 1.01 (2H, ddd) 
     Synthesis of 5-Benzyloxymethyl-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A074] 
     
       
         
         
             
             
         
       
     
     5-Benzyloxymethyl-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A074] 
     A mixture of 5-Chloro-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A061](0.1 g, 0.4 mmol), Potassium benzyloxymethyltrifluoroborate (0.1 g, 0.45 mmol), cesium carbonate (0.4 g, 1.2 mmol) and RuPhos (12 mg, 0.028 mmol) were placed in Biotage 5 mL vessel and suspended in dioxane (1.8 mL) and water (0.2 mL). The mixture was subjected to spurging with vacuum/argon (×3) then the Pd(OAc) 2  (3 mg, 0.014 mmol) was added and the vessel sealed and heated at 104° C. overnight. DMA (1 mL) was added and the mixture was heated in wave at 150° C. for 1 hr. The RM was cooled and acetic acid (0.57 mL) was added and the mixture and stirred for 10 mins. Then flushed down SCX-2 cartridge (10 g) washing with MeOH (30-40 mL). Then washed with ammonia (2N in MeOH, 40 mL). Ammonia washes concentrated in vacuo to yield the title compound [A074] which was used without further purification: method: 1, RT: 3.31 min, MI 345 [M+H]. 
     The following compounds were synthesised according to the general synthesis shown in scheme [A9]: 
     
       
         
           
               
               
               
               
               
               
             
               
                   
               
             
            
               
                   
                   
                 Me- 
                   
                   
                   
               
               
                 Ex 
                 SM 
                 thod 
                 Amine 
                 Analysis 
                 Name 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 140 
                 [A074] 
                 B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 4.78 min, MI: 413 [M + H] 
                 (1H, 500 MHz, d6-dmso), d6-dmso) 9.18 (1H, s), 8.77 (2H, d), 8.69 (1H, s), 8.31 (2H, dd), 7.33-7.25 (5H, m), 4.99 (2H, s), 4.54 (2H, s), 3.51 (4H, br s), 2.79 (4H, t) 
                 1-{5- [(benzyloxy)methyl]-2- (pyridin-4-yl)pyrido[3,4- d]pyrimidin-4- yl}piperazine 
               
               
                   
               
            
           
         
       
     
     Synthesis of 5-Chloro-4-piperazin-1-yl-8-(1H-pyrazol-3-yl)-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine [141] 
     
       
         
         
             
             
         
       
     
     4-(5,8-Dichloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A075] 
     A mixture of 5,8-Dichloro-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A063](0.43 g, 1.47 mmol) Et 3 N (0.51 mL, 3.6 mmol), DCM (10 mL), pyridine (2 mL) was sonicated for 2 mins. Then DMAP (5 mg) was added followed by 2,4,6-triisopropylbenzene sulfonyl chloride (0.53 g, 1.77 mmol). The reaction mixture was left to stir at RT overnight. The dark brown solution was diluted with water and extracted with DCM (×3) and EtOAc (×1). Combined organics washed with brine (×1). Brine re-extracted with EtOAc (×1). Combined organics dried (MgSO4), filtered and concentrated in vacuo. The crude material was purified by normal phase chromatography (SiO 2 , [SP1 (25 g vwr cartridge, 0-10% MeOH/DCM]) to give the title compound [A075](0.19 g, 28% yield): LCMS method: 1, RT: 4.17 min, MI 461 [M+H]; NMR: (1H, 300 MHz, d6-dmso); 8.81 (2H, d), 8.45 (1H, s), 8.33 (2H, d), 3.76 (4H, br s), 3.33 (4H, br s), 1.40 (9H, br s). 
     4-[5-Chloro-8-(1H-pyrazol-3-yl)-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [A076] 
     A mixture of 4-(5,8-Dichloro-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A075](0.07 g, 0.15 mmol), potassium phosphate tribasic [K 3 PO 4  212.27 g/mol 21.2 g in 100 mL deionised water](0.3 mL, 0.3 mmol), tetrakis(triphenylphosphine)palladium (17 mg, 0.015 mmol), 1H-Pyrazole-5-boronic acid (24 mg, 0.21 mmol) and DMA (1 mL) were heated in μwave at 150° C. for 30 min. Acetic acid (0.52 mL) was added and the mixture was left to stir at rt for 20 mins and then the crude product was loaded onto an SCX cartridge and the cartridge was washed with methanol then the product was eluted with 2M ammonia/methanol. The eluent was concentrated under reduced pressure and the crude reaction mixture was purified by normal phase chromatography (SiO 2 , ethyl acetate: cyclohexane elution) to give the title compound [A076]: LCMS method: 1, RT: 5.62 min, MI 493 [M+H]. 
     Chloro-4-piperazin-1-yl-8-(1H-pyrazol-3-yl)-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine [141] 
     A mixture of 4-[5-Chloro-8-(1H-pyrazol-3-yl)-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [A076] and HCl dioxane (4N, 1 mL) was stirred at rt for 48 hours. The crude reaction mixture was evapourated under reduced pressure and the crude product loaded onto a SCX-2 cartridge (1 g) and washed with methanol. The product was released from the cartridge using a solution of 2M ammonia/methanol. The ammonia/methanol eluent was concentrated under reduced pressure and the crude product was purified by preparative HPLC (method A) to yield to the title compound: LCMS: method: 1, RT: 1.98 min, MI 393 [M+H]; NMR: (1H, 300 MHz, d6-dmso); 8.76-8.75 (3H, m), 8.50 (1H, s), 8.17 (2H, dd), 7.90 (1H, d), 6.67 μm (1H, dd), 3.76 (4H, br s), 2.93 (2H, br s), 2.80 (2H, br s) 
     Synthesis of 5-chloro-N,N-dimethyl-4-(piperazin-1-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-8-amine [142] 
     
       
         
         
             
             
         
       
     
     4-(5-Chloro-8-dimethylamino-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A077] 
     4-[5-Chloro-8-(1H-pyrazol-3-yl)-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [A075](0.046 g, 0.1 mmol), DMF (2 mL) and dimethylamine in ethanol (0.5 mL) was warmed to 50° C. in a sealed vessel and left to stir for 24 h. The crude reaction mixture was evapourated under reduced pressure to yield the title compound [A077] which was used in the next step without further purification: LCMS: method: 1, RT: 4.41 min, MI 470 [M+H]. 
     5-chloro-N,N-dimethyl-4-(piperazin-1-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-8-amine [142] 
     A mixture of 4-(5-Chloro-8-dimethylamino-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A077](0.1 g, 0.22 mmol), DCM (3 mL) and HCl (1 mL of a 4N solution in dioxane) was stirred at RT for 2 h. The crude reaction mixture was evaporated under reduced pressure then the crude product was loaded onto an SCX cartridge and the cartridge was washed with methanol then the product was eluted with 2M ammonia/methanol. The eluent was concentrated under reduced pressure and the crude reaction mixture was purified by normal phase chromatography (SiO 2 , SP1 on 4 g cartridge in 0-15% MeOH/DCM) to give the title compound: LCMS: method: 1, RT: 5.40 min, MI 370 [M+H]; NMR: (1H, 300 MHz, d6-dmso); 8.73 (2H, dd), 8.22 (2H, dd), 7.97 (1H, s), 3.76-3.68 (2H, m), 3.56-3.49 (2H, m), 3.16 (3H, s), 3.15 (3H, s), 2.95-2.87 (2H, m), 2.86.2-77 (2H, m) 
     Synthesis of 5-Isopropenyl-4-piperazin-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine [143] 
     
       
         
         
             
             
         
       
     
     Step 1: Synthesis of 4-(5-Bromo-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A078] 
     A mixture of 5-Bromo-2-pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A065](0.74 g, 2.45 mmol) in DMF (15 mL), DIPEA (1.3 mL, 7.3 mmol) and DMAP (5 mg) was stirred at rt for 10 min. 2,4,6-triisopropylbenzene sulfonyl chloride (0.89 g, 2.94 mmol) was added and the mixture was left to stir at rt for 80 mins at RT, then boc-piperazine (0.5 g, 2.94 mmol) was added in one portion and the rm was left to stir at rt over night. Water (30 mL) was added and the mixture was stirred at RT for 20 mins. The resultant solid was collected by filtration and the crude product was purified by column chromatography (SP1 (25 g cartridge) in 0-10% MeOH/DCM (˜20 vols, 4 vols at 10% MeOH/DCM)) to yield the title compound [A078](0.69 g, 60% yield): LCMS: method: 1, RT: 5.83 min, MI 473 [M+H]; NMR: (1H, 300 MHz, d6-dmso); 9.22 (1H, s), 8.78 (3H, m), 8.32 (2H, d), 3.79 (4H, br s), 3.61 (4H, br s), 1.41 (9H, br s). 
     Step 2: Synthesis of 4-(5-Isopropenyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A079] 
     4-(5-Bromo-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A078](0.2 mmol, 0.094 g), potassium phosphate (tribasic) (0.60 mmol, 0.127 g), and Isopropenylboronic acid pinacol ester (0.30 mmol, 0.057 mL) were suspended in anhydrous dioxane (2 mL), in a 5 mL Biotage vessel under nitrogen. The vessel was subjected to vacuum/argon (balloon) sparge (×3) and then dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.01 mmol, 0.008 g) added and the reaction sealed and warmed to 96° C. for 18 hours. The reaction mixture was cooled to room temperature under air, silica for chromatography added (1 g) and the mixture concentrated in vacuo to a brown powder. This was dry loaded onto a silica cartridge and purified by chromatography (SP1 0-10% MeOH/DCM 15 col vols) to yield 4-(5-Isopropenyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A079] (85 mg) as a 85 mg brown glass: NMR: (1H, 500 MHz, CDCl 3 ); 9.31 (1H, s), 8.79 (2H, d), 8.50 (1H, s), 8.36 (2H, d), 5.40 (1H, s), 5.32 (1H, s), 3.58 (8H, br s), 2.21 (3H, s), 1.24 (9H, s); LCMS: method: 1, RT: 5.66 min, MI 433 [M+H]. 
     Step 3: Synthesis of 5-Isopropenyl-4-piperazin-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine 
     To a solution of 4-(5-Isopropenyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A079](0.105 mmol 0.045 g), in DCM (2 mL) at room temperature was added hydrogen chloride (4N in dioxane, 1 mL), to obtain a thick yellowy-brown suspension, that was stirred overnight. The reaction mixture was then concentrated in vacuo, the residue redissolved in MeOH and washed onto SCX-2 cartridge. The cartridge was washed with DCM and MeOH (1:1, 20 mL total). Then the SCX-2 was washed with ammonia (2N in MeOH, 15 mL). The combined ammonia washes were concentrated to an orangey-brown solid, which was purified by column chromatography (SP1 4 g cartridge, 0-20% MeOH/DCM, 15 col vols) to yield 5-Isopropenyl-4-piperazin-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine [143] (0.011 g) as a yellow glass: NMR: (1H, 500 MHz, d4-MeOH) 9.15 (1H, s), 8.76 (2H, dd), 8.49 (1H, s), 8.31 (2H, dd), 5.40 (1H, s), 5.20 (1H, s), 3.56 (4H, br s), 2.79 (4H, t), 2.17 (3H, s); LCMS: method: 1, RT: 1.88 min, MI 333 [M+H]. LC-MS. 
     Example 151. 5-Methoxy-4-piperidin-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine 
     151a) 3-tert-Butoxycarbonylamino-pyrrolidine-1,3-dicarboxylic acid 1-(9H-fluoren-9-ylmethyl) ester: 3-tert-Butoxycarbonylamino-pyrrolidine-3-carboxylic acid (1.50 g, 6.50 mmol) was added to a solution of Sodium carbonate (1.65 g, 15.6 mmol) in Water (16.7 mL, 926 mmol) and 1,4-Dioxane (9 mL, 100 mmol). The resulting solution was stirred and cooled in an ice bath. To the stirring reaction solution was added a solution of 9-Fluorenylmethyl chloroformate (1.76 g, 6.82 mmol) in 1,4-Dioxane (13 mL, 160 mmol). The mixture was stirred at room temperature for 2 h, poured into Water (300 mL) and extracted twice with ether. The aqueous phase was cooled in an ice bath and slowly treated with 3 M of Hydrogen Chloride in Water (7.80 mL, 23.4 mmol) to neutralize. The resulting mix was extracted with EtOAc (2×), the combined organics dried over Na2SO4, filtered, and concentrated. The residue was pumped under high vacuum for 4 h, leaving 3.12 g (106%) of foam, which was used for subsequent step without further manipulation. 
     151b) 3-tert-Butoxycarbonylamino-3-carbamoyl-pyrrolidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester: At rt Di-tert-Butyldicarbonate (655 mg, 3.00 mmol) was added to a mixture of 3-tert-Butoxycarbonylamino-pyrrolidine-1,3-dicarboxylic acid 1-(9H-fluoren-9-ylmethyl) ester (905 mg, 2.00 mmol) and Pyridine (0.324 mL, 4.00 mmol) in 1,4-Dioxane (5 mL, 60 mmol). After 15 minutes, Ammonium Bicarbonate (0.474 g, 6.00 mmol) was added, and the reaction mixture was stirred for 72 h. Added water (10 mL) to resulting solid mass and swirled. Filtered off solid and rinsed liberally with water. After air drying, dried resulting solid under high vacuum at rt. Obtained 1.12 g (124%) of tannish solid. Proceeded and used this tannish solid for subsequent step without further manipulation. 
     151c) (3-Carbamoyl-pyrrolidin-3-yl)-carbamic acid tert-butyl ester 3-tert-Butoxycarbonylamino-3-carbamoyl-pyrrolidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester (410 mg, 0.91 mmol) was suspended in Methanol (5 mL, 100 mmol), then at rt added Piperidine (1 mL, 10 mmol) neat. After 16 hours concentrated reaction under reduced pressure, then pumped on residue under high vacuum overnight (to remove as much piperidine as possible), and used crude directly for subsequent reaction. 
     151d): 5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol (127 mg, 0.501 mmol), Triethylamine (216 uL, 1.55 mmol), 2,4,6-Triisopropylbenzenesulfonyl Chloride (167 mg, 0.552 mmol), and 4-Dimethylaminopyridine (6.9 mg, 0.057 mmol) in N,N-Dimethylformamide (2.0 mL, 26 mmol) were stirred at room temperature for 1 h. Gradual dissolution of starting material was observed, intermediate sulfonate observed by hplc. (3-Carbamoyl-pyrrolidin-3-yl)-carbamic acid tert-butyl ester (126 mg, 0.550 mmol) was then added as a solution in N,N-Dimethylformamide and the reaction was stirred at room temperature. After 45 minutes concentrated reaction under reduced pressure, then partitioned residue between EtOAc and water. Took organic and washed with 3 mL of 1N HCl. Took aqueous solution, added small amount of DMSO and purified over two runs with preparative reverse phase HPLC. Combined purest fractions of each major product and lyophylized. Obtained 32 mg (14%) of yellow lyophilate of front running material [3-Carbamoyl-1-(5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester (LC/MS: M+H=466.2). Also obtained 35 mg (22%) of side product 5-Methoxy-4-piperidin-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine (LC/MS: M+H=322.1), which was generated from piperidine left over from preparation of starting material (3-Carbamoyl-pyrrolidin-3-yl)-carbamic acid tert-butyl ester. Proceeded on with [3-Carbamoyl-1-(5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester for subsequent reaction without further manipulation. 
     Example 152. 3-Amino-1-(5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-pyrrolidine-3-carboxylic acid amide 
     Added a solution of Trifluoroacetic Acid (1 mL, 10 mmol) in Methylene chloride (2 mL, 30 mmol) to [3-Carbamoyl-1-(5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester (30 mg, 0.06 mmol) at rt. After 30 minutes concentrated reaction mixture under reduced pressure, then to residue triturate with Et2O to get a solid. Filtered solid and washed liberally with Et2O. Obtained with 17 mg of title compound as a solid (LC/MS: +H=366.1). 
     Example 153. 3-Amino-1-(5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-pyrrolidine-3-carboxylic acid phenylamide 
     153a) 3-tert-Butoxycarbonylamino-3-phenylcarbamoyl-pyrrolidine-1-carboxylic acid-9H-fluoren-9-ylmethyl ester: N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (575 mg, 3.00 mmol) was added to a mixture of 3-tert-Butoxycarbonylamino-pyrrolidine-1,3-dicarboxylic acid 1-(9H-fluoren-9-ylmethyl) ester (905 mg, 2.00 mmol), 1-Hydroxybenzotriazole (2.70E2 mg, 2.00 mmol) and Aniline (228 uL, 2.50 mmol) in Tetrahydrofuran (25 mL, 310 mmol). After 10 minutes added N,N-Dimethylformamide (10 mL, 100 mmol) to facilitate dissolution. After 1.5 hour concentrated reaction mixture under reduced pressure. The residue was partitioned between EtOAc (2×) and saturated aqueous NaHCO3. The combined organic phases were dried over Na2SO4, filtered, and concentrated under reduced pressure to yield 0.97 g (92%) of foam (LC/MS: M+H=528.1), which was used for subsequent step without further manipulation. 
     153b) (3-Phenylcarbamoyl-pyrrolidin-3-yl)-carbamic acid tert-butyl ester: 3-tert-Butoxycarbonylamino-3-phenylcarbamoyl-pyrrolidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester (960 mg, 1.8 mmol) was combined with Methanol (10 mL, 200 mmol), then at room temperature added Piperidine (2 mL, 20 mmol) neat and the reaction was stirred for 72 h. Concentrated reaction mixture under reduced pressure and Obtained a solid mass. Triturated entire sample with Et2O, filtered and rinsed solid liberally with Et2O. After air drying there remained 0.55 g (99%) of tannish solid. Proceeded and used this material in subsequent reaction without further manipulation. 
     153c) [1-(5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-3-phenylcarbamoyl-pyrrolidin-3-yl]-carbamic acid tert-butyl ester: 5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol (254 mg, 1.00 mmol), Triethylamine (431 uL, 3.10 mmol), 2,4,6-Triisopropylbenzenesulfonyl Chloride (334 mg, 1.10 mmol), and 4-Dimethylaminopyridine (14 mg, 0.11 mmol) in N,N-Dimethylformamide (4.0 mL, 52 mmol) were stirred at room temperature for 1 hour. (3-Phenylcarbamoyl-pyrrolidin-3-yl)-carbamic acid tert-butyl ester (335 mg, 1.10 mmol) was added neat and the reaction was stirred at room temperature overnight. The reaction was then concentrated under reduced pressure and partitioned residue between EtOAc and water. Had to filter before separating layers, as precipiated solid causing some problems between layers. The organic phase was dried over Na2SO4, filtered, and concentrated under reduced pressure to give 500 mg of crude product. Dissolved crude in DMSO (3.6 mL), filtered, and purified via preparative reverse phase HPLC. Took purest fractions and basified with saturated aqueous NaHCO3. Solid which crashed from the solution was filtered, and rinsed with water. After air drying there remained 50 mg (9%) off white solid. (LC/MS: M+H=542.1). Proceeded and used material for subsequent step without further manipulation. 
     153d) At rt dissolved [1-(5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-3-phenylcarbamoyl-pyrrolidin-3-yl]-carbamic acid tert-butyl ester (50.0 mg, 0.0923 mmol) in Methylene chloride (2.0 mL, 31 mmol) then added Trifluoroacetic Acid (1.0 mL, 13 mmol) neat. After 2.5 h concentrated reaction under reduced pressure, dissolved residue in 0.80 mL DMSO, filtered, and purified via preparative reverse phase HPLC. Combined and lyophilized purest fractions. Obtained 32 mg (78%) of title compound as a yellow lyophilate (LC/MS: M+H=442.1). 
     Example 154. 4-Amino-1-(5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperidine-4-carboxylic acid [(S)-1-(4-chloro-phenyl)-3-hydroxy-propyl]-amide 
     154a) 4-tert-Butoxycarbonylamino-1-(5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperidine-4-carboxylic acid methyl ester: 5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol (254 mg, 1.00 mmol), Triethylamine (0.432 mL, 3.10 mmol), 2,4,6-Triisopropylbenzenesulfonyl Chloride (334 mg, 1.10 mmol), and 4-Dimethylaminopyridine (14 mg, 0.11 mmol) were combined in N,N-Dimethylformamide (2.0 mL, 26 mmol), and stirred at room temperature. After 45 minutes 4-tert-Butoxycarbonylamino-piperidine-4-carboxylic acid methyl ester (284 mg, 1.10 mmol; Supplier=Oakwood) was added neat and stirred overnight. The reaction mixture was concentrated under reduced pressure and the residue partitioned between CH2Cl2 and water. The organic phase was dried over Na2SO4, filtered, and concentrated under reduced pressure. Resulting 380 mg (77%) of residue was used for subsequent steps without further manipulation. 
     154b) 4-tert-Butoxycarbonylamino-1-(5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperidine-4-carboxylic acid: Combined a solution of Lithium hydroxide (180 mg, 7.5 mmol) in water (3 mL, 200 mmol) to a solution of 4-tert-Butoxycarbonylamino-1-(5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperidine-4-carboxylic acid methyl ester (370 mg, 0.75 mmol) in Methanol (10 mL, 200 mmol) at rt and let homogeneous solution stir at rt for 16 hours. After cooling, treated reaction mixture with 1 M of Hydrogen Chloride in Water (7.5 mL, 7.5 mmol), then concentrated off most of MeOH, leaving mostly aqueous as solvent. Filtered resulting solid, then took aqueous filtrate and concentrated. Obtained 292 mg. Added 2.5 mL of DMSO, filtered, then purified via preparative reverse phase HPLC, lyopylized purest fractions to yield 45 mg (12%) of desired product as a yellow lyophilate, which was used for subsequent steps without further manipulation. 
     154c) [4-[(S)-1-(4-Chloro-phenyl)-3-hydroxy-propylcarbamoyl]-1-(5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperidin-4-yl]-carbamic acid tert-butyl ester: 4-tert-Butoxycarbonylamino-1-(5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperidine-4-carboxylic acid (30.0 mg, 0.0624 mmol) was combined with N,N-Dimethylformamide (1 mL, 10 mmol), then 1-Hydroxybenzotriazole (8.44 mg, 0.0624 mmol) and (S)-3-Amino-3-(4-chloro-phenyl)-propan-1-ol; hydrochloride (27.7 mg, 0.125 mmol; Supplier=Oakwood) were added followed by N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (35.9 mg, 0.187 mmol). After 3 hours concentrated reaction under reduced pressure, then partitioned residue between EtOAc and water. The organic was then washed with saturated aqueous NaHCO3, dried over Na2SO4, filtered and concentrated. The crude residue was used for the subsequent step without further manipulation 
     154d) At rt dissolved [4-[(S)-1-(4-Chloro-phenyl)-3-hydroxy-propylcarbamoyl]-1-(5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperidin-4-yl]-carbamic acid tert-butyl ester (70 mg, 0.1 mmol) in Methylene chloride (2.0 mL) then added Trifluoroacetic Acid (1.0 mL, 13 mmol) neat. After 2 hours concentrated reaction under reduced pressure, dissolved residue in 1 mL DMSO, filtered, and purified via preparative reverse phase HPLC. Combined purest fractions and lyophylized overnight. Obtained 15 mg (20%) of title compound as a yellow lyophilate (LC/MS: M+H=548.1). 
     Example 155. 4-(5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-2-carboxylic acid methyl ester 
     155a) 4-(5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester: 5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol (508 mg, 2.00 mmol), Triethylamine (863 uL, 6.19 mmol), 2,4,6-Triisopropylbenzenesulfonyl Chloride (668 mg, 2.20 mmol), and 4-Dimethylaminopyridine (28 mg, 0.23 mmol) in N,N-Dimethylformamide (10 mL) were stirred at room temperature for 2 hours. Gradual dissolution of starting material was observed and a considerable darkening of the solution. Piperazine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (536 mg, 2.20 mmol) was added and the reaction was stirred at room temperature for two hours. Water was added, and the resulting solid product was collected by filtration, washed with water, and dried. Obtained 448 mg (47%) tan colored solid product, which was used for subsequent steps without further manipulation). 
     155b) At room temperature (rt) dissolved 4-(5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (50 mg, 0.1 mmol) in Methylene chloride (2.0 mL) then added Trifluoroacetic Acid (1.0 mL, 13 mmol) neat. After 2.5 hours concentrated reaction solution under reduced pressure, then dissolved residue in 1 mL of DMSO and purified via preparative reverse phase HPLC. Combined desired fractions and lyophylized overnight. Obtained 23 mg (60%) of title compound as a yellow lyophilate (LC/MS: M+H=381.1). 
     Example 156. 4-(5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-2-carboxylic acid phenylamide 
     156a) 4-(5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-2-phenylcarbamoyl-piperazine-1-carboxylic acid tert-butyl ester: At rt 4-(5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1,2-dicarboxylic acid 1-tert-butyl ester (77.0 mg, 0.165 mmol) was combined with N,N-Dimethylformamide (3 mL), then 1-Hydroxybenzotriazole (22.3 mg, 0.165 mmol), 4-Methylmorpholine (36.3 uL, 0.330 mmol) and Aniline (22.6 uL, 0.247 mmol) were added followed by N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (94.9 mg, 0.495 mmol). After two hours the reaction mixture was concentrated under reduced pressure, and the resulting residue partitioned between EtOAc and saturated aqueous NaHCO3. The organic phase was dried over Na2SO4, filtered and concentrated. The crude residue was dissolved in 0.95 mL of DMSO, filtered, and purified via preparative reverse phase HPLC. The desired fractions were combined and lyophilized to yield 42 mg (47%) of desired product as a yellow lyophilate (LC/MS: M+H=542.2). 
     156b) Trifluoroacetic Acid (1 mL, 10 mmol) and Methylene chloride (2 mL, 30 mmol) were combined with 4-(5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-2-phenylcarbamoyl-piperazine-1-carboxylic acid tert-butyl ester (42.0 mg, 0.0775 mmol) at rt. After 1.5 h the reaction solution was concentrated under reduced pressure, after which the resulting residue was dissolved in 1.3 mL of DMSO, filtered, and purified via preparative reverse phase HPLC. The desired fractions were combined and lyophylized overnight to yield 29 mg (85%) of title compound as a yellow lypohilate (LC/MS: M+H=442.1). 
     Example 157. 4-(5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-2-carboxylic acid benzylamide 
     157a) 2-Benzylcarbamoyl-4-(5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester: At room temperature 4-(5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1,2-dicarboxylic acid 1-tert-butyl ester (77.0 mg, 0.165 mmol) was combined with N,N-Dimethylformamide (3 mL), then 1-Hydroxybenzotriazole (22.3 mg, 0.165 mmol), 4-Methylmorpholine (36.3 uL, 0.330 mmol) and Benzylamine (27.0 uL, 0.247 mmol) were added followed by N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (94.9 mg, 0.495 mmol). After 1.5 h the reaction mixture was concentrated under reduced pressure and the resulting residue partitioned between EtOAc and saturated aqueous NaHCO3. The organic phase was dried over Na2SO4, filtered and concentrated. The crude residue was dissolved in 0.85 mL of DMSO, filtered, then purified via preparative reverse phase HPLC. The desired fractions were combined and lyophilized to yield 48 mg (52%) of desired product as a yellow lyophilate (LC/MS: M+H=556.2). 
     157b) A solution of Trifluoroacetic Acid (1 mL, 10 mmol) and Methylene chloride (2 mL, 30 mmol) was combined with 2-Benzylcarbamoyl-4-(5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (47.0 mg, 0.0846 mmol) at rt. After 1.5 h concentrated mixture under reduced pressure, then dissolved residue in 1.15 mL of DMSO, filtered, and purified via preparative reverse phase HPLC. The desired fractions were combined and lyophilized to yield 38 mg (99%) of title compound as a yellow lypohilate (LC/MS: M+H=456.1). 
     Example 158. 4-(5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-2-carboxylic acid phenethyl-amide 
     158a) 4-(5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-2-phenethylcarbamoyl-piperazine-1-carboxylic acid tert-butyl ester: At rt 4-(5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1,2-dicarboxylic acid 1-tert-butyl ester (77.0 mg, 0.165 mmol) was combined with N,N-Dimethylformamide (3 mL, 30 mmol), then 1-Hydroxybenzotriazole (22.3 mg, 0.165 mmol), 4-Methylmorpholine (36.3 uL, 0.330 mmol) and Phenethylamine (31.1 uL, 0.248 mmol) were added followed by N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (94.9 mg, 0.495 mmol). After 16 h the reaction mixture was concentrated under reduced pressure and the resulting residue partitioned between EtOAc and saturated aqueous NaHCO3. The organic phase was dried over Na2SO4, filtered and concentrated. The crude residue was dissolved in 0.9 mL of DMSO, filtered, then purified via preparative reverse phase HPLC. The desired fractions were combined and lyophilized to yield 53 mg (56%) of desired product as a yellow lyophilate (LC/MS: M+H=570.2). 
     158b) A solution of Trifluoroacetic Acid (1 mL, 10 mmol) and Methylene chloride (2 mL) was combined with 4-(5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-2-phenethylcarbamoyl-piperazine-1-carboxylic acid tert-butyl ester (48.2 mg, 0.0846 mmol) at rt. After 1.5 h concentrated mixture under reduced pressure, then dissolved residue in 1.2 mL of DMSO, filtered, and purified via preparative reverse phase HPLC. The desired fractions were combined and lyophilized to yield 38 mg (96%) of title compound as a yellow lyophilate (LC/MS: M+H=470.2). 
     Synthesis of 4-(2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A080] 
     
       
         
         
             
             
         
       
     
     A mixture of 2-Pyridin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [A001](1.0 g, 4.5 mmol), DMF (30 mL) and DIPEA (2.35 mL, 13.5 mmol) was stirred at room temperature under nitrogen. DMAP (5 mg) was added followed by 2,4,6-triisopropylbenzene sulfonyl chloride (1.64 g, 5.4 mmol) and the mixture was left to stir for two hours. 1-Boc piperazine (0.83 g, 4.5 mmol) was added and the mixture left to stir at room temperature over night. Water (50 mL) was added and the mixture left to stir for 20 min, filtered and washed with water (×3). The solid was dissolved in DCM (50 mL) and dried (MgSO4), filtered and evaporated under reduced pressure to give the title compound (1.2 g, 68% yield) which was used crude in the next step without further purification. 
     Synthesis of 4-(8-Propyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A081] and 4-(8-Methyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A082] 
     
       
         
         
             
             
         
       
     
     To a solution of 4-(2-Pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [A080](0.196 g, 0.5 mmol), butyraldehyde (0.090 mL, 1.0 mmol), conc sulphuric acid (0.054 mL, 1.0 mmol) and iron sulphate heptahydrate (0.04 g, 0.15 mmol) in DMSO (5 mL) was added hydrogen peroxide (35% solution in water, 0.146 mL, 1.5 mmol) dropwise over 2 min. The reaction mixture was left to stir at room temperature overnight then water (5 mL) was added and the mixture was basified by addition of NaOH (1N) dropwise to pH ˜7-8. The mixture was then extracted with DCM (×3) the organics were combined and washed with water (×1), brine (×1), dried (MgSO4), filtered and evaporated under reduced pressure. The crude residue was purified by column chromatography (SiO2 column, ISCO eluting with 50-90% EtOAc/cHex on 120 g column) to give: 4-(8-Propyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (46 mg): LCMS: method: 5, RT: 5.79 min, MI 435 [M+H];  1 H NMR (1H, CDCl3, 500 MHz), 8.77 (2H, dd), 8.50 (1H, d), 8.38 (2H, dd), 7.46 (1H, d), 3.91-3.89 (4H, m), 3.71-3.69 (4H, m), 3.49 (2H, dd), 2.00-1.92 (2H, dq), 1.51 (9H, s), 1.09 (3H, t) and 4-(8-Methyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (44 mg) as a colourless glass: LCMS: method: 5, RT: 5.11 min, MI 407 [M+H];  1 H NMR (CDCl3, 500 MHz) 8.78 (2H, dd), 8.46 (1H, d), 8.39 (2H, dd), 7.47 (1H, d), 3.91-3.89 (4H, m), 3.71-3.69 (4H, m), 3.09 (3H, s), 1.51 (9H, s). 
     Example 159. 4-Piperazin-1-yl-8-propyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine 
     A mixture of 4-(8-Propyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid [A081](0.046 g, 0.105 mmol), DCM (3 mL) and HCl (4N in dioxane, 1 mL) was stirred at room temperature for 90 min. The mixture was evaporated under reduced pressure then the crude product was dissolved in methanol and added to SCX-2 cartridge (10 g), washed with DCM/MeOH (1:1 10 mL) and MeOH (20 mL), then eluted with ammonia (7N in methanol, 30 mL). The Ammonia washes were evaporated under reduced pressure to give the title compound (34 mg, 75% yield) as a yellow solid: LCMS: method: 5, RT: 2.0 min, MI 335 [M+H];  1 H NMR (d6-dmso, 500 MHz), 8.76 (2H, dd), 8.45 (1H, d), 8.32 (2H, dd), 7.71 (1H, d), 3.89 (4H, t), 3.37 (2H, t), 2.95 (4H, t), 1.86 (2H, dq), 0.99 (3H, t). 
     Example 160. 8-Methyl-4-piperazin-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine 
     A mixture of 4-(8-Methyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid [A082](0.045 g, 0.11 mmol), DCM (3 mL) and HCl (4N in dioxane, 1 mL) was stirred at room temperature for 90 min. The mixture was evaporated under reduced pressure then the crude product was dissolved in methanol and added to SCX-2 cartridge (10 g), washed with DCM/MeOH (1:1 10 mL) and MeOH (20 mL), then eluted with ammonia (7N in methanol, 30 mL). The Ammonia washes were evaporated under reduced pressure to give the title compound (29 mg, 75% yield) as a brown gum: LCMS: method: 5, RT: 2.17 min, MI 307 [M+H];  1 H NMR (d6-dmso, 500 MHz), 8.76 (2H, dd), 8.40 (1H, d), 8.33 (2H, dd), 7.70 (1H, d), 3.88 (4H, t), 2.94-2.92 (4H, m), 2.93 (3H, s) 
     General synthesis of substituted 2-amino pyridyl substituted 2-(2-amino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl amine derivatives of general formula [G-003] Scheme B1 
     2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl amine derivatives of general formula [G-002] were prepared by the reaction of a 2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol derivative of general formula [G-001] with 2,4,6-triisopropylbenzenesulfonyl chloride in a polar aprotic solvent such as DMA, DMF, NMP with a tertiary alkylamine base such as Et 3 N, DIPEA or NMM and a catalytic amount of DMAP. The intermediate 6,7-substituted-(2,4,6-triisopropyl-benzenesulfonic acid)-2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl ester was then reacted with a primary or secondary amino derivative, of general formula [G-004], in a polar aprotic solvent such as DMA, DMF, NMP in the presence of a tertiary amine base such as Et 3 N, DIPEA or NMM at ambient temperature. The 2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl amine derivatives of general formula [G-002] was involved in a Buchwald type reaction utilising a suitable amine, of general formula [G-005], a palladium catalyst such as Pd(dba) 2  or Pd(OAc) 2 , a ligand such as Xantphos and a base such as NaOtBu or Cs 2 CO 3  in a polar solvent such as dioxane or a combination of dioxane and DMA at high temperature either by heating thermally or using a microwave reactor, to yield substituted 2-amino pyridyl substituted 2-(2-amino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl amine derivatives of general formula [G-003]. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the intermediate was purified by column chromatography and the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, HCl in a solvent such as DCM, DCE or 1,4-dioxane or by catch and release sulfonic acidic resins such as polymer supported toluene sulfonic acid and the crude reaction product was purified by normal phase chromatography or reverse phase preparative HPLC. 
     
       
         
         
             
             
         
       
     
     Synthesis of [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-phenyl-amine [200] 
     
       
         
         
             
             
         
       
     
     2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol [B001] 
     To a solution of 2-chloro-4-pyridinecarbonitrile (0.97 g, 7.03 mmol) in MeOH (35 mL) at RT, under nitrogen, was added NaOMe (0.08 g, 1.46 mmol) and left to stir for 60 mins. Then a solution of 3-Amino-5-methoxy-isonicotinic acid (1 g, 5.86 mmol) in MeOH (15 mL) was added to the dark brown mixture dropwise over 5-10 mins (via syringe). The solution was stirred at rt for 2 h and then overnight at 85° C. After cooling down, the solid was filtered and, washed with methanol and used without further purification to yield the title compound [B001](0.97 g 57% yield: LCMS: method: 5, RT: 6.32 min, MI 287.34 [M+H]. 
     
       
         
         
             
             
         
       
     
     4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [B002] 
     A mixture of 2-(2-chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol [B001](0.58 g, 2 mmol), anhydrous DMA (5 mL), triethylamine (0.58 mL, 4 mmol) and DMAP (20 mg, 0.16 mmol) was sonicated for 10 min then stirred at room temperature for 10 min. 2,4,6-Triisopropyl-benzenesulfonyl chloride (0.67 g, 2.2 mmol) was added and the mixture was sonicated for 5 min then left to stir at room temperature for 2 hours. During this time the material went into solution to form a viscous solution. A solution of Boc piperazine (0.56 g, 3 mmol) in anhydrous DMA (1 mL) was added and the reaction mixture was left to stir at room temperature overnight. Water (20 mL) was added and the reaction mixture was extracted with DCM (2×30 mL), the extracts were combined and washed with water (20 mL), saturated bicarbonate solution (2×20 mL) and water (20 mL), dried (MgSO 4 ) filtered and evaporated under reduced pressure to give a pale yellow oil, which was purified by flash column chromatography (SP1, 50 g SiO 2  cartridge 100% EtOAc up to 95% EtOAc: 5% MeOH gradient) to give the title compound [B002] as a colourless solid (0.22 g 24% yield). LCMS: method: 5, RT: 10.86 min, MI 457 [M+H]; NMR: (1H, 500 MHz, CDCl 3 ); 9.0 (1H, s), 8.53 (1H, d), 8.35 (1H, s), 8.28 (1H, 1H, d), 8.23 (1H, s), 3.70 (4H, br s), 3.64 (4H, br s), 1.50 (9H, s) 
     
       
         
         
             
             
         
       
     
     4-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [B003] 
     A mixture of 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [B002](0.100 g, 0.22 mmol), Pd(dba) 2  (10 mg, 0.013 mmol), Xantphos (17.5 mg, 0.025 mmol), NaOtBu (43 mg, 0.440 mmol) and anhydrous dioxane (4 ml) was added to a microwave vial. Aniline was then added the vial was sealed and heated at 150° C. for 20 min. Water (10 mL) was added and the reaction mixture was extracted with DCM (2×10 mL), the extracts were combined and washed with water (10 mL), saturated bicarbonate (2×10 mL) and water (10 mL), dried with MgSO4 filtered and evaporated to give a pale yellow oil, which was purified by flash column chromatography (SP1, 25 g SiO2 cartridge 100% EtOAc up to 95% EtOAc: 5% MeOH gradient) to give the title compound [B003] as a colourless solid (0.04 g 36% yield). LCMS: method: 5, RT: 7.80 min, MI 514 [M+H]; NMR: (1H, 500 MHz, CDCl 3 ); 8.93 (1H, s), 8.65 (1H, d), 8.41 (1H, s), 7.39 (1H, d), 7.58 (5H, m), 6.55 (1H, br s), 3.63 (4H, m), 3.57 (4H, m), 1.49 (9H, s). 
     
       
         
         
             
             
         
       
     
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-phenyl-amine 
     To a mixture of 4-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [B003](0.040 g, 0.080 mmol) in DCM (1 ml) was added TFA (1 ml) and the mixture was left to stir at room temperature for 2 hours. After completion the crude reaction mixture was diluted with DCM (5 mL) and poured onto a 1 g SCX-2 cartridge and washed with DCM and MeOH before eluting with 2N NH3/MeOH which was evaporated to give a pale yellow oil, which was evaporated in a genevac to give a pale yellow solid (25 mg). LCMS: method: 5, RT: 3.12 min, MI: 414.22 [M+H]; NMR: (1H, 500 MHz, d6-dmso); 9.32 (1H, br s), 8.8 (1H, s), 8.29 (2H, m), 7.88 (1H, s), 7.76 (2H, d), 7.64 (1H, d), 7.29 (2H, m), 6.88 (2H, m), 4.04 (3H, s), 3.64 (4H, m), 2.88 (4H, m). 
     
       
         
         
             
             
         
       
     
     2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol [B004] 
     To a solution of 2-chloro-4-pyridinecarbonitrile (2.18 g, 15.77 mmol) in dry THF (20 mL) was added 3-Amino-isonicotinic acid methyl ester (2 g, 13.1 mmol) followed by Potassium tert-pentoxide (15.5 mL, 26.3 mmol 1.7M in toluene). The reaction was stirred overnight at RT. The precipitate was collected by filtration to yield the title compound which was used without further purification: LCMS: method: 5, RT: 4.05 min, MI 259 [M+H]. 
     
       
         
         
             
             
         
       
     
     (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester [B005] 
     A mixture of 2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol [B003](1 g, 3.86 mmol), anhydrous DMA (10 mL), triethylamine (1.1 mL, 7.73 mmol), 2,4,6-Triisopropylbenzenesulfonyl chloride (1.29 g, 3.25 mmol), and DMAP (47 mg, 0.386 mmol) was stirred at room temperature for 1 h and (R)-3-Amino-pyrrolidine-1-carboxylic acid tert-butyl ester (940 mg, 5.02 mmol) was added. The reaction mixture was stirred overnight and the solvent was evaporated under reduced pressure. DCM and Et 2 O were added and the resulting solid was collected and used without further purification in the next step. LCMS: method: 5, RT 6.19 min, MI 427 [M+H]. 
     The following compounds were synthesised according to the general synthesis shown in scheme [B1](Example 1): 
     
       
         
           
               
               
               
               
               
               
            
               
                   
               
               
                   
                 SM 
                   
                   
                 Analysis 
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Ex 
                 [G-002] 
                 Amine 
                 Aniline 
                 LCMS 
                 NMR 
                 Name 
               
               
                   
               
               
                 201 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1:  RT: 1.91 min, MI: 416.17 [M + H] 
                 (1H, 300 MHz, CDCl 3 ) 10.22 (1H, m), 9.16 (1H, m), 8.82 (1H, m), 7.72 (1H, m), 8.43 (1H, m), 8.33 (1H, m), 8.30 (1H, m), 8.26 (1H, m), 7.85 (1H, m), 4.10 (3H, s), 3.71 (4H, m), 2.96 (4H, m) 
                 [4-(5- Methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]-pyrazin- 2-yl-amine 
               
               
                   
               
               
                 202 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1:  RT: 3.27 min, MI: 473.2 [M + H] 
                 (1H, 500 MHz, d6-dmso) 9.35 (1H, s), 9.10 (1H, s), 8.91 (1H, s), 8.53 (1H, m), 8.46 (1H, d), 8.42 (1H, s), 7.99 (1H, dd), 4.09 (3H, s), 3.93 (4H, m, br), 3.27 (4H, m, br) 
                 [4-5- Methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]-(4- trifluoro- methyl- oxazol-2- yl)-amine 
               
               
                   
               
               
                 203 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1:  RT: 2.40 min, MI: 433.1 [M + H] 
                 (1H, 500 MHz, d6-dmso) 10.55 (1H, s), 9.14 (1H, s), 8.81 (1H, s), 8.34 (1H, d), 8.31 (1H, s), 7.84 (1H, d), 4.06 (3H, s), 3.68 (4H, m), 2.90 (4H, m), 2.19 (3H, s), 2.01 (3H, s) 
                 (4,5- Dimethyl- oxazol-2-yl)- [4-(5- methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]-amine 
               
               
                   
               
               
                 204 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.73 min, MI: 461.20 [M + H] 
                 (1H, 500 MHz, d6-dmso) 9.68 (1H, s, br), 9.56 (2H, s, br), 8.96 (1H, s), 8.46 (1H, d), 8.42 (1H, s), 8.23 (1H, s), 7.88 (1H, dd), 4.10 (3H, s), 3.96 (4H, m), 3.32 (1H, m), 3.27 (4H, m), 0.86 (2H, m), 0.80 (2H, m) 
                 (4- Cyclopropyl- thiazol-2-yl)- [4-(5- methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]-amine 
               
               
                   
               
               
                 205 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1:  RT: 3.47 min, MI: 439.2 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.82 (1H, s), 9.10 (1H, s, br), 8.89 (1H, s), 8.41 (2H, s, br), 8.40 (1H, s), 7.97 (1H, s), 7.89 (1H, d), 7.78 (1H, d), 7.48 (1H, t), 7.32 (1H, d), 4.09 (3H, s), 3.90 (4H, m), 3.31 (4H, m) 
                 3-[4-(5- Methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-ylamino]- benzonitrile 
               
               
                   
               
               
                 206 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 2.69 min, MI: 482.03 [M + H] 
                 (1H, 300 MHz, d6-dmso) 8.95 (1H, s), 8.79 (1H, s), 8.31 (1H, s), 8.23 (1H, d), 8.20 (1H, dt), 8.01 (1H, s), 7.68 (1H, dd), 7.21 (1H, ddd), 7.14 (1H, td), 7.01-6.99 (1H, m), 4.06 (3H, s), 3.65 (4H, m, br), 2.87 (4H, m, br) 
                 (2-Fluoro- phenyl)-[4- (5-methoxy- 4-piperazin- l-yl- pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]-amine 
               
               
                   
               
               
                 207 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 (1H, 300 MHz, d6-dmso) 9.83 (1H, s), 8.85 (1H, s), 8.38 (1H, d), 8.36 (1H, s), 7.98 (2H, s), 7.96 (1H, s), 7.76 (1H, d), 7.61 (2H, d), 4.07 (3H, s), 3.79 (4H, m, br), 3.11 (4H, m, br) 
                 [4-(5- Methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]-(4- trifluoro- methyl- phenyl)- amine 
               
               
                   
               
               
                 208 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1: RT: 3.51 min, MI: 338.2 [M + H] 
                 (1H, 300 MHz, d6-dmso) 8.78 (1H, s), 8.30 (1H, s), 8.27 (1H, s), 8.04 (1H, d), 7.47 (1H, s), 7.41 (1H, d), 6.10 (2H, s, br), 4.06 (3H, s), 3.66 (4H, m, br), 2.95 (4H, m, br) 
                 4-(5- Methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-ylamine 
               
               
                   
               
               
                 209 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1:  RT: 1.80 min, MI: 465.2 [M + H] 
                 (1H, 300 MHz, d6-dmso) 10.11 (1H, s), 9.10 (1H, s), 8.88 (1H, s), 8.47 (1H, d), 8.37 (1H, s), 8.05 (1H, d), 4.08 (3H, s), 3.80 (4H, m, br), 3.64 (4H, t, br), 3.23 (2H, s), 3.15 (4H, m, br), 2.55 (4H, m, br) 
                 N-[4-(5- Methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]-2- morpholin-4- yl-acetamide 
               
               
                   
               
               
                 210 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1:  RT: 1.51 min, MI: 463.2  [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.19 (1H, s), 8.79 (1H, s), 8.41 (1H, d), 8.21 (1H, s), 8.10 (1H, d), 4.11 (3H, s), 3.77 (4H, m), 3.19 (2H, s), 3.01 (4H, m), 2.59 (4H, m), 1.73-1.69 (4H, m), 1.52 (2H, m) 
                 N-[4-(5- Methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]-2- piperidin-1- yl-acetamide 
               
               
                   
               
               
                 211 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1:  RT: 2.05 min, MI: 416.14 [M + H] 
                 (1H, 300 MHz, d6-dmso) 10.42 (1H, s), 8.85 (1H, s), 8.75 (2H, s), 8.45 (2H, d), 8.35 (1H, s), 8.22 (1H, s), 7.90 (1H, dd), 4.08 (3H, s), 3.73 (4H, m), 2.98 (4H, m) 
                 [4-(5- Methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]- pyrimidin-4- yl-amine 
               
               
                   
               
               
                 212 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1:  RT: 2.69 min, MI: 442.13 
                 (1H, 300 MHz, d6-dmso) 9.17 (1H, s), 8.85 (1H, s), 8.54 (1H, d), 8.33 (1H, s), 8.22 (1H, s), 8.09-8.05 (3H, m), 7.62-7.59 (1H, m), 7.54-7.51 (2H, m) 
                 N-[4-(5- Methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]- benzamide 
               
               
                   
               
               
                 213 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1:  RT: 3.98 min, MI: 352.3 [M + H] 
                 (1H, 300 MHz, d6-dmso) 8.80 (1H, s), 8.31 (1H, s), 8.11 (1H, d), 7.47 (1H, s), 7.39 (1H, d), 6.72 (1H, d), 4.05 (3H, s), 3.71 (4H, m), 3.03 (4H, m), 2.81 (3H, d) 
                 [4-(5- Methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]-methyl- amine 
               
               
                   
               
               
                 214 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1:  RT: 2.33 min MI: 380.18 [M + H] 
                 (1H, 300 MHz, d6-dmso) 10.58 (1H, s), 9.05 (1H, s), 8.81 (1H, s), 8.43 (1H, d), 8.29 (1H, s), 7.97 (1H, d), 4.05 (3H, s), 3.63 (4H, m), 3.15 (1H, d, br), 2.87 (4H, m), 2.12 (3H, s) 
                 N-[4-(5- Methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]- acetamide 
               
               
                   
               
               
                 215 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1:  RT: 3.87 min, MI: 395.11 [M + H] 
                 (1H, 300 MHz, d6-dmso) 10.58 (1H, s), 9.05 (1H, s), 8.81 (1H, s), 8.43 (1H, d), 8.32 (1H, s), 7.98 (1H, dd), 4.79 (1H, d), 4.06 (3H, s), 4.00 (1H, m, br), 3.81 (1H, m, br), 3.39 (3H, m, br), 2.12 (3H, s), 1.89 (2H, d, br), 1.56  (2H, m, br). 
                 N-{4-[4-(4- Hydroxy- piperidin-1- yl)-5- methoxy- pyrido[3,4- d]pyrimidin- 2-yl]-pyridin- 2-yl}- acetamide 
               
               
                   
               
               
                 216 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1:  RT: 2.66 min, MI: 406.13 [M + H]  
                 (1H, 300 MHz, d6-dmso) 8.28 (1H, s), 8.01 (1H, s), 7.61 (1H, d), 7.42 (1H, s), 7.26 (1H, dd), 3.32 (3H, s), 2.99 (4H, m), 2.27 (4H, m), 1.13 (1H, m), 0.22 (2H, m), 0.12 (2H, m) 
                 Cyclopropane- carboxylic acid [4-(5- methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]-amide 
               
               
                   
               
               
                 217 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1:  RT: 3.13 min, MI: 422.2 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.89 (1H, s), 9.03 (1H, s), 8.84 (1H, s), 8.46 (1H, d), 8.33 (1H, s), 8.01 (1H, dd), 4.06 (3H, s), 3.68 (4H, m, br), 2.95 (4H, m, br), 1.27 (9H, s) 
                 N-[4-(5- Methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]-2,2- dimethyl- propionamide 
               
               
                   
               
               
                 218 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1:  RT: 2.82 min, MI: 450.20 [M + H] 
                 (1H, 300 MHz, d6-dmso) 10.59 (1H, s), 9.10 (1H, s), 8.87 (1H, s), 8.46 (1H, d), 8.36 (1H, s), 8.01 (1H, dd), 4.07 (3H, s), 3.90 (2H, dd, br), 3.78 (4H, m, br), 3.35 (2H, m), 3.13 (4H, m, br), 2.79 (1H, m), 1.74-1.66 (4H, m) 
                 Tetrahydro- pyran-4- carboxylic acid[4-(5- methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]-amide 
               
               
                   
               
               
                 219 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1:  RT: 3.12 min, MI: 241.09 [M + H] 
                 (1H, 300 MHz, d6-dmso) 8.84 (1H, s), 8.43 (1H, d), 8.35 (1H, s), 8.15 (1H, s), 7.82 (1H, dd), 7.40 (1H, d), 7.01 (1H, s), 4.07 (3H, s), 3.75 (4H, m), 3.04 (4H, m) 
                 [4-(5- Methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]-thiazol- 2-yl-amine 
               
               
                   
               
               
                 220 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1:  RT: 2.28 min, MI: 405.10 [M + H] 
                 (1H, 500 MHz, d6-dmso) 10.82 (1H, s), 9.04 (1H, s), 8.84 (1H, s), 8.38 (1H, d), 8.34 (1H, s), 7.87 (1H, d), 7.74 (1H, s), 7.09 (1H, s), 4.07 (3H, s), 3.74 (4H, m), 3.01 (4H, m) 
                 [4-(5- Methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]-oxazol- 2-yl-amine 
               
               
                   
               
               
                 221 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1:  RT: 2.44 min, MI: 419.18 [M + H] 
                 (1H, 500 MHz, d6-dmso) 10.77 (1H, s), 9.19 (1H, s), 8.91 (1H, s), 8.40 (1H, s), 8.39 (1H, d), 7.88 (1H, d), 7.44 (1H, s), 4.09 (3H, s), 3.92 (4H, m), 3.29 (4H, m), 2.10 (3H, s) 
                 [4-(5- Methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]-(4- methyl - oxazol-2-yl)- amine 
               
               
                   
               
               
                 222 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 1:  RT: 2.38 min, MI: 444.2 [M + H] 
                 (1H, 500 MHz, d6-dmso) 9.39 (1H, s), 8.88 (1H, s), 8.39 (1H, s), 8.31 (1H, d), 7.94 (1H, s), 7.75 (2H, d), 7.68 (1H, d), 7.27 (2H, t), 6.89 (1H, t), 4.30 (2H, m), 4.09 (3H, s), 3.70 (2H, m), 3.48-3.36 (5H, m) 
                 {(S)-4-[5- Methoxy-2- (2- phenylamino- pyridin-4-yl)- pyrido[3,4- d]pyrimidin- 4-yl]- piperazin-2- yl}-methanol 
               
               
                   
               
               
                 223 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 4.34 min, MI: 443.19 [M + H]  
                 (1H, 500 MHz, d6-dmso) 9.29 (1H, s), 8.78 (1H, s), 8.30 (1H, s), 8.28 (1H, d), 7.89 (1H, d), 7.73 (2H, d), 7.65 (1H, dd), 7.27 (2H, t), 6.88 (1H, t), 4.47 (1H, s), 4.06 (3H, s), 3.94 (2H, m, br), 3.53 (2H, m), 1.64 (4H, m), 1.19 (3H, s) 
                 1-[5- Methoxy-2- (2- phenylamino- pyridin-4-yl)- pyrido[3,4- d]pyrimidin- 4-yl]-4- methyl- piperidin-4-ol 
               
               
                   
               
               
                 224 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 2.87 min, MI: 456.23 [M + H] 
                 (1H, 500 MHz, d6-dmso) 9.30 (1H, s), 8.81 (1H, s), 8.32 (1H, s), 8.29 (1H, d), 7.88 (1H, s), 7.74 (2H, d), 7.64 (1H, dd), 7.27 (2H, t), 6.89 (1H, t), 4.24-4.12 (2H, m), 4.06 (3H, s), 3.15-3.06 (2H, m), 2.82 (2H, m), 2.59 (1H, m), 1.66 (1H, m), 0.96 (6H, dd) 
                 {4-[4-((S)-3- Isopropyl- piperazin-1- yl)-5- methoxy- pyrido[3,4- d]pyrimidin- 2-yl]-pyridin- 2-yl}-phenyl- amine 
               
               
                   
               
               
                 225 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 2.49 min, MI: 458.18 [M + H]] 
                 (1H, 500 MHz, d6-dmso) 9.30 (1H, s), 8.82 (1H, s), 8.34 (1H, s), 8.29 (1H, d), 7.90 (1H, s), 7.73 (2H, d), 7.67 (1H, dd), 7.27 (2H, t), 6.89 (1H, t), 4.21 (2H, m, br), 4.06 (3H, s), 3.58 (2H, t), 3.22 (1H, t, br), 3.16-3.14 (2H, m), 2.95 (2H, m), 1.63 (2H, m) 
                 2-{(S)-4-[5- Methoxy-2- (2- phenylamino- pyridin-4-yl)- pyrido[3,4- d]pyrimidin- 4-yl]- piperazin-2- yl}-ethanol 
               
               
                   
               
               
                 226 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 2.11 min, MI: 457.20 [M + H] 
                 (1H, 500 MHz, d6-dmso) 8.90 (1H, s, br), 8.75 (1H, s), 8.32 (1H, s), 8.19 (1H, d), 8.07 (1H, d), 7.78 (1H, s), 7.55 (1H, d), 7.47 (2H, d), 6.72 (2H, d), 4.76-4.70 (1H, m), 4.12 (3H, s), 3.29 (1H, dd), 3.10-3.02 (1H, m), 2.93-2.87 (1H, m), 2.83 (6H, s), 2.32- 2.23 (1H, m), 1.90-1.76 (1H, m) 
                 N-{4-[5- Methoxy-4- ((R)- pyrrolidin-3- ylamino)- pyrido[3,4- d]pyrimidin- 2-yl]-pyridin- 2-yl}-N′,N′- dimethyl- benzene-1,4- diamine 
               
               
                   
               
               
                 227 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 2.53 min, MI: 499.26 [M + H] 
                 (1H, 500 MHz, d6-dmso) 9.23 (1H, s, br), 8.75 (1H, s), 8.32 (1H, s), 8.28 (1H, d), 8.09 (1H, d), 7.90 (1H, s), 7.65 (1H,d), 7.36 (1H, s), 7.22 (1H, s), 7.12 (1H, t), 6.53 (1H, dd), 4.81- 4.75 (1H, m), 4.12 (3H, s), 3.75 (4H, m), 3.37- 3.31 (1H, dd), 3.08 (4H, m), 2.95-2.90 (1H, m), 2.35-2.26 (1H, m), 1.88- 1.82 (1H, m) 
                 {5-Methoxy- 2-[2-(3- morpholin-4- yl- phenylamino)- pyridin-4- yl]- pyrido[3,4- d]pyrimidin- 4-yl}-(R)- pyrrolidin-3- yl-amine 
               
               
                   
               
               
                 228 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 2.63 min, MI: 432.14 [M + H] 
                 (1H, 500 MHz, d6-dmso) 9.00 (1H, s), 8.76 (1H, s), 8.33 (1H, s), 8.26 (1H, d), 8.16 (1H, t), 8.10 (1H, d), 8.01 (1H, s), 7.71 (1H, d), 7.23 (1H, t), 7.14 (1H, t), 7.01 (1H, t), 4.82-4.74 (1H, m), 4.13 (3H, s), 3.37-3.31 (1H, m), 3.12- 3.04 (1H, m), 2.97-2.89 (1H, m), 2.35-2.25 (1H, m), 1.89-1.82 (1H, m) 
                 {2-[2-(2- Fluoro- phenylamino)- pyridin-4- yl]-5- methoxy- pyrido[3,4- d]pyrimidin- 4-yl}-(R)- pyrrolidin-3- yl-amine 
               
               
                   
               
               
                 229 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 2.34 min, MI: 499.25 [M + H] 
                 (1H, 500 MHz, d6-dmso) 9.06 (1H, s), 8.76 (1H, s), 8.33 (1H, s), 8.22 (1H, d), 8.09 (1H, d), 7.83 (1H, s), 7.60 (1H, s), 7.58 (2H, d), 6.90 (2H, d), 4.81-4.74 (1H, m), 4.13 (3H, s), 3.73 (4H, t), 3.02 (4H, t), 2.96-2.93 (2H, m), 2.33- 2.25 (1H, m), 1.89-1.82 (1H, m) 
                 {5-Methoxy- 2-[2-(4- morpholin-4- yl- phenylamino)- pyridin-4- yl]-pyrido [3,4-d] pyrimidin- 4-yl}-(R)- pyrrolidin-3- yl-amine 
               
               
                   
               
               
                 230 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 2.48 min, MI: 432.14 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.46 (1H, s), 8.78 (1H, s), 8.35 (1H, s), 8.32 (1H, s), 8.27 (1H, d), 8.15 (1H, d), 7.89 (1H, s), 7.75 (2H, dd), 7.67 (1H, d), 7.11 (2H, t), 4.88-4.84 (1H, m), 4.14 (3H, s), 3.49- 3.44 (1H, m), 3.21-3.16 (1H, m), 3.07-3.02 (1H, m), 2.35-2.32 (1H, m), 1.99-1.94 (1H, m) 
                 {2-[2-(4- Fluoro- phenylamino)- pyridin-4- yl]-5- methoxy- pyrido[3,4- d]pyrimidin- 4-yl}-(R)- pyrrolidin-3- yl-amine 
               
               
                   
               
               
                 231 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 5.08 min, MI: 482.2 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.34 (1H, s), 8.85 (1H, s), 8.36 (1H, s), 8.31 (1H, d), 7.89 (1H, s), 7.74 (2H, d), 7.64 (1H, dd), 7.28 (1H, d), 7.24 (1H, s), 6.89 (1H, t), 4.23 (1H, d), 4.07 (3H, s), 3.71-3.62 (1H, m), 3.22 (2H, dd), 3.08 (2H, d), 2.89-2.81 (1H, m) 
                 {4-[5- Methoxy-4- (3- trifluoro- methyl- piperazin- 1-yl)- pyrido[3,4- d]pyrimidin- 2-yl]-pyridin- 2-yl}-phenyl- 
               
               
                   
                   
                   
                   
                   
                   
                 amine 
               
               
                   
               
               
                 232 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 2.68 min, MI: 453.17 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.28 (1H, s), 8.82 (1H, s), 8.33 (1H, s), 8.29 (1H, d), 7.89 (1H, s), 7.75 (2H, d), 7.67 (1H, d), 7.27 (2H, t), 6.89 (1H, t), 4.18 (1H, dd), 4.07 (3H, s), 3.29 (1H, m), 3.12-3.02 (3H, m), 2.93 (1H, t), 2.82 (1H, t), 2.71 (2H, d) 
                 {(S)-4-[5- Methoxy-2- (2- phenylamino- pyridin-4-yl)- pyrido[3,4- d]pyrimidin- 4-yl]- piperazin-2- yl}- acetonitrile 
               
               
                   
               
               
                 233 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 2.43 min, MI: 446.18 [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.30 (1H, s), 8.81 (1H, s), 8.33 (1H, s), 8.29 (1H, d), 7.88 (1H, s), 7.73 (2H, d), 7.65 (1H, d), 7.27 (1H, t), 6.89 (1H, t), 4.49 (1H, dd), 4.39 (1H, dd), 4.15 (2H, t, br), 4.06 (3H, s), 3.15-3.11 (2H, m), 3.04 (1H, dd), 2.97 (1H, dd), 2.83 (1H, t, br), 2.60 (1H, m, br) 
                 {4-[4-((R)-3- Fluoromethyl- piperazin-1- yl)-5- methoxy- pyrido[3,4- d]pyrimidin- 2-yl]-pyridin- 2-yl}-phenyl- amine 
               
               
                   
               
               
                 234 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 4.39 min, MI: 421.20 [M + H] 
                 (1H, 500 MHz, d6- dmso) 10.89 (1H, s), 9.06 (1H, s), 8.80 (1H, s), 8.44 (1H, d), 8.31 (1H, s), 7.98 (1H, d), 4.79 (1H, d), 4.06 (1H, s), 3.99 (2H, d, br), 3.80 (1H, m), 3.38 (1H, m), 2.04 (1H, m), 1.89 (2H, d, br), 1.56 (2H, d, br), 0.86-0.81 (4H, m) 
                 Cyclopropane- carboxylic acid {4-[4-(4- hydroxy- piperidin-1- yl)-5- methoxy- pyrido[3,4- d]pyrimidin- 2-yl]-pyridin- 2-yl}-amide 
               
               
                   
               
               
                 235 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 2.43 min, MI: 446.18 [M + H] 
                 (1H, 500 MHz, d6-dmso) 9.30 (1H, s), 8.81 (1H, s), 8.33 (1H, s), 8.29 (1H, d), 7.89 (1H, s), 7.73 (2H, d), 7.65 (1H, d), 7.27 (2H, t), 6.89 (1H, t), 4.49 (1H, d, br), 4.39 (1H, d, br), 4.15 (2H, t, br), 4.06 (3H, s), 3.13 (2H, m, br), 3.03 (1H, d, br), 2.97 (1H, t, br), 2.83 (1H, t, br) 
                 {4-[4-((S)-3- Fluoromethyl- piperazin-1- yl)-5- methoxy- pyrido[3,4- d]pyrimidin- 2-yl]-pyridin- 2-yl}-phenyl- amine 
               
               
                   
               
               
                 236 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 5.50 min, MI: 454.40 [M + H] 
                 (1H, 500 MHz, d6-dmso) 9.31 (1H, s), 8.80 (1H, s), 8.32 (1H, s), 8.30 (1H, d), 7.88 (1H, s), 7.73 (2H, d), 7.63 (1H, dd), 7.27 (2H, t), 6.89 (1H, t), 4.20 (1H, d, br), 4.09 (1H, d, br), 4.04 (3H, s), 3.12 (1H, t), 3.00 (1H, d), 2.93 (1H, t), 2.73 (1H, t), 2.05 (1H, t), 0.76 (1H, m), 0.42 (2H, d, br), 0.28 (2H, m) 
                 {4-[4-((S)-3- Cyclopropyl- piperazin-1- yl)-5- methoxy- pyrido[3,4- d]pyrimidin- 2-yl]-pyridin- 2-yl}-phenyl- amine 
               
               
                   
               
               
                 237 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 3.15 min, MI: 500.18 [M + H] 
                 (1H, 500 MHz, d6-dmso) 9.02 (1H, s), 8.82 (1H, s), 8.33 (1H, s), 8.18 (1H, d), 7.84 (1H, s), 7.68 (1H, dd), 7.30 (1H, m), 7.19 (1H, m), 4.48 (1H, d), 4.39 (1H, d), 4.18 (1H, d, br), 4.12 (1H, m), 4.06 (3H, s), 3.13 (2H, m), 2.98 (2H, m), 2.84 (1H, t, br) 
                 {4-[4-((R)-3- Fluoromethyl- piperazin-1- yl)-5- methoxy- pyrido[3,4- d]pyrimidin- 2-yl]-pyridin- 2-yl}-(2,3,6- trifluoro- phenyl)- amine 
               
               
                   
               
               
                 238 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 2.41 min, MI: 414 [M + H] 
                 (1H, 300 MHz, d6-dmso) 2.03 (m, 1H), water peak very broad!!, 4.13 (s, 3H), 4.87 (brs, 1H), 6.89 (t, 1H), 7.27 (t, 2H), 7.68 (d, 1H), 7.76 (d, 2H), 7.93 (s, 1H), 8.30 (d, 1H), 8.35 (s, 1H), 8.79 (s, 1H), 9.44 (s, 1H) 
                 [5-Methoxy- 2-(2- phenylamino- pyridin-4-yl)- pyrido[3,4- d]pyrimidin- 4-yl]-(R)- pyrrolidin-3- yl-amine 
               
               
                   
               
               
                 239 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 2.10 min, MI: 416 [M + H] 
                 (1H, 300 MHz, d6-dmso) large water peak . . . 4.84 (brs, 1H), 6.60 (brs, 1H), 7.90 (d, 1H), 8.12 (d, 2H), 8.26 (d, 1H), 8.36 (s, 1H), 8.44 (d, 1H), 8.78 (d, 1H), 8.81 (s, 1H), 9.11 (s, 1H), 10.30 (s, 1H) 
                 {5-Methoxy- 2-[2-(pyrazin- 2-ylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin- 4-yl}-(R)- pyrrolidin-3- yl-amine 
               
               
                   
               
               
                 240 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 3.23 min, MI: 448 [M + H] 
                 (1H, 300 MHz, d6-dmso) 1.92-2.05 (m, 2H), huge water peak, 3.81 (s, 3H), 4.87 (brs, 1H), 7.22 (dd, 1H), 7.91 (d, 1H), 8.11 (d, 1H), 8.19 (d, 1H), 8.26- 8.29 (m, 2H), 8.37 (s, 1H), 8.55 (d, 1H), 8.83 (s, 1H), 9.16 (s, 1H), 11.07 (br s, 1H) 
                 Thiophene-2- carboxylic acid {4-[5- methoxy-4- ((R)- pyrrolidin-3- ylamino)- pyrido[3,4- d]pyrimidin- 2-yl]-pyridin- 2-yl}-amide 
               
               
                   
               
               
                 241 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 2.05 min, MI: 406.20 [M + H] 
                 (1H, 300 MHz, d6-dmso) 8.84 (1H, s), 8.36 (1H, s), 8.09 (1H, d), 7.52 (1H, s), 7.37 (1H, dd), 6.79 (1H, s), 4.18 (1H, m), 4.07 (3H, s), 3.87 (4H, m, br), 3.27 (4H, m, br), 1.92 (2H, m, br), 1.69 (2H, m, br), 1.55-1.45 (4H, m). 
                 Cyclopentyl- [4-(5- methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]-amine 
               
               
                   
               
               
                 242 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 2.18 min, MI: 420.23 [M + H] 
                 (1H, 500 MHz, d6-dmso) 8.79 (1H, s), 8.31 (1H, s), 8.06 (1H, d), 7.49 (1H, s), 7.34 (1H, dd), 6.62 (1H, d), 4.06 (3H, s), 3.74 (1H, m), 3.70 (4H, m), 3.01 (4H, m), 1.93 (2H, d, br), 1.71 (2H, m), 1.58 (1H, m), 1.33-1.28 (2H, m), 1.20-1.16 (3H, m) 
                 Cyclohexyl- [4-(5- methoxy-4- piperazin-1- yl-pyrido[3,4- d]pyrimidin- 2-yl)-pyridin- 2-yl]-amine 
               
               
                   
               
               
                 243 
                 [B003] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5:  RT: 1.84 min, MI: 386.0 [M + H] 
                 (1H, 500 MHz, d6-dmso): 10.32 (1H, s), 9.20 (1H, s), 9.15 (1H, d), 8.79 (1H, d), 8.66 (1H, d), 8.35-8.44 (2H, m), 8.29 (1H, s), 8.10 (1H, s), 7.92 (1H, d), 4.95 (1H, br s), 3.58 (1H, dd), 3.26 (3H, m), 2.35 (1H, m), 2.17 (1H, m). 
                 {2-[2- (Pyrazin-2- ylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin- 4-yl}-(R)- pyrrolidin-3- yl-amine 
               
               
                   
               
            
           
         
       
     
     Synthesis of {1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol [244] 
     
       
         
         
             
             
         
       
     
     5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol [B006] 
     A mixture of 4 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol [B003](0.100 g, 0.346 mmol), Pd(OAc) 2  (4 mg, 0.018 mmol), Xantphos (21 mg, 0.035 mmol), cesium carbonate (225 mg, 0.695 mmol) and anhydrous dioxane (1 ml) was heated at 900 overnight. Water (5 mL) was added and the reaction mixture triturated for 30 min after which a yellow solid was collected by filtration and washed with water (20 ml) and DCM (20 ml) to give the title compound as a yellow solid (0.07 g, 59% yield) which was used without further purification in the next step. LCMS method: 1, RT: 2.23 min, MI 346.24 [M+H]; NMR: (1H, 300 MHz, d6-dmso); 9.30 (1H, s), 8.60 (1H, s), 8.25 (1H, d), 7.71 (2H, d), 7.65 (1H, s), 7.45 (1H, dd), 7.26 (2H, t), 6.89 (1H, t), 3.96 (3H, s). 
     {1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol [244] 
     5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol [B003](70 mg, 0.203 mmol), TEA (84 μl, 0.609 mmol) and DMAP (25 mg, 0.203 mmol) were sonicated in DMF (1.5 ml) for 30 min. 2,4,6-Triisopropylbenzenesulfonyl chloride (74 mg, 0.243 mmol) was then added and the reaction mixture stirred at room temperature for 3 hr. 4-Piperidinemethanol (28 mg, 0.243 mmol) was then added and the reaction mixture stirred at room temperature overnight. The solvent was evaporated under reduced pressure to give a pale yellow solid, which was purified by flash column chromatography (SP1, 12 g SiO 2  cartridge 100% DCM up to 95% DCM: 5% MeOH gradient) to give the title compound as a yellow solid (38 mg, 42% yield). LCMS method: 1, RT: 5.26 min, MI 443.35 [M+H]; NMR: (1H, 300 MHz, d6-dmso); 9.30 (1H, s), 8.79 (1H, s), 8.31 (1H, s), 8.28 (1H, d), 7.89 (1H, s), 7.74 (2H, d), 7.65 (1H, d), 7.27 (2H, t), 6.88 (1H, t), 4.52 (1H, t), 4.30 (2H, d, br), 4.07 (3H, s), 3.16 (1H, d), 3.11 (2H, t, br), 1.83 (2H, d, br), 1.72 (1H, s, br), 1.33 (2H, q, br), 1.13 (2H, dd) 
     Synthesis of 2-{3-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-R-pyrrolidin-1-yl}-acetamide [245] 
     
       
         
         
             
             
         
       
     
     To a mixture of [5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-(R)-pyrrolidin-3-yl-amine [238](50 mg, 0.121 mmol) and K 2 CO 3  (50 mg, 0.363 mmol) in DMF (1 mL) was added 2-bromoacetamide (17 mg, 0.121 mmol). The reaction mixture was heated at 80° C. for 4 hr. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (2×10 mL), the extracts were combined and washed with brine (20 mL), dried (MgSO 4 ) filtered and evaporated under reduced pressure to give a pale yellow oil, which was diluted with MeOH (5 mL) and poured onto a 1 g SCX-2 cartridge and washed with MeOH before eluting with 2N NH3/MeOH which was evaporated. The resulting oil was triturated in Et 2 O to give the title compound as a white solid (12 mg, 17% yield). LCMS method: 1, RT: 2.17 min, MI 471 [M+H]; NMR: (1H, 300 MHz, d6-dmso); 9.32 (1H, s), 8.78 (1H, s), 8.35 (1H, s), 8.31 (1H, d), 8.23 (1H, d), 7.76 (2H, d), 7.70 (1H, d), 7.28 (2H, t), 7.13 (1H, s), 6.90 (1H, t), 4.82 (1H, s), 4.15 (3H, s), 3.10 (2H, d), 3.00 (1H, m), 2.89 (1H, m), 2.81 (1H, m), 2.57 (1H, m), 2.40 (1H, m), 1.88 (1H, m). 
     General synthesis of 5-chloro substituted 2-amino pyridyl substituted 2-(2-amino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl amine derivatives of general formula [G-008] Scheme B2 
     5-chloro 2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl amine derivatives of general formula [G-007] were prepared by the reaction of a 5-chloro 2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol derivative of general formula [G-006] with 2,4,6-triisopropylbenzenesulfonyl chloride in a polar aprotic solvent such as DMA, DMF, NMP with a tertiary alkylamine base such as Et 3 N, DIPEA or NMM and a catalytic amount of DMAP. The intermediate 6,7-substituted-(2,4,6-triisopropyl-benzenesulfonic acid)-2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl ester was then reacted with a primary or secondary amino derivative, of general formula [G-004], in a polar aprotic solvent such as DMA, DMF, NMP in the presence of a tertiary amine base such as Et 3 N, DIPEA or NMM at ambient temperature. 5-chloro 2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl amine derivatives of general formula [G-007] was involved in a Buchwald type reaction utilising a suitable amine, of general formula [G-005], a palladium catalyst such as Pd(dba) 2  or Pd(OAc) 2 , a ligand such as Xantphos and a base such as NaOtBu or Cs 2 CO 3  in a polar solvent such as dioxane or a combination of dioxane and DMA at high temperature either by heating thermally or using a microwave reactor. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the intermediate was purified by column chromatography and the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, HCl in a solvent such as DCM, DCE or 1,4-dioxane or by catch and release sulfonic acidic resins such as polymer supported toluene sulfonic acid and the crude reaction product was purified by normal phase chromatography or reverse phase preparative HPLC. 
     
       
         
         
             
             
         
       
     
     Synthesis of [4-(5-Chloro-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-phenyl-amine [246] 
     
       
         
         
             
             
         
       
     
     3,5-Dichloro-N-[(2-chloro-pyridin-4-yl)-imino-methyl]-isonicotinamide [B007] 
     A mixture of 3,5-dichloropyridine-4-carboxylic acid (15 g, 78.12 mmol), DIPEA (37.5 mL, 214 mmol) in DMF (400 mL) was stirred at room temperature then HATU (29.7 g, 78.12 mmol) was added in one portion and the mixture was left to stir for 45 min. 2-Chloro-isonicotinamide (14.25 g, 74.2 mmol) was added and the mixture left to stir for a further 2 hours. The crude reaction mixture was then poured onto water (800 mL) and left to stir overnight. The crude reaction mixture was filtered and the solid washed with water, then dried in in a vacuum oven over night to give the title compound (22 g, 85% yield) as an off white solid: LCMS method: 1, RT: 4.89 min, MI 330 [M+H]; NMR: (1H, 300 MHz, d6-dmso); 10.25 (1H, br s), 10.10 (1H, br s), 8.70 (2H, s), 8.57 (1H, s), 7.99 (1H, s), 7.88 (1H, s). 
     
       
         
         
             
             
         
       
     
     5-Chloro-2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol [B008] 
     3,5-Dichloro-N-[(2-chloro-pyridin-4-yl)-imino-methyl]-isonicotinamide [B007](10 g, 30.34 mmol) cesium carbonate (19.8 g, 60.69 mmol) and DMA (180 mL) were stirred at room temperature. The mixture was flushed with nitrogen then iron(III) chloride (0.98 g, 6.07 mmol) was added and the mixture heated at 140 C overnight under an atmosphere of nitrogen. The crude reaction mixture was cooled then poured onto a mixture of ice water, the mixture was then acidified by the addition of glacial acetic acid, and the mixture was then left to stir at room temperature for 2 hours. The solid precipitate was collected by filtration, washed with water then dried in a vacuum oven over night to give the title compound (5.26 g, 59% yield) as a pale brown solid: LCMS method: 1, RT: 4.83 min, MI 293 [M+H]; 
     
       
         
         
             
             
         
       
     
     4-[5-Chloro-2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [B009] 
     A mixture of 5-Chloro-2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol [B008](1.05 g, 3.58 mmol), anhydrous DMF (40 mL), triethylamine (1.5 mL, 10.7 mmol) and DMAP (440 mg, 3.58 mmol) was sonicated for 45 min. 2,4,6-Triisopropyl-benzenesulfonyl chloride (1.3 g, 4.3 mmol) was added and the reaction mixture left to stir at room temperature for 2 hr. During this time the material went into solution to form a viscous solution. 1-Boc-piperazine (0.800 g, 4.3 mmol) was added and the reaction mixture was left to stir at room temperature overnight. The solvent was evaporated under reduced pressure and residue triturated in DCM to give brown solid, which was purified by flash column chromatography (SP1, 20 g SiO 2  cartridge 100% DCM up to 95% DCM: 5% MeOH gradient) to give the title compound [B009] as a beige solid (1.1 g, 67% yield). LCMS method: 1, RT: 5.50 min, MI: 461 [M+H]; NMR: (1H, 300 MHz, d6-dmso); 9.20 (1H, s), 8.67 (1H, s), 8.62 (1H, d), 8.33 (1H, d), 8.32 (1H, s), 7.94 (1H, s), 3.72 (4H, m, br), 3.53 (4H, m, br), 1.41 (9H, s). 
     
       
         
         
             
             
         
       
     
     4-[5-Chloro-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [B010] 
     A mixture of 4-[5-Chloro-2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [B009](0.150 g, 0.325 mmol), Aniline (61 μL, 0.650 mml), Pd(OAc) 2  (4 mg, 0.017 mmol), Xantphos (19 mg, 0.033 mmol), cesium carbonate (212 mg, 0.650 mmol) and anhydrous dioxane (1 ml) was heated at 900 overnight. Solvent evaporated under reduced pressure and residue purified by flash column chromatography (SP1, 20 g SiO 2  cartridge 100% DCM up to 97% DCM: 3% MeOH gradient) to give the title compound [B010] as a beige solid (65 mg, 39% yield). LCMS method: 1, RT: 4.34 min, MI: 518.31 [M+H]. 
     
       
         
         
             
             
         
       
     
     [4-(5-Chloro-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-phenyl-amine [246] 
     A mixture of 4-[5-Chloro-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [B010](60 mg, 0.125 mmol) in 4N HCl in dioxane (1 mL) was stirred at room temperature for 2 hours. After completion solvent was evaporated in vacuo and residue diluted with MeOH (5 mL) and poured onto a 1 g SCX-2 cartridge and washed with DCM and MeOH before eluting with 2N NH3/MeOH which was evaporated evaporated under reduced pressure. The residue purified by flash column chromatography (SP1, 20 g SiO 2  cartridge 100% DCM up to 90% DCM: 10% MeOH gradient) to give the title compound [246] as a yellow solid (23 mg, 44% yield). LCMS method: 1, RT: 5.48 min, MI: 418.29 [M+H]; NMR: (1H, 300 MHz, d6-dmso); 9.33 (1H, s), 9.12 (1H, s), 8.60 (1H, s), 8.32 (1H, d), 7.89 (1H, s), 7.74 (2H, d), 7.65 (1H, dd), 7.27 (2H, t), 6.89 (1H, t), 3.68 (4H, m), 3.15 (1H, d), 2.86 (4H, m). 
     The following compounds were synthesised according to the general synthesis shown in scheme [B2] 
     
       
         
           
               
               
               
               
               
            
               
                   
               
               
                   
                   
                   
                 Analysis 
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Ex 
                 Amine 
                 Aniline 
                 LCMS 
                 NMR 
                 Name 
               
               
                   
               
               
                 247 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.18 min, MI: 436 [M + H] 
                 (1H, 500 MHz, d6-dmso) 8.99 (1H, s), 8.60 (1H, s),  8.29 (1H, d), 8.19 (1H, m), 8.02 (1H, d), 7.69 (1H, d),  7.22 (1H, m), 7.14 (1H, m),  7.00 (1H, m), 3.68 (4H,  br s), 2.86 (4H, br s) 
                 [4-(5-Chloro-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)-pyridin-2-yl]- (2-fluoro- phenyl)-amine 
               
               
                   
               
               
                 248 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.37 min, MI: 511 [M + H] 
                 (1H, 500 MHz, d6-dmso) 8.97 (1H, s), 8.74 (1H s), 8.41 (1H, s), 8.29 (1H, d),  8.22 (1H, t), 8.04 (1H, s),  7.72 (1H, d), 7.31 (1H, m), 7.22 (1H, m), 7.14 (1H, m),  7.09 (2H, m), 7 (1H, m), 3.54 (4H, s), 2.83 (4H, s). 
                 (2-Fluoro- phenyl)-{2-[2- (2-fluoro- phenylamino)- pyridin-4-yl]-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-5- yl}-amine 
               
               
                   
               
               
                 249 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 2.58 min, MI: 444 [M + H] 
                 (1H, 500 MHz, d6-dmso) 10.51 (1H, s), 9.25 (1H, s), 8.70 (1H, s), 8.65 (1H, s), 8.50 (2H, dd), 7.91 (1H, d), 7.31 (1H, d), 3.91 (4H,  br s), 3.33 (4H, br s) 
                 4-{5-(4-Cyano- pyridin-2- ylamino)-2-[2- (4-cyano- pyridin-2- ylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4- yl}-piperazine 
               
               
                   
               
               
                 250 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 2.80 min, MI: 432.15 [M + H] 
                 (1H, 500 MHz, d6-dmso) 9.33 (1H, s), 9.12 (1H, s),  8.59 (1H, s), 8.31 (1H, d), 7.89 (1H, s), 7.73 (2H, d),  7.64 (1H, d), 7.27 (2H, t),  6.90 (1H, t), 4.09 (2H, m,  br), 3.31 (2H, m, br),  3.16 (1H, d), 2.88 (2H, m, br), 1.01 (3H, s) 
                 {4-[5-Chloro-4 ((S)-3-methyl- piperazin-1-yl) pyrido[3,4- d]pyrimidin-2- yl]-pyridin-2- yl}-phenyl- amine 
               
               
                   
               
               
                 251 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 2.64 min, MI: 384.08  [M + H] 
                 (1H, 500 MHz, d6-dmso) 10.64 (1H, s), 9.20 (1H, s), 9.09 (1H, s), 8.64 (1H, s), 8.47 (1H, d), 8.00 (1H, d), 3.77 (4H, m), 3.05  (4H, m), 2.13 (3H, s) 
                 N-[4-(5-Chloro- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)-pyridin-2-yl]- acetamide 
               
               
                   
               
               
                 252 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.60 min, MI: 454  [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.26 (1H, bs), 9.19 (1H, s), 8.66 (1H, s), 8.35 (1H, d), 8.09 (2H, m), 7.75 (1H, dd), 7.14 (1H, m), 7.04 (1H, m), 3.79 (4H, s), 3.08 (4H, s) 
                 [4-(5-Chloro-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)-pyridin-2-yl]- (2,3-difluoro- phenyl)-amine 
               
               
                   
               
               
                 253 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 2.69 min, MI: 437 [M + H] 
                 (1H, 500 MHz, d6-dmso) 10.15 (1H, s), 9.16 (1H, s), 8.69 (1H, s), 8.63 (1H, s), 8.38 (1H, s), 7.82 (2H, s),  7.72 (1H, s), 6.58 (1H, s), 3.88 (4H, s), 3.25 (4H, s) 
                 [4-(5-Chloro-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)-pyridin-2-yl]- (6-fluoro- pyridin-2-yl)- amine 
               
               
                   
               
               
                 254 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 2.17 min, MI: 454  [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.24 (1H, s), 8.85 (1H, s),  8.71 (1H, s), 8.20 (1H, d), 7.82 (1H, s), 7.69 (1H, dd), 7.17 (2H, m), 3.87 (4H, s), 3.31 (4H, s) 
                 [4-(5-Chloro-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)-pyridin-2-yl]- (2,6-difluoro- phenyl)-amine 
               
               
                   
               
               
                 255 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.29 min, MI: 454  [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.15 (1H, s), 8.98 (1H, s), 8.62 (1H, s), 8.27 (1H, d), 8.20 (1H, s), 8.13 (1H, m), 7.97 (1H, s), 7.70 (1H, dd),  7.30 (1H, m), 7.06 (1H, m), 3.72 (4H, s), 2.93 (4H, s) 
                 [4-(5-Chloro-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)-pyridin-2-yl]- (2,4-difluoro- phenyl)-amine 
               
               
                   
               
               
                 256 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 2.24 min, MI: 433  [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.83 (1H, s), 9.16 (1H, s), 8.79 (1H, s), 8.61 (1H, s), 8.38 (1H, d), 8.13 (1H, d), 7.78 (1H, dd), 7.64 (1H, s), 6.76 (1H, d), 3.71 (4H, s),  2.88 (4H, s), 2.29 (3H, s) 
                 [4-(5-Chloro-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)-pyridin-2-yl]- (4-methyl- pyridin-2-yl)- amine 
               
               
                   
               
               
                 257 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.42 min, MI: 472 [M + H] 
                 (1H, 500 MHz, d6-dmso) 9.19 (1H, s), 9.08 (1H, s), 8.65 (1H, s), 8.22 (1H, d), 7.88 (1H, s), 7.71 (1H, d),  7.35-7.29 (1H, m), 7.23- 7.14 (1H, m), 3.79 (4H, s), 3.12 (4H, s). 
                 [4-(5-Chloro-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)-pyridin-2-yl]- (2,3,6-trifluoro- phenyl)-amine 
               
               
                   
               
               
                 258 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 5.38 min, MI: 437  [M + H] 
                 (1H, 500 MHz, d6-dmso) 10.02 (1H, s), 9.25 (1H, s), 8.72 (1H, s), 8.69 (1H, s), 8.41 (1H, d), 8.28 (1H, d),  7.93 (1H, dd), 7.82 (1H, dd),  7.69 (1H, m), 3.89 (4H, s),  3.27 (4H, s) 
                 [4-(5-Chloro-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)-pyridin-2-yl]- (5-fluoro- pyridin-2-yl)- amine 
               
               
                   
               
               
                 259 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 5.92 min, MI: 487  [M + H] 
                 (1H, 500 MHz, d6-dmso) 10.40 (1H, s), 9.21 (1H, s), 8.72 (1H, s), 8.66 (1H, s),  8.52 (1H, d), 8.47 (1H, d), 8.32 (1H, s), 7.88 (1H, d), 7.23 (1H, d), 3.81 (4H, s), 3.07 (4H, s) 
                 [4-(5-Chloro-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)-pyridin-2-yl]- (4- trifluoromethyl- pyridin-2-yl)- amine 
               
               
                   
               
               
                 260 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 5.32 min, MI: 444  [M + H] 
                 (1H, 500 MHz, d6-dmso) 10.25 (1H, s), 9.19 (1H, s), 8.94 (1H, s), 8.66 (1H, s), 8.58 (1H, dd), 8.48 (1H, d),  8.03 (1H, s), 7.93 (1H, d), 7.89 (1H, d), 3.80 (4H, s), 3.08 (4H, s) 
                 5-[4-(5-Chloro- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)-pyridin-2- ylamino]- pyridine-2- carbonitrile 
               
               
                   
               
               
                 261 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 5.27 min, MI: 583  [M + H] 
                 (1H, 500 MHz, d6-dmso) 9.05 (1H, s), 8.74 (1H, s), 8.37 (1H, s), 8.23 (1H, s), 8.21 (1H, s), 7.88 (1H, s),  7.72 (1H, dd), 7.37-7.17  (4H, m), 3.62 (4H, s),  2.88 (4H, s) 
                 {4-Piperazin-1- yl-2-[2-(2,3,6- trifluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-5- yl}-(2,3,6- trifluoro- phenyl)-amine 
               
               
                   
               
               
                 262 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.37 min, MI: 511  [M + H] 
                 (1H, 500 MHz, d6-dmso) 8.97 (1H, s), 8.74 (1H, s), 8.41 (1H, s), 8.29 (1H, d), 8.22 (1H, t), 8.04 (1H, s), 7.72 (1H, d), 7.31 (1H, m), 7.22 (1H, m), 7.14 (1H, m), 7.09 (2H, m), 7 (1H, m),  3.54 (4H, m), 2.83 (4H, s) 
                 (2,6-Difluoro- phenyl)-{2-[2- (2,6-difluoro- phenylamino)- pyridin-4-yl]-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-5- yl}-amine 
               
               
                   
               
            
           
         
       
     
     General synthesis of substituted 2-amino pyridyl substituted 2-(2-amino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl amine derivatives of general formula [G-003] Scheme B3 
     5-chloro 2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl amine derivatives of general formula [G-007] were prepared by the reaction of a 5-chloro 2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol derivative of general formula [G-006] with 2,4,6-triisopropylbenzenesulfonyl chloride in a polar aprotic solvent such as DMA, DMF, NMP with a tertiary alkylamine base such as Et 3 N, DIPEA or NMM and a catalytic amount of DMAP. The intermediate 6,7-substituted-(2,4,6-triisopropyl-benzenesulfonic acid)-2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl ester was then reacted with a primary or secondary amino derivative, of general formula [G-004], in a polar aprotic solvent such as DMA, DMF, NMP in the presence of a tertiary amine base such as Et 3 N, DIPEA or NMM at ambient temperature. 5-chloro 2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl amine derivatives of general formula [G-007] was involved in a Buchwald type reaction utilising a suitable amine, of general formula [G-005], a palladium catalyst such as Pd(dba) 2  or Pd(OAc) 2 , a ligand such as Xantphos and a base such as NaOtBu or Cs 2 CO 3  in a polar solvent such as dioxane or a combination of dioxane and DMA at high temperature either by heating thermally or using a microwave reactor. The 5-chlotro 2-amino-pyridyl substituted 2-(2-amino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl amine derivatives of general formula [G-008]. were reacted in a Suzuki type reaction utilising a suitable boronic acid or boronic ester, of general formula [G-009], a palladium catalyst such as Pd(PPh 3 ) 4  or Pd(PPh 3 ) 2 Cl 2  a base such as Et 3 N, KOH, Na 2 CO 3  or NaOH in a polar solvent such as EtOH, THF, DMA or dioxane at high temperature either by heating thermally or using a microwave reactor. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the intermediate was purified by column chromatography and the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, HCl in a solvent such as DCM, DCE or 1,4-dioxane or by catch and release sulfonic acidic resins such as polymer supported toluene sulfonic acid and the crude reaction product was purified by normal phase chromatography or reverse phase preparative HPLC. 
     
       
         
         
             
             
         
       
     
     Synthesis of [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-phenyl)-amine [263] 
     
       
         
         
             
             
         
       
     
     4-{5-Chloro-2-[2-(2-fluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperazine-1-carboxylic acid tert-butyl ester [B010] 
     A mixture of 4-[5-Chloro-2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [B009](3 g, 6.48 mmol), 2-fluoroaniline (654 μL, 6.48 mml), Pd(OAc) 2  (79 mg, 0.324 mmol), Xantphos (375 mg, 0.648 mmol), ceasium carbonate (4.11 g, 12.6 mmol) and anhydrous dioxane (20 ml) was heated at 900 overnight. Solvent was evaporated under reduced pressure and residue purified by flash column chromatography (ISCO, 120 g SiO 2  cartridge 100% cyclohexane up to 70% cyclohexane: 30% Ethylacetate gradient) to give the title compound [B010] as a yellow solid (1.2 g, 52% yield). LCMS method: 5, RT: 4.19 min, MI 516.57 [M+H]. 
     
       
         
         
             
             
         
       
     
     4-{5-Cyclopropyl-2-[2-(2-fluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperazine-1-carboxylic acid tert-butyl ester [B011] 
     A mixture of 4-{5-Chloro-2-[2-(2-fluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperazine-1-carboxylic acid tert-butyl ester [B010](1.8 g, 3.36 mmol), Pd(dppf)Cl 2 .CH 2 Cl 2  (137 mg, 0.168 mmol), K 3 PO 4  (2.14 g, 10.075 mmol), cyclopropyl boronic acid (578 mg, 6.72 mmol) and anhydrous dioxane (30 ml) plus few drops of DMA was added to a microwave vial. Solvent was evaporated under reduced pressure and residue purified by flash column chromatography (ISCO, 40 g SiO 2  cartridge 100% cyclohexane up to 70% cyclohexane: 30% Ethylacetate gradient) to give the title compound [B011] as a yellow solid (950 mg, 52% yield). LCMS method: 5, RT: 4.72 min, MI 542 [M+H]. 
     
       
         
         
             
             
         
       
     
     [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-phenyl)-amine [263] 
     A mixture of 4-{5-Cyclopropyl-2-[2-(2-fluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperazine-1-carboxylic acid tert-butyl ester [B011](300 mg, 0.554 mmol) in 4N HCl in dioxane (1.5 mL) was stirred at room temperature for 2 hours. Solvent was evaporated under reduced pressure and residue purified by reverse phase flash column chromatography (ISCO, 24 g SiO 2  cartridge, 100% H 2 O:0.1% formic acid up to 20% H 2 O:0.1% formic acid: 80% MeOH: 0.1% formic acid gradient) The residue was diluted with MeOH (5 mL) and poured onto a 1 g SCX-2 cartridge and washed with DCM and MeOH before eluting with 2N NH3/MeOH which was evaporated under reduced pressure to give the title compound [263] as a yellow solid (110 mg, 45% yield). LCMS method: 1, RT: 4.03 min, MI 442 [M+H]; NMR: (1H, 500 MHz, d6-dmso); 8.95 (1H, s), 8.27 (1H, d), 8.21 (1H, m), 8.08 (1H, s), 8.03 (1H, s), 7.70-7.69 (1H, dd), 7.23 (1H, m), 7.14 (1H, m), 6.99 (1H, m), 3.78-3.62 (4H, m), 2.84 (4H, s), 2.61 (1H, m), 1.25-1.24 (2H, m), 1.02-1.01 (2H, m). 
     The following compounds were synthesised according to the general synthesis shown in scheme [B3] 
     
       
         
           
               
               
               
               
               
            
               
                   
               
               
                   
                   
                   
                 Analysis 
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Ex 
                 Amine 
                 Aniline 
                 LCMS 
                 NMR 
                 Name 
               
               
                   
               
               
                 264 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.01 min, MI: 460  [M + H] 
                 (1H, 500 MHz, d6-dmso) 8.95 (1H, s), 8.14 (1H, d), 8.08 (1H, s), 7.79 (1H, s), 7.64 (1H, d), 7.26 (1H, m), 7.15 (2H, m), 3.68 (4H, br s), 2.83 (4H, s), 2.61  (1H, m), 1.23 (2H, m), 1.02  (2H, m) 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidin- 2-yl)-pyridin-2-yl]-(2,6- difluoro-phenyl)-amine 
               
               
                   
               
               
                 265 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 2.62 min, MI: 450  [M + H] 
                 (1H, 500 MHz, d6-dmso) 10.39 (1H, s), 9.05 (1H, s), 8.36 (1H, s), 8.48 (2H, dd), 8.35 (1H, s), 7.91 (1H, d), 7.31 (1H, d), 3.91 (4H, s), 3.33 (4H, s), 2.67 (1H, s), 1.24-1.26 (2H, m),  1.07-1.09 (2H, m). 
                 2-[4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidin- 2-yl)-pyridin-2- ylamino]- isonicotinonitrile 
               
               
                   
               
               
                 266 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 2.60 min, MI: 478  [M + H] 
                 (1H, 500 MHz, d6-dmso) 9.04 (1H, s), 9.00 (1H, s), 8.21 (1H, d, 8.13 (1H, s), 7.88 (1H, s), 7.72 (1H, dd), 7.32 (1H, m), 7.20 (1H, m), 3.76 (4H, s), 3.02 (4H, s), 2.63 (1H, m), 1.25 (2 H, m), 1.05 (2H, m) 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidin- 2-yl)-pyridin-2-yl]- (2,3,6-trifluoro-phenyl)- amine 
               
               
                   
               
               
                 267 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 9.34 min, MI: 439  [M + H] 
                 (1H, 300 MHz, d6-dmso) 9.80 (1H, s), 8.99 (1H, s), 8.78 (1H, s), 8.38 (1H, d), 8.10 (2H, m), 7.79 (1H, d), 7.66 (1H, s), 6.74 (1H, d), 3.73 (4H, bs), 2.92 (4H, s), 2.63 (1H, m), 2.29 (3H, s), 1.27 (2H, m), 1.04 (2H, m) 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidin- 2-yl)-pyridin-2-yl]-(4- methyl-pyridin-2-yl)- amine 
               
               
                   
               
               
                 268 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 4.80 min, MI: 511  [M + H] 
                 (1H, 500 MHz, d6-dmso) 10.19 (1H, s), 9.02 (1H, s), 8.72 (1H, s), 8.43 (1H, d), 7.86 (2H, m), 7.74 (1H, d), 7.62-7.53 (1H, m), 6.60 (1H, dd), 4.05 (1H, m), 3.61 (2H, m), 3.05 (4H, s), 2.63 (1H, t), 1.29 (2H, m), 1.08 (2H, m) 
                 {4-[5-Cyclopropyl-4- (3-trifluoromethyl- piperazin-1-yl)- pyrido[3,4-d]pyrimidin- 2-yl]-pyridin-2-yl}-(6- fluoro-pyridin-2-yl)- amine 
               
               
                   
               
               
                 269 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.21 min, MI: 493  [M + H] 
                 (1H, 500 MHz, d6-dmso) 10.39 (s, 1H), 9.08 (s, 1H), 8.73 (s, 1H), 8.53 (d, 1H), 8.47 (d, 1H), 8.33 (s, 1H), 8.19 (s, 1H), 7.90 (d, 1H), 7.23 (d, 1H), 3.93 (s, 4H), 3.32 (s, 4H), 2.69 (m, 1H), 1.27 (m, 2H), 1.078 (m, 2H) 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidin- 2-yl)-pyridin-2-yl]-(4- trifluoromethyl-pyridin- 2-yl)-amine 
               
               
                   
               
               
                 270 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 5.71 min, MI: 493  [M + H] 
                 (1H, 500 MHz, d6-dmso) 10.11 (s, 1H), 9.06 (s, 1H), 8.96 (d, 1H), 8.62 (dd, 1H), 8.46 (d, 1H), 8.18 (s, 1H), 8.05 (s, 1H), 7.87 (dd, 1H), 7.82 (d, 1H), 3.85 (s, 4H), 3.28 (s, 4H), 2.68 (m, 1H), 1.27 (m, 2H), 1.08 (m, 2H) 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidin- 2-yl)-pyridin-2-yl]-(6- trifluoromethyl-pyridin- 3-yl)-amine 
               
               
                   
               
               
                 271 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 5.25 min, MI: 433  [M + H] 
                 (1H, 500 MHz, d6-dmso) 9.99 (1H, s), 9.07 (1H, s), 8.71 (1H, s), 8.40 (1H, d), 8.27 (1H, d), 8.18 (1H, s), 7.94 (1H, dd), 7.83 (1H,  dd), 7.68 (1H, m), 3.93  (4H, s), 3.27 (4H, s), 2.70 (1H, m), 1.26 (2H, m), 1.07 (2H, m) 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidin- 2-yl)-pyridin-2-yl]-(5- fluoro-pyridin-2-yl)- amine 
               
               
                   
               
            
           
         
       
     
     General synthesis of 5-cyclopropyl substituted 2-amino pyridyl substituted 2-(2-amino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl amine derivatives of general formula [G-012] 
     
       
         
         
             
             
         
       
     
     5-cyclopropyl 2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl amine derivatives of general formula [G-011] were prepared by the reaction of a 5-cyclopropylo 2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol derivative of general formula [G-010] with 2,4,6-triisopropylbenzenesulfonyl chloride in a polar aprotic solvent such as DMA, DMF, NMP with a tertiary alkylamine base such as Et 3 N, DIPEA or NMM and a catalytic amount of DMAP. The intermediate 6,7-substituted-(2,4,6-triisopropyl-benzenesulfonic acid)-2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl ester was then reacted with a primary or secondary amino derivative, of general formula [G-004], in a polar aprotic solvent such as DMA, DMF, NMP in the presence of a tertiary amine base such as Et 3 N, DIPEA or NMM at ambient temperature. 5-cyclopropyl 2-(2-chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl amine derivatives of general formula [G-011] was involved in a Buchwald type reaction utilising a suitable amine, of general formula [G-005], a palladium catalyst such as Pd(dba) 2  or Pd(OAc) 2 , a ligand such as Xantphos and a base such as NaOtBu or Cs 2 CO 3  in a polar solvent such as dioxane or a combination of dioxane and DMA at high temperature either by heating thermally or using a microwave reactor. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the intermediate was purified by column chromatography and the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, HCl in a solvent such as DCM, DCE or 1,4-dioxane or by catch and release sulfonic acidic resins such as polymer supported toluene sulfonic acid and the crude reaction product was purified by normal phase chromatography or reverse phase preparative HPLC. 
     Synthesis of [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4,5-dimethyl-oxazol-2-yl)-amine [272] 
     
       
         
         
             
             
         
       
     
     Synthesis of 3-Bromo-5-fluoro-isonicotinic acid tert-butyl ester [B012] 
     To a solution of LDA (2M, 72 mL, 144 mmol) in THF (100 mL) cooled to approximately −70° C. was added dropwise via cannula a solution of 3-bromo-5-fluoropyridine (21.12 g, 120 mmol) in anhydrous THF (50 mL) pre-cooled to −70° C. The rate of addition was controlled such that the internal temperature did not rise above −65° C. The dark red-brown solution was stirred for 1 hour. Di-tert-butyldicarbonate (52.4 g, 240 mmol) in THF (50 mL) was cooled to −10° C. in a methanol/ice bath then added dropwise via cannula to the dark red-brown solution. The mixture was stirred for 2 hours then allowed to warm to room temperature and stirred for another 1 hour. Saturated aqueous ammonium chloride (100 mL) was added slowly and then water (200 mL) and EtOAc (200 mL) and the mixture was vigorously stirred for 45 minutes. The mixture was transferred to a separatory funnel and the layers were separated. The aqueous layer was extracted with EtOAc (200 mL). The THF and EtOAc layers were combined, dried over magnesium sulfate, filtered and evaporated. The recovered dark red-brown oil was purified by column chromatography (Cyclohexane/AcOEt: 1/0 to 97/3). Fractions containing desired material were concentrated in vacuo to yield the title compound [B012] as a pale yellow oil (14 g, 85%). LCMS method: 1, RT: 5.44 min, MI: 277 [M+H]; NMR: (1H, 300 MHz, d6-dmso); 8.56 (s, 1H), 8.43 (s, 1H), 1.62 (s, 9H). 
     
       
         
         
             
             
         
       
     
     Synthesis of 3-Cyclopropyl-5-fluoro-isonicotinic acid tert-butyl ester [B013] 
     A solution containing 3-Bromo-5-fluoro-isonicotinic acid tert-butyl ester [B012](5.52 g, 20 mmol), potassium phosphate tribasic (12.74 g, 60 mmol) and cyclopropyl boronic acid (2.58 g, 30 mmol), in anhydrous dioxane (100 mL) was subjected to vacuum/argon balloon (three times). Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.408 g, 0.5 mmol) was added and the reaction heated at 96° C. overnight under positive pressure of nitrogen. The mixture was cooled to room temperature and was filtered through a pad of 200 g silica and washed with EtOAc (1 L). The filtrate was concentrated in vacuo and the crude was purified by column chromatography (Cyclohexane/AcOEt: 98:2 to 96:4). The combined fractions were concentrated under reduced pressure to yield the title compound [B013] as a colourless oil (3.42 g, 72%). LCMS method: 1, RT: 5.36 min, MI: 238 [M+H]. 
     
       
         
         
             
             
         
       
     
     Synthesis of 3-Cyclopropyl-5-fluoro-isonicotinic acid [B014] 
     In a microwave vial, 3-cyclopropyl-5-fluoro-isonicotinic acid tert-butyl ester [B013](1.186 g, 5 mmol) was dissolved in anhydrous methanol and then heated in microwave at 140° C. for 1 hr. The reaction was concentrated in vacuo to give the title compound [B014] 0.84 g (92%) as a white crystalline solid. LCMS method: 1, RT: 1.51 min, MI: 182 [M+H]. 
     
       
         
         
             
             
         
       
     
     Synthesis of 2-(2-Chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-ol [B015] 
     A mixture of 3-Cyclopropyl-5-fluoro-isonicotinic acid [B014](5 g, 27.6 mmol) and HATU (10.5 g, 82.86 mmol) was stirred in DMF (35 mL) and DIPEA (14.5 mL, 82.86 mmol) was added. The mixture was left to stir at rt for 1 hour then 2-Chloro-isonicotinamidine hydrochloride (5.3 g, 27.52 mmol) was added in one portion and the mixture was left to stir at rt for 18 hours. The crude reaction mixture was poured onto water (180 mL) and left to stir for stirred for 2 hours and then the beige solid was collected by filtration, washed with water and dried in a vacuum oven to give N-[(2-Chloro-pyridin-4-yl)-imino-methyl]-3-cyclopropyl-5-fluoro-isonicotinamide (6.60 g, 75% yield) which was used in the next step without further purification: LCMS method: 1, RT: 3.45 min, MI: 319 [M+H]; NMR: (1H, 300 MHz, d6-dmso); 10.25 (s, br, 1H), 9.92 (s, br, 1H), 8.59 (d, 1H), 8.42 (s, 1H), 8.11 (s, 1H), 8.00 (s, 1H), 7.92 (dd, 1H), 2.01 (m, 1H), 0.98 (m, 2H), 0.85 (m, 2H). 
     A mixture of N-[(2-Chloro-pyridin-4-yl)-imino-methyl]-3-cyclopropyl-5-fluoro-isonicotinamide (6.60 g, 20.70 mmol) and Cs2CO3 (6.7 g, 20.7 mmol) and DMA (90 mL) was heated at 90° C. overnight. The reaction mixture was poured into ice/water (100 ml), then acidified by the dropwise addition of glacial acetic acid and the mixture was left to stir at 0 OC for 1 hour. The beige precipitate was collected by filtration and washed with water then dried in a vacuum oven to give the title compound [B015](4.8 g, 78% yield). LCMS method: 1, RT: 3.90 min, MI: 299 [M+H]; NMR: (1H, 300 MHz, d6-dmso); 12.92 (s, 1H), 8.88 (s, 1H), 8.66 (d, 1H), 8.25 (dd, 2H), 8.16 (dd, 1H), 3.39 (m, 1H), 1.11 (m, 2H), 0.94 (m, 2H). 
     
       
         
         
             
             
         
       
     
     4-[2-(2-Chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [B016] 
     A mixture of 2-(2-Chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-ol [B015](280 mg, 0.937 mmol), anhydrous DMF (9 mL), triethylamine (0.390 mL, 2.81 mmol) and DMAP (115 mg, 0.937 mmol) was sonicated for 10 min then stirred at room temperature for 10 min. 2,4,6-Triisopropyl-benzenesulfonyl chloride (340 mg, 1.12 mmol) was added and the mixture was sonicated for 5 min then left to stir at room temperature for 2 hours. During this time the material went into solution to form a viscous solution. 1-Boc-piperazine (190 mg, 1.03 mmol) was added and the reaction mixture was left to stir at room temperature overnight. Solvent was evaporated under reduced pressure and residue purified by flash column chromatography (SP1, 20 g SiO 2  cartridge 100% DCM up to 95% DCM: 5% MeOH gradient) to give the title compound [B016] as a yellow solid (276 mg, 63% yield). LCMS method: 5, RT: 5.16 min, MI: 467 [M+H]; NMR: (1H, 500 MHz, d6-dmso); 9.02 (1H, s), 8.61 (1H, dd), 8.34 (2H, m), 8.15 (1H, s), 3.68-3.83 (4H, very broad s), 3.51 (4H, br s), 2.59 (1H, m), 1.24 (2H, m), 1.16 (2H, m). 
     
       
         
         
             
             
         
       
     
     4-{5-Cyclopropyl-2-[2-(4,5-dimethyl-oxazol-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperazine-1-carboxylic acid tert-butyl ester [B017] 
     A mixture of 4-[2-(2-Chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [B016](280 mg, 0.591 mmol), 4,5-dimethyl-oxazol-2-ylamine (132 mg, 1.18 mml), Pd(OAc) 2  (7 mg, 0.030 mmol), Xantphos (35 mg, 0.060 mmol), ceasium carbonate (384 mg, 1.18 mmol) and anhydrous dioxane (1.5 ml) was heated at 900 overnight. Solvent was evaporated under reduced pressure and residue purified by flash column chromatography (SP1, 20 g SiO 2  cartridge 100% DCM up to 96% DCM: 4% MeOH gradient) to give the title compound [B017] as a beige solid (61 mg, 19% yield). LCMS method: 5, RT: 4.07 min, MI: 543 [M+H]. 
     
       
         
         
             
             
         
       
     
     [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4,5-dimethyl-oxazol-2-yl)-amine [272] 
     A mixture of 4-{5-Cyclopropyl-2-[2-(4,5-dimethyl-oxazol-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperazine-1-carboxylic acid tert-butyl ester [B017](60 mg, 0.112 mmol) in 4N HCl in dioxane (1 mL) was stirred at room temperature for 2 hours. After completion solvent was evaporated under reduced pressure and residue diluted with MeOH (5 mL) and poured onto a 1 g SCX-2 cartridge and washed with DCM and MeOH before eluting with 2N NH3/MeOH which was evaporated under reduced pressure. The residue was then purified by flash column chromatography (SP1, 10 g SiO 2  cartridge 100% DCM up to 90% DCM: 10% MeOH gradient) to give the title compound [272] as a yellow solid (22 mg, 44% yield). LCMS method: 5, RT: 2.70 min, MI: 443 [M+H]; NMR: (1H, 500 MHz, d6-dmso); 10.61 (1H, s), 9.17 (1H, s), 9.05 (1H, s), 8.38 (1H, d), 8.16 (1H, s), 7.87 (1H, d), 3.94 (1H, s, br), 3.26 (4H, m, br), 2.69 (2H, m), 2.19 (3H, s), 2.04 (3H, s), 1.25-1.22 (3H, m), 1.06-1.05 (2H, m). 
     The following compounds were synthesised according to the general synthesis shown in scheme [B4] 
     
       
         
           
               
               
               
               
               
            
               
                   
               
               
                   
                   
                   
                 Analysis 
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Ex 
                 Amine 
                 Aniline 
                 LCMS 
                 NMR 
                 Name 
               
               
                   
               
               
                 273 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 1.91 min, MI: 416.17 [M + H] 
                 (1H, 500 MHz, d6-dmso) 8.98 (1H, s), 8.93 (1H, s), 8.32 (1H, d), 8.13 (1H, s), 7.92 (1H, s), 7.71- 7.67 (3H, m), 7.29 (2H, t), 6.93 (1H, t), 4.28 (1H, d), 4.16 (1H, d), 3.28 (1H, t), 3.05 (1H, dd), 2.78 (1H, t), 2.63 (1H, m), 2.17 (1H, m), 1.25 (2H, m), 1.02-0.95 (2H, m), 0.77 (1H, m), 0.43 (2H, dd), 0.29-0.25 (2H, m) 
                 {4-[5- Cyclopropyl-4- ((S)-3- cyclopropyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}- phenyl-amine 
               
               
                   
               
               
                 274 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 4.93 min, MI: 457 [M + H] 
                 (1H, 500 MHz, d6-dmso) 8.97 (1H, s), 8.95 (1H, s), 8.26 (1H, d), 8.20 (1H, t), 8.08 (1H, s), 8.04 (1H, s), 7.70 (1H, dd), 7.22 (1H, dd), 7.14 (1H, t), 7.00 (1H, m), 4.07 (2H, m, br), 3.78 (1H, m, br), 3.54-3.40 (2H, m, br), 3.15 (1H, d), 2.59 (1H, m, br), 1.86 (2H, d, br), 1.25 (2H, d, br), 1.02 (2H, m, br). 
                 1-{5- Cyclopropyl-2-[2- (2-fluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4- yl}-piperidin-4-ol 
               
               
                   
               
               
                 275 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.24 min, MI: 466 [M + H] 
                 (1H, 400 MHz, d6-dmso 90° C.) 8.98 (1H, s), 8.91 (1H, s), 8.31 (1H, d), 8.12 (1H, s), 7.92 (1H, s), 7.71-7.68 (3H, m), 7.29 (2H, t), 6.93 (1H, t), 4.31 (1H, d), 4.20 (1H, d), 3.70 (1H, s, br), 3.29 (1H, t), 3.22 (2H, s), 3.05 (1H, dd), 2.81 (1H, t), 2.68-1.63 (1H, m), 1.65 (1H, m), 1.27-1.25 (2H, m), 1.03 (1H, m), 0.96 (6H, dd) 
                 {4-[5- Cyclopropyl-4- ((S)-3-isopropyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}- phenyl-amine 
               
               
                   
               
               
                 276 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 2.48 min, MI: 482.25 [M + H] 
                 (1H, 400 MHz, d6-dmso 90° C.) 8.97 (1H, s), 8.53 (1H, s), 8.29 (1H, dd), 8.13 (1H, s), 8.07 (1H, td), 7.95 (1H, s), 7.71 (1H, dd), 7.23 (1H, dd), 7.21- 7.14 (1H, m), 7.07-7.04 (1H, m), 4.28 (1H, d), 4.14 (1H, d), 3.27 (1H, t), 3.22 (1H, s), 3.04 (1H, m), 2.77 (1H, t), 2.62 (1H, m), 2.16 (1H, t), 1.24 (1H, m), 1.02-0.95 (2H, m), 0.78 (1H, m), 0.42 (2H, dd), 0.29- 0.24 (2H, m) 
                 {4-[5- Cyclopropyl-4- ((S)-3- cyclopropyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(2- fluoro-phenyl)- amine 
               
               
                   
               
               
                 277 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.20 min, MI: 483 [M + H] 
                 (1H, 400 MHz, d6-dmso 90° C.) 9.75 (1H, s), 8.99 (1H, s), 8.69 (1H, s), 8.41 (1H, d), 8.14 (1H, s), 7.86 (1H, dd), 7.82 (1H, qd), 7.70 (1H, dd), 6.55 (1H, dd), 4.29 (1H, d), 4.20 (1H, d), 3.30 (1H, t), 3.09-3.05 (1H, m), 2.80 (1H, t), 2.68-2.63 (1H, m), 2.16 (1H, t), 1.26-1.24 (2H, m), 1.03-0.95 (2H, m), 0.81-0.75 (1H, m), 0.42- 0.40 (2H, m), 0.28-0.24 (2H, m) 
                 {4-[5- Cyclopropyl-4- ((S)-3- cyclopropyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(6- fluoro-pyridin-2- yl)-amine 
               
               
                   
               
               
                 278 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 5.65 min, MI: 488 [M + H] 
                 (1H, 500 MHz, d6-dmso) 9.52 (1H, s, br), 9.18 (1H, s, br), 8.51 (1H, s), 8.30 (1H, s), 8.09 (1H, s), 7.94 (2H, d, br), 7.86 (1H, s), 7.46 (2H, m, br), 7.09 (1H, t, br), 4.27 (2H, m, br), 3.34 (2H, m, br), 3.09 (2H, m, br), 2.82 (1H, m, br), 1.88- 1.81 (3H, m, br), 1.48 (1H, s, br), 1.38 (3H, m, br), 1.24-1.19 (2H, m, br) 
                 (4-{5- Cyclopropyl-4-[3- (1,1-difluoro- ethyl)-piperazin- 1-yl]-pyrido[3,4- d]pyrimidin-2- yl}-pyridin-2-yl)- phenyl-amine 
               
               
                   
               
               
                 279 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 5.48 min, MI: 424 [M + H] 
                 (1H, 500 MHz, d6-dmso) 9.10 (1H, s), 8.35 (1H, d), 8.04 (1h, s), 8.00 (1H, s), 7.79 (1H, d), 7.44 (2H, d), 7.36 (2H, t), 7.06 (1H, t), 6.77 (1H, s), 3.76 (4H, m, br), 3.01 (4H, m), 2.68 (1H, m), 1.26 (2H, m), 0.99 (2H, m) 
                 [4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- phenyl-amine 
               
               
                   
               
               
                 280 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.26 min, MI: 463 [M + H] 
                 (1H, 500 MHz, d6-dmso) 9.28 (1H, s), 8.98 (1H, s), 8.31 (1H, d), 8.11 (1H, s), 7.91 (1H, s), 7.75 (2H, d), 7.69 (1H, d), 7.27 (1H, t), 6.89 (1H, t), 4.12 (2H, m, br), 3.20 (1H, m, br), 2.94 (3H, m, br), 2.71 (4H, m, br), 1.25 (2H, m, br), 1.03 (2H, m, br) 
                 {(S)-4-[5- Cyclopropyl-2-(2- phenylamino- pyridin-4-yl)- pyrido[3,4- d]pyrimidin-4-yl]- piperazin-2-yl}- acetonitrile 
               
               
                   
               
            
           
         
       
     
     Synthesis of Cyclopentyl-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine [281] 
     
       
         
         
             
             
         
       
     
     4-[2-(2-Cyclopentylamino-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [B018] 
     A mixture of 4-[2-(2-Chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [B016][prepared according to the general synthesis shown in Scheme B4](170 mg, 0.364 mmol), cyclopentylamine (73 μL, 0.728 mmol), Pd(t-Bu 3 P) 2  (38 mg, 0.073 mmol), sodium tert-butoxide (54 mg, 0.546 mmol) and anhydrous dioxane (2 ml) was heated at 110° C. overnight. Solvent was evaporated under reduced pressure and residue purified by flash column chromatography (SP1, 20 g SiO 2  cartridge 100% DCM up to 96% DCM: 4% MeOH gradient) to give the title compound [B018] as a yellow solid (92 mg, 48% yield). LCMS: method: 5, RT: 4.19 min, MI 516.57 [M+H]. 
     
       
         
         
             
             
         
       
     
     Cyclopentyl-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine [281] 
     A mixture of 4-[2-(2-Cyclopentylamino-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [B018](90 mg, 0.178 mmol) in 4N HCl in dioxane (2 mL) was stirred at room temperature for 2 hours. Solvent was evaporated under reduced pressure and residue diluted with MeOH (5 mL) and poured onto a 1 g SCX-2 cartridge and washed with DCM and MeOH before eluting with 2N NH3/MeOH which was evaporated under reduced pressure. The residue was then purified by flash column chromatography (SP1, 10 g SiO 2  cartridge 100% DCM up to 95% DCM: 5% MeOH gradient) to give the title compound [281] as a yellow solid to give the title compound as a yellow solid (26 mg, 37% yield). LCMS: method: 5, RT: 2.22 min, MI 416.25 [M+H]; NMR: (1H, 500 MHz, d6-dmso); 8.95 (1H, s), 8.10 (2H, d), 8.08 (1H, s), 7.51 (1H, s), 7.38 (1H, dd), 6.75 (1H, d), 4.17 (1H, m), 3.84-3.65 (4H, m), 3.11 (4H, m), 2.91 (1H, m), 2.62 (2H, m), 1.98-1.92 (2H, m), 1.69 (2H, m), 1.55 (2H, m), 1.46 (2H, m), 1.24-1.22 (2H, m), 1.03 (2H, m). 
     The following compounds were synthesised according to the general synthesis shown in scheme [B4] 
     
       
         
           
               
               
               
               
               
            
               
                   
               
               
                   
                   
                   
                 Analysis 
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Ex 
                 Amine 1 
                 Amine 2 
                 LCMS 
                 NMR 
                 Name 
               
               
                   
               
               
                 282 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 2.43 min, MI: 430.28 [M + H] 
                 (1H, 500 MHz, d6-dmso) 8.93 (1H, s), 8.07 (1H, d), 8.06 (1H, s), 7.50 (1H, s), 7.35 (1H, dd), 6.63 (1H, d), 3.76-3.58 (4H, m, br), 2.87 (4H, m, br), 2.67 (2H, m), 1.94 (2H, d, br), 1.72 (2H, dt, br), 1.59 (1H, d, br), 1.37-1.17 (7H, m), 1.02 (2H, m) 
                 Cyclohexyl-[4- (5-cyclopropyl- 4-piperazin-1- yl-pyrido[3,4- d]pyrimidin-2- yl)-pyridin-2- yl]-amine 
               
               
                   
               
               
                 283 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 1.93 min, MI: 432.23 [M + H] 
                 (1H, 500 MHz, d6-dmso) 8.94 (1H, s), 8.10 (1H, d), 8.07 (1H, s), 7.53 (1H, s), 7.40 (1H, d), 6.77 (1H, d), 4.09-3.97 (2H, m), 3.88-3.86 (2H, m), 3.75-3.57 (4H, m), 3.41 (2H, t), 3.15 (1H, d), 2.93 (4H, m), 2.62 (1H, m), 1.90 (2H, d, br), 1.48-1.40 (2H, m), 1.28-1.23 (2H, m), 1.03 (2H, m) 
                 [4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)-pyridin-2- yl]-(tetrahydro- pyran-4-yl)- amine 
               
               
                   
               
               
                 284 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.75 min, MI: 484.21 [M + H] 
                 (1H, 400 MHz, d4-MeOH 50° C.) 9.01 (1H, s), 8.09 (1H, s), 8.07 (1H, d), 7.59 (1H, s), 7.54 (1H, dd), 4.16-4.07 (1H, m), 3.71-3.66 (1H, m), 3.13-3.07 (1H, m), 2.75-2.68 (1H, m), 2.13-2.05 (2H, m), 1.82-1.76 (2H, m), 1.69-1.65 (2H, m), 1.60-1.52 (2H, m), 1.28-1.23 (3H, m), 1.06-0.96 (2H, m) 
                 Cyclopentyl-{4- [5-cyclopropyl- 4-(3- trifluoromethyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2- yl]-pyridin-2- yl]-amine 
               
               
                   
               
               
                 285 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.05 min, MI: 482.25 [M + H] 
                 (1H, 500 MHz, d6-dmso) 8.92 (1H, s), 8.05 (2H, m), 7.55 (1H, s), 7.33 (1H, d), 6.36 (1H, s), 3.80- 3.52 (4H, m), 2.85 (4H, m, br), 2.62- 2.60 (1H, m), 2.10 (6H, m, br), 2.05 (3H, m, br), 1.66 (6H, m, br), 1.24- 1.23 (2H, m, br), 1.18-1.16 (1H, m), 1.10-1.08 (1H, m), 1.03-1.00 (2H, m) 
                 Adamantan-1- yl-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)-pyridin-2- yl]-amine 
               
               
                   
               
            
           
         
       
     
     Example 303. 2-Amino-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-benzamide 
     303a) 2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol was prepared from 2-Chloro-isonicotinonitrile (0.60 g, 4.3 mmol) and 3-Amino-isonicotinic acid (0.50 g, 3.6 mmol) in an analogous manner to Example 1a. Product isolated as a tan solid (0.479 g, 51%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 13.13 (br s, 1H), 9.19 (s, 1H), 8.74 (d, J=4.2 Hz, 1H), 8.66 (d, J=5.1 Hz, 1H), 8.24 (s, 1H), 8.15 (d, J=5.1 Hz, 1H), 8.02 (d, J=4.8 Hz, 1H). MS=259, 261 (MH)+. 
     303b) (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester was prepared from 2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol (1.50 g, 5.80 mmol) and (R)-3-Amino-pyrrolidine-1-carboxylic acid tert-butyl ester (1.1 mL, 6.6 mmol) in an analogous manner to [B016]. Product was isolated as a yellow foam (2.15 g, 87%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.22 (s, 1H), 8.76 (d, J=5.7 Hz, 1H), 8.69 (d, J=5.4 Hz, 1H), 8.61 (d, J=4.6 Hz, 1H), 8.37-8.29 (m, 3H), 4.94 (br s, 1H), 3.88-3.71 (m, 1H), 3.55-3.29 (m, 3H), 2.37-2.25 (m, 1H), 2.19-2.04 (m, 1H), 1.46-1.39 (m, 9H). MS=427, 429 (MH)+. 
     303c) A tube was charged with (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2342 mmol), 2-Amino-benzamide (35.0 mg, 0.257 mmol), Palladium Acetate (5.0 mg, 0.022 mmol), 4,5-Bis-(di-tert-butyl-phosphanyl)-9,9-dimethyl-9H-xanthene (12.0 mg, 0.0241 mmol), Cesium Carbonate (115.0 mg, 0.3530 mmol) and 1,4-Dioxane (1 mL, 10 mmol) under an atmosphere of Nitrogen. The tube was carefully evacuated and backflushed with nitrogen once. The tube was sealed and heated at 100° C. and stirred overnight. The mixture was cooled to room temperature, diluted with dichloromethane (10 mL), filtered through a plug of diatomaceous earth and evaporated to a dark resin. To the residue was added Trifluoroacetic acid (0.5 mL) and dichloromethane (0.5 mL). The mixture was stirred for 1 hour and the volatiles were evaporated. The residue was purified via reverse phase chromatography using a Gilson apparatus (10%→0% Acetonitrile:Water w/TFA modifier). 2-Amino-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-benzamide as the trifluoroacetic acid salt was isolated as a yellow lyophilate (0.009 g, 9%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.28 (s, 1H), 9.15 (s, 1H), 8.88 (br s, 2H), 8.75-8.70 (m, 2H), 8.55 (d, J=5.1 Hz, 1H), 8.27 (d, J=5.4 Hz, 1H), 8.13 (d, J=4.3 Hz, 1H), 7.77 (d, J=8.4 Hz, 1H), 7.24 (t, J=8.4 Hz, 1H), 6.80 (d, J=8.6 Hz, 1H), 6.60 (t, J=7.2 Hz, 1H), 4.93 (br s, 1H), 3.80-3.70 (m, 1H), 3.52-3.35 (m, 3H), 2.53-2.40 (m, 2H), 2.32-2.24 (m, 1H). MS=427 (MH)+. 
     Example 304. 4-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-benzamide 
     4-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-benzamide was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2342 mmol) and 4-Amino-benzamide (35.0 mg, 0.257 mmol) in an analogous manner to Example 303c. Product was isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.008 g, 8%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.67 (s, 1H), 9.24 (s, 1H), 8.87 (br s, 2H), 8.74-8.69 (m, 1H), 8.40 (d, J=5.2 Hz, 1H), 8.26 (d, J=5.7 Hz, 1H), 8.02 (s, 1H), 7.84-7.74 (m, 6H), 7.13 (br s, 1H), 4.95 (br s, 1H), 3.80-3.30 (m, 3H), 2.52-2.38 (m, 2H), 2.31-2.22 (m, 1H). MS=427 (MH)+. 
     Example 305. 4-Amino-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-benzamide 
     4-Amino-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-benzamide was a byproduct from Example 304 isolated as the trifluoroacetic acid salt as an orange-brown lyophilate (0.012 g, 12%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.41 (s, 1H), 9.28 (s, 1H), 9.23 (s, 1H), 8.87 (br s, 2H), 8.75-8.70 (m, 2H), 8.54-8.50 (m, 1H), 8.27 (d, J=5.2 Hz, 1H), 8.10 (d, J=4.8 Hz, 1H), 7.85 (d, J=8.1 Hz, 2H), 6.61 (d, J=7.7 Hz, 2H), 4.95-4.88 (m, 1H), 3.82-3.30 (m, 3H), 2.55-2.40 (m, 2H), 2.33-2.25 (m, 1H). MS=427 (MH)+. 
     Example 306. {4-[(1S,4S)-4-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine 
     306a) (1S,4S)-5-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester was prepared from 2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol (250.0 mg, 0.9665 mmol) and (1S,4S)-2,5-Diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (215.0 mg, 1.084 mmol) in an analogous manner to Example 301b. Product isolated as a yellow resin (0.110 g, 26%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.22 (s, 1H), 8.62-8.55 (m, 2H), 8.37-8.32 (m, 2H), 8.07-8.03 (m, 1H), 5.53 (d, J=18.5 Hz, 1H), 4.62 (d, J=18.5 Hz, 1H), 4.33 (br s, 1H), 3.92 (br s, 1H), 3.62-3.44 (m, 2H), 2.08-2.00 (m, 2H), 1.45-1.30 (m, 9H). MS=439, 441 (MH)+. 
     306b) {4-[(1S,4S)-4-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine was prepared from (1S,4S)-5-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (115.0 mg, 0.2620 mmol) and Aniline (27.0 μL, 0.296 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.133 g, 128%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.49 (br s, 1H), 9.28 (s, 1H), 9.23 (br s, 1H), 8.65 (d, J=5.4 Hz, 1H), 8.45 (br s, 1H), 8.33-8.29 (m, 1H), 8.03 (d, J=5.6 Hz, 1H), 7.99 (s, 1H), 7.76-7.70 (m, 3H), 7.32 (t, J=7.4 Hz, 2H), 7.00-6.93 (m, 1H), 5.49 (s, 1H), 4.62 (s, 1H), 4.44 (d, J=10.8 Hz, 1H), 4.12 (d, J=11.1 Hz, 1H), 3.61-3.41 (m, 2H), 2.34 (d, J=10.4 Hz, 1H), 2.07 (d, J=10.9 Hz, 1H). MS=396 (MH)+. 
     Example 307. Pyrazine-2-carboxylic acid {4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-amide 
     Pyrazine-2-carboxylic acid {4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-amide was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2342 mmol) and Pyrazine-2-carboxylic acid amide (32.0 mg, 0.260 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a pale yellow lyophilate (0.099 g, 100%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.50 (s, 1H), 9.40 (s, 1H), 9.34 (s, 1H), 9.30 (s, 1H), 9.02-8.86 (m, 4H), 8.77 (d, J=4.4 Hz, 1H), 8.74 (d, J=5.4 Hz, 1H), 8.60 (d, J=5.0 Hz, 1H), 8.28 (d, J=5.5 Hz, 1H), 8.21 (d, J=5.1 Hz, 1H), 4.98-4.90 (m, 1H), 3.84-3.74 (m, 2H), 3.54-3.38 (m, 3H), 2.53-2.42 (m, 1H), 2.35-2.25 (m, 1H). MS=414 (MH)+. 
     Example 308. 3-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-benzamide 
     3-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-benzamide was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2342 mmol) and 3-Amino-benzamide (35.0 mg, 0.257 mmol) in an analogous manner to Example 303c. Product isolated as the bis-trifluoroacetic acid salt as yellow lyophilate (0.005 g, 5%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.49 (s, 1H), 9.24 (s, 1H), 8.85 (br s, 1H), 8.72 (d, J=5.1 Hz, 1H), 8.70-8.67 (m, 1H), 8.36 (d, J=5.4 Hz, 1H), 8.24 (d, J=5.0 Hz, 1H), 8.18 (s, 1H), 7.99 (s, 1H), 7.95-7.88 (m, 2H), 7.77 (d, J=4.5 Hz, 1H), 7.41 (d, J=7.2 Hz, 1H), 7.37 (d, J=8.1 Hz, 1H), 7.34-7.29 (m, 1H), 4.99-4.91 (m, 1H), 3.76-3.69 (m, 1H), 3.51-3.45 (m, 1H), 3.43-3.34 (m, 3H), 2.50-2.38 (m, 2H), 2.31-2.22 (m, 1H). MS=427 (MH)+. 
     Example 309. 3-Amino-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-benzamide 
     3-Amino-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-benzamide was a byproduct from Example 309 isolated as a free base as an off-white solid (0.007 g, 7%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.53 (s, 1H), 9.21 (s, 2H), 8.66 (d, J=5.3 Hz, 1H), 8.54 (br s, 1H), 8.53 (d, J=4.5 Hz, 1H), 8.35-8.30 (m, 1H), 8.12 (d, J=4.8 Hz, 1H), 7.24-7.19 (m, 2H), 7.15 (t, J=7.5 Hz, 1H), 6.77 (d, J=7.7 Hz, 1H), 5.31 (s, 2H), 4.77 (br s, 1H), 3.24 (br s, 1H), 3.05-2.80 (m, 3H), 2.23 (br s, 1H), 1.90 (br s, 1H). MS=427 (MH)+. 
     Example 310. 2-(4-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenoxy)-acetamide 
     310a) To a stirred suspension of 4-Nitrophenol (2.00 g, 14.4 mmol) and Potassium carbonate (3.0 g, 22 mmol) in Acetone (20 mL, 300 mmol) was added Ethyl bromoacetate (1.60 mL, 14.4 mmol). The mixture was heated at 30° C. overnight. The mixture was cooled to room temperature, diluted with ether (50 mL) and filtered through a plug of diatomaceous earth and evaporated. (4-Nitro-phenoxy)-acetic acid ethyl ester was isolated as an off-white solid (3.20 g, 99%).  1 HNMR (400 MHz, CDCl3, δ, ppm): 8.22 (d, J=7.8 Hz, 2H), 6.98 (d, J=7.8 Hz, 2H), 4.72 (s, 2H), 4.29 (q, J=7.1 Hz, 2H), 1.31 (t, J=7.1 Hz, 3H). MS=226 (MH)+. 
     310b) A Paar bottle (500 mL) was charged with 10% Palladium on Carbon (50% Wet)(5:45:50, Palladium:carbon black:Water, 3.0 g, 1.4 mmol) followed by a solution of (4-Nitro-phenoxy)-acetic acid ethyl ester (3.20 g, 14.2 mmol) in 2:1 Ethyl acetate:Methanol(2:1, Ethyl acetate:Methanol, 75 mL, 510 mmol). The mixture was degassed and charged with Hydrogen (50 psi). The mixture was shaken on a Paar apparatus until adsorption of Hydrogen ceased. The mixture was degassed and backflushed with nitrogen. The mixture was filtered through a plug of diatomaceous earth and evaporated. (4-Amino-phenoxy)-acetic acid ethyl ester was isolated as a tan solid (2.65 g, 96%).  1 HNMR (400 MHz, CDCl3, δ, ppm): 6.77 (d, J=7.9 Hz, 1H), 6.63 (d, J=7.8 Hz, 1H), 4.54 (s, 2H), 4.26 (q, J=7.1 Hz, 2H), 3.40 (br s, 2H), 1.29 (t, J=7.1 Hz, 3H). MS=196 (MH)+. 
     310c) (R)-3-{2-[2-(4-Ethoxycarbonylmethoxy-phenylamino)-pyridin-4-yl]-pyrido[3, 4-d]pyrimidin-4-ylamino}-pyrrolidine-1-carboxylic acid tert-butyl ester was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (200.0 mg, 0.4685 mmol) and (4-Amino-phenoxy)-acetic acid ethyl ester (100.0 mg, 0.5122 mmol) in an analogous manner to Example 303c. The orange residue was suspended in Methanol (1 mL, 20 mmol) and Water (1 mL, 60 mmol) and Lithium hydroxide monohydrate (25.0 mg, 0.596 mmol) was added. The mixture was stirred at room temperature overnight. The volatiles were evaporated to yield an orange solid. The orange solid was suspended in 1,4-Dioxane (5 mL, 60 mmol). Pyridine (0.1 mL, 1 mmol) was added followed by Di-tert-Butyldicarbonate (105.0 mg, 0.4811 mmol) and Ammonium Carbonate (70.0 mg, 0.728 mmol). The mixture was stirred at room temperature for overnight. The mixture was diluted with dichloromethane (25 mL) and filtered through a plug of diatomaceous earth and the filtrate was evaporated. The solid was dissolved in dichloromethane (1 mL) and trifluoroacetic acid (0.5 mL) was added. The mixture was stirred for 1 hour at room temperature then the volatiles were evaporated. The residue was purified via reverse phase chromatography using a Gilson apparatus (5%-30% Acetonitrile:Water w/ 0.1% TFA modifier). 2-(4-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenoxy)-acetamide was isolated as the trifluoroacetic acid salt as an orange-yellow lyophilate (0.118 g, 55%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.62 (br s, 1H), 9.24 (s, 1H), 8.98 (br s, 2H), 8.76 (d, J=4.5 Hz, 1H), 8.73 (d, J=5.3 Hz, 1H), 8.27 (d, J=5.6 Hz, 1H), 8.21 (d, J=5.3 Hz, 1H), 7.96 (s, 1H), 7.74 (d, J=5.5 Hz, 1H), 7.57 (d, J=8.1 Hz, 2H), 7.54 (s, 1H), 7.42 (s, 1H), 6.99 (d, J=8.4 Hz, 2H), 4.96-4.86 (m, 1H), 4.43 (s, 2H), 3.74-3.64 (m, 1H), 3.54-3.34 (m, 3H), 2.45-2.35 (m, 1H), 2.31-2.21 (m, 1H). MS=457 (MH)+. 
     Example 311. 2-(3-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenoxy)-acetamide 
     311a) (3-Nitro-phenoxy)-acetic acid ethyl ester was prepared from m-Nitrophenol (2.00 g, 14.4 mmol) and Ethyl bromoacetate (1.60 mL, 14.4 mmol) in an analogous manner to Example 310a. Product isolated as a yellow oil (3.20 g, 99%).  1 HNMR (400 MHz, CDCl3, δ, ppm): 7.88 (d, J=8.1 Hz, 1H), 7.73 (s, 1H), 7.46 (t, J=8.3 Hz, 1H), 7.27 (d, J=8.5 Hz, 1H), 4.71 (s, 2H), 4.30 (q, J=7.1 Hz, 2H), 1.32 (t, J=7.1 Hz, 3H). LC/MS=248 (M+Na)+. 
     311b) (3-Amino-phenoxy)-acetic acid ethyl ester was prepared from (3-Nitro-phenoxy)-acetic acid ethyl ester (3.20 g, 14.2 mmol) in an analogous manner to Example 310b. Product isolated as an orange oil (2.60 g, 94%).  1 HNMR (400 MHz, CDCl3, δ, ppm): 7.05 (t, J=7.8 Hz, 1H), 6.35-6.26 (m, 3H), 4.57 (s, 2H), 4.27 (q, J=7.2 Hz, 2H), 3.67 (br s, 2H), 1.30 (t, J=7.1 Hz, 3H). MS=196 (MH)+. 
     311c) 2-(3-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenoxy)-acetamide was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (200.0 mg, 0.4685 mmol) and (3-Amino-phenoxy)-acetic acid ethyl ester (100.0 mg, 0.5122 mmol) in an analogous manner to Example 310c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.011 g, 5%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.40 (br s, 1H), 9.23 (s, 1H), 8.85 (br s, 2H), 8.72 (d, J=5.3 Hz, 1H), 8.69 D, J=5.1 Hz, 1H), 8.35 (d, J=4.8 Hz, 1H), 8.26 (d, J=5.3 Hz, 1H), 7.98 (s, 1H), 7.75 (d, J=5.2 Hz, 1H), 7.55 (s, 1H), 7.52 (s, 1H), 7.39 (s, 1H), 7.28 (d, J=7.9 Hz, 1H), 7.20 (t, J=7.9 Hz, 1H), 6.51 (d, J=8.3 Hz, 1H), 4.98-4.90 (m, 1H), 4.41 (s, 2H), 3.76-3.70 (m, 1H), 3.52-3.33 (m, 3H), 2.45-2.38 (m, 1H), 2.30-2.23 (m, 1H). MS=457 (MH)+. 
     Example 313. 2-(4-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenyl)-acetamide 
     313a) To a stirred suspension of [A]4-Nitrophenylacetic Acid (1.0 g, 5.5 mmol) and Pyridine (0.27 mL, 3.3 mmol) in 1,4-Dioxane (10 mL, 100 mmol) was added Di-tert-Butyldicarbonate (1.3 g, 6.1 mmol). The mixture was stirred for 10 minutes at room temperature then Ammonium Carbonate (0.80 g, 8.3 mmol) was added. The mixture was stirred at room temperature overnight. The volatiles were evaporated to a leave an off-white solid. The solid was triturated with methanol, filtered and rinsed with methanol. The methanolic filtrate was evaporated. 2-(4-Nitro-phenyl)-acetamide was isolated as an off-white solid (0.65 g, 65%).  1 HNMR (400 MHz, d6-DMSO, 6, ppm):8.18 (d, J=7.9 Hz, 2H), 7.59 (br s, 1H), 7.54 (d, J=7.9 Hz, 2H), 7.01 (br s, 1H), 3.55 (s, 2H). LC/MS=181 (MH)+. 
     313b) 2-(4-Amino-phenyl)-acetamide was prepared from 2-(4-Nitro-phenyl)-acetamide (0.65 g, 3.6 mmol) in an analogous manner to Example 310b. Product isolated as a pale yellow solid (0.57 g, 99%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 7.25 (br s, 1H), 6.89 (d, J=8.1 Hz, 2H), 6.74 (br s, 1H), 6.47 (d, J=8.2 Hz, 2H), 4.89 (br s, 2H), 3.14 (s, 2H). MS=151 (MH)+. 
     313c). 2-(4-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenyl)-acetamide was prepared from [A](R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (200.0 mg, 0.4685 mmol) and 2-(4-Amino-phenyl)-acetamide (85.0 mg, 0.566 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.029 g, 14%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.36 (br s, 1H), 9.23 (s, 1H), 8.85 (br s, 2H), 8.72 (d, J=5.6 Hz, 1H), 8.70-8.67 (m, 1H), 8.30 (d, J=5.1 Hz, 1H), 8.25 (d, J=5.5 Hz, 1H), 7.96 (s, 1H), 7.72 (d, J=5.2 Hz, 1H), 7.63 (d, J=7.4 Hz, 2H), 7.42 (br s, 1H), 7.20 (d, J=8.3 Hz, 2H), 6.86 (br s, 1H), 4.96-4.87 (m, 1H), 3.75-3.65 (m, 1H), 3.51-3.30 (m, 5H), 2.46-2.36 (m, 1H), 2.31-2.21 (m, 1H). MS=441 (MH)+. 
     Example 314. 2-(4-Amino-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide 
     2-(4-Amino-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[34-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide was a byproduct from Example 313. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.018 g, 8%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.84 (s, 1H), 9.24 (s, 1H), 9.12 (s, 1H), 8.94 (br s, 2H), 8.71 (d, J=5.5 Hz, 2H), 8.50 (d, J=5.2 Hz, 1H), 8.26 (d, J=5.7 Hz, 1H), 8.09 (d, J=4.6 Hz, 1H), 7.34 (d, J=8.0 Hz, 2H), 7.08 (d, J=7.5 Hz, 2H), 4.95-4.87 (m, 1H), 3.77-3.65 (m, 3H), 3.51-3.33 (m, 3H), 2.47-2.36 (m, 1H), 2.31-2.21 (m, 1H). MS=441 (MH)+. 
     Example 316. 2-(3-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenyl)-acetamide 
     316a) 2-(3-Nitro-phenyl)-acetamide was prepared from (3-Nitro-phenyl)-acetic acid (1.0 g, 5.5 mmol) in an analogous manner to Example 13a. Product isolated as a crude off-white solid (1.2 g, 50%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.15 (s, 1H), 8.10 (d, J=8.2 Hz, 1H), 7.71 (d, J=7.7 Hz, 1H), 7.63-7.54 (m, 2H), 7.01 (br s, 1H), 3.56 (s, 2H). MS=181 (MH)+. 
     316b) 2-(3-Amino-phenyl)-acetamide was prepared from 2-(3-Nitro-phenyl)-acetamide (1.2 g, 6.7 mmol) in an analogous manner to Example 10b. Product isolated as an off-white solid (1.0 g, 70%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 7.32 (br s, 1H), 6.90 (t, J=7.7 Hz, 1H), 6.79 (br s, 1H), 6.46 (s, 1H), 6.42-6.37 (m, 2H), 4.97 (br s, 2H), 3.18 (s, 2H). MS=151 (MH)+. 
     316c) 2-(3-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenyl)-acetamide was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (200.0 mg, 0.4685 mmol) and 2-(3-Amino-phenyl)-acetamide (85.0 mg, 0.566 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.055 g, 26%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.50 (br s, 1H), 9.24 (s, 1H), 8.91 (br s, 2H), 8.72 (d, J=5.5 Hz, 1H), 8.31 (d, J=5.4 Hz, 1H), 8.26 (d, J=5.7 Hz, 1H), 7.99 (s, 1H), 7.75 (d, J=5.4 HZ, 1H), 7.66 (d, J=8.6 Hz, 1H), 7.54 (s, 1H), 7.48 (br s, 1H), 7.25 (t, J=7.7 Hz, 1H), 6.93-6.86 (m, 2H), 4.97-4.87 (m, 1H), 3.76-3.66 (m, 1H), 3.54-3.34 (m, 5H), 2.46-2.36 (m, 1H), 2.31-2.21 (m, 1H). MS=441 (MH)+. 
     Example 317. 2-(3-Amino-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide 
     2-(3-Amino-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[34-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide was a byproduct from Example 16. Product isolated as the trifluoroacetic acid salt as a pale yellow lyophilate (0.047 g, 23%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.90 (s, 1H), 9.24 (s, 1H), 9.14 (s, 1H), 8.94 (br s, 2H), 8.75-8.70 (m, 2H), 8.51 (d, J=5.1 Hz, 1H), 8.26 (d, J=5.5 Hz, 1H), 8.10 (dd, J=5.1, 1.1 Hz, 1H), 7.28 (t, J=7.8 Hz, 1H), 7.10-7.02 (m, 3H), 6.94 (d, J=6.6 Hz, 1H), 6.40-4.00 (m, 3H), 3.76 (s, 2H), 3.75-3.65 (m, 1H), 3.52-3.32 (m, 3H), 2.47-2.36 (m, 1H), 2.31-2.21 (m, 1H). MS=441 (MH)+. 
     Example 318. {2-[2-(5-Phenyl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine 
     2-[2-(5-Phenyl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (75.0 mg, 0.176 mmol) and 5-Phenyl-pyridin-2-ylamine (36.0 mg, 0.212 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.098 g, 97%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.28 (s, 1H), 8.92 (br s, 2H), 8.78-8.74 (m, 2H), 8.66-8.63 (m, 2H), 8.49 (d, J=5.8 Hz, 1H), 8.29 (d, J=5.2 Hz, 1H), 8.24-8.18 (m, 1H), 8.04-8.01 (m, 1H), 7.80-7.71 (m, 3H), 7.55-7.49 (m, 2H), 7.44-7.39 (m, 1H), 5.00-4.92 (m, 1H), 3.80-3.71 (m, 1H), 3.55-3.35 (m, 3H), 2.48-2.40 (m, 1H), 2.34-2.25 (m, 1H). MS=461 (MH)+. 
     Example 319. {2-[2-(6-Morpholin-4-yl-pyridin-3-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine 
     {2-[2-(6-Morpholin-4-yl-pyridin-3-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (75.0 mg, 0.176 mmol) and 6-Morpholin-4-yl-pyridin-3-ylamine (39.0 mg, 0.218 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as an orange-brown lyophilate (0.082 g, 80%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.71 (br s, 1H), 9.24 (s, 1H), 9.01 (br s, 2H), 8.77 (d, J=5.5 Hz, 1H), 8.73 (d, J=5.5 Hz, 1H), 8.62 (br s, 1H), 8.29-8.24 (m, 2H), 8.01-7.95 (m, 2H), 7.78 (dd, J=5.5, 1.3 Hz, 1H), 7.15 (d, J=9.2 Hz, 1H), 4.98-4.90 (m, 1H), 3.78-3.67 (m, 5H), 3.55-3.34 (m, 8H), 2.46-2.36 (m, 1H), 2.31-2.21 (m, 1H). MS=470 (MH)+. 
     Example 320. (2-{2-[6-(4-Methyl-piperazin-1-yl)-pyridin-3-ylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-(R)-pyrrolidin-3-yl-amine 
     (2-{2-[6-(4-Methyl-piperazin-1-yl)-pyridin-3-ylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (75.0 mg, 0.176 mmol) and 6-(4-Methyl-piperazin-1-yl)-pyridin-3-ylamine (41.0 mg, 0.213 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a brown lyophilate (0.094 g, 90%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.86 (br s, 1H), 9.45 (br s, 1H), 9.22 (s, 1H), 9.04 (br s, 2H), 8.76 (d, J=5.4 Hz, 1H), 8.72 (d, J=5.6 Hz, 1H), 8.51 (d, J=2.7 Hz, 1H), 8.27 (d, J=5.8 Hz, 1H), 8.24 (d, J=5.6 Hz, 1H), 8.02 (dd, J=9.0, 2.6 Hz, 1H), 7.93 (s, 1H), 7.73 (dd, J=5.4, 1.2 Hz, 1H), 7.02 (d, J=9.2 Hz, 1H), 4.99-4.90 (m, 1H), 4.38-4.25 (m, 2H), 3.78-3.68 (m, 1H), 3.59-3.34 (m, 5H), 3.18-3.02 (m, 4H), 2.87 (s, 3H), 2.47-2.36 (m, 1H), 2.31-2.22 (m, 1H). MS=483 (MH)+. 
     Example 321. 2-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile 
     2-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (75.0 mg, 0.176 mmol) and 2-Amino-isonicotinonitrile (25.0 mg, 0.210 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a pale yellow lyophilate (0.012 g, 13%). 
     Example 322. {2-[2-(4-Imidazol-1-ylmethyl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine 
     {2-[2-(4-Imidazol-1-ylmethyl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (75.0 mg, 0.176 mmol) and 4-Imidazol-1-ylmethyl-phenylamine (37.0 mg, 0.214 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.097 g, 95%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.56 (s, 1H), 9.24 (t, J=1.4 Hz, 1H), 9.22 (s, 1H), 9.06 (br s, 2H), 8.77 (d, J=5.4 Hz, 1H), 8.71 (d, J=5.5 Hz, 1H), 8.33 (d, J=5.5 Hz, 1H), 8.27 (d, J=5.8 Hz, 1H), 7.97 (s, 1H), 7.83-7.76 (m, 4H), 7.70 (t, J=1.7 Hz, 1H), 7.38 (d, J=8.7 Hz, 2H), 5.36 (s, 2H), 5.01-4.92 (m, 1H), 3.78-3.69 (m, 1H), 3.55-3.34 (m, 3H), 2.47-2.36 (m, 1H), 2.31-2.22 (m, 1H). MS=464 (MH)+. 
     Example 323. 2-(3-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenoxy)-acetamide 
     2-(3-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenoxy)-acetamide was prepared from R)-3-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (150.0 mg, 0.3283 mmol) and (3-Amino-phenoxy)-acetic acid ethyl ester (75.0 mg, 0.384 mmol) in an analogous manner to Example 303c and Example 10c and Example 1c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.082 g, 41%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.42 (s, 1H), 8.94 (br s, 1H), 8.89-8.80 (m, 2H), 8.41 (s, 1H), 8.34 (d, J=5.2 Hz, 1H), 8.16 (d, J=6.2 Hz, 1H), 7.95 (s, 1H), 7.72 (dd, J=5.4, 1.3 Hz, 1H), 7.54 (t, J=2.1 Hz, 1H), 7.52 (s, 1H), 7.38 (s, 1H), 7.30-7.25 (m, 1H), 7.20 (t, J=8.2 Hz, 1H), 6.51 (dd, J=7.8, 1.7 Hz, 1H), 5.05-4.95 (m, 1H), 4.41 (s, 2H), 4.16 (m, 3H), 3.73-3.64 (m, 1H), 3.52-3.30 (m, 3H), 2.53-2.45 (m, 1H), 2.27-2.16 (m, 1H). MS=487 (MH)+. 
     Example 324. 2-(3-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenyl)-acetamide 
     2-(3-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenyl)-acetamide was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (150.0 mg, 0.3283 mmol) and 2-(3-Amino-phenyl)-acetamide (60.0 mg, 0.400 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.043 g, 22%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.36 (s, 1H), 9.00-8.77 (m, 3H), 8.40 (s, 1H), 8.31 (d, J=5.4 Hz, 1H), 8.15 (d, J=6.2 Hz, 1H), 7.94 (s, 1H), 7.72-7.65 (m, 2H), 7.56 (s, 1H), 7.46 (s, 1H), 7.22 (t, J=7.7 Hz, 1H), 6.90-6.83 (m, 2H), 5.05-4.95 (m, 1H), 4.16 (s, 3H), 3.73-3.63 (m, 1H), 3.50-3.23 (m, 5H), 2.55-2.45 (m, 1H), 2.26-2.16 (m, 1H). MS=471 (MH)+. 
     Example 325. 2-(3-Amino-phenyl)-N-{4-[5-methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide 
     2-(3-Amino-phenyl)-N-{4-[5-methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide was a byproduct from Example 24. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.033 g, 17%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.84 (s, 1H), 9.11 (s, 1H), 9.00-8.78 (m, 3H), 8.50 (d, J=5.5 Hz, 1H), 8.40 (s, 1H), 8.15 (d, J=5.9 Hz, 1H), 8.06 (dd, J=5.2, 1.4 Hz, 1H), 7.25-7.10 (m, 1H), 7.00-6.65 (m, 3H), 5.00-4.01 (m, 1H), 4.15 (s, 3H), 3.80-3.28 (m, 8H), 2.55-2.45 (m, 1H), 2.26-2.16 (m, 1H). MS=471 (MH)+ 
     Example 326. 2-(4-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenyl)-acetamide 
     2-(4-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenyl)-acetamide was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (150.0 mg, 0.3283 mmol) and 2-(4-Amino-phenyl)-acetamide (60.0 mg, 0.400 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.072 g, 37%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.29 (s, 1H), 9.10-8.80 (m, 3H), 8.40 (s, 1H), 8.31 (d, J=5.3 Hz, 1H), 8.15 (d, J=6.1 Hz, 1H), 7.92 (s, 1H), 7.68 (dd, J=5.3, 1.3 Hz, 1H), 7.63 (d, J=8.5 Hz, 2H), 7.43-7.39 (m, 1H), 7.18 (d, J=8.5 Hz, 2H), 6.84 (s, 1H), 5.05-4.95 (m, 1H), 4.16 (s, 3H), 3.72-3.63 (m, 1H), 3.50-3.20 (m, 5H), 2.54-2.45 (m, 1H), 2.26-2.16 (m, 1H). MS=471 (MH)+. 
     Example 327. 2-(4-Amino-phenyl)-N-{4-[5-methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide 
     2-(4-Amino-phenyl)-N-{4-[5-methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide was a byproduct from Example 26. Product isolated as the trifluoroacetic acid salt was isolated as a yellow lyophilate (0.025 g, 13%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.81 (s, 1H), 9.09 (s, 1H), 9.02-8.83 (m, 3H), 8.49 (dd, J=5.2, 0.70 Hz, 1H), 8.40 (s, 1H), 8.16 (d, J=6.0 Hz, 1H), 8.05 (dd, J=5.2, 1.5 Hz, 1H), 7.28 (d, J=7.8 Hz, 2H), 7.00-6.93 (m, 2H), 5.01-4.91 (m, 1H), 4.15 (s, 3H), 3.72-3.61 (m, 3H), 3.47-3.28 (m, 3H), 2.54-2.44 (m, 1H), 2.26-2.16 (m, 1H). MS=471 (MH)+. 
     Example 328. 1-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile 
     1-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (75.0 mg, 0.176 mmol) and 1H-Pyrrolo[2,3-b]pyridine-4-carbonitrile (30.0 mg, 0.210 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as an off-white lyophilate (0.068 g, 71%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.83 (s, 1H), 9.31 (s, 1H), 8.89 (br s, 2H), 8.79-8.75 (m, 4H), 8.72 (d, J=4.9 Hz, 1H), 8.37 (d, J=5.2 Hz, 1H), 8.30 (d, J=5.6 Hz, 1H), 7.87 (d, J=4.9 Hz, 1H), 7.04 (d, J=3.9 Hz, 1H), 5.00-4.91 (m, 1H), 3.83-3.74 (m, 1H), 3.57-3.39 (m, 3H), 2.54-2.44 (m, 1H), 2.37-2.30 (m, 1H). MS=434 (MH)+. 
     Example 329. {5-Methoxy-2-[2-(5-phenyl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine 
     {5-Methoxy-2-[2-(5-phenyl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (75.0 mg, 0.164 mmol) and 5-Phenyl-pyridin-2-ylamine (31.0 mg, 0.182 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.043 g, 43%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.04-8.85 (m, 3H), 8.66-8.61 (m, 2H), 8.48 (d, J=5.5 Hz, 1H), 8.44 (s, 1H), 8.23-8.15 (m, 2H), 8.00-7.95 (m, 1H), 7.82-7.75 (m, 1H), 7.74-7.71 (m, 2H), 7.51 (t, J=7.6 Hz, 2H), 7.41 (t, J=7.1 Hz, 1H), 5.07-5.00 (m, 1H), 4.18 (s, 3H), 3.76-3.66 (m, 1H), 3.54-3.30 (m, 3H), 2.55-2.45 (m, 1H), 2.30-2.20 (m, 1H). MS=491 (MH)+. 
     Example 330. {5-Methoxy-2-[2-(6-morpholin-4-yl-pyridin-3-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine 
     {5-Methoxy-2-[2-(6-morpholin-4-yl-pyridin-3-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (75.0 mg, 0.164 mmol) and 6-Morpholin-4-yl-pyridin-3-ylamine (33.0 mg, 0.184 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a tan lyophilate (0.033 g, 33%)  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.02-8.82 (m, 3H), 8.60-8.52 (m, 1H), 8.41 (s, 1H), 8.26 (d, J=4.8 Hz, 1H), 8.17 (d, J=4.4 Hz, 1H), 8.00-7.95 (m, 1H), 7.89 (s, 1H), 7.72-7.68 (m, 1H), 7.10-6.98 (m, 1H), 5.05-4.95 (m, 1H), 4.16 (s, 3H), 3.76-3.63 (m, 5H), 3.50-3.29 (m, 7H), 2.54-2.45 (m, 1H), 2.26-2.16 (m, 1H). MS=500 (MH)+. 
     Example 331. (5-Methoxy-2-{2-[6-(4-methyl-piperazin-1-yl)-pyridin-3-ylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-(R)-pyrrolidin-3-yl-amine 
     (5-Methoxy-2-{2-[6-(4-methyl-piperazin-1-yl)-pyridin-3-ylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (75.0 mg, 0.164 mmol) and 6-(4-Methyl-piperazin-1-yl)-pyridin-3-ylamine (35.0 mg, 0.182 mmol) in an analogous manner to Example 303c. Product isolated as the bis-trifluoroacetic acid salt as a brown lyophilate (0.036 g, 29%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.69 (br s, 1H), 9.26 (br s, 1H), 9.06-8.81 (m, 3H), 8.51 (d, J=2.6 Hz, 1H), 8.40 (s, 1H), 8.25 (d, J=5.5 Hz, 1H), 8.16 (d, J=6.0 Hz, 1H), 8.04 (dd, J=9.1, 2.6 Hz, 1H), 7.86 (s, 1H), 7.67 (d, J=5.3 Hz, 1H), 6.98 (d, J=9.0 Hz, 1H), 5.04-4.98 (m, 1H), 4.32-4.26 (m, 2H), 4.16 (s, 3H), 3.71-3.65 (m, 1H), 3.55-3.50 (m, 2H), 3.50-3.30 (m, 3H), 3.16-3.01 (m, 4H), 2.86 (d, J=4.3 Hz, 3H), 2.53-2.43 (m, 1H), 2.26-2.16 (m, 1H). MS=513 (MH)+. 
     Example 332. 2-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile 
     2-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (75.0 mg, 0.164 mmol) and 2-Amino-isonicotinonitrile (22.0 mg, 0.185 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.014 g, 15%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.42 (s, 1H), 8.98-8.80 (m, 3H), 8.60 (s, 1H), 8.51 (d, J=5.1 Hz, 1H), 8.48 (d, J=5.3 Hz, 1H), 8.42 (s, 1H), 8.34 (s, 1H), 8.16 (d, J=5.8 Hz, 1H), 7.92 (dd, J=5.2, 1.3 Hz, 1H), 7.32 (dd, J=5.0, 1.3 Hz, 1H), 5.03-4.95 (m, 1H), 4.17 (s, 3H), 3.75-3.66 (m, 1H), 3.50-3.30 (m, 3H), 2.55-2.45 (m, 1H), 2.28-2.18 (m, 1H). MS=440 (MH)+. 
     Example 333. {2-[2-(4-Imidazol-1-ylmethyl-phenylamino)-pyridin-4-yl]-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine 
     {2-[2-(4-Imidazol-1-ylmethyl-phenylamino)-pyridin-4-yl]-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (75.0 mg, 0.164 mmol) and 4-Imidazol-1-ylmethyl-phenylamine (32.0 mg, 0.185 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a yellow-orange lyophilate (0.037 g, 37%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.53 (s, 1H), 9.24-9.22 (m, 1H), 9.18-8.92 (m, 2H), 8.82 (s, 1H), 8.40 (s, 1H), 8.33 (d, J=5.3 Hz, 1H), 8.18 (d, J=6.3 Hz, 1H), 7.94 (s, 1H), 7.81 (d, J=8.6 Hz, 2H), 7.78 (t, J=1.7 Hz, 1H), 7.74 (dd, J=5.2, 1.3 Hz, 1H), 7.70 (t, J=1.7 Hz, 1H), 7.37 (d, J=8.7 Hz, 2H), 5.36 (s, 2H), 5.08-4.99 (m, 1H), 4.16 (s, 3H), 3.74-3.64 (m, 1H), 3.52-3.29 (m, 3H), 2.53-2.43 (m, 1H), 2.26-2.16 (m, 1H). MS=494 (MH)+. 
     Example 334. 2-Phenyl-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide 
     2-Phenyl-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (75.0 mg, 0.176 mmol) and Benzeneacetamide (27.0 mg, 0.200 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a tan lyophilate (0.036 g, 38%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.89 (s, 1H), 9.25 (s, 1H), 9.14 (s, 1H), 8.90 (br s, 2H), 8.73-8.69 (m, 2H), 8.50 (dd, J=5.2, 0.6 Hz, 1H), 8.25 (d, J=5.2 Hz, 1H), 8.09 (dd, J=5.2, 1.4 Hz, 1H), 7.41-7.24 (m, 5H), 4.93-4.85 (m, 1H), 3.79 (s, 2H), 3.75-3.65 (m, 1H), 3.51-3.33 (m, 3H), 2.47-2.37 (m, 1H), 2.31-2.21 (m, 1H). MS=426 (MH)+. 
     Example 335. 2-(4-Methoxy-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide 
     2-(4-Methoxy-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (75.0 mg, 0.176 mmol) and 4-Methoxyphenylacetamide (33.0 mg, 0.200 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.021 g, 21%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.81 (s, 1H), 9.24 (s, 1H), 9.13 (s, 1H), 8.88 (br s, 2H), 8.71 (d, J=5.6 Hz, 1H), 8.69 (d, J=4.8 Hz, 1H), 8.49 (d, J=5.2 Hz, 1H), 8.25 (d, J=5.3 Hz, 1H), 8.08 (dd, J=5.1, 1.5 Hz, 1H), 7.30 (d, J=8.7 Hz, 2H), 6.91 (d, J=8.7 Hz, 2H), 4.93-4.85 (m, 1H), 3.75-3.65 (m, 6H), 3.49-3.34 (m, 3H), 2.47-2.37 (m, 1H), 2.31-2.21 (m, 1H). MS=456 (MH)+. 
     Example 336. 2-(2-Methoxy-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide 
     336a) 2-(2-Methoxy-phenyl)-acetamide was prepared from 2-Methoxybenzeneacetic acid (1.0 g, 6.0 mmol) in an analogous manner to Example 13a. Product isolated as a white solid (0.64 g, 64%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 7.24-7.18 (m, 2H), 7.15 (dd, J=7.5, 1.6 Hz, 1H), 6.95 (d, J=7.7 Hz, 1H), 6.90-6.84 (m, 1H), 6.81 (br s, 1H), 3.75 (s, 3H), 3.35 (s, 2H). MS=166 (MH)+. 
     336b) 2-(2-Methoxy-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (75.0 mg, 0.176 mmol;) and 2-(2-Methoxy-phenyl)-acetamide (32.0 mg, 0.194 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a tan lyophilate (0.048 g, 48%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.66 (s, 1H), 9.24 (s, 1H), 9.12 (s, 1H), 8.84 (br s, 2H), 8.71 (d, J=5.7 Hz, 1H), 8.69-8.65 (m, 1H), 8.50 (d, J=5.2 Hz, 1H), 8.25 (d, J=5.3 Hz, 1H), 8.08 (dd, J=5.3, 1.3 Hz, 1H), 7.30-7.23 (m, 2H), 7.01 (d, J=7.8 Hz, 1H), 6.95-6.90 (m, 1H), 4.93-4.85 (m, 1H), 3.80-3.74 (m, 5H), 3.72-3.63 (m, 1H), 3.49-3.30 (m, 3H), 2.45-2.37 (m, 1H), 2.30-2.20 (m, 1H). MS=456 (MH)+. 
     Example 337. 2-(3-Methoxy-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide 
     2-(3-Methoxy-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (75.0 mg, 0.176 mmol) and 2-(3-Methoxy-phenyl)-acetamide (32.0 mg, 0.194 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a tan lyophilate (0.099 g).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.86 (s, 1H), 9.25 (s, 1H), 9.13 (s, 1H), 8.89 (br s, 2H), 8.73-8.68 (m, 2H), 8.50 (d, J=5.2 Hz, 1H), 8.25 (d, J=5.2 Hz, 1H), 8.09 (dd, J=5.2, 1.5 Hz, 1H), 7.26 (t, J=7.8 Hz, 1H), 6.98-6.94 (m, 2H), 6.86-6.82 (m, 1H), 4.94-4.85 (m, 1H), 3.77-3.65 (m, 6H), 3.51-3.34 (m, 3H), 2.47-2.37 (m, 1H), 2.31-2.21 (m, 1H). MS=456 (MH)+. 
     Example 338. {2-[2-(4-Methyl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine 
     {2-[2-(4-Methyl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2342 mmol) and 4-Methyl-pyridin-2-ylamine (31.0 mg, 0.287 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a pale yellow lyophilate (0.107 g).  1 HNMR=31550651 (400 MHz, d6-DMSO, δ, ppm): 9.28-9.27 (m, 1H), 8.99 (br s, 2H), 8.84-8.79 (m, 1H), 8.77-8.74 (m, 1H), 8.55 (d, J=5.4 Hz, 1H), 8.42-8.36 (m, 1H), 8.31-8.26 (m, 2H), 8.18-8.14 (m, 1H), 7.27 (s, 1H), 7.16-7.12 (m, 1H), 5.04-4.94 (m, 1H), 3.78-3.68 (m, 1H), 3.54-3.34 (m, 3H), 2.48 (s, 3H), 2.46-2.36 (m, 1H), 2.32-2.22 (m, 1H). MS=399 (MH)+. 
     Example 339. {2-[2-(4-Chloro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine 
     {2-[2-(4-Chloro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (105.0 mg, 0.2460 mmol) and 4-Chloro-pyridin-2-ylamine (37.0 mg, 0.288 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a pale yellow lyophilate (0.124 g, 96%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.43 (br s, 1H), 9.26 (s, 1H), 8.90 (br s, 2H), 8.75-8.70 (m, 2H), 8.64 (s, 1H), 8.46 (d, J=5.6 Hz, 1H), 8.30-8.25 (m, 2H), 8.01 (s, 1H), 7.95 (d, J=5.4 Hz, 1H), 7.07 (d, J=5.3 Hz, 1H), 4.97-4.89 (m, 1H), 3.80-3.70 (m, 1H), 3.53-3.35 (m, 3H), 2.49-2.39 (m, 1H), 2.34-2.24 (m, 1H). MS=419 (MH)+. 
     Example 340. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyrazin-2-yl-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyrazin-2-yl-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (352.0 mg, 0.7704 mmol) and 2-Aminopyrazine (81 mg, 0.85 mmol) in an analogous manner to Example 303c. Product was isolated as the free base as an off-white solid (0.050 g, 16%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.22 (s, 1H), 9.17 (d, J=1.4 Hz, 1H), 8.83 (s, 1H), 8.72 (s, 1H), 8.43 (d, J=5.2 Hz, 1H), 8.33 (s, 1H), 8.28 (dd, J=1.6, 2.6 Hz, 1H), 8.12 (d, J=2.7 Hz, 1H), 7.86 (dd, J=1.3, 5.2 Hz, 1H), 4.07 (s, 3H), 3.70-3.65 (m, 4H), 2.90-2.85 (m, 4H). MS=416 (MH)+. 
     Example 341. 6-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-nicotinonitrile 
     6-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-nicotinonitrile was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2342 mmol) and 6-Amino-nicotinonitrile (33.0 mg, 0.277 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a pale yellow lyophilate (0.016 g, 13%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.60 (s, 1H), 9.26 (s, 1H), 8.92-8.80 (m, 3H), 8.75-8.72 (m, 2H), 8.69 (d, J=4.6 Hz, 1H), 8.48 (d, J=5.3 Hz, 1H), 8.28 (d, J=5.2 Hz, 1H), 8.10 (dd, J=8.9, 2.3 Hz, 1H), 8.00 (dd, J=5.2, 1.3 Hz, 1H), 7.90 (d, J=8.9 Hz, 1H), 4.94-4.89 (m, 1H), 3.78-3.70 (m, 1H), 3.51-3.35 (m, 3H), 2.46-2.40 (m, 1H), 2.35-2.25 (m, 1H). MS=410 (MH)+. 
     Example 342. 2-[4-(4-Piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-isonicotinonitrile 
     342a) 4-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester was prepared from 2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol (500.0 mg, 1.933 mmol) and tert-Butyl 1-Piperazinecarboxylate (432.0 mg, 2.320 mmol) in an analogous manner to [B016]. Product isolated as a yellow foam (0.817 g, 99%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.30 (s, 1H), 8.64-8.60 (m, 2H), 8.38-8.35 (m, 2H), 8.01-7.98 (m, 1H), 4.06-4.01 (m, 4H), 3.67-3.62 (m, 4H), 3.32 (s, 3H), 1.45 (s, 9H). MS=427 (MH)+. 
     342b) 2-[4-(4-Piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-isonicotinonitrile was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2342 mmol) and 2-Amino-isonicotinonitrile (31.0 mg, 0.260 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a pale yellow lyophilate (0.015 g, 12%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.44 (s, 1H), 9.36 (s, 1H), 8.90 (br s, 2H), 8.69-8.66 (m, 2H), 8.53-8.48 (m, 2H), 8.36 (s, 1H), 8.04 (d, J=5.7 Hz, 1H), 7.95 (dd, J=5.3, 1.3 Hz, 1H), 7.33 (dd, J=5.1, 1.3 Hz, 1H), 4.18-4.13 (m, 4H), 3.42-3.37 (m, 4H). MS=410 (MH)+. 
     Example 343. {2-[2-(4-Morpholin-4-yl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine 
     {2-[2-(4-Morpholin-4-yl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2342 mmol) and 4-Morpholin-4-yl-pyridin-2-ylamine (47.0 mg, 0.262 mmol)[prepared as described in WO2006/040520] in an analogous manner to Example 303c. Product isolated the free base as a pale yellow solid (0.016 g, 14%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.51 (s, 1H), 9.17 (s, 1H), 8.86 (s, 1H), 8.67-8.52 (m, 2H), 8.35-8.27 (m, 2H), 7.95 (d, J=6.0 Hz, 1H), 7.81-7.78 (m, 1H), 7.30-7.27 (m, 1H), 6.52-6.47 (m, 1H), 4.97-4.75 (m, 1H), 3.77-3.72 (m, 4H), 3.35-3.30 (m, 1H), 3.26-3.22 (m, 4H), 3.06-2.98 (m, 1H), 2.92-2.84 (m, 2H), 2.31-2.21 (m, 1H), 1.93-1.83 (m, 1H). MS=470 (MH)+. 
     Example 344. 6-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-nicotinonitrile 
     344a) 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol was prepared from 2-Chloro-isonicotinonitrile (0.96 g, 6.9 mmol) and 3-Amino-5-methoxy-isonicotinic acid (0.97 g, 5.8 mmol) in an analogous manner to example 1501a. Product isolated as a tan solid (0.774 g, 46%).  1 HNMR (400 MHz, d1-TFA, δ, ppm): 9.24 (s, 1H), 9.11 (d, J=6.2 Hz, 1H), 8.93 (s, 1H), 8.85 (d, J=6.0 Hz, 1H), 8.71 (s, 1H), 4.36 (s, 3H). MS=289 (MH)+. 
     344b) R)-3-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (0.50 g, 1.7 mmol) and (R)-3-Amino-pyrrolidine-1-carboxylic acid tert-butyl ester (0.32 mL, 1.9 mmol) in an analogous manner to [B016]. Product isolated as a light brown solid (0.50 g, 63%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.84 (s, 1H), 8.61 (d, J=5.0 Hz, 1H), 8.39 (s, 1H), 8.36-8.32 (m, 2H), 8.24-8.17 (m, 1H), 5.09-4.92 (m, 1H), 4.14 (s, 3H), 3.86-3.72 (m, 1H), 3.55-3.32 (m, 3H), 2.37-2.25 (m, 1H), 2.21-2.07 (m, 1H), 1.45-1.38 (m, 9H). MS=457 (MH)+. 
     344c) 6-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-nicotinonitrile was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (160.0 mg, 0.3502 mmol) and 6-Amino-nicotinonitrile (50.0 mg, 0.420 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a pale yellow lyophilate (0.043 g, 22%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.60 (s, 1H), 9.00-8.80 (m, 4H), 8.72 (d, J=2.2 Hz, 1H), 8.48 (d, J=5.3 Hz, 1H), 8.42 (s, 1H), 8.15 (d, J=5.8 Hz, 1H), 8.10 (dd, J=8.9, 2.4 Hz, 1H), 7.97 (dd, J=5.3, 1.5 Hz, 1H), 7.90 (d, J=9.0 Hz, 1H), 5.01-4.93 (m, 1H), 4.17 (s, 3H), 3.75-3.65 (m, 1H), 3.52-3.30 (m, 3H), 2.55-2.45 (m, 1H), 2.29-2.19 (m, 1H). MS=440 (MH)+. 
     Example 345. {2-[2-(5-Methyl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine 
     {2-[2-(5-Methyl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2342 mmol) and 5-Methyl-pyridin-2-ylamine (30.0 mg, 0.277 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a pale yellow lyophilate (0.033 g, 27%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.27 (s, 1H), 8.93 (br s, 2H), 8.81-8.77 (m, 1H), 8.76 (d, J=5.6 Hz, 1H), 8.52-8.45 (m, 2H), 8.29 (d, J=5.5 Hz, 1H), 8.20 (s, 1H), 8.08 (br s, 1H), 7.87 (br s, 1H), 7.49 (br s, 1H), 5.00-4.90 (m, 1H), 3.79-3.69 (m, 1H), 3.55-3.35 (m, 3H), 2.47-2.37 (m, 1H), 2.34-2.24 (m, 4H). MS=399 (MH)+. 
     Example 346. {2-[2-(5-Chloro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine 
     {2-[2-(5-Chloro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2342 mmol) and 2-Amino-5-chloropyridine (36.0 mg, 0.280 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.081 g, 65%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.36 (br s, 1H), 9.26 (s, 1H), 8.89 (br s, 2H), 8.74 (d, J=5.6 Hz, 1H), 8.71 (d, J=4.8 Hz, 1H), 8.67 (s, 1H), 8.42 (d, J=5.5 Hz, 1H), 8.34-8.32 (m, 1H), 8.27 (d, J=5.1 Hz, 1H), 7.93 (d, J=5.5 Hz, 1H), 7.88-7.82 (m, 2H), 4.97-4.87 (m, 1H), 3.79-3.70 (m, 1H), 3.55-3.35 (m, 3H), 2.50-2.40 (m, 1H), 2.34-2.24 (m, 1H). MS=419 (MH)+. 
     Example 347. 2-[2-(Pyrimidin-4-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine 
     {2-[2-(Pyrimidin-4-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2342 mmol) and Pyrimidin-4-ylamine (27.0 mg, 0.284 mmol) in an analogous manner to Example 303c. Product isolated as the trifluoroacetic acid salt as an off-white lyophilate (0.033 g, 28%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 11.07 (br s, 1H), 9.26 (s, 1H), 9.07 (br s, 2H), 8.95 (s, 1H), 8.87 (d, J=5.3 Hz, 1H), 8.84 (s, 1H), 8.73 (d, J=5.6 Hz, 1H), 8.56-8.53 (m, 2H), 8.35 (d, J=5.5 Hz, 1H), 8.10 (d, J=5.2, 1.2 Hz, 1H), 7.97-7.90 (m, 1H), 5.00-4.92 (m, 1H), 3.79-3.69 (m, 1H), 3.55-3.35 (m, 3H), 2.49-2.39 (m, 1H), 2.35-2.25 (m, 1H). MS=386 (MH)+. 
     Example 348. 2-(3-Cyano-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide 
     348a) 2-(3-Cyano-phenyl)-acetamide was prepared from (3-Cyano-phenyl)-acetic acid (1.0 g, 6.2 mmol) in an analogous manner to Example 313a. Product isolated as an off-white solid (0.50 g, 50%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 7.72-7.69 (m, 2H), 7.61-7.58 (m, 1H), 7.56-7.50 (m, 2H), 6.97 (br s, 1H), 3.47 (s, 2H). MS=161 (MH)+. 
     348b) 2-(3-Cyano-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2342 mmol) and 2-(3-Cyano-phenyl)-acetamide (45.0 mg, 0.281 mmol) in an analogous manner to Example 303c and Example 1c. Product isolated as the trifluoroacetic acid salt as a pale yellow lyophilate (0.125 g, 94%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.97 (s, 1H), 9.24 (s, 1H), 9.12 (s, 1H), 8.90 (br s, 2H), 8.73-8.69 (m, 2H), 8.51 (dd, J=5.1, 0.5 Hz, 1H), 8.25 (dd, J=5.6, 0.7 Hz, 1H), 8.10 (dd, J=5.2, 1.5 Hz, 1H), 7.84-7.82 (m, 1H), 7.78-7.75 (m, 1H), 7.74-7.70 (m, 1H), 7.58 (t, J=7.8 Hz, 1H), 4.94-4.85 (m, 1H), 3.90 (s, 2H), 3.74-3.64 (m, 1H), 3.51-3.33 (m, 3H), 2.47-2.37 (m, 1H), 2.30-2.20 (m, 1H). MS=451 (MH)+. 
     Example 349. 2-(4-Cyano-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide 
     349a) 2-(4-Cyano-phenyl)-acetamide was prepared from (4-Cyano-phenyl)-acetic acid (1.0 g, 6.2 mmol) in an analogous manner to Example 313a. Product isolated as an off-white solid (0.71 g, 71%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 7.77 (d, J=8.3 Hz, 2H), 7.55 (br s, 1H), 7.45 (d, J=8.3 Hz, 2H), 6.98 (br s, 1H), 3.49 (s, 2H). MS=161 (MH)+. 
     349b) 2-(4-Cyano-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (120.0 mg, 0.2811 mmol) and 2-(4-Cyano-phenyl)-acetamide (45.0 mg, 0.281 mmol) in an analogous manner to Example 303c and Example 1c. Product isolated as the trifluoroacetic acid salt as a pale orange lyophilate (0.148 g, 93%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.98 (s, 1H), 9.23 (s, 1H), 9.12 (s, 1H), 8.87 (br s, 2H), 8.73-8.68 (m, 2H), 8.51 (dd, J=5.1, 0.6 Hz, 1H), 8.25 (dd, J=5.7, 0.6 Hz, 1H), 8.10 (dd, J=5.1, 1.4 Hz, 1H), 7.83 (d, J=8.4 Hz, 2H), 7.58 (d, J=8.4 Hz, 2H), 4.93-4.84 (m, 1H), 3.92 (s, 2H), 3.73-3.64 (m, 1H), 3.51-3.32 (m, 3H), 2.47-2.36 (m, 1H), 2.30-2.21 (m, 1H). MS=451 (MH)+. 
     Example 350. (R)-Pyrrolidin-3-yl-{2-[2-(4-trifluoromethyl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-amine 
     (R)-Pyrrolidin-3-yl-{2-[2-(4-trifluoromethyl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2342 mmol) and 4-Trifluoromethyl-pyridin-2-ylamine (46.0 mg, 0.284 mmol) in an analogous manner to Example 303c and Example 1c. Product isolated as the trifluoroacetic acid salt as a pale yellow lyophilate (0.127 g, 95%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.57 (s, 1H), 9.26 (d, J=0.4 Hz, 1H), 8.94 (br s, 2H), 8.75-8.72 (m, 2H), 8.69 (s, 1H), 8.56 (d, J=5.1 Hz, 1H), 8.47 (d, J=5.4 Hz, 1H), 8.28 (dd, J=5.7, 0.6 Hz, 1H), 8.26 (s, 1H), 7.97 (dd, J=5.4, 1.5 Hz, 1H), 7.25 (dd, J=5.9, 1.0 Hz, 1H), 4.99-4.90 (m, 1H), 3.80-3.71 (m, 1H), 3.55-3.35 (m, 3H), 2.48-2.40 (m, 1H), 2.34-2.24 (m, 1H). MS=453 (MH)+. 
     Example 351. (R)-Pyrrolidin-3-yl-{2-[2-(5-trifluoromethyl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-amine 
     (R)-Pyrrolidin-3-yl-{2-[2-(5-trifluoromethyl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2342 mmol) and 5-Trifluoromethyl-pyridin-2-ylamine (46.0 mg, 0.284 mmol) in an analogous manner to Example 303c and Example 1c. Product isolated as a trifluoroacetic acid salt as a pale yellow lyophilate (0.102 g, 76%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.64 (s, 1H), 9.27 (d, J=0.6 Hz, 1H), 8.94 (br s, 2H), 8.75-7.73 (m, 3H), 8.66-8.63 (m, 1H), 8.48 (dd, J=5.2, 0.3 Hz, 1H), 8.28 (dd, J=5.6, 0.7 Hz, 1H), 8.08 (dd, J=9.1, 2.5 Hz, 1H), 8.03-7.98 (m, 2H), 4.99-4.90 (m, 1H), 3.80-3.70 (m, 1H), 3.55-3.35 (m, 3H), 2.50-2.40 (m, 1H), 2.34-2.24 (m, 1H). MS=453 (MH)+. 
     Example 352. 2-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-isonicotinonitrile 
     352a) 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (2.0 g, 6.9 mmol) and tert-Butyl 1-Piperazinecarboxylate (1.5 g, 8.3 mmol; Supplier=Aldrich) in an analogous manner to [B016]. Product isolated as an off-white solid (1.35 g, 43%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.88 (s, 1H), 8.61 (dd, J=4.9, 0.8 Hz, 1H), 8.39 (s, 1H), 8.34-8.31 (m, 2H), 4.09 (s, 3H), 3.72-3.67 (m, 4H), 3.57-3.52 (m, 4H), 1.44 (s, 9H). MS=457, 459 (MH)+. 
     352b) 2-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-isonicotinonitrile was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2-Amino-isonicotinonitrile (31.0 mg, 0.260 mmol) in an analogous manner to Example 303c and Example 1c. Product isolated as the trifluoroacetic acid salt as a pale yellow lyophilate (0.105 g, 86%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.49 (s, 1H), 8.93 (s, 1H), 8.88 (br s, 2H), 8.64 (s, 1H), 8.51 (dd, J=5.1, 0.6 Hz, 1H), 8.48 (d, J=5.5 Hz, 1H), 8.43 (s, 1H), 8.34 (s, 1H), 7.92 (dd, J=5.4, 1.4 Hz, 1H), 7.34 (dd, J=5.0, 1.3 Hz, 1H), 4.11 (s, 3H), 3.93-3.88 (m, 4H), 3.37-3.30 (m, 4H). MS=440 (MH)+. 
     Example 353. 6-[4-(5-Methoxy-4-piperazin-1-yl-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-nicotinonitrile 
     6-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-nicotinonitrile was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 6-Amino-nicotinonitrile (31.0 mg, 0.260 mmol) in an analogous manner to Example 303c and Example 1c. Product isolated as the trifluoroacetic acid salt as pale yellow lyophilate (0.109 g, 89%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.64 (s, 1H), 8.93 (s, 1H), 8.90-8.82 (m, 3H), 8.72 (d, J=2.2 Hz, 1H), 8.49 (d, J=5.4 Hz, 1H), 8.43 (s, 1H), 8.11 (dd, J=8.9, 2.4 Hz, 1H), 7.96 (dd, J=5.2, 1.4 Hz, 1H), 7.92 (d, J=8.9 Hz, 1H), 4.11 (s, 3H), 3.93-3.88 (m, 4H), 3.37-3.31 (m, 4H). MS=440 (MH)+. 
     Example 354. {4-[5-Methoxy-4-(4-morpholin-4-yl-piperidin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine 
     354a) 2-(2-Chloro-pyridin-4-yl)-5-methoxy-4-(4-morpholin-4-yl-piperidin-1-yl)-pyrido[3,4-d]pyrimidine was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (190.0 mg, 0.6581 mmol) and 4-Piperidin-4-yl-morpholine (134.0 mg, 0.7871 mmol) in an analogous manner to [B016]. Product isolated as a red-orange solid (0.146 g, 50%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.84 (s, 1H), 8.60 (dd, J=4.9, 0.6 Hz, 1H), 8.36 (s, 1H), 8.32-8.29 (m, 2H), 4.28 (d, J=11.6 Hz, 2H), 4.08 (s, 3H), 3.60-3.55 (m, 4H), 3.15 (t, J=11.6 Hz, 2H), 2.53-2.46 (m, 5H), 1.96 (d, J=11.3 Hz, 2H), 1.61-1.49 (m, 2H). (400 MHz, CDCl3, δ, ppm): 8.97 (s, 1H), 8.52 (d, J=4.9 Hz, 1H), 8.37 (s, 1H), 8.28 (dd, J=5.2, 1.3 Hz, 1H), 8.21 (s, 1H), 4.36 (d, J=13.2 Hz, 2H), 4.09 (s, 3H), 3.77-3.73 (m, 4H), 3.18-3.09 (m, 2H), 2.63-2.58 (m, 4H), 2.53-2.43 (m, 1H), 2.06 (d, J=12.7 Hz, 2H), 1.74-1.63 (m, 2H). MS=441, 443 (MH)+. 
     354b) {4-[5-Methoxy-4-(4-morpholin-4-yl-piperidin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-4-(4-morpholin-4-yl-piperidin-1-yl)-pyrido[3,4-d]pyrimidine (80.0 mg, 0.181 mmol) and Aniline (18.6 μL, 0.204 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.108 g, 97%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.74 (br s, 1H), 9.46 (br s, 1H), 8.87 (s, 1H), 8.39 (s, 1H), 8.31 (d, J=5.4 Hz, 1H), 7.94 (s, 1H), 7.75-7.73 (m, 2H), 7.70 (dd, J=5.3, 1.3 Hz, 1H), 7.31 (t, J=7.6 Hz, 2H), 6.95 (t, J=7.2 Hz, 1H), 4.42 (d, J=12.6 Hz, 2H), 4.12 (s, 3H), 4.04 (d, J=11.7 Hz, 2H), 3.67 (t, J=12.1 Hz, 2H), 3.62-3.54 (m, 1H), 3.51 (d, J=12.1 Hz, 2H), 3.22-3.10 (m, 4H), 2.25 (d, J=10.4 Hz, 2H), 1.85-1.72 (m, 2H). MS=498 (MH)+. 
     Example 355. 2-(4-Cyano-phenyl)-N-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide 
     2-(4-Cyano-phenyl)-N-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2-(4-Cyano-phenyl)-acetamide (45.0 mg, 0.281 mmol) in an analogous manner to Example 303c and Example 1c. Product isolated as the trifluoroacetic acid salt as a pale orange lyophilate (0.102 g, 78%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.99 (s, 1H), 9.08 (s, 1H), 8.90 (s, 1H), 8.83 (br s, 2H), 8.51 (dd, J=5.2, 0.6 Hz, 1H), 8.41 (s, 1H), 8.06 (dd, J=5.1, 1.5 Hz, 1H), 7.83 (d, J=8.4 Hz, 2H), 7.58 (d, J=8.4 Hz, 2H), 4.09 (s, 3H), 3.92 (s, 2H), 3.87-3.83 (m, 4H), 3.31 (br s, 4H). MS=481 (MH)+. 
     Example 356. 2-(3-Cyano-phenyl)-N-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide 
     2-(3-Cyano-phenyl)-N-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2-(3-Cyano-phenyl)-acetamide (45.0 mg, 0.281 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as a pale yellow lyophilate (0.125 g, 96%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.97 (s, 1H), 9.07 (s, 1H), 8.91 (s, 1H), 8.87 (br s, 2H), 8.52 (dd, J=5.1, 0.4 Hz, 1H), 8.41 (s, 1H), 8.06 (dd, J=5.2, 1.4 Hz, 1H), 7.84-7.82 (m, 1H), 7.78-7.74 (m, 1H), 7.73-7.70 (m, 1H), 7.57 (t, J=7.7 Hz, 1H), 4.09 (s, 3H), 3.89 (s, 2H), 3.87-3.83 (m, 4H), 3.31 (br s, 4H). MS=481 (MH)+. 
     Example 357. {2-[2-(5-Morpholin-4-yl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine 
     {2-[2-(5-Morpholin-4-yl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2342 mmol) and 5-Morpholin-4-yl-pyridin-2-ylamine (48.0 mg, 0.268 mmol) [prepared as described in Toogood, P. L.; et. al.  J. Med. Chem.  2005, 48(7), 2388-2406.] in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as an orange lyophilate (0.103 g, 60%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.27 (s, 1H), 8.93 (br s, 2H), 8.83-8.79 (m, 1H), 8.76 (d, J=5.5 Hz, 1H), 8.14 (d, J=5.9 Hz, 1H), 8.40 (s, 1H), 8.26 (d, J=5.5 Hz, 1H), 8.07-8.01 (m, 1H), 7.94 (d, J=2.9 Hz, 1H), 7.87-7.86 (m, 1H), 7.49-7.40 (m, 1H), 5.00-4.91 (m, 1H), 3.81-3.77 (m, 4H), 3.76-3.69 (m, 1H), 3.55-3.36 (m, 3H), 3.17-3.13 (m, 4H), 2.47-2.37 (m, 1H), 2.33-2.23 (m, 1H). MS=470 (MH)+. 
     Example 358. {2-[2-(2-Methoxy-4-morpholin-4-yl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine 
     {2-[2-(2-Methoxy-4-morpholin-4-yl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (115.0 mg, 0.2694 mmol) and 2-Methoxy-4-morpholin-4-yl-phenylamine (58.0 mg, 0.278 mmol) [prepared as described in WO2008/051547] in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as an orange-brown lyophilate (0.155 g, 93%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.25 (br s, 1H), 9.27 (s, 1H), 9.08 (br s, 2H), 8.87 (d, J=5.1 Hz, 1H), 8.77 (d, J=5.6 Hz, 1H), 8.30 (d, J=5.3 Hz, 1H), 8.16 (s, 1H), 7.98 (d, J=6.5 Hz, 1H), 7.81 (dd, J=6.6, 1.3 Hz, 1H), 7.31 (d, J=8.5 Hz, 1H), 6.76 (d, J=2.3 Hz, 1H), 6.64 (dd, J=8.8, 2.4 Hz, 1H), 4.94-4.85 (m, 1H), 3.82 (s, 3H), 3.80-3.75 (m, 4H), 3.73-3.63 (m, 1H), 3.55-3.33 (m, 3H), 3.25-3.20 (m, 4H), 2.43-2.34 (m, 1H), 2.31-2.22 (m, 1H). MS=499 (MH)+. 
     Example 359. (2-Methoxy-4-morpholin-4-yl-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     (2-Methoxy-4-morpholin-4-yl-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (115.0 mg, 0.2517 mmol) and 2-Methoxy-4-morpholin-4-yl-phenylamine (55.0 mg, 0.264 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as an orange-brown lyophilate (0.150 g, 92%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.25 (br s, 1H), 9.05 (br s, 2H), 8.93 (s, 1H), 8.47 (s, 1H), 8.13 (s, 1H), 8.00 (d, J=6.6 Hz, 1H), 7.76 (dd, J=6.5, 1.3 Hz, 1H), 7.31 (d, J=8.5 Hz, 1H), 6.76 (d, J=2.4 Hz, 1H), 6.64 (dd, J=8.7, 2.4 Hz, 1H), 4.11 (s, 3H), 3.91-3.86 (m, 4H), 3.81 (s, 3H), 3.80-3.76 (m, 4H), 3.32 (br s, 4H), 3.25-3.21 (m, 4H). MS=529 (MH)+. 
     Example 360. {5-Methoxy-2-[2-(2-methoxy-4-morpholin-4-yl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine 
     {5-Methoxy-2-[2-(2-methoxy-4-morpholin-4-yl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2-Methoxy-4-morpholin-4-yl-phenylamine (55.0 mg, 0.264 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as an orange-brown lyophilate (0.057 g, 40%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.13 (br s, 1H), 9.21-9.00 (m, 2H), 8.86 (s, 1H), 8.46 (s, 1H), 8.26 (d, J=6.2 Hz, 1H), 8.10 (s, 1H), 7.99 (d, J=6.4 Hz, 1H), 7.74 (dd, J=6.4, 1.2 Hz, 1H), 7.33 (d, J=8.2 Hz, 1H), 6.76 (d, J=2.4 Hz, 1H), 6.63 (dd, J=8.7, 2.4 Hz, 1H), 5.01-4.91 (m, 1H), 4.17 (s, 3H), 3.81 (s, 3H), 3.80-3.75 (m, 4H), 3.69-3.59 (m, 1H), 3.53-3.40 (m, 2H), 3.37-3.26 (m, 1H), 3.25-3.20 (m, 4H), 2.51-2.41 (m, 1H), 2.26-2.16 (m, 1H). MS=529 (MH)+. 
     Example 361. (5-Methoxy-2-{2-[4-(tetrahydro-pyran-4-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-(R)-pyrrolidin-3-yl-amine 
     (5-Methoxy-2-{2-[4-(tetrahydro-pyran-4-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 4-(Tetrahydro-pyran-4-yl)-phenylamine (43.0 mg, 0.243 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic salt as a yellow lyophilate (0.109 g, 81%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.41 (br s, 1H), 8.99 (br s, 1H), 8.88 (br s, 1H), 8.83 (s, 1H), 8.41 (s, 1H), 8.28 (d, J=5.5 Hz, 1H), 8.16 (d, J=6.2 Hz, 1H), 7.93 (s, 1H), 7.69 (dd, J=5.5, 1.2 Hz, 1H), 7.64 d, J=8.5 Hz, 2H), 7.20 (d, J=8.5 Hz, 2H), 5.05-4.95 (m, 1H), 4.16 (s, 3H), 3.98-3.92 (m, 2H), 3.72-3.63 (m, 1H), 3.50-3.28 (m, 5H), 2.76-2.68 (m, 1H), 2.50-2.43 (m, 1H), 2.27-2.17 (m, 1H), 1.73-1.60 (m, 4H). MS=498 (MH)+. 
     Example 362. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[4-(tetrahydro-pyran-4-yl)-phenyl]-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[4-(tetrahydro-pyran-4-yl)-phenyl]-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 4-(Tetrahydro-pyran-4-yl)-phenylamine (43.0 mg, 0.243 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.099 g, 74%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.43 (br s, 1H), 8.95-8.83 (m, 3H), 8.42 (s, 1H), 8.28 (d, J=5.5 Hz, 1H), 7.93 (s, 1H), 7.68 (dd, J=5.4, 1.2 Hz, 1H), 7.64 (d, J=8.4 Hz, 2H), 7.20 (d, J=8.5 Hz, 2H), 4.10 (s, 3H), 3.98-3.92 (m, 2H), 3.90-3.85 (m, 4H), 3.44 (ddd, J=11.2, 11.2, 3.0 Hz, 2H), 3.35-3.29 (m, 4H), 2.76-2.68 (m, 1H), 1.72-1.60 (m, 4H). MS=498 (MH)+. 
     Example 363. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-methyl-pyridin-2-yl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-methyl-pyridin-2-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 4-Methyl-pyridin-2-ylamine (27.0 mg, 0.250 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.100 g, 84%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 11.72 (br s, 1H), 9.03-8.90 (m, 3H), 8.55 (d, J=5.5 Hz, 1H), 8.46 (s, 1H), 8.37 (s, 1H), 8.27 (d, J=6.1 Hz, 1H), 8.12 (d, J=5.2 Hz, 1H), 7.27 (s, 1H), 7.14 (d, J=4.5 Hz, 1H), 4.12 (s, 3H), 3.94-3.88 (m, 4H), 3.37-3.30 (m, 4H), 2.47 (s, 3H). MS=429 (MH)+. 
     Example 364. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-methyl-pyridin-2-yl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-methyl-pyridin-2-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (110.0 mg, 0.2407 mmol) and 5-Methyl-pyridin-2-ylamine (27.0 mg, 0.250 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.122 g, 93%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 11.73 (br s, 1H), 8.98 (br s, 2H), 8.94 (s, 1H), 8.54 (d, J=5.7 Hz, 1H), 8.46 (s, 1H), 8.37 (s, 1H), 8.22 (s, 1H), 8.12-8.08 (m, 1H), 8.00-7.94 (m, 1H), 7.42 (d, J=7.6 Hz, 1H), 4.12 (s, 3H), 3.94-3.88 (m, 4H), 3.37-3.30 (m, 4H), 2.34 (s, 3H). MS=429 (MH)+. 
     Example 365. (4-Chloro-pyridin-2-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     (4-Chloro-pyridin-2-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 4-Chloro-pyridin-2-ylamine (32.0 mg, 0.249 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid as a yellow lyophilate (0.107 g, 86%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.56 (br s, 1H), 9.00-8.85 (m, 3H), 8.63 (s, 1H), 8.46 (d, J=5.4 Hz, 1H), 8.43 (s, 1H), 8.29 (d, J=5.6 Hz, 1H), 7.99 (s, 1H), 7.92 (dd, J=5.4, 1.2 Hz, 1H), 7.10 (dd, J=5.6, 1.8 Hz, 1H), 4.10 (s, 1H), 3.94-3.88 (m, 4H), 3.37-3.29 (m, 4H). MS=449 (MH)+. 
     Example 366. (5-Chloro-pyridin-2-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     (5-Chloro-pyridin-2-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (110.0 mg, 0.2407 mmol) and 2-Amino-5-chloropyridine (32.0 mg, 0.249 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.134 g, 98%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.45 (br s, 1H), 8.93 (s, 1H), 8.87 (br s, 2H), 8.67 (s, 1H), 8.44-8.41 (m, 2H), 8.34-8.32 (s, 1H), 7.90 (d, J=5.4 Hz, 1H), 7.88-7.81 (m, 2H), 4.10 (s, 3H), 3.94-3.87 (m, 4H), 3.37-3.30 (m, 4H). MS=449 (MH)+. 
     Example 367. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-trifluoromethyl-pyridin-2-yl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-trifluoromethyl-pyridin-2-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 4-Trifluoromethyl-pyridin-2-ylamine (40.0 mg, 0.247 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow solid (0.116 g, 88%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.49 (br s, 1H), 8.93 (s, 1H), 8.87 (br s, 2H), 8.70 (s, 1H), 8.54 (d, J=5.3 Hz, 1H), 8.47 (d, J=5.3 Hz, 1H), 8.42 (s, 1H), 8.30 (s, 1H), 7.91 (dd, J=5.3, 1.3 Hz, 1H), 7.25 (d, J=4.4 Hz, 1H), 4.11 (s, 3H), 3.94-3.88 (m, 4H), 3.37-3.30 (m, 4H). MS=483 (MH)+. 
     Example 368. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-trifluoromethyl-pyridin-2-yl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-trifluoromethyl-pyridin-2-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 5-Trifluoromethyl-pyridin-2-ylamine (40.0 mg, 0.247 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.116 g, 88%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.56 (br s, 1H), 8.94 (s, 1H), 8.88 (br s, 2H), 8.78 (s, 1H), 8.64 (s, 1H), 8.47 (d, J=5.3 Hz, 1H), 8.43 (s, 1H), 8.07 (dd, J=9.0, 2.3 Hz, 1H), 8.01 (d, J=9.0 Hz, 1H), 7.94 (dd, J=5.3, 1.3 Hz, 1H), 4.11 (s, 3H), 3.94-3.88 (m, 4H), 3.37-3.30 (m, 4H). MS=483 (MH)+. 
     Example 369. 2-(4-Chloro-phenyl)-N-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide 
     369a) 2-(4-Chloro-phenyl)-acetamide was prepared from (4-Chloro-phenyl)-acetic acid (1.0 g, 5.9 mmol) in an analogous manner to Example 313a. Product isolated as a white solid (0.97 g, 97%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 7.47 (br s, 1H), 7.35 (d, J=8.5 Hz, 2H), 7.27 (d, J=8.5 Hz, 2H), 6.90 (br s, 1H), 3.37 (s, 2H). MS=170, 172 (MH)+. 
     369b) 2-(4-Chloro-phenyl)-N-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2-(4-Chloro-phenyl)-acetamide (42.0 mg, 0.248 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a pale yellow lyophilate (0.101 g, 76%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.92 (s, 1H), 9.08 (s, 1H), 8.91 (s, 1H), 8.85 (br s, 2H), 8.51 (dd, J=5.1, 0.5 Hz, 1H), 8.41 (s, 1H), 8.05 (dd, J=5.1, 1.5 Hz, 1H), 7.43-7.37 (m, 4H), 4.09 (s, 3H), 3.88-3.83 (m, 4H), 3.79 (s, 2H), 3.35-3.28 (m, 4H). MS=490 (MH)+. 
     Example 370. 2-(3-Chloro-phenyl)-N-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide 
     370a) 2-(3-Chloro-phenyl)-acetamide was prepared from (3-Chloro-phenyl)-acetic acid (1.0 g, 5.9 mmol) in an analogous manner to Example 313a. Product isolated as a white solid (0.82 g, 82%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 7.50 (br s, 1H), 7.35-7.27 (m, 3H), 7.23-7.19 (m, 1H), 6.93 (br s, 1H), 3.39 (s, 2H). MS=170, 172 (MH)+. 
     370b) 2-(3-Chloro-phenyl)-N-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2-(3-Chloro-phenyl)-acetamide (42.0 mg, 0.248 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.103 g, 77%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.94 (s, 1H), 9.08 (s, 1H), 8.91 (s, 1H), 8.88 (br s, 2H), 8.51 (dd, J=5.0, 0.5 Hz, 1H), 8.41 (s, 1H), 8.06 (dd, J=5.1, 1.5 Hz, 1H), 7.47-7.45 (m, 1H), 7.41-7.32 (m, 3H), 4.09 (s, 3H), 3.88-3.83 (m, 4H), 3.81 (s, 2H), 3.35-3.29 (m, 4H). MS=490 (MH)+. 
     Example 371. N-[4-(5-Methoxy-4-piperazin-1-yl-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-phenyl-acetamide 
     N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-phenyl-acetamide was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and Benzeneacetamide (34.0 mg, 0.252 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a pale yellow lyophilate (0.120 g, 96%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.90 (s, 1H), 9.09 (s, 1H), 8.91 (s, 1H), 8.87 (br s, 2H), 8.51 (d, J=5.2 Hz, 1H), 8.41 (s, 1H), 8.05 (dd, J=5.0, 1.3 Hz, 1H), 7.40-7.32 (m, 4H), 7.29-7.23 (m, 1H), 4.09 (s, 3H), 3.88-3.83 (m, 4H), 3.78 (s, 2H), 3.35-3.28 (m, 4H). MS=456 (MH)+. 
     Example 372. 2-(3-Methoxy-phenyl)-N-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide 
     2-(3-Methoxy-phenyl)-N-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2-(3-Methoxy-phenyl)-acetamide (43.0 mg, 0.260 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.056 g, 42%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.87 (s, 1H), 9.09 (s, 1H), 8.91 (s, 1H), 8.87 (br s, 2H), 8.51 (dd, J=5.1, 0.6 Hz, 1H), 8.41 (s, 1H), 8.05 (dd, J=5.1, 1.4 Hz, 1H), 7.25 (t, J=7.8 Hz, 1H), 6.97-6.93 (m, 2H), 6.86-6.82 (m, 1H), 4.09 (s, 3H), 3.88-3.83 (m, 4H), 3.78 (s, 3H), 3.74 (s, 2H), 3.35-3.29 (m, 4H). MS=486 (MH)+. 
     Example 373. N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-(3-trifluoromethyl-phenyl)-acetamide 
     373a) 2-(3-Trifluoromethyl-phenyl)-acetamide was prepared from (3-Trifluoromethyl-phenyl)-acetic acid (1.0 g, 4.9 mmol) in an analogous manner to Example 313a. Product isolated as white solid (0.88 g, 88%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 7.63-7.51 (m, 5H), 6.96 (br s, 1H), 3.50 (s, 2H). MS=204 (MH)+. 
     373b) N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-(3-trifluoromethyl-phenyl)-acetamide was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2-(3-Trifluoromethyl-phenyl)-acetamide (53.0 mg, 0.261 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.037 g, 26%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.98 (s, 1H), 9.07 (s, 1H), 8.91 (s, 1H), 8.87 (br s, 2H), 8.52 (dd, J=5.1, 0.4 Hz, 1H), 8.41 (s, 1H), 8.06 (dd, J=5.1, 1.4 Hz, 1H), 7.75 (s, 1H), 7.70-7.57 (m, 3H), 4.09 (s, 3H), 3.92 (s, 2H), 3.88-3.83 (m, 4H), 3.35-3.28 (m, 4H). MS=524 (MH)+. 
     Example 374. 2-(4-Methoxy-phenyl)-N-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide 
     2-(4-Methoxy-phenyl)-N-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 4-Methoxyphenylacetamide (43.0 mg, 0.260 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.067 g, 50%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.83 (s, 1H), 9.08 (s, 1H), 8.91 (s, 1H), 8.85 (br s, 2H), 8.50 (dd, J=5.1, 0.6 Hz, 1H), 8.41 (s, 1H), 8.04 (dd, J=5.1, 1.4 Hz, 1H), 7.29 (d, J=8.8 Hz, 2H), 6.90 (d, J=8.8 Hz, 2H), 4.09 (s, 3H), 3.88-3.83 (m, 4H), 3.73 (s, 3H), 3.69 (s, 2H), 3.35-3.29 (m, 4H). MS=486 (MH)+. 
     Example 375. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-morpholin-4-yl-pyridin-3-yl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-morpholin-4-yl-pyridin-3-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (106.0 mg, 0.2320 mmol) and 6-Morpholin-4-yl-pyridin-3-ylamine (48.0 mg, 0.268 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as a yellow lyophilate (0.148 g, 87%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.52 (br s, 1H), 8.98-8.85 (m, 3H), 8.59 (br s, 1H), 8.43 (s, 1H), 8.26 (d, J=5.3 Hz, 1H), 8.01-7.96 (m, 1H), 7.90 (s, 1H), 7.70 (d, J=5.2 Hz, 1H), 7.09 (br s, 1H), 4.10 (s, 3H), 3.90-3.85 (m, 4H), 3.77-3.72 (m, 4H), 3.48-3.42 (m, 4H), 3.36-3.29 (m, 4H). MS=500 (MH)+. 
     Example 376. {2-[2-(Pyridin-3-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine 
     {2-[2-(Pyridin-3-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (103.0 mg, 0.2413 mmol) and 3-aminopyridine (27.0 mg, 0.287 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as a pale yellow lyophilate (0.141 g, 95%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.25 (br s, 1H), 9.39 (s, 1H), 9.24 (d, J=0.6 Hz, 1H), 8.97 (br s, 2H), 8.76 (d, J=5.5 Hz, 1H), 8.73 (d, J=5.6 Hz, 1H), 8.51-8.45 (m, 2H), 8.38 (d, J=5.2 Hz, 1H), 8.28 (dd, J=5.6, 0.7 Hz, 1H), 8.07 (s, 1H), 7.93 (dd, J=5.3, 1.2 Hz, 1H), 7.81 (dd, J=8.2, 5.34 Hz, 1H), 5.02-4.93 (m, 1H), 3.78-3.69 (m, 1H), 3.55-3.34 (m, 3H), 2.47-2.37 (m, 1H), 2.32-2.22 (m, 1H). MS=385 (MH)+. 
     Example 377. {5-Methoxy-2-[2-(pyridin-3-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine 
     {5-Methoxy-2-[2-(pyridin-3-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (107.0 mg, 0.2342 mmol) and 3-aminopyridine (25.0 mg, 0.266 mmol) in an analogous manner to Example 303c and Example 1501c. Product Isolated as the Bis-Trifluoroacetic Acid Salt as a Pale Yellow Lyophilate (0.063 g, 41%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.15 (br s, 1H), 9.31 (s, 1H), 9.05 (br s, 1H), 8.92 (br s, 1H), 8.84 (s, 1H), 8.48-8.41 (m, 3H), 8.34 (d, J=5.0 Hz, 1H), 8.20 (d, J=6.3 Hz, 1H), 8.03 (s, 1H), 7.87 (d, J=5.3 Hz, 1H), 7.74-7.71 (m, 1H), 5.09-5.00 (m, 1H), 4.17 (s, 3H), 3.74-3.65 (m, 1H), 3.52-3.29 (m, 3H), 2.54-2.44 (m, 1H), 2.27-2.17 (m, 1H). MS=415 (MH)+. 
     Example 378. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyridin-3-yl-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyridin-3-yl-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 3-aminopyridine (25.0 mg, 0.266 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis trifluoroacetic acid salt as a yellow lyophilate (0.123 g, 87%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.17 (br s, 1H), 9.33 (s, 1H), 9.02-8.88 (m, 3H), 8.49-8.42 (m, 3H), 8.34 (d, J=4.6 Hz, 1H), 8.03 (s, 1H), 7.87 (dd, J=5.2, 1.3 Hz, 1H), 7.74 (dd, J=8.3, 5.2 Hz, 1H), 4.11 (s, 3H), 3.92-3.86 (m, 4H), 3.37-3.30 (m, 4H). MS=415 (MH)+. 
     Example 379. 2-[4-(5-Methoxy-4-piperazin-1-yl-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-isonicotinamide 
     2-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-isonicotinamide was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2-Amino-isonicotinamide (36.0 mg, 0.262 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.004 g, 2%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.94 (s, 1H), 8.86 (br s, 2H), 8.69 (s, 1H), 8.46 (d, J=5.5 Hz, 1H), 8.44 (s, 1H), 8.41 (d, J=5.3 Hz, 1H), 8.19 (br s, 1H), 8.09 (br s, 1H), 7.95-7.91 (m, 1H), 7.71 (br s, 1H), 7.36-7.33 (m, 1H), 4.11 (s, 3H), 3.93-3.89 (m, 4H), 3.37-3.30 (m, 4H). MS=458 (MH)+. 
     Example 380. 6-[4-(5-Methoxy-4-piperazin-1-yl-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-nicotinamide 
     6-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-nicotinamide was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 6-Amino-nicotinamide (36.0 mg, 0.262 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a pale yellow lyophilate (0.047 g, 37%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.08 (br s, 2H), 8.94 (s, 1H), 8.83 (s, 1H), 8.72 (s, 1H), 8.50 (d, J=5.4 Hz, 1H), 8.45 (s, 1H), 8.26 (br s, 1H), 8.10-7.99 (m, 2H), 7.72 (br s, 1H), 7.47 (br s, 1H), 4.11 (s, 3H), 3.96-3.92 (m, 4H), 3.36-3.29 (m, 4H). MS=458 (MH)+. 
     Example 382. (3-Methoxy-4-morpholin-4-yl-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     (3-Methoxy-4-morpholin-4-yl-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (110.0 mg, 0.2407 mmol) and 3-Methoxy-4-morpholin-4-yl-phenylamine (55.0 mg, 0.264 mmol) [prepared as described in WO2008/051547] in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as an orange lyophilate (0.147 g, 95%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.71 (br s, 1H), 9.12-8.95 (m, 2H), 8.91 (s, 1H), 8.43 (s, 1H), 8.25 (d, J=5.3 Hz, 1H), 7.99 (s, 1H), 7.72 (d, J=4.9 Hz, 1H), 7.44 (br s, 1H), 7.25 (d, J=7.5 Hz, 1H), 7.06 (br s, 1H), 4.11 (s, 3H), 3.92-3.86 (m, 4H), 3.84 (s, 3H), 3.82-3.76 (m, 4H), 3.35-3.29 (m, 4H), 3.17-3.00 (m, 4H). MS=529 (MH)+. 
     Example 383. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-methyl-4-morpholin-4-yl-phenyl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-methyl-4-morpholin-4-yl-phenyl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2-Methyl-4-morpholin-4-yl-phenylamine (50.0 mg, 0.260 mmol)[prepared as described in WO2008/051547] in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as an orange lyophilate (0.125 g, 91%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.06 (br s, 1H), 9.07-8.95 (m, 2H), 8.92 (s, 1H), 8.46 (s, 1H), 8.01 (d, J=5.9 Hz, 1H), 7.74 (dd, J=6.3, 1.1 Hz, 1H), 7.27 (d, J=8.7 Hz, 1H), 7.00 (d, J=2.5 Hz, 1H), 6.92 (dd, J=8.8, 2.7 Hz, 1H), 4.11 (s, 3H), 3.89-3.84 (m, 4H), 3.79-3.75 (m, 4H), 3.34-3.27 (m, 4H), 3.20-3.16 (m, 4H), 2.20 (s, 3H). MS=513 (MH)+. 
     Example 384. 5-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-pyridine-2-carbonitrile 
     5-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-pyridine-2-carbonitrile was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 5-Amino-pyridine-2-carbonitrile (32.0 mg, 0.269 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.093 g, 76%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.24 (s, 1H), 8.95 (d, J=2.4 Hz, 1H), 8.91 (s, 1H), 8.88 (br s, 2H), 8.56 (dd, J=8.7, 2.6 Hz, 1H), 8.47 (d, J=5.4 Hz, 1H), 8.43 (s, 1H), 8.05 (s, 1H), 7.93 (d, J=8.6 Hz, 1H), 7.90 (dd, J=5.4, 1.4 Hz, 1H), 4.11 (s, 3H), 3.91-3.87 (m, 4H), 3.36-3.30 (m, 4H). MS=440 (MH)+. 
     Example 385. {5-Methoxy-2-[2-(pyrimidin-5-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine 
     {5-Methoxy-2-[2-(pyrimidin-5-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (108.0 mg, 0.2364 mmol) and Pyrimidin-5-ylamine (25.0 mg, 0.263 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.029 g, 22%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.77 (s, 1H), 9.22-9.21 (m, 2H), 9.00-8.80 (m, 3H), 8.74 (s, 1H), 8.43-8.40 (m, 2H), 8.18 (d, J=6.3 Hz, 1H), 7.99 (s, 1H), 7.83 (dd, J=5.3, 1.4 Hz, 1H), 5.08-4.98 (m, 1H), 4.17 (s, 3H), 3.74-3.64 (m, 1H), 3.50-3.30 (m, 3H), 2.52-2.44 (m, 1H), 2.28-2.18 (m, 1H). MS=416 (MH)+. 
     Example 386. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyrimidin-5-yl-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyrimidin-5-yl-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and Pyrimidin-5-ylamine (25.0 mg, 0.263 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.073 g, 62%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.79 (s, 1H), 9.22-9.21 (m, 2H), 8.98-8.95 (m, 3H), 8.74 (s, 1H), 8.43-8.40 (m, 2H), 7.99 (s, 1H), 7.82 (dd, J=5.3, 1.4 Hz, 1H), 4.11 (s, 3H), 3.92-3.86 (m, 4H), 3.37-3.29 (m, 4H). MS=416 (MH)+. 
     Example 387. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyridin-2-yl-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyridin-2-yl-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (102.0 mg, 0.2232 mmol) and 2-Pyridinamine (25.0 mg, 0.266 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.056 g, 47%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 11.54 (br s, 1H), 9.05-8.90 (m, 3H), 8.53 (d, J=4.9 Hz, 1H), 8.50-8.45 (m, 2H), 8.39 (d, J=5.2 Hz, 1H), 8.11-8.00 (m, 2H), 7.54 (s, 1H), 7.21 (s, 1H), 4.12 (s, 3H), 3.94-3.89 (m, 4H), 3.37-3.30 (m, 4H). MS=415 (MH)+. 
     Example 388. 2-[4-(5-Methoxy-4-morpholin-4-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-isonicotinonitrile 
     388a) 2-(2-Chloro-pyridin-4-yl)-5-methoxy-4-morpholin-4-yl-pyrido[3,4-d]pyrimidine was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (0.25 g, 0.86 mmol) and Morpholine (0.10 mL, 1.1 mmol) in an analogous manner to [B016]. Product isolated as a tan solid (0.269 g, 87%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.87 (s, 1H), 8.60 (dd, J=5.0, 0.9 Hz, 1H), 8.38 (s, 1H), 8.33-8.30 (m, 2H), 4.08 (s, 3H), 3.81-3.71 (m, 8H). MS=358 (MH)+. 
     388b) 2-[4-(5-Methoxy-4-morpholin-4-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-isonicotinonitrile was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-4-morpholin-4-yl-pyrido[3,4-d]pyrimidine (100.0 mg, 0.2795 mmol) and 2-Amino-isonicotinonitrile (40.0 mg, 0.336 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.014 g, 9%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.63 (br s, 1H), 8.87 (s, 1H), 8.58 (s, 1H), 8.51 (d, J=5.0 Hz, 1H), 8.47 (d, J=5.4 Hz, 1H), 8.37 (s, 1H), 8.29 (s, 1H), 7.92 (d, J=5.4 Hz, 1H), 7.35 (d, J=4.9 Hz, 1H), 4.09 (s, 3H), 3.82-3.74 (m, 8H). MS=441 (MH)+. 
     Example 389. 2-(3-Cyano-phenyl)-N-[4-(5-methoxy-4-morpholin-4-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide 
     2-(3-Cyano-phenyl)-N-[4-(5-methoxy-4-morpholin-4-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-4-morpholin-4-yl-pyrido[3,4-d]pyrimidine (110.0 mg, 0.3074 mmol) and 2-(3-Cyano-phenyl)-acetamide (54.0 mg, 0.337 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.082 g, 44%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.96 (s, 1H), 9.03 (s, 1H), 8.85 (s, 1H), 8.49 (dd, J=5.1, 0.6 Hz, 1H), 8.35 (s, 1H), 8.04 (dd, J=5.1, 1.5 Hz, 1H), 7.84-7.82 (m, 1H), 7.77-7.74 (m, 1H), 7.73-7.70 (m, 1H), 7.57 (t, J=7.8 Hz, 1H), 4.07 (s, 3H), 3.89 (s, 2H), 3.79-3.69 (m, 8H). MS=482 (MH)+. 
     Example 390. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,4,5-trimethoxy-phenyl)-amine 
     4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,4,5-trimethoxy-phenyl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (106.0 mg, 0.2320 mmol) and 3,4,5-Trimethoxyaniline (48.0 mg, 0.262 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as an orange lyophilate (0.074 g, 52%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.45 (br s, 1H), 8.98-8.84 (m, 3H), 8.42 (s, 1H), 8.30 (d, J=5.4 Hz, 1H), 7.94 (s, 1H), 7.70 (d, J=5.6 Hz, 1H), 7.13-7.10 (m, 2H), 4.10 (s, 3H), 3.90-3.85 (m, 4H), 3.79 (s, 6H), 3.64 (s, 3H), 3.36-3.29 (m, 4H). MS=504 (MH)+. 
     Example 391. N-[4-(5-Methoxy-4-piperazin-1-yl-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-(4-trifluoromethyl-phenyl)-acetamide 
     391a) 2-(4-Trifluoromethyl-phenyl)-acetamide was prepared from (4-Trifluoromethyl-phenyl)-acetic acid (1.0 g, 4.9 mmol) in an analogous manner to Example 313a. Product isolated as a white solid (0.92 g, 92%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 7.66 (d, J=8.1 Hz, 2H), 7.54 (br s, 1H), 7.47 (d, J=8.0 Hz, 2H), 6.96 (br s, 1H), 3.49 (s, 2H). MS=204 (MH)+. 
     391b) N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-(4-trifluoromethyl-phenyl)-acetamide was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2-(4-Trifluoromethyl-phenyl)-acetamide (54.0 mg, 0.266 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.051 g, 36%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.99 (s, 1H), 9.08 (s, 1H), 8.91 (s, 1H), 8.84 (br s, 2H), 8.52 (dd, J=5.1, 0.5 Hz, 1H), 8.41 (s, 1H), 8.06 (dd, J=5.1, 1.4 Hz, 1H), 7.72 (d, J=8.1 Hz, 2H), 7.60 (d, J=8.0 Hz, 2H), 4.09 (s, 3H), 3.92 (s, 2H), 3.87-3.83 (m, 4H), 3.34-3.28 (m, 4H). MS=524 (MH)+. 
     Example 392. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-phenyl-pyridin-3-yl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-phenyl-pyridin-3-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 6-Phenyl-pyridin-3-ylamine (45.0 mg, 0.264 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.086 g, 65%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.82 (s, 1H), 9.01 (d, J=2.3 Hz, 1H), 8.95-8.85 (m, 3H), 8.46-8.40 (m, 3H), 8.06-7.95 (m, 4H), 7.80 (dd, J=5.3, 1.3 Hz, 1H), 7.49 (t, J=7.4 Hz, 2H), 7.42-7.37 (m, 1H), 4.11 (s, 3H), 3.92-3.87 (m, 4H), 3.37-3.30 (m, 4H). MS=491 (MH)+. 
     Example 393. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-methyl-pyridin-3-yl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-methyl-pyridin-3-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 6-Methyl-pyridin-3-ylamine (29.0 mg, 0.268 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.068 g, 56%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.22 (s, 1H), 9.34 (s, 1H), 8.96 (br s, 2H), 8.91 (s, 1H), 8.46 (d, J=5.4 Hz, 1H), 8.43 (s, 1H), 8.38 (dd, J=8.8, 2.4 Hz, 1H), 8.02 (s, 1H), 7.88 (dd, J=5.3, 1.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 1H), 4.11 (s, 3H), 3.91-3.87 (m, 4H), 3.36-3.30 (m, 4H), 2.61 (s, 3H). MS=429 (MH)+. 
     Example 394. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-methoxy-pyridin-3-yl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-methoxy-pyridin-3-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 5-Amino-2-methoxypyridine (33.0 mg, 0.266 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as an orange lyophilate (0.091 g, 74%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.43 (s, 1H), 9.00-8.85 (m, 3H), 8.48 (d, J=2.8 Hz, 1H), 8.42 (s, 1H), 8.26 (d, J=5.4 Hz, 1H), 8.06 (dd, J=8.8, 2.7 Hz, 1H), 7.89 (s, 1H), 7.69 (dd, J=5.3, 1.1 Hz, 1H), 6.83 (d, J=8.8 Hz, 1H), 4.10 (s, 3H), 3.90-3.86 (m, 4H), 3.84 (s, 3H), 3.35-3.29 (m, 4H). MS=445 (MH)+. 
     Example 395. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-trifluoromethyl-pyridin-3-yl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-trifluoromethyl-pyridin-3-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 6-Trifluoromethyl-pyridin-3-ylamine (43.0 mg, 0.265 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as an orange lyophilate (0.084 g, 64%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.09 (s, 1H), 8.96 (d, J=2.5 Hz, 1H), 8.94-8.84 (m, 3H), 8.61 (dd, J=8.7, 2.3 Hz, 1H), 8.46-8.42 (m, 2H), 8.04 (s, 1H), 7.86 (dd, J=5.3, 1.3 Hz, 1H), 7.81 (d, J=8.9 Hz, 1H), 4.11 (s, 3H), 3.93-3.86 (m, 4H), 3.37-3.30 (m, 4H). MS=483 (MH)+. 
     Example 396. N-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-2-pyridin-3-yl-acetamide 
     N-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-2-pyridin-3-yl-acetamide was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2-Pyridin-3-yl-acetamide (35.0 mg, 0.257 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.008 g, 6%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.99 (s, 1H), 9.09 (s, 1H), 8.95-8.75 (m, 3H), 8.64 (s, 1H), 8.56 (d, J=4.7 Hz, 1H), 8.51 (d, J=5.1 Hz, 1H), 8.40 (s, 1H), 8.15 (d, J=6.1 Hz, 1H), 8.07 (dd, J=5.2, 1.4 Hz, 1H), 7.93 (d, J=7.7 Hz, 1H), 7.54-7.48 (m, 1H), 4.98-4.90 (m, 1H), 4.15 (s, 3H), 3.49 (s, 2H), 3.70-3.60 (m, 1H), 3.48-3.28 (m, 3H), 2.53-2.43 (m, 1H), 2.25-2.15 (m, 1H). MS=457 (MH)+. 
     Example 397. 2-{4-[5-Methoxy-4-(4-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile 
     397a) 2-(2-Chloro-pyridin-4-yl)-5-methoxy-4-(4-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidine was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (0.25 g, 0.86 mmol) and 1-Methylpiperazine (0.12 mL, 1.0 mmol) in an analogous manner to [B016]. Product isolated as tan needles (0.283 g, 88%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.85 (s, 1H), 8.60 (d, J=5.1 Hz, 1H), 8.37 (s, 1H), 8.33-8.29 (m, 2H), 4.07 (s, 3H), 3.75-3.70 (m, 4H), 2.52-2.48 (m, 4H), 2.24 (s, 3H). MS=371, 373 (MH)+. 
     397b) 2-{4-[5-Methoxy-4-(4-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-4-(4-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidine (100.0 mg, 0.2697 mmol) and 2-Amino-isonicotinonitrile (39.0 mg, 0.327 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.123 g, 80%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.46 (s, 1H), 9.83 (s, 1H), 8.94 (s, 1H), 8.64 (s, 1H), 8.51 (dd, J=5.0, 0.6 Hz, 1H), 8.49 (d, J=5.3 Hz, 1H), 8.44 (s, 1H), 8.35 (s, 1H), 7.93 (dd, J=5.3, 1.4 Hz, 1H), 7.33 (dd, J=5.1, 1.4 Hz, 1H), 4.43 (d, J=13.4, 2H), 4.12 (s, 3H), 3.60 (d, J=11.8 Hz, 2H), 3.46 (t, J=12.9 Hz, 2H), 3.30-3.20 (m, 2H), 2.97-2.85 (m, 3H). MS=454 (MH)+. 
     Example 398. 2-(3-Chloro-phenyl)-N-{4-[5-methoxy-4-(4-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide 
     2-(3-Chloro-phenyl)-N-{4-[5-methoxy-4-(4-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-4-(4-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidine (100.0 mg, 0.2697 mmol) and 2-(3-Chloro-phenyl)-acetamide (55.1 mg, 0.325 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as an orange lyophilate (0.050 g, 29%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.94 (s, 1H), 9.89 (br s, 1H), 9.09 (s, 1H), 8.92 (s, 1H), 8.52 (dd, J=5.1, 0.6 Hz, 1H), 8.42 (s, 1H), 8.07 (dd, J=5.2, 1.5 Hz, 1H), 7.47-7.75 (m, 1H), 7.41-7.32 (m, 3H), 4.37 (d, J=13.9 Hz, 2H), 4.11 (s, 3H), 3.81 (s, 2H), 3.59 (d, J=11.8 Hz, 2H), 3.41 (t, J=13.1 Hz, 2H), 3.29-3.17 (m, 2H), 2.89 (s, 3H). MS=504, 506 (MH)+. 
     Example 399. N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-pyridin-3-yl-acetamide 
     N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-pyridin-3-yl-acetamide was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2-Pyridin-3-yl-acetamide (36.0 mg, 0.264 mmol), in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.115 g, 91%). HNMR (400 MHz, d6-DMSO, δ, ppm): 11.03 (s, 1H), 9.07 (s, 1H), 8.92-8.83 (m, 3H), 8.71 (d, J=1.5 Hz, 1H), 8.64 (dd, J=5.1, 1.2 Hz, 1H), 8.52 (dd, J=5.1, 0.6 Hz, 1H), 8.41 (s, 1H), 8.11-8.05 (m, 2H), 7.68-7.63 (m, 1H), 4.09 (s, 3H), 3.96 (s, 2H), 3.87-3.82 (m, 4H), 3.34-3.28 (m, 4H). MS=457 (MH)+. 
     Example 400. N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-pyridin-4-yl-acetamide 
     N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-pyridin-4-yl-acetamide was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2-Pyridin-4-yl-acetamide (35.0 mg, 0.257 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as an orange lyophilate resin (0.113 g, 90%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 11.06 (s, 1H), 9.07 (s, 1H), 8.90 (s, 1H), 8.86 (br s, 2H), 8.71 (s, 2H), 8.53 (dd, J=5.1, 0.6 Hz, 1H), 8.41 (s, 1H), 8.08 (dd. J=5.2, 1.5 Hz, 1H), 7.71 (br s, 2H), 4.09 (s, 3H), 4.03 (s, 2H), 3.87-3.83 (m, 4H), 3.34-3.28 (m, 4H). MS=457 (MH)+. 
     Example 401. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-methoxy-pyridin-2-yl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-methoxy-pyridin-2-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 4-Methoxy-pyridin-2-ylamine (33.0 mg, 0.266 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.098 g, 79%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.00-8.90 (m, 3H), 8.55 (d, J=5.4 Hz, 1H), 8.45 (s, 1H), 8.31 (s, 1H), 8.24 (d, J=6.9 Hz, 1H), 8.12-8.08 (m, 1H), 6.92 (br s, 2H), 4.11 (s, 3H), 4.00 (s, 3H), 3.93-3.88 (m, 4H), 3.37-3.30 (m, 4H). MS=445 (MH)+. 
     Example 402. 2-{4-[4-(4-Hydroxy-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile 
     402a) 1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-ol was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (0.40 g, 1.4 mmol) and Piperidin-4-ol (0.17 g, 1.7 mmol) in an analogous manner to [B016]. Product isolated as an orange solid (0.317 g, 62%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.84 (s, 1H), 8.60 (dd, J=4.9, 0.7 Hz, 1H), 8.36 (s, 1H), 8.32-8.29 (m, 2H), 4.81 (d, J=4.1 Hz, 1H), 4.08 (s, 3H), 4.05-3.97 (m, 2H), 3.85-3.77 (m, 1H), 3.45-3.37 (m, 2H), 1.96-1.88 (m, 2H), 1.61-1.51 (m, 2H). MS=372, 374 (MH)+. 
     402b) 2-{4-[4-(4-Hydroxy-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile was prepared from 1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-ol (100.0 mg, 0.2689 mmol) and 2-Amino-isonicotinonitrile (39.0 mg, 0.327 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.082 g, 53%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.76 (br s, 1H), 8.84 (s, 1H), 8.58 (s, 1H), 8.52 (d, J=5.2 Hz, 1H), 8.47 (d, J=5.6 Hz, 1H), 8.36 (s, 1H), 8.23 (s, 1H), 7.93 (d, J=5.6 Hz, 1H), 7.37 (d, J=4.3 Hz, 1H), 4.09 (s, 3H), 4.08-4.00 (m, 2H), 3.87-3.80 (m, 1H), 3.50-3.40 (m, 2H), 1.97-1.89 (m, 2H), 1.64-1.54 (m, 2H). MS=455 (MH)+. 
     Example 403. 2-(3-Cyano-phenyl)-N-{4-[4-(4-hydroxy-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide 
     2-(3-Cyano-phenyl)-N-{4-[4-(4-hydroxy-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide was prepared from 1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-ol (100.0 mg, 0.2689 mmol) and 2-(3-Cyano-phenyl)-acetamide (52.0 mg, 0.325 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.072 g, 43%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.95 (s, 1H), 9.03 (s, 1H), 8.82 (s, 1H), 8.49 (dd, J=5.2, 0.6 Hz, 1H), 8.34 (s, 1H), 8.03 (dd, J=5.2, 1.6 Hz, 1H), 7.84-7.82 (m, 1H), 7.77-7.74 (m, 1H), 7.73-7.70 (m, 1H), 7.57 (t, J=7.8 Hz, 1H), 4.07 (s, 3H), 4.03-3.95 (m, 2H), 3.89 (s, 2H), 3.85-3.77 (m, 1H), 3.45-3.36 (m, 2H), 1.94-1.86 (m, 2H), 1.60-1.50 (m, 2H). MS=496 (MH)+. 
     Example 404. 2-(3-Cyano-phenyl)-N-{4-[5-methoxy-4-(4-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide 
     2-(3-Cyano-phenyl)-N-{4-[5-methoxy-4-(4-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-4-(4-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidine (100.0 mg, 0.2697 mmol) and 2-(3-Cyano-phenyl)-acetamide (52.0 mg, 0.325 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.044 g, 26%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.97 (s, 1H), 9.79 (br s, 1H), 9.08 (s, 1H), 8.92 (s, 1H), 8.52 (dd, J=5.1, 0.6 Hz, 1H), 8.42 (s, 1H), 8.08 (dd, J=5.1, 1.5 Hz, 1H), 7.84-7.82 (m, 1H), 7.78-7.75 (m, 1H), 7.73-7.70 (m, 1H), 7.58 (t, J=7.8 Hz, 1H), 4.37 (d, J=13.9 Hz, 2H), 4.11 (s, 3H), 3.89 (s, 2H), 3.59 (d, J=11.0 Hz, 2H), 3.45-3.35 (m, 2H), 3.28-3.18 (m, 2H), 2.91-2.87 (m, 3H). MS=495 (MH)+. 
     Example 405. (6-Chloro-pyridin-3-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     (6-Chloro-pyridin-3-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 6-Chloro-pyridin-3-ylamine (34.0 mg, 0.264 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as a yellow solid (0.010 g, 9%). MP=206-208° C.  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.71 (s, 1H), 8.81 (s, 1H), 8.74 (d, J=2.8 Hz, 1H), 8.37-8.32 (m, 3H), 7.92 (s, 1H), 7.75 (dd, J=5.4, 1.1 Hz, 1H), 7.42 (d, J=8.7 Hz, 1H), 4.07 (s, 3H), 3.68-3.63 (m, 4H), 2.90-2.85 (m, 4H). MS=449, 451 (MH)+. 
     Example 406. (R)—N-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-2-phenyl-propionamide 
     406a) (R)-2-Phenyl-propionamide was prepared from (R)-2-Phenyl-propionic acid (0.941 g, 6.27 mmol) in an analogous manner to Example 313a. Product isolated as a white solid (0.457 g, 48%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 7.35 (s, 1H), 7.33-7.18 (m, 5H), 6.79 (s, 1H), 3.55 (q, J=7.0 Hz, 1H), 1.30 (d, J=7.0 Hz, 3H). MS=150 (MH)+. 
     406b) (R)—N-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-2-phenyl-propionamide was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and (R)-2-Phenyl-propionamide (45.0 mg, 0.302 mmol) in an analogous manner to Example 303c and Example 4501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.100 g, 78%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.79 (s, 1H), 9.12 (s, 1H), 8.97-8.77 (m, 3H), 8.47 (dd, J=5.3, 0.6 Hz, 1H), 8.41 (s, 1H), 8.15 (d, J=6.0 Hz, 1H), 8.03 (dd, J=5.2, 1.5 Hz, 1H), 7.47-7.43 (m, 2H), 7.37-7.32 (m, 2H), 7.27-7.22 (m, 1H), 5.00-4.90 (m, 1H), 4.16 (s, 3H), 4.09 (q, J=6.9 Hz, 1H), 3.72-3.62 (m, 1H), 3.50-3.30 (m, 3H), 2.53-2.47 (m, 1H), 2.27-2.17 (m, 1H), 1.46 (d, J=7.0, 3H). MS=470 (MH)+. 
     Example 407. (S)—N-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-2-phenyl-propionamide 
     407a) (S)-2-Phenyl-propionamide was prepared from (S)-2-Phenyl-propionic acid (1.25 g, 8.32 mmol) in an analogous manner to Example 313a. Product isolated as a white solid.  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 7.35 (s, 1H), 7.33-7.18 (m, 5H), 6.79 (s, 1H), 3.55 (q, J=7.1 Hz, 1H), 1.30 (d, J=7.1 Hz, 3H). 
     407b) (S)—N-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-2-phenyl-propionamide was prepared from (R)-3-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and (S)-2-Phenyl-propionamide (45.0 mg, 0.302 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.100 g, 78%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.79 (s, 1H), 9.12 (s, 1H), 8.99-8.79 (m, 3H), 8.47 (dd, J=5.2, 0.6 Hz, 1H), 8.41 (s, 1H), 8.15 (d, J=5.9 Hz, 1H), 8.04 (dd, J=5.2, 1.5 Hz, 1H), 7.47-7.43 (m, 2H), 7.37-7.32 (m, 2H), 7.27-7.22 (m, 1H), 5.00-4.90 (m, 1H), 4.16 (s, 3H), 4.09 (q, J=6.8 Hz, 1H), 3.72-3.62 (m, 1H), 3.50-3.30 (m, 3H), 2.53-2.47 (m, 1H), 2.27-2.17 (m, 1H), 1.46 (d, J=7.0 Hz, 3H). MS=470 (MH)+. 
     Example 408. (R)—N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-phenyl-propionamide 
     (R)—N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-phenyl-propionamide was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and (R)-2-Phenyl-propionamide (45.0 mg, 0.302 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.115 g, 89%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.82 (s, 1H), 9.11 (s, 1H), 8.93 (s, 1H), 8.88 (br s, 2H), 8.48 (dd, J=5.1, 0.7 Hz, 1H), 8.42 (s, 1H), 8.04 (dd, J=5.1, 1.4 Hz, 1H), 7.46-7.43 (m, 2H), 7.37-7.33 (m, 2H), 7.27-7.22 (m, 1H), 4.12-4.05 (m, 4H), 3.90-3.86 (m, 4H), 3.36-3.29 (m, 4H), 1.45 (d, J=7.0 Hz, 3H). MS=470 (MH)+. 
     Example 409. (S)—N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-phenyl-propionamide 
     (S)—N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-phenyl-propionamide was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and (S)-2-Phenyl-propionamide (45.0 mg, 0.302 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.104 g, 81%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.81 (s, 1H), 9.11 (s, 1H), 8.93 (s, 1H), 8.88 (br s, 2H), 8.48 (dd, J=5.1, 0.5 Hz, 1H), 8.42 (s, 1H), 8.04 (d, J=5.1, 1.4 Hz, 1H), 7.47-7.41 (m, 2H), 7.37-7.32 (m, 2H), 7.27-7.22 (m, 1H), 4.12-4.05 (m, 4H), 3.89-3.84 (m, 4H), 3.36-3.29 (m, 4H), 1.45 (d, J=7.0 Hz, 3H). MS=470 (MH)+. 
     Example 410. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-methyl-pyridin-2-yl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-methyl-pyridin-2-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (90.0 mg, 0.197 mmol) and 3-Methyl-pyridin-2-ylamine (30.0 mg, 0.277 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as a yellow foam (0.062 g, 73%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.97 (s, 1H), 8.81 (s, 1H), 8.52 (s, 1H), 8.35 (dd, J=5.2, 0.5 Hz, 1H), 8.32 (s, 1H), 8.15 (dd, J=4.7, 1.4 Hz, 1H), 7.80 (dd, J=5.2, 1.4 Hz, 1H), 7.59-7.55 (m, 1H), 6.94 (dd, J=7.3, 5.0 Hz, 1H), 4.07 (s, 3H), 3.68-3.64 (m, 4H), 2.90-2.85 (m, 4H), 2.32 (s, 3H). MS=429 (MH)+. 
     Example 411. (3-Fluoro-pyridin-2-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     (3-Fluoro-pyridin-2-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (90.0 mg, 0.197 mmol) and 3-Fluoro-pyridin-2-ylamine (31.0 mg, 0.276 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as a yellow lyophilate (0.110 g, 84%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.34 (br s, 1H), 8.97-8.79 (m, 4H), 8.48-8.44 (m, 2H), 8.27 (d, J=4.8 Hz, 1H), 8.04 (dd, J=5.6, 1.2 Hz, 1H), 7.86-7.80 (m, 1H), 7.21-7.16 (m, 1H), 4.11 (s, 3H), 3.94-3.88 (m, 4H), 3.37-3.30 (m, 4H). MS=433 (MH)+. 
     Example 412. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-piperazin-1-ylpyridin-3-yl)-amine 
     4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-piperazin-1-yl-pyridin-3-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (106 mg, 0.232 mmol) and 4-(5-Amino-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester (73.0 mg, 0.262 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as a brown lyophilate (0.107 g, 63%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.28 (s, 1H), 8.95-8.85 (m, 3H), 8.73 (br s, 2H), 8.51 (d, J=2.8 Hz, 1H), 8.42 (s, 1H), 8.25 (d, J=5.4 Hz, 1H), 8.03 (dd, J=9.1, 2.8 Hz, 1H), 7.59 (s, 1H), 7.66 (dd, J=5.4, 1.2 Hz, 1H), 6.97 (d, J=9.2 Hz, 1H), 4.10 (s, 3H), 3.90-3.85 (m, 4H), 3.65-3.60 (m, 4H), 3.36-3.29 (m, 4H), 3.25-3.19 (m, 4H). MS=499 (MH)+. 
     Example 413. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[2-methyl-4-(4-methyl-piperazin-1-yl)-phenyl]-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[2-methyl-4-(4-methyl-piperazin-1-yl)-phenyl]-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (102.0 mg, 0.2232 mmol) and 2-Methyl-4-(4-methyl-piperazin-1-yl)-phenylamine (54.0 mg, 0.263 mmol)[prepared as described in WO2008/051547] in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as a brown lyophilate (0.128 g, 75%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.00-9.30 (m, 2H), 9.07 (br s, 2H), 8.90 (s, 1H), 8.44 (s, 1H), 8.06 (d, J=5.9 Hz, 1H), 7.95 (s, 1H), 7.70 (d, J=5.7 Hz, 1H), 7.34 (d, J=8.7 Hz, 1H), 7.02 (d, J=2.3 Hz, 1H), 6.94 (dd, J=8.7, 2.4 Hz, 1H), 4.11 (s, 3H), 3.95-3.80 (m, 6H), 3.55 (d, J=11.5 Hz, 2H), 3.35-3.28 (m, 4H), 3.23-3.12 (m, 2H), 2.99 (t, J=13.8 Hz, 2H), 2.89 (s, 3H), 2.21 (s, 3H). MS=526 (MH)+. 
     Example 414. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(1-piperidin-4-yl-1H-pyrazol-4-yl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(1-piperidin-4-yl-1H-pyrazol-4-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 4-(4-Amino-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (70.0 mg, 0.263 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as a brown lyophilate (0.123 g, 78%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.40 (br s, 1H), 9.00 (br s, 2H), 8.90 (s, 1H), 8.75-8.65 (m, 1H), 8.50-8.37 (m, 2H), 8.25 (d, J=5.6 Hz, 1H), 8.10 (s, 1H), 7.84 (s, 1H), 7.62 (d, J=5.5 Hz, 1H), 7.55 (s, 1H), 4.54-4.44 (m, 1H), 4.10 (s, 3H), 3.90-3.85 (m, 4H), 3.47-3.40 (m, 2H), 3.36-3.30 (m, 4H), 3.15-3.02 (m, 2H), 2.23-2.06 (m, 4H). MS=487 (MH)+. 
     Example 415. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-methyl-pyridin-2-yl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-methyl-pyridin-2-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 6-Methyl-pyridin-2-ylamine (30.0 mg, 0.277 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.095 g, 80%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.96-8.87 (m, 3H), 8.56 (br s, 1H), 8.53 (d, J=5.6 Hz, 1H), 8.45 (s, 1H), 8.05-8.00 (m, 1H), 7.85 (br s, 1H), 7.45-7.39 (m, 1H), 7.04-6.99 (m, 1H), 4.11 (s, 3H), 3.93-3.88 (m, 4H), 3.37-3.30 (m, 4H). MS=429 (MH)+. 
     Example 416. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-methyl-pyridin-3-yl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-methyl-pyridin-3-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (104.0 mg, 0.2276 mmol) and 5-Methyl-pyridin-3-ylamine (30.0 mg, 0.277 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a pale yellow lyophilate (0.123 g, 99%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.13 (br s, 1H), 9.17 (br s, 1H), 8.95-8.85 (m, 3H), 8.46 (d, J=5.4 Hz, 1H), 8.43 (s, 1H), 8.30 (s, 1H), 8.24 (s, 1H), 8.02 (s, 1H), 7.87 (dd, J=5.4, 1.3 Hz, 1H), 4.11 (s, 3H), 3.91-3.86 (m, 4H), 3.36-3.30 (m, 4H), 2.43 (s, 3H). MS=429 (MH)+. 
     Example 417. (5-Chloro-pyridin-3-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     (5-Chloro-pyridin-3-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 5-Chloro-pyridin-3-ylamine (35.0 mg, 0.272 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a pale yellow lyophilate (0.112 g, 90%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.88 (s, 1H), 8.91 (s, 1H), 8.84 (br s, 2H), 8.69 (d, J=2.3 Hz, 1H), 8.64 (t, J=2.2 Hz, 1H), 8.45-8.42 (m, 2H), 8.13 (d, J=2.2 Hz, 1H), 7.99 (s, 1H), 7.82 (dd, J=5.3, 1.3 Hz, 1H), 4.11 (s, 3H), 3.91-3.86 (m, 4H), 3.36-3.30 (m, 4H). MS=406, 408 (MH)+. 
     Example 418. (2-Fluoro-4-morpholin-4-yl-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     418a) 2-Fluoro-4-morpholin-4-yl-phenylamine was prepared from 4-(3-Fluoro-4-nitro-phenyl)-morpholine (0.52 g, 2.3 mmol) [prepared as described in Quan, M. L.; et. al. J. Med. Chem. 2005, 48, 1729-1744.] in an analogous manner to Example 10b. Product isolated as a pale pink solid (0.40 g, 88%).  1 HNMR 400 MHz, d6-DMSO, δ, ppm): 6.71-6.63 (m, 2H), 6.53 (dd, J=8.5, 2.3 Hz, 1H), 4.56 (br s, 2H), 3.71-3.67 (m, 4H), 2.93-2.89 (m, 4H). MS=197 (MH)+. 
     418b) (2-Fluoro-4-morpholin-4-yl-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (105.0 mg, 0.2298 mmol) and 2-Fluoro-4-morpholin-4-yl-phenylamine (52.0 mg, 0.265 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as an orange lyophilate (0.120 g, 70%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.27 (br s, 1H), 8.96-8.89 (m, 3H), 8.43 (s, 1H), 8.16 (d, J=5.7 Hz, 1H), 7.94 (s, 1H), 7.70 (dd, J=5.6, 1.1 Hz, 1H), 7.61 (t, J=9.2 Hz, 1H), 6.93 (dd, J=14.1, 2.5 Hz, 1H), 6.82 (dd, J=8.9, 2.3 Hz, 1H), 4.10 (s, 3H), 3.90-3.85 (m, 4H), 3.77-3.73 (m, 4H), 3.34-3.28 (m, 4H), 3.17-3.08 (m, 4H). MS=517 (MH)+. 
     Example 419. 3-Fluoro-4-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-benzonitrile 
     3-Fluoro-4-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-benzonitrile was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 4-Amino-3-fluoro-benzonitrile (36.0 mg, 0.264 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as a yellow solid (0.019 g, 19%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.58 (d, J=2.5 Hz, 1H), 8.91 (s, 1H), 8.85-8.70 (m, 2H), 8.45 (m, 2H), 8.30 (s, 1H), 7.89 (dd, J=5.3, 1.3 Hz, 1H), 7.83 (dd, J=11.7, 1.9 Hz, 1H), 7.66-7.62 (m, 1H), 4.10 (s, 3H), 3.91-3.87 (m, 4H), 3.33-3.30 (m, 4H). MS=457 (MH)+. 
     Example 420. 4-Fluoro-3-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-benzonitrile 
     420a) A 100 mL round bottom flask equipped with a large magnetic stir bar, reflux condenser and nitrogen inlet adapter was charged with 4-Fluoro-3-nitro-benzonitrile (1.0 g, 6.0 mmol), Ammonium chloride (1.6 g, 30 mmol), Ethanol (20 mL, 300 mmol) and Water (10 mL, 600 mmol). To the suspension was added powdered Iron (1.1 g, 20 mmol). The suspension was stirred vigorously to allow iron to disperse into the suspension without clinging to the stir bar. The mixture was kept under an atmosphere of Nitrogen. An induction period (˜20 minutes) was observed before the reaction began to darken to a rusty brown color and maintain a mild exotherm from 23° C. to 26° C. over the course of three hours. After 3 hours, the reaction was complete by HPLC. The reaction was filtered through a plug of diatomaceous earth. The filter pad was rinsed with methanol (˜100 mL). The filtrate was evaporated to dryness. The solid was triturated with dichloromethane (˜100 mL) and filtered. The filtrate was evaporated. 3-Amino-4-fluoro-benzonitrile was isolated as a brown solid (0.78 g, 95%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 7.19 (dd, J=11.5, 8.3 Hz, 1H), 7.09 (dd, J=8.3, 2.1 Hz, 1H), 6.96 (ddd, J=8.3, 4.3, 2.1 Hz, 1H), 5.69 (br s, 2H). MS=137 (MH)+. 
     420b) 4-Fluoro-3-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-benzonitrile was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 3-Amino-4-fluoro-benzonitrile (36.0 mg, 0.264 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as a yellow lyophilate (0.096 g)  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.41 (d, J=2.0 Hz, 1H), 8.99-8.85 (m, 1H), 8.93-8.84 (m, 3H), 8.44-8.41 (m, 2H), 8.22 (s, 1H), 7.84 (dd, J=5.3, 1.4 Hz, 1H), 7.53-7.46 (m, 2H), 4.11 (s, 3H), 3.92-3.87 (m, 4H), 3.36-3.30 (m, 4H). MS=457 (MH)+. 
     Example 421. (2,6-Difluoro-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     (2,6-Difluoro-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2,6-Difluoro-phenylamine (30.0 μL, 0.279 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as a yellow lyophilate (0.132 g, 88%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.91-8.80 (m, 4H), 8.41 (s, 1H), 8.18 (d, J=5.6 Hz, 1H), 7.82 (s, 1H), 7.69-7.66 (m, 1H), 7.33-7.25 (m, 1H), 7.21-7.12 (m, 2H), 4.10 (s, 3H), 3.89-3.84 (m, 4H), 3.35-3.27 (m, 4H). MS=450 (MH)+. 
     Example 422. (2-Fluoro-6-methyl-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     (2-Fluoro-6-methyl-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2-Fluoro-6-methyl-phenylamine (33.0 mg, 0.264 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as a yellow lyophilate (0.099 g, 67%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.98-8.83 (m, 4H), 8.42 (s, 1H), 8.14 (d, J=5.5 Hz, 1H), 7.75 (br s, 1H), 7.65 (d, J=5.3 Hz, 1H), 7.26-7.10 (m, 3H), 4.10 (s, 3H), 3.88-3.82 (m, 4H), 3.36-3.27 (m, 4H), 2.25 (s, 3H). MS=446 (MH)+. 
     Example 423. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyrimidin-2-yl-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyrimidin-2-yl-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2-amino-pyrimidine (25.0 mg, 0.263 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as a yellow solid (0.009 g, 10%). MP=200-203° C.  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.94 (s, 1H), 9.31 (s, 1H), 8.39 (s, 1H), 8.59 (d, J=4.8 Hz, 2H), 8.44-8.41 (m, 1H), 8.33 (s, 1H), 7.90 (dd, J=5.2, 1.5 Hz, 1H), 7.00 (t, J=4.8 Hz, 1H), 4.07 (s, 3H), 3.71-3.66 (m, 4H), 2.92-2.87 (m, 4H). MS=416 (MH)+. 
     Example 424. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-methoxy-pyridin-3-yl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-methoxy-pyridin-3-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (108.0 mg, 0.2364 mmol) and 5-Methoxy-pyridin-3-ylamine (33.0 mg, 0.266 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.104 g, 99%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.84 (s, 1H), 8.91 (s, 1H), 8.85 (br s, 2H), 8.62 (s, 1H), 8.44-8.41 (m, 2H), 8.10 (t, J=2.2 Hz, 1H), 7.99 (s, 2H), 7.81 (d, J=5.3 Hz, 1H), 4.11 (s, 3H), 3.91-3.86 (m, 7H), 3.36-3.30 (m, 4H). MS=445 (MH)+. 
     Example 425. (S)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-3-ol 
     425a) (S)-1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-3-ol was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (1000.0 mg, 3.4639 mmol) and (S)-Piperidin-3-ol; hydrochloride (570.0 mg, 4.142 mmol) in an analogous manner to [B016]. Product isolated as a yellow foam (0.747 g, 58%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.83 (s, 1H), 8.60 (dd, J=5.0, 0.6 Hz, 1H), 8.35 (s, 1H), 8.32-8.29 (m, 2H), 4.88 (d, J=3.9 Hz, 1H), 4.14-4.05 (m, 4H), 3.95-3.89 (m, 1H), 3.69-3.61 (m, 1H), 3.48-3.38 (m, 1H), 3.09 (dd, J=12.4, 8.3 Hz, 1H), 1.96-1.84 (m, 2H), 1.62-1.40 (m, 2H). MS=372, 374 (MH)+. 
     425b) (S)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-3-ol was prepared from (S)-1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-3-ol (101.0 mg, 0.2716 mmol) and Aniline (30.0 μL, 0.329 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.102 g, 69%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.60 (br s, 1H), 8.81 (s, 1H), 8.35 (s, 1H), 8.27 (d, J=5.6 Hz, 1H), 7.94 (s, 1H), 7.72-7.68 (m, 3H), 7.33 (t, J=7.7 Hz, 2H), 6.99 (t, J=6.8 Hz, 1H), 4.11-4.04 (m, 5H), 3.97-3.90 (m, 1H), 3.70-3.62 (m, 1H), 3.49-3.40 (m, 1H), 3.11 (dd, J=12.8, 8.3 Hz, 1H), 1.98-1.85 (m, 2H), 1.65-1.43 (m, 2H). MS=429 (MH)+. 
     Example 426. 2-{4-[4-((S)-3-Hydroxy-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile 
     2-{4-[4-((S)-3-Hydroxy-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile was prepared from (S)-1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-3-ol (109.0 mg, 0.2932 mmol) and 2-Amino-isonicotinonitrile (39.0 mg, 0.327 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.121 g, 72%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.60 (br s, 1H), 8.83 (s, 1H), 8.61 (s, 1H), 8.52 (d, J=5.2 Hz, 1H), 8.46 (d, J=5.4 Hz, 1H), 8.35 (s, 1H), 8.26 (s, 1H), 7.91 (d, J=5.1 Hz, 1H), 7.34 (d, J=4.9 Hz, 1H), 4.15-4.05 (m, 5H), 4.00-3.92 (m, 1H), 3.70-3.62 (m, 1H), 3.52-3.40 (m, 1H), 3.11 (dd, J=12.7, 8.3 Hz, 1H), 1.98-1.87 (m, 2H), 1.67-1.43 (m, 2H). MS=455 (MH)+. 
     Example 427. 1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-ol 
     1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-ol was prepared from 1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-ol (104.0 mg, 0.2797 mmol) and Aniline (30.0 μL, 0.329 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.093 g, 61%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.66 (br s, 1H), 8.82 (s, 1H), 8.36 (s, 1H), 8.25 (d, J=5.6 Hz, 1H), 7.96 (s, 1H), 7.72-7.67 (m, 3H), 7.34 (t, J=7.8 Hz, 2H), 7.02 (t, J=7.2 Hz, 1H), 4.08 (s, 3H), 4.05-3.97 (m, 2H), 3.87-3.79 (m, 1H), 3.47-3.39 (m, 2H), 1.96-1.88 (m, 2H), 1.63-1.52 (m, 2H). MS=429 (MH)+. 
     Example 428. (R)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-3-ol 
     428a) (R)-1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-3-ol was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (1000.0 mg, 3.4639 mmol) and (R)-Piperidin-3-ol; hydrochloride (570.0 mg, 4.142 mmol) in an analogous manner to [B016]. Product isolated as a tan solid (0.561 g, 44%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.83 (s, 1H), 8.60 (dd, J=5.0, 0.5 Hz, 1H), 8.35 (s, 1H), 8.32-8.29 (m, 2H), 4.88 (d, J=3.9 Hz, 1H), 4.15-4.05 (m, 4H), 3.95-3.88 (m, 1H), 3.70-3.60 (m, 1H), 3.47-3.37 (m, 1H), 3.09 (dd, J=12.7, 8.3 Hz, 1H), 1.96-1.84 (m, 2H), 1.60-1.40 (m, 2H). MS=372, 374 (MH)+. 
     Example 429. 2-{4-[4-((R)-3-Hydroxy-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile 
     2-{4-[4-((R)-3-Hydroxy-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile was prepared from (R)-1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-3-ol (105.0 mg, 0.2824 mmol) and 2-Amino-isonicotinonitrile (39.0 mg, 0.327 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.013 g, 8%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.60 (br s, 1H), 8.83 (s, 1H), 8.61 (s, 1H), 8.52 (d, J=5.1 Hz, 1H), 8.46 (d, J=5.7 Hz, 1H), 8.35 (s, 1H), 8.26 (s, 1H), 7.91 (d, J=5.4 Hz, 1H), 7.34 (d, J=5.3 Hz, 1H), 4.14-4.04 (m, 4H), 4.00-3.92 (m, 1H), 3.70-3.62 (m, 1H), 3.51-3.41 (m, 1H), 3.12 (dd, J=12.9, 8.2 Hz, 1H), 1.98-1.88 (m, 2H), 1.65-1.43 (m, 2H). MS=455 (MH)+. 
     Example 430. [5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-(S)-1-pyrrolidin-2-ylmethyl-amine 
     430a) (S)-2-{[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (1000.0 mg, 3.4639 mmol) and (S)-2-Aminomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (840.0 mg, 4.194 mmol) in an analogous manner to [B016]. Product isolated as a yellow foam (0.817 g, 50%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.87-8.25 (m, 6H), 4.30-4.22 (m, 1H), 4.14 (s, 3H), 4.01-3.91 (m, 1H), 3.72-3.50 (m, 1H), 3.37-3.27 (m, 1H), 2.03-1.78 (m, 5H), 1.45-1.10 (m, 9H). MS=471, 473 (MH)+. 
     430b) [5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-(S)-1-pyrrolidin-2-ylmethyl-amine was prepared from (S)-2-{[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (108.0 mg, 0.2293 mmol) and Aniline (25.0 μL, 0.274 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.109 g, 87%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.42 (br s, 1H), 8.97 (br s, 1H), 8.82 (s, 1H), 8.64 (t, J=5.7 Hz, 1H), 8.54 (br s, 1H), 8.40 (s, 1H), 8.31 (d, J=5.4 Hz, 1H), 7.94 (s, 1H), 7.75-7.70 (m, 3H), 7.31 (t, J=7.7 Hz, 2H), 6.95 (t, J=7.4 Hz, 1H), 4.15 (s, 3H), 4.12-3.85 (m, 3H), 3.34-3.14 (m, 2H), 2.20-1.74 (m, 4H). MS=428 (MH)+. 
     Example 431. [5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-(R)-1-pyrrolidin-2-ylmethyl-amine 
     431a) (R)-2-{[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (1000.0 mg, 3.4639 mmol) and (R)-2-Aminomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (840.0 mg, 4.194 mmol) in an analogous manner to [B016]. Product isolated as a yellow foam (0.869 g, 53%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.86-8.25 (m, 6H), 4.31-4.21 (m, 1H), 4.14 (s, 3H), 4.00-3.90 (m, 1H), 3.72-3.50 (m, 1H), 3.36-3.28 (m, 1H), 2.02-1.78 (m, 5H), 1.45-1.10 (m, 9H). LC/MS=471, 473 (MH)+. 
     431b) [5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-(R)-1-pyrrolidin-2-ylmethyl-amine was prepared from (R)-2-{[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (105.0 mg, 0.2230 mmol) and Aniline (25.0 μL, 0.274 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.117 g, 97%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.42 (br s, 1H), 8.97 (br s, 1H), 8.82 (s, 1H), 8.64 (t, J=5.9 Hz, 1H), 8.53 (br s, 1H), 8.40 (s, 1H), 8.31 (d, J=5.4 Hz, 1H), 7.94 (s, 1H), 7.75-7.70 (m, 3H), 7.31 (t, J=7.5 Hz, 2H), 6.95 (t, J=7.4 Hz, 1H), 4.15 (s, 3H), 4.12-3.85 (m, 3H), 3.34-3.15 (m, 2H), 2.20-1.74 (m, 4H). MS=428 (MH)+. 
     Example 432. 2-{4-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-1-yl}-ethanol 
     432a) 2-{4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-1-yl}-ethanol was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (1000.0 mg, 3.4639 mmol) and 2-Piperazin-1-yl-ethanol (550.0 mg, 4.225 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as a yellow solid (0.414 g, 30%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.84 (s, 1H), 8.60 (dd, J=5.1, 0.7 Hz, 1H), 8.36 (s, 1H), 8.32-8.29 (m, 2H), 4.46 (t, J=5.4 Hz, 1H), 4.07 (s, 3H), 3.75-3.70 (m, 4H), 3.58-3.52 (m, 2H), 2.63-2.58 (m, 4H), 2.46 (t, J=6.2 Hz, 2H). LC/MS=401, 403 (MH)+. 
     Example 433. {1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-azetidin-3-yl}-methanol 
     433a) {1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-azetidin-3-yl}-methanol was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (1000.0 mg, 3.4639 mmol) and Azetidin-3-yl-methanol; hydrochloride (550.0 mg, 4.450 mmol) in an analogous manner to [B016]. Product isolated as a tan solid (0.925 g, 75%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.80 (s, 1H), 8.59 (dd, J=4.8, 1.1 Hz, 1H), 8.33-8.29 (m, 3H), 4.83 (t. J=5.5 Hz, 1H), 4.60-4.53 (m, 1H), 4.41-4.34 (m, 1H), 4.27-4.21 (m, 1H), 4.16-4.10 (m, 1H), 4.06 (s, 3H), 3.59 (t, J=5.7 Hz, 2H), 2.85-2.75 (m, 1H). MS=358, 360 (MH)+. 
     433b) {1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-azetidin-3-yl}-methanol was prepared from {1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-azetidin-3-yl}-methanol (114.0 mg, 0.3186 mmol) and Aniline (31.0 μL, 0.340 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.117 g, 69%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.65 (br s, 1H), 8.79 (s, 1H), 8.33 (s, 1H), 8.25 (d, J=5.5 Hz, 1H), 7.97 (s, 1H), 7.72-7.67 (m, 3H), 7.34 (t, J=7.8 Hz, 2H), 7.01 (t, J=7.3 Hz, 1H), 4.61-4.11 (m, 4H), 4.07 (s, 3H), 3.60 (d, J=6.2 Hz, 2H), 2.87-2.76 (m, 1H). MS=415 (MH)+. 
     Example 434. {(R)-4-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-2-yl}-methanol 
     434a) (R)-4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-2-hydroxymethyl-piperazine-1-carboxylic acid tert-butyl ester was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (1.00 g, 3.46 mmol) and (R)-2-Hydroxymethyl-piperazine-1-carboxylic acid tert-butyl ester (0.90 g, 4.2 mmol) in an analogous manner to [B016]. Product isolated as an off-white solid (1.23 g, 72%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.86 (s, 1H), 8.60 (d, J=5.4 Hz, 1H), 8.38 (s, 1H), 8.36-8.32 (m, 2H), 4.78 (t, J=5.2 Hz, 1H), 4.48 (d, J=12.7 Hz, 1H), 4.17-4.11 (m, 1H), 4.09 (s, 3H), 4.06-3.99 (m, 1H), 3.88-3.80 (m, 1H), 3.47-3.35 (m, 3H), 3.29-3.21 (m, 2H), 1.42 (s, 9H). LC/MS=487, 489 (MH)+. 
     434b) {(R)-4-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-2-yl}-methanol was prepared from (R)-4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-2-hydroxymethyl-piperazine-1-carboxylic acid tert-butyl ester (104.0 mg, 0.2136 mmol) and Aniline (23.0 μL, 0.252 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as a yellow foam (0.033 g, 34%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.31 (s, 1H), 8.81 (s, 1H), 8.33 (s, 1H), 8.30 (d, J=5.3 Hz, 1H), 7.89 (s, 1H), 7.77-7.73 (m, 2H), 7.66 (dd, J=5.3, 1.3 Hz, 1H), 7.30-7.25 (m, 2H), 6.92-6.87 (m, 1H), 4.71 (t, J=5.5 Hz, 1H), 4.24-4.15 (m, 2H), 4.07 (s, 3H), 3.44-3.36 (m, 2H), 3.16-3.02 (m, 2H), 2.88-2.78 (m, 3H). MS=444 (MH)+. 
     Example 435. (R)-7-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-hexahydro-oxazolo[3,4-a]pyrazin-3-one 
     (R)-7-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-hexahydro-oxazolo[3,4-a]pyrazin-3-one was a byproduct from Example 434. Product isolated as the free base as a yellow foam (0.023 g, 23%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.31 (s, 1H), 8.87 (s, 1H), 8.38 (s, 1H), 8.32 (d, J=5.2 Hz, 1H), 7.91 (s, 1H), 7.77-7.74 (m, 2H), 7.69 (dd, J=5.3, 1.4 Hz, 1H), 7.31-7.26 (m, 2H), 6.93-6.88 (m, 1H), 4.50-4.39 (m, 2H), 4.29 (d, J=13.1 Hz, 1H), 4.12-4.03 (m, 6H), 3.77 (dd, J=13.2, 2.1 Hz, 1H), 3.17-3.06 (m, 2H). MS=470 (MH)+. 
     Example 436. (±)-cis-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol 
     436a) To a solution of 3,6-Dihydro-2H-pyridine-1-carboxylic acid benzyl ester (1.16 g, 5.34 mmol) [prepared as described in Solares, F. L.; et. al.  Tetrahedron  2006, 62, 3284-3291] in Acetone (4 mL,) and Water (4 mL,) was added N-Methylmorpholine N-oxide (0.88 g, 7.5 mmol) followed by 2.5 wt % (w/v) OsO4 in t-BuOH(2.5:97.5, Osmium tetraoxide:tert-Butyl alcohol, 0.8 mL, 0.06 mmol). The mixture was stirred at room temperature for 1 hour. Reaction was complete by LC/MS. Saturated aqueous sodium thiosulfate (50 mL) was added and mixture was stirred for 5 minutes then extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over sodium sulfate, filtered and evaporated to a red-brown oil. The recovered oil was purified via chromatography using an ISCO apparatus (silica gel column (24 g) and 2:1 Ethyl Acetate:Hexane). (±)-cis-3,4-Dihydroxy-piperidine-1-carboxylic acid benzyl ester was isolated as a pale yellow oil (1.13 g, 84%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 7.43-7.27 (m, 5H), 5.05 (s, 2H), 4.66 (d, J=4.1 Hz, 1H), 4.55 (d, J=3.7 Hz, 1H), 3.75-3.64 (m, 1H), 3.51-3.18 (m, 5H), 1.69-1.60 (m, 1H), 1.52-1.43 (m, 1H). MS=274 (M+Na)+. 
     436b) A Paar bottle (500 mL) was charged with 10% Palladium on Carbon (50% Wet)(5:45:50, Palladium:carbon black:Water, 1.0 g, 0.47 mmol) followed by a solution of (±)-cis-3,4-Dihydroxy-piperidine-1-carboxylic acid benzyl ester (1.13 g, 4.50 mmol) in 2:1 Ethyl Acetate:Methanol (50 mL). The reaction mixture was degassed and charged with Hydrogen (50 psi). The mixture was shaken on a Paar apparatus for 4 hours. The reaction mixture was degassed and kept under an atmosphere of Nitrogen. The mixture was filtered through a plug of diatomaceous earth and rinsed with dichloromethane. The filtrate was evaporated. (±)-cis-Piperidine-3,4-diol was isolated as a pale yellow oil (0.569 g, 100%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 4.11 (br s, 3H), 3.57-3.53 (m, 1H), 3.46-3.42 (m, 1H), 2.79-2.67 (m, 2H), 2.57-2.49 (m, 1H), 2.47-2.37 (m, 1H), 1.61-1.51 (m, 1H), 1.47-1.39 (m, 1H). MS=118 (MH)+. 
     436c) (±)-cis-1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (1.00 g, 3.46 mmol) and (±)-cis-Piperidine-3,4-diol (0.56 g, 4.8 mmol) in analogous manner to [B016]. Product isolated as a pale yellow solid (0.927 g, 69%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.82 (s, 1H), 8.60 (dd, J=5.0, 0.5 Hz, 1H), 8.35 (s, 1H), 8.32-8.29 (m, 2H), 4.65-4.61 (m, 2H), 4.07 (s, 3H), 3.94 (br s, 1H), 3.83-3.74 (m, 2H), 3.65-3.53 (m, 3H), 1.94-1.85 (m, 1H), 1.73-1.65 (m, 1H). MS=388, 390 (MH)+. 
     436d) (1)-cis-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol was prepared from (1)-cis-1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol (100.0 mg, 0.2578 mmol) and Aniline (29.0 μL, 0.318 mmol) in an analogous manner to Example 303c. Product isolated as the free base as a yellow solid (0.039 g, 34%). MP=241-243° C.  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.32 (s, 1H), 8.79 (s, 1H), 8.32-8.29 (m, 2H), 7.90 (s, 1H), 7.77-7.74 (m, 2H), 7.67 (dd, J=5.3, 1.3 Hz, 1H), 7.30-7.25 (m, 2H), 6.92-6.87 (m, 1H), 4.64-4.60 (m, 2H), 4.07 (s, 3H), 3.98-3.88 (m, 1H), 3.85-3.72 (m, 2H), 3.66-3.53 (m, 3H), 1.97-1.87 (m, 1H), 1.76-1.66 (m, 1H). MS=445 (MH)+. 
     Example 437. (±)-trans-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol 
     437a) (±)-trans-Piperidine-3,4-diol was prepared from (1)-trans-3,4-Dihydroxy-piperidine-1-carboxylic acid benzyl ester (1.0 g, 4.0 mmol) [prepared as described in Solares, F. L.; et. al.  Tetrahedron  2006, 62, 3284-3291] in an analogous manner to Example 436a. Product isolated as a pale yellow oil (0.451 g, 97%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 4.59 (br s, 2H), 4.09 (br s, 1H), 3.20-3.13 (m, 1H), 3.11-3.04 (m, 1H), 2.88 (ddd, J=4.4, 12.1, 1.2 Hz, 1H), 2.77 (dddd, J=12.6, 4.1, 4.1, 1.2 Hz, 1H), 2.35 (dddd, J=14.1, 11.3, 2.9 Hz, 1H), 2.15 (dd, J=12.2, 9.1 Hz, 1H), 1.71 (dddd, J=12.6, 3.8, 3.8, 3.8 Hz, 1H), 1.25-1.15 (m, 1H). MS=118 (MH)+. 
     437b) (±)-trans-1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (1.00 g, 3.46 mmol) and (±)-trans-Piperidine-3,4-diol (0.46 g, 3.9 mmol) in an analogous manner to [B016]. Product isolated as a tan solid (0.700 g, 52%). MP=213-216° C.  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.83 (s, 1H), 8.61 (dd, J=5.0, 0.6 Hz, 1H), 8.36 (s, 1H), 8.32-8.29 (m, 2H), 5.00 (d, J=4.1 Hz, 1H), 4.94 (d, J=4.2 Hz, 1H), 4.11-4.03 (m, 4H), 4.00-3.90 (m, 1H), 3.59-3.47 (m, 2H), 3.44-3.37 (m, 1H), 3.16 (dd, J=13.1, 7.9 Hz, 1H), 2.07-1.99 (m, 1H), 1.54-1.44 (m, 1H). MS=388, 390 (MH)+. 
     437c) desired (1)-trans-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol was prepared from (±)-trans-1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol (100.0 mg, 0.2578 mmol) and Aniline (29.0 μL, 0.318 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as tan foam (0.1126 g, 98%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.32 (s, 1H), 8.80 (s, 1H), 8.33 (s, 1H), 8.30 (d, J=5.4 Hz, 1H), 7.90 (s, 1H), 7.77-7.74 (m, 2H), 7.67 (dd, J=5.3, 1.3 Hz, 1H), 7.40-7.36 (m, 1H), 7.30-7.25 (m, 2H), 6.92-6.87 (m, 1H), 5.00 (d, J=4.1 Hz, 1H), 4.94 (d, J=4.2 Hz, 1H), 4.10-4.04 (m, 4H), 3.98 (d, J=13.4 Hz, 1H), 3.55-3.46 (m, 1H), 3.40 (dddd, J=7.7, 7.7, 4.2, 4.2 Hz, 1H), 3.13 (dd, J=13.0, 7.7 Hz, 1H), 2.09-2.00 (m, 1H), 1.57-1.46 (m, 1H). MS=445 (MH)+. 
     Example 438. 4-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-2-one 
     438a) 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-2-one was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (1.0 g, 3.5 mmol) and Piperazin-2-one (0.42 g, 4.2 mmol) in an analogous manner to [B016]. Product isolated as a tan solid (1.12 g, 87%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.89 (s, 1H), 8.63-8.60 (m, 1H), 8.41 (s, 1H), 8.34-8.32 (m, 2H), 8.15 (s, 1H), 4.23 (s, 2H), 4.10 (s, 3H), 3.95-3.90 (m, 2H), 3.43-3.39 (m, 2H). LC/MS=371, 373 (MH)+. 
     438b) 4-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-2-one was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-2-one (100.0 mg, 0.2697 mmol) and Aniline (30.0 μL, 0.329 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.022 g, 19%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.66 (br s, 1H), 8.87 (s, 1H), 8.40 (s, 1H), 8.27 (d, J=5.5 Hz, 1H), 8.18 (s, 1H), 7.97 (s, 1H), 7.74-7.69 (m, 3H), 7.34 (t, J=7.7 Hz, 2H), 7.00 (t, J=7.0 Hz, 1H), 4.23 (s, 2H), 4.10 (s, 3H), 3.92-3.87 (m, 2H), 3.46-3.41 (m, 2H). MS=428 (MH)+. 
     Example 439. (2,3-Difluoro-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     (2,3-Difluoro-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2,3-Difluoro-phenylamine (27.0 μL, 0.266 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as a yellow lyophilate (0.125 g, 84%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.24 (s, 1H), 8.91 (s, 1H), 8.86 (br s, 2H), 8.42 (s, 1H), 8.33 (d, J=5.4 Hz, 1H), 8.10 (s, 1H), 8.07-8.03 (m, 1H), 7.78 (dd, J=5.3, 1.4 Hz, 1H), 7.19-7.11 (m, 1H), 7.06-6.98 (m, 1H), 4.10 (s, 3H), 3.91-3.86 (m, 4H), 3.36-3.29 (m, 4H). MS=450 (MH)+. 
     Example 440. (2,5-Difluoro-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     (2,5-Difluoro-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine was prepared 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2,5-Difluoro-phenylamine (27.0 μL, 0.268 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as a yellow lyophilate (0.036 g, 24%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.25 (s, 1H), 8.91 (s, 1H), 8.89 (br s, 2H), 8.45-8.38 (m, 3H), 8.21 (s, 1H), 7.81 (dd, J=5.3, 1.4 Hz, 1H), 7.31-7.24 (m, 1H), 6.80-6.74 (m, 1H), 4.11 (s, 3H), 3.92-3.87 (m, 4H), 3.36-3.30 (m, 4H). MS=450 (MH)+. 
     Example 441. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,4,6-trifluoro-phenyl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,4,6-trifluoro-phenyl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2,4,6-Trifluoro-phenylamine (39.0 mg, 0.265 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as a yellow lyophilate (0.092 g, 60%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.93 (br s, 2H), 8.90 (s, 1H), 8.82 (s, 1H), 8.42 (s, 1H), 8.17 (dd, J=5.4, 0.5 Hz, 1H), 7.83 (s, 1H), 7.68 (dd, J=5.3, 1.4 Hz, 1H), 7.34-7.23 (m, 2H), 4.10 (s, 3H), 3.90-3.84 (m, 4H), 3.35-3.29 (m, 4H). MS=468 (MH)+. 
     Example 442. ((R)-4-{2-[2-(2,6-Difluoro-phenylamino)-pyridin-4-yl]-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl}-piperazin-2-yl)-methanol 
     ((R)-4-{2-[2-(2,6-Difluoro-phenylamino)-pyridin-4-yl]-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl}-piperazin-2-yl)-methanol was prepared from (R)-4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-2-hydroxymethyl-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2054 mmol) and 2,6-Difluoro-phenylamine (32.0 mg, 0.248 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as a tan foam (0.066 g, 66%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.80 (s, 1H), 8.76 (s, 1H), 8.32 (s, 1H), 8.15 (d, J=5.3 Hz, 1H), 7.77 (s, 1H), 7.64 (d, J-5.2, 1.3 Hz, 1H), 7.31-7.10 (m, 3H), 4.70 (t, J=5.5 Hz, 1H), 4.21-4.12 (m, 2H), 4.06 (s, 3H), 3.42-3.35 (m, 2H), 3.15-3.00 (m, 2H), 2.86-2.77 (m, 3H). MS=480 (MH)+. 
     Example 443. 3-Hydroxymethyl-1-[5-methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-ol 
     443a) To a cooled solution of 4-Oxo-piperidine-3-carboxylic acid ethyl ester; hydrochloride (5.0 g, 24 mmol) and Sodium bicarbonate (4.40 g, 52.4 mmol) in Water (50 mL) at 5° C. was added Benzyl chloroformate (3.40 mL, 23.8 mmol) dropwise. The mixture was stirred at room temperature overnight. Saturated aqueous sodium carbonate (10 mL) was added and stirred for 30 minutes. The reaction mixture was extracted dichloromethane (3×30 mL). The combined organic layer was dried over magnesium sulfate, filtered and evaporated. The crude material was purified via chromatography using an ISCO apparatus (silica gel column 120 g and 10%→50% Ethyl Acetate:hexane). 4-Oxo-piperidine-1,3-dicarboxylic acid 1-benzyl ester 3-ethyl ester was isolated as a clear oil (7.30 g, 100%).  1 HNMR (400 MHz, CDCl3, δ, ppm): 12.07 (s, 1H), 7.43-7.29 (m, 5H), 5.20-5.15 (m, 2H), 4.24 (q, J=7.2 Hz, 2H), 4.14 (br s, 2H), 3.65 (t, J=5.9 Hz, 2H), 2.39 (br s, 2H), 1.31 (t, J=7.2 Hz, 3H). MS=328 (M+Na)+. 
     443b) Sodium borohydride (4.5 g, 120 mmol) was added in 0.5 g portions over 1 hour to a stirred solution of 4-Oxo-piperidine-1,3-dicarboxylic acid 1-benzyl ester 3-ethyl ester (3.0 g, 9.8 mmol) in Methanol (30 mL) under an atmosphere of Nitrogen at room temperature. Gas evolution and exotherm was noted during each addition. The slow portionwise addition kept reaction temperatures below 25° C. during the course of additions. The mixture was stirred for 1 hour at room temperature then slowly warmed. The reaction was refluxed for 4 hours, cooled to room temperature and stirred overnight. A 1:1 mixture of water:methanol (100 mL) was added dropwise to the reaction over 1 hour. No exotherm or gas evolution was noted. The mixture was stirred for 4 hours. The methanol was evaporated under reduced pressure. Methanol (50 mL) was added and the white suspension was heated at reflux for 30 minutes. The methanol was evaporated under reduced pressure. This was repeated twice. The mixture was evaporated to a white oily solid. The solid was triturated with dichloromethane (3×50 mL) and decanted. The combined organic was dried over magnesium sulfate, filtered and evaporated. 4-Hydroxy-3-hydroxymethyl-piperidine-1-carboxylic acid benzyl ester was isolated as a clear oil (0.655 g, 25%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 7.41-7.28 (m, 5H), 5.13-5.00 (m, 2H), 4.70-4.56 (m, 1H), 4.50-4.39 (m, 1H), 4.09-3.60 (m, 3H), 3.47-2.58 (m, 4H), 1.80-1.20 (m, 3H). MS=288 (M+Na)+. 
     443c) 3-Hydroxymethyl-piperidin-4-ol was prepared from 4-Hydroxy-3-hydroxymethyl-piperidine-1-carboxylic acid benzyl ester (0.655 g, 2.47 mmol) in an analogous manner to Example 436b. Product isolated as a viscous oil (0.324 g, 100%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 4.60-3.18 (m, 7H), 3.3-2.78 (m, 1H), 2.70-2.56 (m, 1H), 2.43-2.10 (m, 1H), 1.74-1.18 (m, 3H). 
     443d) 1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-3-hydroxymethyl-piperidin-4-ol was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (0.70 g, 2.4 mmol) and 3-Hydroxymethyl-piperidin-4-ol (0.324 g, 2.47 mmol) in an analogous manner to [B016]. Product isolated as a pale yellow foam (0.342 g, 35%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.83 (d, J=5.4 Hz, 1H), 8.61-5.85 (m, 1H), 8.35 (d, J=6.2 Hz, 1H), 8.33-8.29 (m, 2H), 4.78-4.69 (m, 1H), 4.58-4.46 (m, 1H), 4.36-3.70 (m, 6H), 3.56-3.12 (m, 4H), 2.02-1.45 (m, 3H). MS=402, 404 (MH)+. 
     443e) 3-Hydroxymethyl-1-[5-methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-ol was prepared from 1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-3-hydroxymethyl-piperidin-4-ol (100.0 mg, 0.2488 mmol) and Aniline (28.0 μL, 0.307 mmol) in an analogous manner to Example 303c and Example 1501c. Product was isolated as the free base as a mixture of enantiomers as a yellow foam (0.071 g, 62%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.31 (d, J=3.0 Hz, 1H), 8.80 (d, J=4.5 Hz, 1H), 8.34-8.29 (m, 2H), 7.90 (s, 1H), 7.75 (d, J=7.7 H, 2H), 7.68 (dd, J=5.3, 1.2 Hz, 1H), 7.31-7.25 (m, 2H), 6.92-6.87 (m, 1H), 4.79-4.69 (m, 1H), 4.55-4.43 (m, 1H), 4.30-3.70 (m, 6H), 3.56-3.25 (m, 3H), 3.19-2.91 (m, 1H), 2.04-1.50 (m, 3H). MS=459 (MH)+. 
     Example 444. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,3,6-trifluoro-phenyl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,3,6-trifluoro-phenyl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (121.0 mg, 0.2648 mmol) and 2,3,6-Trifluoro-phenylamine (33.9 μL, 0.320 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as a yellow lyophilate (0.155 g, 84%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.07 (s, 1H), 8.94-8.84 (m, 3H), 8.42 (s, 1H), 8.21 (d, J=5.3 Hz, 1H), 7.89 (s, 1H), 7.72 (dd, J=5.3, 1.4 Hz, 1H), 7.33 (dddd, J=9.7, 9.7, 9.7, 4.9 Hz, 1H), 7.21 (dddd, J=9.6, 4.7, 4.7, 2.2 Hz, 1H), 4.10 (s, 3H), 3.91-3.84 (m, 4H), 3.36-3.28 (m, 4H). MS=468 (MH)+. 
     Example 445. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-trifluoromethyl-phenyl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-trifluoromethyl-phenyl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (124.0 mg, 0.2714 mmol) and 2-(trifluoromethyl)-Benzenamine (40.0 μL, 0.318 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as a yellow lyophilate (0.134 g, 69%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.00-8.85 (m, 4H), 8.42 (d, J=2.3 Hz, 1H), 8.19 (dd, J=5.4, 1.4 Hz, 1H), 7.99 (s, 1H), 7.80-7.66 (m, 4H), 7.44-7.37 (m, 1H), 4.11 (s, 3H), 3.90-3.84 (m, 4H), 3.35-3.28 (m, 4H). MS=482 (MH)+. 
     Example 446. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-trifluoromethyl-phenyl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-trifluoromethyl-phenyl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (140.0 mg, 0.3064 mmol) and 3-(trifluoromethyl)-Benzenamine (46.2 μL, 0.370 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.179 g, 98%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.76 (s, 1H), 8.93-8.83 (m, 3H), 8.42 (s, 1H), 8.41 (d, J=5.4 Hz, 1H), 8.34 (s, 1H), 7.97 (s, 1H), 7.92 (d, J=8.3 Hz, 1H), 7.78 (dd, J=5.3, 1.3 Hz, 1H), 7.52 (t, J=7.9 Hz, 1H), 7.23 (d, J=7.6 Hz, 1H), 4.11 (s, 3H), 3.91-3.86 (m, 4H), 3.36-3.30 (m, 4H). MS=482 (MH)+. 
     Example 447. (6-Fluoro-pyridin-2-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     (6-Fluoro-pyridin-2-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 6-Fluoro-pyridin-2-ylamine (30.0 mg, 0.268 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as an off-white solid (0.003 g, 2%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.15 (s, 1H), 8.81 (s, 1H), 8.74 (s, 1H), 8.40 (d, J=5.1 Hz, 1H), 8.32 (s, 1H), 7.88-7.81 (m, 2H), 7.75 (dd, J=8.1, 2.6 Hz, 1H), 6.59 (dd, J=7.7, 2.3 Hz, 1H), 4.07 (s, 3H), 3.71-3.66 (m, 4H), 2.90-2.85 (m, 4H). MS=433 (MH)+. 
     Example 448. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-methoxy-pyridin-2-yl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-methoxy-pyridin-2-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (124.0 mg, 0.2714 mmol) and 6-Methoxy-pyridin-2-ylamine (40.0 mg, 0.322 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as an off-white solid (0.098 g, 80%). MP=189-191° C.  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.79 (s, 1H), 9.04 (s, 1H), 8.73 (s, 1H), 8.37 (d, J=5.2 Hz, 1H), 8.31 (s, 1H), 7.79 (dd, J=5.2, 1.4 Hz, 1H), 7.58 (t, J=7.9 Hz, 1H), 7.16 (d, J=7.8 Hz, 1H), 6.30 (d, J=7.7 Hz, 1H), 4.07 (s, 3H), 4.04 (s, 3H), 3.67-3.62 (m, 4H), 2.89-2.84 (m, 4H). MS=445 (MH)+. 
     Example 449. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-trifluoromethyl-pyridin-2-yl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-trifluoromethyl-pyridin-2-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 6-Trifluoromethyl-pyridin-2-ylamine (43.0 mg, 0.265 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as off-white solid (0.005 g, 5%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.34 (s, 1H), 8.80-8.78 (m, 2H), 8.42 (d, J=4.7 Hz, 1H), 8.32 (s, 1H), 8.08 (d, J=8.1 Hz, 1H), 7.94 (t, J=8.1 Hz, 1H), 7.89 (dd, J=5.1, 1.3 Hz, 1H), 7.36 (d, J=7.4 Hz, 1H), 4.07 (s, 3H), 3.68-3.63 (m, 4H), 2.90-2.85 (m, 4H). MS=483 (MH)+. 
     Example 450. (2-Fluoro-pyridin-3-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     (2-Fluoro-pyridin-3-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (124.0 mg, 0.2714 mmol) and 2-Fluoro-pyridin-3-ylamine (40.0 mg, 0.357 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as a yellow lyophilate (0.156 g, 86%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.26 (s, 1H), 8.91 (br s, 3H), 8.86 (ddd, J=10.0, 8.0, 1.7 Hz, 1H), 8.42 (s, 1H), 8.36 (dd, J=5.5 Hz, 1H), 8.19 (s, 1H), 7.81 (dd, J=5.3, 1.3 Hz, 1H), 7.77 (ddd, J=4.6, 1.5, 1.5 Hz, 1H), 7.32 (ddd, J=7.9, 4.8, 0.9 Hz, 1H), 4.11 (s, 3H), 3.93-3.87 (m, 4H), 3.36-3.30 (m, 4H). MS=433 (MH)+. 
     Example 451. (2-Fluoro-3-methyl-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     (2-Fluoro-3-methyl-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (111.0 mg, 0.2429 mmol) and 2-Fluoro-3-methyl-phenylamine (36.0 mg, 0.288 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the tris-trifluoroacetic acid salt as a yellow lyophilate (0.146 g, 76%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.04 (br s, 1H), 8.90 (s, 1H), 8.87 (br s, 2H), 8.42 (s, 1H), 8.28 (d, J=5.3 Hz, 1H), 8.06 (s, 1H), 7.98 (t, J=7.8 Hz, 1H), 7.73 (dd, J=5.3, 1.3 Hz, 1H), 7.05 (t, J=7.8 Hz, 1H), 6.93 (t, J=7.2 Hz, 1H), 4.10 (s, 3H), 3.91-3.86 (m, 4H), 3.35-3.29 (m, 4H), 2.28 (d, J=1.8 Hz, 3H). MS=446 (MH)+. 
     Example 452. (2-Fluoro-3-trifluoromethyl-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     (2-Fluoro-3-trifluoromethyl-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (102.0 mg, 0.2232 mmol) and 2-Fluoro-3-trifluoromethyl-phenylamine (48.0 mg, 0.268 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as a yellow lyophilate (0.050 g, 30%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.32 (s, 1H), 8.91 (s, 1H), 8.85 (br s, 2H), 8.63 (ddd, J=7.8, 7.8, 2.3 Hz, 1H), 8.42 (s, 1H), 8.35 (d, J=5.3 Hz, 1H), 8.14 (s, 1H), 7.81 (dd, J=5.3, 1.4 Hz, 1H), 7.39-7.30 (m, 2H), 4.11 (s, 3H), 3.92-3.86 (m, 4H), 3.36-3.29 (m, 4H). MS=500 (MH)+. 
     Example 453. 2,4-Difluoro-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     (2,4-Difluoro-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2,4-Difluoro-phenylamine (27.0 μL, 0.265 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as a yellow lyophilate (0.059 g, 39%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.03 (s, 1H), 8.90 (s, 1H), 8.87 (br s, 2H), 8.42 (s, 1H), 8.27 (d, J=5.3 Hz, 1H), 8.10 (ddd, J=9.3, 9.3, 6.3 Hz, 1H), 8.00 (s, 1H), 7.72 (dd, J=5.4, 1.3 Hz, 1H), 7.31 (ddd, J=11.5, 9.0, 2.9 Hz, 1H), 7.11-7.04 (m, 1H), 4.10 (s, 3H), 3.90-3.85 (m, 4H), 3.35-3.29 (m, 4H). MS=450 (MH)+. 
     Example 454. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,3,4-trifluoro-phenyl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,3,4-trifluoro-phenyl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2,3,4-Trifluoro-phenylamine (28.0 μL, 0.265 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as a yellow lyophilate (0.104 g, 68%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.21 (s, 1H), 8.95-8.85 (m, 3H), 8.42 (s, 1H), 8.30 (d, J=5.3 Hz, 1H), 8.04 (s, 1H), 7.99-7.91 (m, 1H), 7.77 (dd, J=5.3, 1.3 Hz, 1H), 7.33-7.24 (m, 1H), 4.10 (s, 1H), 3.91-3.86 (m, 4H), 3.36-3.29 (m, 4H). MS=468 (MH)+. 
     Example 455. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,4,5-trifluoro-phenyl)-amine 
     [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,4,5-trifluoro-phenyl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2188 mmol) and 2,4,5-Trifluoro-phenylamine (39.0 mg, 0.265 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the bis-trifluoroacetic acid salt as a yellow lyophilate (0.027 g, 17%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.21 (s, 1H), 8.91 (s, 1H), 8.86 (br s, 2H), 8.54 (ddd, J=13.6, 8.5, 8.5 Hz, 1H), 8.42 (s, 1H), 8.36 (d, J=5.4 Hz, 1H), 8.14 (s, 1H), 7.79 (dd, J=5.3, 1.4 Hz, 1H), 7.60 (ddd, J=10.9, 10.9, 7.7 Hz, 1H), 4.10 (s, 3H), 3.91-3.86 (m, 4H), 3.36-3.29 (m, 4H). MS=468 (MH)+. 
     Example 456. (3S,4S)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol or (3R,4R)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol 
     (3S,4S)- or (3R,4R)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol was prepared from (1)-trans-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol (67.52 mg) via super critical fluid chiral chromatography using Chiralcel OJ-H (10×250 mm) column using 30% MeOH (w/ 0.1% diethylamine modifier):70% CO2 eluent at 6.0 mL/min over 4 injections of 150 μL, T=35° C., P=120 bar, UV=220 nm. Product isolated as the initial peak as a yellow solid (0.0166 g, 24%). Purity: &gt;99% ee @100% purity. RT: 8.6 min,  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.31 (s, 1H), 8.80 (s, 1H), 8.33 (s, 1H), 8.31 (d, J=5.4 Hz, 1H), 7.90 (s, 1H), 7.77-7.74 (m, 2H), 7.67 (dd, J=5.3, 1.3 Hz, 1H), 7.30-7.25 (m, 2H), 6.92-6.87 (m, 1H), 5.01-4.98 (m, 1H), 4.94 (d, J=4.1 Hz, 1H), 4.11-3.94 (m, 5H), 3.55-3.38 (m, 3H), 3.16-3.10 (m, 1H), 2.08-2.00 (m, 1H), 1.57-1.47 (m, 1H). MS=445 (MH)+. 
     Example 457. (3R,4R)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol or (3S,4S)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol 
     (3R,4R)- or (3S,4S)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol was prepared from (±)-trans-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol (67.52 mg) via super critical fluid chiral chromatography using Chiralcel OJ-H (10×250 mm) column using 30% MeOH (w/ 0.1% diethylamine modifier):70% CO2 eluent at 6.0 mL/min over 4 injections of 150 μL, T=35° C., P=120 bar, UV=220 nm. Product isolated as the secondary peak as a yellow solid (0.0209 g, 31%). Purity: &gt;97.6% ee @98% purity. RT: 12.98 min.  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.32 (s, 1H), 8.80 (s, 1H), 8.33 (s, 1H), 8.31 (d, J=5.2 Hz, 1H), 7.90 (s, 1H), 7.77-7.74 (m, 2H), 7.67 (dd, J=5.4, 1.3 Hz, 1H), 7.30-7.25 (m, 2H), 6.92-6.87 (m, 1H), 5.02-4.98 (m, 2H), 4.11-3.93 (m, 5H), 3.55-3.37 (m, 3H), 3.16-3.10 (m, 1H), 2.08-2.00 (m, 1H), 1.57-1.47 (m, 1H). MS=445 (MH)+. 
     Example 458. 3-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-propionamide 
     458a) 3-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-propionamide was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (1.00 g, 3.46 mmol) and 3-Amino-propionamide; hydrochloride (0.52 g, 4.2 mmol) in an analogous manner to [B016]. Product isolated as a tan solid (0.303 g, 24%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.93 (t, J=5.5 Hz, 1H), 8.79 (s, 1H), 8.61-8.58 (m, 1H), 8.35 (s, 1H), 8.34-8.32 (m, 2H), 7.50 (br s, 1H), 7.00 (br s, 1H), 4.11 (s, 3H), 3.94-3.87 (m, 2H), 2.57-2.52 (m, 2H). MS=359, 361 (MH)+. 
     458b) 3-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-propionamide was prepared from 3-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ylamino]-propionamide (100.0 mg, 0.2787 mmol) and Aniline (30.0 μL, 0.329 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.043 g, 28%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.55 (br s, 1H), 8.88 (t, J=5.4 Hz, 1H), 8.77 (s, 1H), 8.34 (s, 1H), 8.26 (d, J=5.4 Hz, 1H), 7.96 (s, 1H), 7.74-7.69 (m, 3H), 7.50 (s, 1H), 7.33 (t, J=7.9 Hz, 2H), 7.04-6.95 (m, 2H), 4.12 (s, 3H), 3.95-3.89 (m, 2H), 2.58-2.53 (m, 2H). MS=416 (MH)+. 
     Example 459. [4-(5-Methoxy-4-piperidin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-phenyl-amine 
     459a) 2-(2-Chloro-pyridin-4-yl)-5-methoxy-4-piperidin-1-yl-pyrido[3,4-d]pyrimidine was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (1.0 g, 3.5 mmol) and Piperidine (0.41 mL, 4.2 mmol) in an analogous manner to [B016]. Product isolated as a yellow-orange solid (0.61 g, 49%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.83 (s, 1H), 8.59 (d, J=5.0 Hz, 1H), 8.35 (s, 1H), 8.31-8.28 (m, 2H), 4.08 (s, 3H), 3.71-3.65 (m, 4H), 1.75-1.65 (m, 6H). MS=356, 358 (MH)+. 
     459b) [4-(5-Methoxy-4-piperidin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-phenyl-amine was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-4-piperidin-1-yl-pyrido[3,4-d]pyrimidine (100.0 mg, 0.2810 mmol) and Aniline (31.0 μL, 0.340 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as a yellow solid (0.075 g, 64%). MP=221-223° C.  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.31 (s, 1H), 8.80 (s, 1H), 8.32 (s, 1H), 8.30 (d, J=5.2 Hz, 1H), 7.90 (s, 1H), 7.77-7.73 (m, 2H), 7.66 (dd, J=5.2, 1.3 Hz, 1H), 7.30-7.25 (m, 2H), 6.92-6.87 (m, 1H), 4.08 (s, 3H), 3.70-3.65 (m, 4H), 1.75-1.67 (m, 6H). MS=413 (MH)+. 
     Example 460. {4-[4-(4,4-Difluoro-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine 
     460a) 2-(2-Chloro-pyridin-4-yl)-4-(4,4-difluoro-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidine was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (1.0 g, 3.5 mmol) and 4,4-Difluoro-piperidine; hydrochloride (0.66 g, 4.2 mmol) in an analogous manner to [B016]. Product isolated as an orange solid (0.806 g, 59%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.90 (s, 1H), 8.61 (dd, J=4.9, 0.8 Hz, 1H), 8.41 (s, 1H), 8.34-8.31 (m, 2H), 4.10 (s, 3H), 3.84-3.79 (m, 4H), 2.26-2.14 (m, 4H). MS=392, 394 (MH)+. 
     460b) {4-[4-(4,4-Difluoro-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine was prepared from 2-(2-Chloro-pyridin-4-yl)-4-(4,4-difluoro-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidine (100.0 mg, 0.2552 mmol) and Aniline (28.0 μL, 0.307 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as an orange solid (0.027 g, 23%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.32 (s, 1H), 8.87 (s, 1H), 8.38 (s, 1H), 8.32 (d, J=5.2 Hz, 1H), 7.92 (s, 1H), 7.78-7.74 (m, 2H), 7.68 (dd, J=5.3, 1.4 Hz, 1H), 7.31-7.25 (m, 2H), 6.93-6.88 (m, 1H), 4.10 (s, 3H), 3.82-3.78 (m, 4H), 2.27-2.15 (m, 4H). MS=449 (MH)+. 
     Example 461. 1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-4-carbonitrile 
     461a) 1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-4-carbonitrile was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (1.0 g, 3.5 mmol) and Piperidine-4-carbonitrile (0.46 g, 4.2 mmol) in an analogous manner to [B016]. Product isolated as an orange solid (0.80 g, 61%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.87 (s, 1H), 8.61 (dd, J=5.0, 0.7 Hz, 1H), 8.39 (s, 1H), 8.34-8.31 (m, 2H), 4.10 (s, 3H), 3.96-3.88 (m, 2H), 3.57-3.49 (m, 2H), 3.25-3.17 (m, 1H), 2.14-2.05 (m, 2H), 1.96-1.86 (m, 2H). MS=381, 383 (MH)+. 
     461b) 1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-4-carbonitrile was prepared from 1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-4-carbonitrile (100.0 mg, 0.2626 mmol) and Aniline (29.0 μL, 0.318 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as a yellow solid (0.090 g, 77%). MP=242-244° C.  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.32 (s, 1H), 8.84 (s, 1H), 8.36 (s, 1H), 8.31 (d, J=5.2 Hz, 1H), 7.91 (s, 1H), 7.77-7.74 (m, 2H), 7.67 (dd, J=5.4, 1.4 Hz, 1H), 7.31-7.26 (m, 2H), 6.93-6.88 (m, 1H), 4.09 (s, 3H), 3.96-3.88 (m, 2H), 3.56-3.48 (m, 2H), 3.26-3.19 (m, 1H), 2.15-2.06 (m, 2H), 1.98-1.88 (m, 2H). MS=438 (MH)+. 
     Example 462. {4-[4-(4-Fluoro-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine 
     462a) 2-(2-Chloro-pyridin-4-yl)-4-(4-fluoro-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidine was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (1.0 g, 3.5 mmol) and 4-Fluoro-piperidine; hydrochloride (0.58 g, 4.2 mmol) in an analogous manner to [B016]. Product isolated as an orange solid (0.61 g, 47%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.87 (s, 1H), 8.61 (dd, J=4.9, 0.7 Hz, 1H), 8.38 (s, 1H), 8.33-8.30 (m, 2H), 5.08-4.90 (m, 1H), 4.09 (s, 3H), 3.83-3.68 (m, 4H), 2.16-2.00 (m, 2H), 1.97-1.85 (m, 2H). MS=374, 376 (MH)+. 
     462b) {4-[4-(4-Fluoro-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine was prepared from 2-(2-Chloro-pyridin-4-yl)-4-(4-fluoro-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidine (100.0 mg, 0.2675 mmol) and Aniline (30.0 μL, 0.329 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as a yellow solid (0.057 g, 49%). MP=202-205° C.  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.32 (s, 1H), 8.83 (s, 1H), 8.35 (s, 1H), 8.31 (d, J=5.3 Hz, 1H), 7.91 (s, 1H), 7.77-7.74 (m, 2H), 7.67 (dd, J=5.3, 1.3 Hz, 1H), 7.31-7.25 (m, 2H), 6.92-6.87 (m, 1H), 5.10-4.90 (m, 1H), 4.09 (s, 3H), 3.84-3.67 (m, 4H), 2.17-2.02 (m, 2H), 1.98-1.85 (m, 2H). MS=431 (MH)+. 
     Example 463. (3R,4S)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol or (3S,4R)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol 
     (3R,4S)- or (3S,4R)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol was prepared from (±)-cis-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol via super critical fluid chiral chromatography was performed using a Chiralpak AD-H (10×250 mm) column using 40% MeoH (w/ 0.1% diethylamine modifier):60% CO2 eluent at 6.0 mL/min over 2 injections of 400 μL, T=35° C., P=120 bar, UV=220 nm. Product isolated as the initial peak as a yellow solid (0.0254 g, 38%). Purity: &gt;99% ee @100% purity. RT: 9.4 min.  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.32 (s, 1H), 8.79 (s, 1H), 8.32-8.29 (m, 2H), 7.90 (s, 1H), 7.77-7.73 (m, 2H), 7.67 (dd, J=5.3, 1.4 Hz, 1H), 7.30-7.25 (m, 2H), 6.92-6.87 (m, 1H), 4.63 (br s, 2H), 4.07 (s, 3H), 4.00-3.88 (m, 1H), 3.84-3.72 (m, 2H), 3.65-3.52 (m, 3H), 1.97-1.88 (m, 1H), 1.75-1.68 (m, 1H). MS=445 (MH)+. 
     Example 464. (3S,4R)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol or (3R,4S)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol 
     (3S,4R)- or (3R,4S)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol was prepared from (±)-cis-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol via super critical fluid chiral chromatography was performed using a Chiralpak AD-H (10×250 mm) column using 40% MeOH (w/ 0.1% diethylamine modifier):60% CO2 eluent at 6.0 mL/min over 2 injections of 400 μL, T=35° C., P=120 bar, UV=220 nm. Product isolated as the secondary peak as a yellow solid (0.0255 g, 38%). Purity: &gt;99% ee @100% Purity. RT: 8.6 min.  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.32 (s, 1H), 8.79 (s, 1H), 8.32-8.29 (m, 2H), 7.90 (s, 1H), 7.77-7.74 (m, 2H), 7.67 (dd, J=5.2, 1.3 Hz, 1H), 7.30-7.25 (m, 2H), 6.92-6.87 (m, 1H), 4.64 (br s, 2H), 4.07 (s, 3H), 3.99-3.73 (m, 3H), 3.65-3.54 (m, 3H), 1.97-1.87 (m, 1H), 1.76-1.66 (m, 1H). MS=445 (MH)+. 
     Example 465. {(R)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-pyrrolidin-3-yl}-methanol 
     465a) {(R)-1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-pyrrolidin-3-yl}-methanol was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (0.50 g, 1.7 mmol) and (R)-3-Hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.42 g, 2.1 mmol) [deprotected with 1:1 trifluoroacetic acid:methylene chloride before addition] in an analogous manner to [B016]. Product isolated as a yellow foam (0.186 g, 28%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.78 (s, 1H), 8.59 (dd, J=5.0, 0.6 Hz, 1H), 8.34 (s, 1H), 8.32-8.29 (m, 2H), 4.72 (br s, 1H), 4.07 (s, 3H), 3.90-3.37 (m, 6H), 2.37 (br s, 1H), 1.99 (br s, 1H), 1.68 (br s, 1H). MS=372, 374 (MH)+. 
     465b) {(R)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-pyrrolidin-3-yl}-methanol was prepared from {(R)-1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-pyrrolidin-3-yl}-methanol (186.0 mg, 0.5002 mmol) and Aniline (55.0 μL, 0.604 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as a yellow solid (0.091 g, 42%). MP=208-209° C.  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.31 (s, 1H), 8.75 (s, 1H), 8.30 (s, 1H), 8.29 (d, J=5.2 Hz, 1H), 7.90 (s, 1H), 7.78-7.74 (m, 2H), 7.68 (dd, J=5.3, 1.3 Hz, 1H), 7.30-7.25 (m, 2H), 6.91-6.86 (m, 1H), 4.73 (br s, 1H), 4.07 (s, 3H), 3.88-3.35 (m, 6H), 2.37 (br s, 1H), 2.00 (br s, 1H), 1.70 (br s, 1H). MS=429 (MH)+. 
     Example 466. {(S)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-pyrrolidin-3-yl}-methanol 
     466a) desired {(S)-1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-pyrrolidin-3-yl}-methanol was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (0.50 g, 1.7 mmol) and (S)-3-Hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.42 g, 2.1 mmol) [deprotected with 1:1 trifluoroacetic acid:methylene chloride before addition] in an analogous manner to [B016]. Product isolated as a yellow resin (0.185 g, 29%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.78 (s, 1H), 8.59 (d, J=5.0 Hz, 1H), 8.34 (s, 1H), 8.32-8.29 (m, 2H), 4.72 (br s, 1H), 4.07 (s, 3H), 3.90-3.35 (m, 6H), 2.42 (br s, 1H), 1.99 (br s, 1H), 1.70 (br s, 1H). MS=372, 374 (MH)+. 
     466b) {(S)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-pyrrolidin-3-yl}-methanol was prepared from {(S)-1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-pyrrolidin-3-yl}-methanol (185.0 mg, 0.4976 mmol) and Aniline (55.0 μL, 0.604 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as a yellow foam (0.093 g, 43%). MP=210-211° C.  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.31 (s, 1H), 8.75 (s, 1H), 8.30 (s, 1H), 8.29 (d, J=5.3 Hz, 1H), 7.90 (s, 1H), 7.78-7.74 (m, 2H), 7.68 (dd, J=5.3, 1.4 Hz, 1H), 7.30-7.25 (m, 2H), 6.92-6.86 (m, 1H), 4.73 (br s, 1H), 4.07 (s, 1H), 3.88-3.35 (m, 6H), 2.37 (br s, 1H), 2.00 (br s, 1H), 1.71 (br s, 1H). MS=429 (MH)+. 
     Example 467. (meso)-cis-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-azepane-4,5-diol 
     467a) To a round bottom flask equipped a stir bar and a reflux condenser containing But-3-enylamine (0.58 g, 8.1 mmol) and Tetrahydrofuran (50 mL) was added 4-Bromo-but-1-ene (1.0 g, 7.4 mmol) and the mixture was heated at 60° C. for 18 hours. The mixture was cooled to room temperature. Triethylamine (1.1 mL, 8.1 mmol) was added followed Di-tert-Butyldicarbonate (1.8 g, 8.1 mmol). The suspension was stirred at room temperature for 1 hour. The suspension was filtered through a plug of diatomaceous earth and the filtrate was evaporated to a yellow suspension. To the residue was added methanol (40 mL) followed by 1N aqueous Sodium hydroxide (5 mL). The mixture was stirred for 1 hour. The resulting suspension was filtered through a plug of diatomaceous earth. The filtrate was evaporated. The residue was purified via chromatography using an ISCO apparatus (silica gel column 24 g 0%-5% Ethyl Acetate:Hexane). Di-but-3-enyl-carbamic acid tert-butyl ester was isolated as clear oil (0.304 g, 18%).  1 HNMR (400 MHz, CDCl3, δ, ppm): 5.83-5.70 (m, 2H), 5.10-4.99 (m, 4H), 3.23 (br s, 4H), 2.31-2.24 (m, 4H), 1.46 (s, 9H). MS=248 (M+Na)+. 
     467b) To a solution of Di-but-3-enyl-carbamic acid tert-butyl ester (0.30 g, 1.3 mmol) in dry Toluene (30 mL) under an atmosphere of Nitrogen was added (1,3-Bis-(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(o-isopropoxyphenylmethylene)ruthenium (45.0 mg, 0.0717 mmol). The mixture was heated at 50° C. for 5 hours. The mixture was cooled to room temperature and stirred overnight. The volatiles were evaporated. The residue was triturated with hexane (30 mL) and the suspension was filtered through a plug of diatomaceous earth. The filtrate was evaporated. The residue was purified via chromatography using an ISCO apparatus (silica gel column 24 g with 0%→5% Ethyl Acetate:Hexane). 2,3,6,7-Tetrahydro-azepine-1-carboxylic acid tert-butyl ester was isolated as a clear oil (0.166 g, 63%).  1 HNMR (400 MHz, CDCl3, δ, ppm): 5.79-5.66 (m, 2H), 3.50-3.38 (m, 4H), 2.28 (br s, 4H), 1.47 (s, 9H). MS=220 (M+Na)+. 
     467c) (meso)-cis-4,5-Dihydroxy-azepane-1-carboxylic acid tert-butyl ester was prepared from 2,3,6,7-Tetrahydro-azepine-1-carboxylic acid tert-butyl ester (0.166 g, 0.841 mmol) in an analogous manner to Example 436a. Product isolated as an off-white solid (0.151 g, 77%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 4.48 (d, J=4.3 Hz, 2H), 3.67-3.60 (m, 2H), 3.45-3.32 (m, 2H), 3.19-3.05 (m, 2H), 1.84-1.73 (m, 2H), 1.64-1.52 (m, 2H), 1.38 (s, 9H). MS=254 (M+Na)+. 
     467d) (meso)-cis-1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-azepane-4,5-diol was prepared from 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (0.20 g, 0.69 mmol), and (meso)-cis-4,5-Dihydroxy-azepane-1-carboxylic acid tert-butyl ester (0.15 g, 0.65 mmol) [deprotected with 1:1 trifluoroacetic acid:methylene chloride before addition] in an analogous manner to [B016]. Product isolated as an orange resin (0.115 g, 44%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.77 (s, 1H), 8.59 (dd, J=4.8, 1.0 Hz, 1H), 8.32-8.28 (m, 3H), 4.45-4.42 (m, 2H), 4.04 (s, 3H), 3.88-3.60 (m, 6H), 2.10-2.00 (m, 2H), 1.86-1.77 (m, 2H). MS=402, 404 (MH)+. 
     467e) (meso)-cis-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-azepane-4,5-diol was prepared from (meso)-cis-1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-azepane-4,5-diol (115.0 mg, 0.2862 mmol) and Aniline (33.0 μL, 0.362 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as a yellow foam (0.033 g, 25%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.29 (s, 1H), 8.74 (s, 1H), 8.29 (d, J=5.2 Hz, 1H), 8.26 (s, 1H), 7.90 (s, 1H), 7.77-7.74 (m, 2H), 7.67 (dd, J=5.3, 1.3 Hz, 1H), 7.30-7.25 (m, 2H), 6.92-6.87 (m, 1H), 4.45 (d, J=4.2 Hz, 2H), 4.05 (s, 3H), 3.87-3.60 (m, 6H), 2.12-2.02 (m, 2H), 1.87-1.78 (m, 2H). MS=459 (MH)+. 
     Example 468. 1-{2-[2-(6-Fluoro-pyridin-2-ylamino)-pyridin-4-yl]-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-ol 
     1-{2-[2-(6-Fluoro-pyridin-2-ylamino)-pyridin-4-yl]-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-ol was prepared from 1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-ol (90.0 mg, 0.242 mmol) and 6-Fluoro-pyridin-2-ylamine (33.0 mg, 0.294 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as a yellow foam (0.048 g, 35%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.43 (br s, 1H), 8.83 (s, 1H), 8.71 (s, 1H), 8.43 (d, J=5.3 Hz, 1H), 8.36 (s, 1H), 7.92-7.85 (m, 2H), 7.69-7.65 (m, 1H), 6.65 (dd, J=7.9, 2.2 Hz, 1H), 4.11-4.01 (m, 5H), 3.87-3.80 (m, 1H), 3.51-3.42 (m, 2H), 1.97-1.89 (m, 2H), 1.64-1.54 (m, 2H). MS=448 (MH)+. 
     Example 469. 1-{5-Methoxy-2-[2-(6-methoxy-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-ol 
     1-{5-Methoxy-2-[2-(6-methoxy-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-ol was prepared from 1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-ol (90.0 mg, 0.242 mmol) and 6-Methoxy-pyridin-2-ylamine (36.0 mg, 0.290 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as a yellow foam (0.031 g, 27%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.45 (br s, 1H), 8.86 (s, 1H), 8.78 (s, 1H), 8.43 (d, J=5.6 Hz, 1H), 8.36 (s, 1H), 7.90 (d, J=6.0 Hz, 1H), 7.69 (t, J=7.9 Hz, 1H), 7.05 (d, J=8.0 Hz, 1H), 6.44 (d, J=8.0 Hz, 1H), 4.10-3.98 (m, 8H), 3.87-3.80 (m, 1H), 3.48-3.39 (m, 2H), 1.97-1.89 (m, 2H), 1.63-1.53 (m, 2H). MS=460 (MH)+. 
     Example 470. ((S)-1-{2-[2-(6-Fluoro-pyridin-2-ylamino)-pyridin-4-yl]-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl}-pyrrolidin-3-yl)-methanol 
     ((S)-1-{2-[2-(6-Fluoro-pyridin-2-ylamino)-pyridin-4-yl]-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl}-pyrrolidin-3-yl)-methanol was prepared from {(S)-1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-pyrrolidin-3-yl}-methanol (90.0 mg, 0.242 mmol) and 6-Fluoro-pyridin-2-ylamine (40.0 mg, 0.357 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.026 g, 19%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.43 (br s, 1H), 8.79 (s, 1H), 8.68 (s, 1H), 8.43 (d, J=5.5 Hz, 1H), 8.37 (s, 1H), 7.92-7.85 (m, 2H), 7.68 (d, J=7.9 Hz, 1H), 6.65 (d, J=8.0 Hz, 1H), 4.09 (s, 3H), 3.92-3.40 (m, 6H), 2.45-2.30 (m, 1H), 2.08-1.98 (m, 1H), 1.80-1.65 (m, 1H). MS=448 (MH)+. 
     Example 471. ((S)-1-{5-Methoxy-2-[2-(6-methoxy-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-pyrrolidin-3-yl)-methanol 
     ((S)-1-{5-Methoxy-2-[2-(6-methoxy-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-pyrrolidin-3-yl)-methanol was prepared from {(S)-1-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-pyrrolidin-3-yl}-methanol (90.0 mg, 0.242 mmol) and 6-Methoxy-pyridin-2-ylamine (45.0 mg, 0.362 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the trifluoroacetic acid salt as a yellow lyophilate (0.044 g, 31%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 10.44 (br s, 1H), 8.86 (s, 1H), 8.73 (s, 1H), 8.43 (d, J=5.6 Hz, 1H), 8.36 (s, 1H), 7.91 (d, J=5.0 Hz, 1H), 7.68 (t, J=8.2 Hz, 1H), 7.03 (d, J=8.0 Hz, 1H), 6.44 (d, J=7.8 Hz, 1H), 4.08 (s, 3H), 4.04 (s, 3H), 3.90-3.35 (m, 6H), 2.45-2.30 (m, 1H), 2.05-1.95 (m, 1H), 1.77-1.64 (m, 1H). MS=460 (MH)+. 
     Example 473. 2-(4-Cyano-phenyl)-N-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide 
     2-(4-Cyano-phenyl)-N-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2141 mmol) and 2-(4-Cyano-phenyl)-acetamide (50.0 mg, 0.312 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as a tan solid (0.094 g, 89%). MP=200-203° C.  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.05 (s, 1H), 8.97 (s, 1H), 8.49 (dd, J=5.1, 0.6 Hz, 1H), 8.09 (s, 1H), 8.04 (dd, J=5.2, 1.4 Hz, 1H), 7.84-7.81 (m, 2H), 7.60-7.57 (m, 2H), 3.91 (s, 2H), 3.85-3.45 (m, 4H), 2.83 (m, 4H), 2.63-2.55 (m, 1H), 1.28-1.22 (m, 2H), 1.04-0.99 (m, 2H). LC/MS=491 (MH)+. 
     Example 474. [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-methyl-4-morpholin-4-yl-phenyl)-amine 
     [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyridin-2-yl)-pyridin-2-yl]-(2-methyl-4-morpholin-4-yl-phenyl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2141 mmol) and 2-Methyl-4-morpholin-4-yl-phenylamine (61.0 mg, 0.317 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as an orange-brown solid (0.085 g, 75%). MP=214-220° C.  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.93 (s, 1H), 8.23 (s, 1H), 8.14 (d, J=5.3 Hz, 1H), 8.07 (s, 1H), 7.58 (s, 1H), 7.52 (dd, J=5.2, 1.3 Hz, 1H), 7.28 (d, J=8.6 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H), 6.79 (dd, J=8.6, 2.8 Hz, 1H), 3.80-3.50 (m, 8H), 3.10-3.06 (m, 4H), 2.81 (br s, 4H), 2.64-2.56 (m, 1H), 2.19 (s, 3H), 1.27-1.21 (m, 2H), 1.04-0.99 (m, 2H). LC/MS=523 (MH)+. 
     Example 475. [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-morpholin-4-yl-pyridin-3-yl)-amine 
     [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-morpholin-4-yl-pyridin-3-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (107.0 mg, 0.2291 mmol) and 6-Morpholin-4-yl-pyridin-3-ylamine (57.0 mg, 0.318 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as a yellow solid (0.103 g, 87%). MP=217-219° C.  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.08 (s, 1H), 8.96 (s, 1H), 8.45 (d, J=2.6 Hz, 1H), 8.24 (d, J=5.4 Hz, 1H), 8.09 (s, 1H), 7.99 (dd, J=9.1, 2.7 Hz, 1H), 7.81 (s, 1H), 7.62 (dd, J=5.3, 1.3 Hz, 1H), 6.85 (d, J=9.1 Hz, 1H), 3.90-3.50 (m, 8H), 3.37-3.34 (m, 4H), 2.86 (br s, 4H), 2.66-2.58 (m, 1H), 1.29-1.23 (m, 2H), 1.05-1.00 (m, 2H). LC/MS=510 (MH)+. 
     Example 476. [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyridin-3-yl-amine 
     [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyridin-3-yl-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2141 mmol) and 3-aminopyridine (30.0 mg, 0.319 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as a pale yellow solid (0.067 g, 74%). MP=226-228° C.  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 9.55 (s, 1H), 8.98 (s, 1H), 8.87 (d, J=2.5 Hz, 1H), 8.35 (d, J=5.4 Hz, 1H), 8.32-8.28 (m, 1H), 8.12-8.09 (m, 2H), 7.95 (s, 1H), 7.75 (dd, J=5.3, 1.2 Hz, 1H), 7.30 (dd, J=8.4, 4.7 Hz, 1H), 3.96-3.46 (m, 4H), 2.87 (br s, 4H), 2.66-2.58 (m, 1H), 1.30-1.23 (m, 2H), 1.06-1.01 (m, 2H). LC/MS=425.0 (MH)+. 
     Example 477. (2-Chloro-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     (2-Chloro-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2141 mmol) and o-Chloroaniline (52.0 uL, 0.315 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as an orange foam (0.086 g, 88%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.97 (s, 1H), 8.68 (s, 1H), 8.26 (d, J=5.3 Hz, 1H), 8.09 (s, 1H), 8.04-8.00 (m, 2H), 7.72 (dd, J=5.3, 1.4 Hz, 1H), 7.48 (dd, J=8.0, 1.5 Hz, 1H), 7.34-7.29 (m, 1H), 7.09-7.04 (m, 1H), 3.96-3.46 (m, 4H), 2.86 (br s, 4H), 2.65-2.57 (m, 1H), 1.29-1.23 (m, 2H), 1.05-1.00 (m, 2H). LC/MS=458.0 (MH)+. 
     Example 478. [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-methyl-pyridin-3-yl)-amine 
     [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-methyl-pyridin-3-yl)-amine was prepared from 4-[2-(2-Chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100.0 mg, 0.2141 mmol) and 4-Methyl-pyridin-3-ylamine (34.0 mg, 0.314 mmol) in an analogous manner to Example 303c and Example 1501c. Product isolated as the free base as a pale yellow foam (0.070 g, 74%).  1 HNMR (400 MHz, d6-DMSO, δ, ppm): 8.98 (s, 1H), 8.81 (s, 1H), 8.64 (s, 1H), 8.22 (d, J=5.4 Hz, 1H), 8.16 (d, J=4.9 Hz, 1H), 8.11 (s, 1H), 7.87 (s, 1H), 7.67 (dd, J=5.2, 1.3 Hz, 1H), 7.25 (d, J=4.9 Hz, 1H), 3.95-3.45 (m, 4H), 2.93 (br s, 4H), 2.65-2.59 (m, 1H), 2.28 (s, 3H), 1.29-1.23 (m, 2H), 1.06-1.01 (m, 2H). LC/MS=439.2 (MH)+. 
     Example 481. [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-phenyl-amine 
     481a) 3-Bromo-5-fluoro-isonicotinic acid tert-butyl ester (1.9 g, 6.9 mmol), cyclopropyltrifluoroborate (1.18 g, 7.97 mmol), palladium acetate (81.3 mg, 0.36 mmol), butyl-ditricyclo[3.3.1.1(3,7)]decan-1-yl-phosphane (194.8 mg, 0.54 mmol), and cesium carbonate (7 g, 21.7 mmol) was heated at 85° C. in toluene (35 mL)/water (4 mL) overnight, under nitrogen. Cooled, partitioned between ether and water. Organic extracts dried (MgSO 4 ), filtered, solvent evaporated; product isolated by flash chromatography (ISCO, Silica gel, EtOAc/Hexanes 0-10%; 2nd fraction is product): 3-cyclopropyl-5-fluoro-isonicotinic acid tert-butyl ester (50% yield). 
     481b) 3-Cyclopropyl-5-fluoro-isonicotinic acid tert-butyl ester (700.0 mg, 2.95 mmol) was treated with trifluoroacetic acid (2.0 mL, 26.0 mmol) in methylene chloride (5 mL) at 25° C. overnight. Solvent was evaporated, and the crude residue was dried on high vacuum, and then used without further purification: 3-cyclopropyl-5-fluoro-isonicotinic acid; compound with trifluoro-acetic acid (quant.). 
     481c) 3-Cyclopropyl-5-fluoro-isonicotinic acid; compound with trifluoro-acetic acid (995 mg, 3.37 mmol) and 2-chloro-isonicotinamidine; hydrochloride (1.3 g, 6.7 mmol) were treated with N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (1.35 g, 3.54 mmol) and N,N-diisopropylethylamine (3.5 mL, 20.2 mmol) in N,N-dimethylformamide (14 mL) at room temperature overnight. The reaction mixture was partitioned between DCM and water, organic layer washed extensively with water, dried (MgSO 4 ), solvent evaporated when a precipitate formed. Trituration from ether followed by filtration afforded N-[(2-chloro-pyridin-4-yl)-imino-methyl]-3-cyclopropyl-5-fluoro-isonicotinamide, which was used in the next step without further purification. 
     481d) N-[(2-Chloro-pyridin-4-yl)-imino-methyl]-3-cyclopropyl-5-fluoro-isonicotinamide (solid product from step c) and cesium carbonate (1.4 g, 4.2 mmol) were mixed in N,N-dimethylacetamide (17 mL). The reaction was microwaved on 300 watts, 120° C. for 20 minutes. Reaction mixture was diluted with ice/water and neutralized with AcOH to pH 5 at 0 OC, and the precipitate was collected by filtration, washed with water and dried: 2-(2-chloro-pyridin-4-yl)-5-cyclopropyl-3H-pyrido[3,4-d]pyrimidin-4-one (33% yield over 2 steps). 
     481e) A suspension of 2-(2-chloro-pyridin-4-yl)-5-cyclopropyl-3H-pyrido[3,4-d]pyrimidin-4-one (0.85 g, 2.8 mmol), triethylamine (1.3 mL, 9.3 mmol) and 4-dimethylaminopyridine (43.0 mg, 0.352 mmol) in N,N-dimethylformamide (10 mL, 100 mmol) was treated with 2,4,6-triisopropylbenzenesulfonyl chloride (0.98 g, 3.2 mmol) and the mixture was stirred at room temperature for 1 hour. tert-Butyl-1-piperazinecarboxylate (0.65 g, 3.5 mmol) was added and the mixture was stirred at room temperature overnight. Water (40 mL) was added and the mixture was stirred vigorously for 1 hour. The suspension was filtered, rinsed with water and dried. The solid was dissolved in DCM, the solution was dried (MgSO 4 ), filtered and the solvent was evaporated under vacuum. The product was isolated by flash chromatography (Isco, Silica Gel, 20%→100% Ethyl Acetate/Hexane): 4-[2-(2-chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester, tan solid (1.03 g). 
     481f) A reaction tube was charged with 4-[2-(2-chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (200 mg, 0.428 mmol), aniline (43.9 μL, 0.482 mmol), palladium acetate (16 mg, 0.07 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (38.8 mg, 0.067 mmol), and cesium carbonate (366 mg, 1.125 mmol) in 1,4-dioxane (2 mL). The tube was evacuated and back-filled with nitrogen three times, and then flushed with argon, capped, and heated at 100° C. for 3 h. The reaction mixture was cooled to room temperature and partitioned between ether and water. The organic extracts were dried (MgSO 4 ), then the solvent was evaporated under reduced pressure. The product was used in the next step without further purification. The crude product obtained in step 1 was treated with trifluoroacetic acid (1.48 mL, 19.2 mmol) in methylene chloride (5.92 mL) at room temperature until reaction was complete (by hplc); approx. 1 h. The volatiles were evaporated under reduced pressure and the product was isolated by reverse phase chromatography (Gilson) followed by neutralization by cation-exchange column (Strata, from Phenomenex) filtration and releasing with methanolic ammonia: [4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-phenyl-amine (133 mg, 73% yield over 2 steps); bright yellow solid; MP: 221-226 C;  1 H-NMR (CDCl 3 ) δ: 9.11 (s, 1H), 8.36 (d, J=5.2 Hz, 1H), 8.04 (s, 1H), 8.00 (s, 1H), 7.80 (dd, J=5.2; 1.3 Hz, 1H), 7.45 (d, J=8.3 Hz, 2H), 7.37 (dd, J=8.4; 8.4 Hz, 2H), 7.07 (t, J=8.4 Hz, 1H), 6.68 (br s, 1H), 3.75 (br s, 4H), 3.01 (m, 4H), 269 (m, 1H), 1.59 (water and exchangeable NH), 1.26 (m, 2H), 1.00 (m, 2H); LC/MS (ESI+): 424.17 (M+H). 
     Example 482. 2-{4-[5-Cyclopropyl-4-(4-hydroxy-piperidin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile 
     This product was prepared from 2-(2-chloro-pyridin-4-yl)-5-cyclopropyl-3H-pyrido[3,4-d]pyrimidin-4-one according to a procedure similar to Example 481e,f: white solid;  1 H NMR (dmso-d) δ: 10.40 (s, 1H), 8.98 (s, 1H), 8.64 (br s, 1H), 8.49 (dd, J=6.0; 0.4 Hz, 1H), 8.45 (d, J=5.2 Hz, 1H), 8.37 (br s, 1H), 8.10 (s, 1H), 7.88 (dd, J=5.2; 1.4 Hz, 1H), 7.30 (dd, J=6.0; 1.4 Hz, 1H), 7.81 (br s, 1H), 4.11 (m, 2H), 3.80 (br s, 1H), 3.50 (br s, 2H), 2.60 (br s, 1H), 1.90 (m, 2H), 1.52 (br s, 1H), 1.26 (m, 2H), 1.04 (m, 2H); LC/MS (ESI+): 465.2 (M+H). 
     Example 483. [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-fluoro-pyridin-2-yl)-amine 
     This product was prepared from 2-(2-chloro-pyridin-4-yl)-5-cyclopropyl-3H-pyrido[3,4-d]pyrimidin-4-one according to a procedure similar to Example 481e,f: yellow lyophilate;  1 H NMR (dmso-d 6 ) δ: 10.40 (s, 1H), 9.08 (s, 1H), 9.03 (br s, 2H), 8.81 (s, 1H), 8.45 (d, J=5.3 Hz, 1H), 8.20 (s, 1H), 7.92 (m, 1H), 7.86 (m, 1H), 7.69 (m, 1H), 6.65 (m, 1H), 3.97 (br s, 4H), 3.34 (br s, 4H), 2.69 (m, 1H), 1.27 (m, 2H), 1.09 (m, 2H); LC/MS (ESI+): 443.2 (M+H). 
     Example 484. [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-phenyl)-amine 
     This product was prepared from 4-[2-(2-chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester according to a procedure similar to Example 481f: off-white foam;  1 H-NMR (CDCl 3 ) δ: 9.12 (s, 1H), 8.39 (d, J=5.3 Hz, 1H), 8.23 (m, 1H), 8.05 (s, 1H), 7.93 (s, 1H), 7.85 (m, 1H), 7.14 (m, 2H), 6.97 (m, 2H), 6.86 (br s, 1H), 3.76 (br s, 4H), 3.03 (m, 4H), 2.69 (m, 1H), 1.93 (br s, water and exch. protons), 1.27 (m, 2H), 1.01 (m, 2H); LC/MS (ESI+): 442.1 (M+H). 
     Example 485. (±)-2-{4-[5-Cyclopropyl-4-cis-3,4-dihydroxy-piperidin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile 
     This product was prepared from 2-(2-chloro-pyridin-4-yl)-5-cyclopropyl-3H-pyrido[3,4-d]pyrimidin-4-one according to a procedure similar to Example 481e,f: tan solid;  1 H-NMR (CDCl 3 ) δ: 9.18 (s, 1H), 8.52 (s, 1H), 8.44 (d, J=5.2 Hz, 1H), 8.39 (m, 2H), 8.15 (m, 2H), 7.93 (m, 1H), 7.04 (m, 1H), 3.95 (m, 7H), 2.78 (br s, 1H), 2.60 (m, 1H), 1.87 (m, 2H), 1.63 (br s, water), 1.27 (m, 2H), 1.01 (m, 2H); LC/MS (ESI+): 481.0 (M+H). 
     Example 486. [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-o-tolyl-amine 
     This product was prepared from 4-[2-(2-chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester according to a procedure similar to Example 481f: yellow foam;  1 H-NMR (CDCl 3 ) δ: 9.08 (s, 1H), 8.33 (d, J=5.2 Hz, 1H), 8.02 (s, 1H), 7.81 (s, 1H), 7.76 (m, 1H), 7.60 (m, 1H), 7.24 (m, 2H), 7.08 (m, 1H), 6.54 (br s, 1H), 3.72 (br s, 4H), 2.97 (m, 4H), 2.67 (m, 1H), 3.04 (s, 3H), 1.95 (br s, NH), 1.25 (m, 2H), 0.99 (m, 2H); LC/MS (ESI+): 438.1 (M+H). 
     Example 487. 2-{4-[5-Cyclopropyl-4-((3R,4S)-3,4-dihydroxy-piperidin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile 
     This product was obtained by separation of enantiomers (SCF chiral chromatography) of racemic Example 485. 
     Example 488. 2-{4-[5-Cyclopropyl-4-((3S,4R)-3,4-dihydroxy-piperidin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile 
     This product was obtained by separation of enantiomers (SCF chiral chromatography) of racemic Example 485. It is the optical antipode of Example 487. 
     Example 489. 4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-N-(1-phenylpyrazol-4-yl)pyridin-2-amine 
     A tube was charged with 4-[2-(2-chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (131.4 mg, 0.2877 mmol), 1-phenyl-1H-pyrazol-4-ylamine (55.0 mg, 0.346 mmol), Palladium Acetate (7.9 mg, 0.035 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (21.0 mg, 0.0364 mmol), cesium carbonate (144.6 mg, 0.4438 mmol) and 1,4-dioxane (1 mL). The tube was evacuated and back flushed with nitrogen. The tube was sealed and the reaction mixture was heated at 90° C. for 18 hours. The mixture was cooled to room temperature and diluted with water (10 mL). The suspension was stirred for 15 minutes, filtered, rinsed with water and dried by suction to yield a dark solid. 
     The dark solid was suspended in methylene chloride (3 mL) and stirred at room temperature. Trifluoroacetic Acid (1 mL, 20 mmol) was added dropwise and the mixture was stirred at room temperature for 1 hour. The volatiles were evaporated. The residue was purified via reverse phase chromatography using a Gilson apparatus with 5%→30% acetonitrile: water (w/ 0.1% TFA as modifier) solvent gradient. The desired fractions were combined, frozen and lyophilized. The recovered lyophilate was consistent for desired 4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-N-(1-phenylpyrazol-4-yl)pyridin-2-amine (14 mg, 10%).  1 H NMR (DMSO-d 6 ): δ-8.91 (bs, 1H), 8.71 (bs, 3H), 8.41 (s, 1H), 8.34 (d, 1H, J=5.43 Hz), 7.88 (s, 1H), 7.84 (s, 1H), 7.83 (dd, 2H, JJ=1.09, 8.69 Hz), 7.66 (dd, 1H, JJ=1.30, 5.65), 7.47-7.53 (m, 2H), 7.25-7.31 (m, 1H), 4.10 (s, 3H), 3.88 (bs, 4H), 3.33 (bs, 4H). LCMS (ESI+) 480.3 (M+H). 
     Example 490. (2,3-Dimethyl-2H-indazol-6-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3, 4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     A tube was charged with 4-[2-(2-chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (131.4 mg, 0.2877 mmol), 2,3-dimethyl-2H-indazol-6-ylamine (55.7 mg, 0.346 mmol), palladium acetate (7.9 mg, 0.035 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (21.0 mg, 0.0364 mmol), cesium carbonate (144.6 mg, 0.4438 mmol) and 1,4-dioxane (1 mL). The tube was evacuated and back flushed with nitrogen. The tube was sealed and the reaction mixture was heated at 90° C. for 18 hours. The mixture was cooled to room temperature and diluted with water (10 mL). The suspension was stirred for 15 minutes, filtered, rinsed with water and dried by suction to yield a dark solid. 
     The dark solid was suspended in methylene chloride (3 mL, 40 mmol) and stirred at room temperature. Trifluoroacetic Acid (1 mL, 20 mmol) was added dropwise and the mixture was stirred at room temperature for 1 hour. The volatiles were evaporated. The residue was purified via reverse phase chromatography using a Gilson apparatus with 5%-30% acetonitrile: water (w/0.1% TFA as modifier) solvent gradient. The desired fractions were combined, frozen and lyophilized. The recovered lyophilate was consistent for desired (2,3-dimethyl-2H-indazol-6-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3, 4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine (38 mg, 27%).  1 H NMR (DMSO-d 6 ): δ-9.50 9 bs, 1H), 8.91 (bs, 3H), 8.42 (s, 1H), 8.36 (d, 1H, J=5.19 Hz), 8.24 (bs, 1H), 8.01 (bs, 1H), 7.72 (dd, 1H, J=1.20, 5.28 Hz), 7.58 (d, 1H, J=9.07 Hz), 7.06 (dd, 1H, JJ=1.65, 8.87 Hz), 4.10 (s, 3H), 3.99 (s, 3H0, 3.89 (bs, 4H), 3.33 (bs, 3H), 2.57 (s, 3H). LCMS (ESI+) 482.1 (M+H). 
     Example 491. [1-(2-Fluoro-phenyl)-1H-pyrazol-4-yl]-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3, 4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     A tube was charged with 4-[2-(2-chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (131.4 mg, 0.2877 mmol), 1-(2-fluoro-phenyl)-1H-pyrazol-4-ylamine (61.2 mg, 0.346 mmol), palladium acetate (7.9 mg, 0.035 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (21.0 mg, 0.0364 mmol), cesium carbonate (144.6 mg, 0.4438 mmol) and 1,4-dioxane (1 mL). The tube was evacuated and backflushed with nitrogen. The tube was sealed and the reaction mixture was heated at 90° C. for 18 hours. The mixture was cooled to room temperature and diluted with water (10 mL). The suspension was stirred for 15 minutes, filtered, rinsed with water and dried by suction to yield a dark solid. 
     The dark solid was suspended in methylene chloride (3 mL) and stirred at room temperature. Trifluoroacetic Acid (1 mL, 20 mmol) was added dropwise and the mixture was stirred at room temperature for 1 hour. The volatiles were evaporated. The residue was purified via reverse phase chromatography using a Gilson apparatus with 5%-*30% acetonitrile: water (w/ 0.1% TFA as modifier) solvent gradient. The desired fractions were combined, frozen and lyophilized. The recovered lyophilate was consistent for desired [1-(2-fluoro-phenyl)-1H-pyrazol-4-yl]-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3, 4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine (12 mg, 8.4%)  1 H NMR (DMSO-d 6 ): δ-9.51 (bs, 1H), 8.90 (bs, 3H), 8.59 (d, 1H, J=3.17 Hz), 8.41 (s, 1H), 8.33 (d, 1H, J=5.50 Hz), 7.83-7.88 (m, 3H), 7.69 (dd, 1H, J=1.33, 5.50 Hz), 7.33-7.51 (m, 3H), 4.10 (s, 3H), 3.88 (bs, 4H), 3.33 (bs, 4H). LCMS (ESI+) 490.1 (M+H). HPLC&gt;95% pure (retaintion time=1.7 min. in G method). 
     Example 492. [4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(1-phenyl-1H-pyrazol-4-yl)-amine 
     A tube was charged with 4-[2-(2-Chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (403.0 mg, 0.8631 mmol), 1-Phenyl-1H-pyrazol-4-ylamine (165.0 mg, 1.036 mmol), Palladium Acetate (24 mg, 0.10 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (63.1 mg, 0.109 mmol), Cesium Carbonate (433.8 mg, 1.331 mmol) and 1,4-Dioxane (4 mL). The tube was evacuated and backflushed with nitrogen. The tube was sealed and the reaction mixture was heated at 90° C. for 18 hours. The mixture was cooled to room temperature and diluted with water (10 mL). The suspension was stirred for 15 minutes, filtered, rinsed with water and dried by suction to yield a dark solid. 
     The dark solid was suspended in methylene chloride (8 mL) and stirred at room temperature. Trifluoroacetic Acid (4 mL, 50 mmol) was added dropwise and the mixture was stirred at room temperature for 1 hour. The volatiles were evaporated. The residue was purified via reverse phase chromatography using a Gilson apparatus with 5%-*30% acetonitrile: water (w/ 0.1% TFA as modifier) solvent gradient. The desired fractions were combined, frozen and lyophilized. The recovered lyophilate was consistent for desired [4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(1-phenyl-1H-pyrazol-4-yl)-amine (10 mg, 4%). 
       1 H NMR (DMSO-d 6 ): δ-9.40 (s, 1H), 8.97 (s, 1H), 8.7 (s, 1H), 8.35 (d, 1H, J=5.65 Hz), 8.09 (s, 1H), 7.78-7.85 (m, 4H), 7.63 (dd, 1H, J=1.42, 5.34 Hz), 7.49 (t, 2H, J=8.37 Hz), 7.27 (t, 1H, J=7.48 Hz), 3.52-3.88 (bm, 4H), 2.58-2.85 (bm, 5H), 1.20-1.32 (m, 2H), 1.00-1.06 (m, 2H). LCMS (ESI+) 490.19 (M+H). HPLC&gt;95% pure (retaintion time=1.8 min. in G method). 
     Example 493. [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,3-dimethyl-2H-indazol-6-yl)-amine 
     A tube was charged with 4-[2-(2-Chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (241.2 mg, 0.5166 mmol), 2,3-Dimethyl-2H-indazol-6-ylamine (100.0 mg, 0.6203 mmol), Palladium Acetate (14 mg, 0.063 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (37.8 mg, 0.0653 mmol), Cesium Carbonate (259.6 mg, 0.7968 mmol) and 1,4-Dioxane (2 mL). The tube was evacuated and backflushed with nitrogen. The tube was sealed and the reaction mixture was heated at 90° C. for 18 hours. The mixture was cooled to room temperature and diluted with water (10 mL). The suspension was stirred for 15 minutes, filtered, rinsed with water and dried by suction to yield a brown solid. The dark solid was suspended in Methylene chloride (5 mL, 70 mmol) and stirred at room temperature. Trifluoroacetic Acid (2 mL, 30 mmol) was added dropwise and the mixture was stirred at room temperature for 1 hour. The volatiles were evaporated. The residue was purified via reverse phase chromatography using a Gilson apparatus with 5%→30% Acetonitrile: Water (w/0.1% TFA as modifier) solvent gradient. The desired fractions were combined, frozen and lyophilized. The recovered lyophilate was consistent with [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,3-dimethyl-2H-indazol-6-yl)-amine (60 mg, 24%).  1 H NMR (DMSO-d 6 ): δ-9.32 (s, 1H), 8.96 (s, 1H), 8.35 (d, 1H, J=5.25 Hz), 8.28 (bs, 1H), 8.08 (s, 1H), 7.95 (bs, 1H), 7.68 (dd, 1H, J=1.36, 5.45 Hz), 7.52 (d, 1H, J=8.95 Hz), 7.04 (dd, 1H, J=1.56, 8.95 Hz), 3.97 (s, 3H), 2.53-2.70 (m, 5H), 2.45 (bs, 4H), 2.45 (s, 3H), 1.21-1.29 (m, 2H), 1.00-1.06 (m, 2H). LCMS (ESI+) 492.20 (M+H). HPLC&gt;95% pure (retaintion time=1.7 min. in G method). 
     Example 494. Phenyl-[4-(4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine 
     Following a procedure similar to 303c, 4-[2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (180 mg, 0.42 mmol), and Aniline (51.1 uL, 0.561 mmol) were converted to the title compound 35.28 mgs, 22% yield. LC/MS=384.2 (M+H)+ 
     Example 495. [4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-pyridin-3-yl)-amine 
     A tube was charged with 4-[2-(2-chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (100 mg, 0.214 mmol), 2-fluoro-pyridin-3-ylamine (46.2 mg, 0.412 mmol), palladium acetate (12.0 mg, 0.053 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (34.0 mg, 0.058 mmol), cesium carbonate (120 mg, 0.368 mmol) and 1,4-dioxane (0.7 mL, 8 mmol). The tube was evacuated and backflushed with nitrogen. The tube was sealed and the reaction mixture was heated at 100° C. for 3 h. The mixture was cooled to room temperature and diluted with dichloromethane (10 mL) and filtered through celite. The filtrate was evaporated to a dark resin. 
     The brown resin was dissolved in methylene chloride (0.7 mL, 10 mmol) and trifluoroacetic acid (0.7 mL, 9 mmol) was added. The mixture was stirred for 1 hour at room temperature and concentrated. The residue was purified via reverse phase chromatography using a Gilson apparatus. The desired fractions were loaded onto a SCX cartridge and rinsed with methanol and the product was released with 2M ammonia in methanol. The ammonia filtrate was evaporated and placed under high vacuum for 2 hours. The recovered yellow solid (35 mg, 37%) was consistent for the title compound. 1H NMR (300 MHz, DMSO-d6): 9.26 (s, 1H), 8.98 (s, 1H), 8.88 (t, J=9 Hz, 1H), 8.34 (d, J=5 Hz, 1H), 8.18 (s, 1H), 8.10 (s, 1H), 7.79 (d, J=5 Hz, 1H), 7.75 (d, J=4 Hz, 1H), 7.31 (m, 1H), 3.72 (m, 4H), 2.88 (br s, 4H), 2.62 (m, 1H), 1.26 (d, J=8 Hz, 2H), 1.04 (d, J=5 Hz, 2H), MS: 433 (M+H). 
     Example 496. [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-methyl-isoxazol-3-yl)-amine 
     4-[2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (75 mg, 0.16 mmol), 5-methyl-isoxazol-3-ylamine (32.2 mg, 0.3283 mmol), bis(dibenzylideneacetone)palladium(0) (5 mg, 0.0085 mmol), XANTPHOS (10 mg, 0.171 mmol), and lithium hexamethylsilazide (55 mg, 0.328 mmol) were combined in tetrahydrofuran (3 mL), degassed with Argon and subjected to reaction in a microwave at 120 C for six hours. Additional palladium, isoxazole, and silazide were added and the microwave temperature was raised to 150 C for an additional six hours. The reaction was concentrated and purification was effected via reverse phase chromatography to afford the title compound (2 mg, 3%). MS: 419.23 (M+H). 
     Example 497. 2-[2-(3-Piperazin-1-yl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-ol 
     Following a procedure similar to Example 303c, 2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol (67 mg, 0.26 mmol) and 4-(3-Amino-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (1.1 eq) were converted to the title compound isolated as the bis-TFA salt (21 mg, 13%). LC/MS: M+H+=400. 
     Example 498. 2-[2-(3-Piperazin-1-ylmethyl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-ol 
     Following a procedure similar to Example 303c, 2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol (143 mg, 0.56 mmol) and 4-(3-Amino-benzyl)-piperazine-1-carboxylic acid tert-butyl ester (1.1 eq) were converted to the title compound isolated as the bis TFA salt (51.4 mg, 14%). LC/MS: M+H+=414. 
     Example 499. 2-[2-(1-Piperidin-4-ylmethyl-1H-pyrazol-4-ylamino)-pyridin-4-yl]-pyrido[3, 4-d]pyrimidin-4-ol 
     Following a procedure similar to Example 303c, 2-(2-Chloro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol (145 mg, 0.56 mmol) and 4-(4-Amino-pyrazol-1-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester (1.1 eq) were converted to the title compound isolated as the bis TFA salt (20.56 mg, 6%). LC/MS: M+H+=403. 
     Example 500. {5-Methoxy-2-[2-(3-piperazin-1-yl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-amine 
     Following a procedure similar to Example 303b, 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (362 mgs, 1.25 mmol) and methylamine.HCl (1.1 eq) were converted to [2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-methyl-amine (64% yield) which was converted using a procedure analogous to Example 497 to the title compound isolated as a bis TFA salt (14 mgs, 5% yield), LC/MS: M+H+=443.25 
     Example 501. (5-Methoxy-2-{2-[4-(2-pyrrolidin-1-yl-ethoxy)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-methyl-amine 
     Following a procedure analogous to Example 500, 4-(2-Pyrrolidin-1-yl-ethoxy)-phenylamine (44 mg, 0.21 mmol) was converted to the title compound isolated as the bis-TFA salt (6.35 mgs, 5% yield) LC/MS: M+H+=472. 
     Example 502. {5-Methoxy-2-[2-(3-piperidin-4-yl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-amine 
     Following a procedure analogous to Example 500, 4-(3-Amino-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (0.1468 g, 0.5312 mmol) was converted to the title compound isolated as a bis-TFA salt (23.61 mgs, 7% yield). LC/MS: M+H+=442. 
     Example 503. [4-(5-Methoxy-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-piperazin-1-yl-phenyl)-amine 
     503a) 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol (208 mg, 0.720 mmol), 2,4,6-Triisopropylbenzenesulfonyl Chloride (221.1 mg, 0.7301 mmol), Triethylamine (0.31 mL, 2.2 mmol), and 4-Dimethylaminopyridine (8.8 mg, 0.072 mmol) in N,N-Dimethylformamide (2 mL, 30 mmol) were stirred at room temperature for 1 h, Hydrazine hydrate (0.05410 g, 1.081 mmol) was added and the reaction was stirred overnight. The product precipitated and was triturated from ether. Taking on without further purification. 
     503b) [2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl]-hydrazine (0.218 g, 0.720 mmol) was treated with 1,4-Dioxane (5.0 mL, 65 mmol) and Water (0.6 mL, 30 mmol) and then Silver(I) Oxide (334 mg, 1.44 mmol) and stirred at room temperature. After 1.5 h, LC/MS indicated major product (M+H)+=273. Filtered off silver salts and concentrated and put on high vac. Purified by ISCO chomatography 12 g SiO2, gradient elution 0% to 100% EA/hexane over 13 minutes to give 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidine 
     503c) Using a procedure analogous to Example 497 to the title compound 2-(2-Chloro-pyridin-4-yl)-5-methoxy-pyrido[3,4-d]pyrimidine (31 mgs, 0.11 mmol) was converted to the title compound (6.37 mgs, 13% yield). LC/MS: M+H+=414. 
     The following compounds were synthesised according to the general synthesis shown in scheme [B4] 
     
       
         
           
               
               
               
               
               
            
               
                   
               
               
                   
                   
                   
                 Analysis 
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Ex 
                 Amine 1 
                 Amine 2 
                 LCMS 
                 NMR 
                 Name 
               
               
                   
               
               
                 504 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.87 min, MI: 456 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.04 (1H, s), 8.30 (1H, d), 8.17 (1H, s), 8.05 (1H, s), 7.94 (1H, d), 7.73 (1H, d), 7.13 (1H, d), 6.87 (1H, m), 3.90 (4H, very broad s), 3.31 (4H, 1H NMR (DMSO, 500 MHz) 9.04 (1H, s), 8.30 (1H, d), 8.17 (1H, s), 8.05 (1H, s), 7.94 (1H, d), 7.73 (1H, d), 7.13 (1H, d), 6.87 (1H, m), 3.90 (4H, 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2- fluoro-5-methyl- phenyl)- amine 
               
               
                   
                   
                   
                   
                 very broad s), 3.31 (4H, broad s), 
                   
               
               
                   
                   
                   
                   
                 2.68 (1H, m), 2.29 (3H, s), 1.25 (2H, 
                   
               
               
                   
                   
                   
                   
                 m), 1.06 (2H, m). 
                   
               
               
                   
               
               
                 505 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.20 min, MI: 452 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.07 (1H, s), 8.19 (1H, s), 8.14 (1H, d), 7.98 (1H, s), 7.73 (1H, d), 7.33 (1H, s), 7.22 (1H, d), 7.03 (1H, d), 3.89 (4H, very broad s), 3.30 (4H, 1H NMR (DMSO, 500 MHz) 9.07 (1H, s), 8.19 (1H, s), 8.14 (1H, d), 7.98 (1H, s), 7.73 (1H, d), 7.33 (1H, s), 7.22 (1H, d), 7.03 (1H, d), 3.89 (4H, 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,5- dimethyl-phenyl)- amine 
               
               
                   
                   
                   
                   
                 very broad s), 3.30 (4H, broad s), 
                   
               
               
                   
                   
                   
                   
                 2.48 (1H, m), 2.29 (3H, s), 2.20 
                   
               
               
                   
                   
                   
                   
                 (3H, s), 1.25 (2H, m), 1.07 (2H, m) 
                   
               
               
                   
               
               
                 506 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 5.19 min, MI: 450 [M + H] 
                 NMR: (DMSO) 10.27 ppm (s, 1H), 9.06 ppm (s, 1H), 8.95 ppm (d, 1H), 8.58 ppm (dd, 1H), 8.48 ppm (d, 1H), 8.19 ppm (s, 1H), 8.06 ppm (s, 1H), 7.91 ppm (m, 2H), 3.85 ppm (s, 4H), 3.90 ppm (broad s, 4H), 2.68 ppm (m, 1H), 1.27 ppm (m, 2H), 1.09 ppm (m, 2H). A second set of piperazine 4H is suspected to be running under the 
                 5-[4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2- ylamino]-pyridine- 2-carbonitrile 
               
               
                   
                   
                   
                   
                 DMSO water peak at 3.33 ppm. 
                   
               
               
                   
               
               
                 507 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.10 min, MI: 426 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.08 (1H, s), 8.78 (1H, s), 8.47 (1H, d), 8.31 (1H, m), 8.19 (1H, s), 8.16 (1H, d), 7.94 (2H, dd), 3.93 (4H, very broad s), 3.31 (4H, br s), 2.68 (1H, m), 1.26-1.24 (2H, m), 1.08- 1.05 (2H, m). 
                 4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- pyrazin-2-yl-amine 
               
               
                   
               
               
                 508 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT 3.28 min, MI: 456.17 [M + H] 
                 1H NMR (DMSO, 500 MHz) 8.99 (1H, s), 8.15 (1H, d), 8.10 (1H, s), 7.64 (1H, s), 7.49 (1H, d), 6.98 (1H, s), 4.56-4.25 (1H, m, br), 3.95 (1H, d, br), 3.65 (s, br, 4H), 3.03 (4H, s, br), 1.28-1.22 (3H, m, br), 1.05-1.01 2H, m, br), 0.73 (2H, d, br), 0.47 (2H, s, br). 
                 Cyclopropyl-{4-[5- cyclopropyl-4-(3- trifluoromethyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2- yl}-amine 
               
               
                   
               
               
                 509 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT 1.73 min:, MI: 418.19 [M + H] 
                 1H NMR (DMSO, 500 MHz) 8.99 (1H, s), 8.13 (1H, d), 8.12 (1H, s), 7.58 (1H, s), 7.45 (1H, d), 7.05 (1H, d), 4.43 (1H, m, br), 3.91-3.82 (2H, m), 3.80 (4H, m, br), 3.75-3.70 1H NMR (DMSO, 500 MHz) 8.99 (1H, s), 8.13 (1H, d), 8.12 (1H, s), 7.58 (1H, s), 7.45 (1H, d), 7.05 (1H, d), 4.43 (1H, m, br), 3.91-3.82 (2H, m), 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(R)- tetrahydro-furan-3- yl-amine 
               
               
                   
                   
                   
                   
                 3.80 (4H, m, br), 3.75-3.70 (1H, m), 
                   
               
               
                   
                   
                   
                   
                 3.54 (1H, dd), 3.20 (4H, m, br), 
                   
               
               
                   
                   
                   
                   
                 2.70-2.67 (1H, m), 2.21-2.14 (1H, 
                   
               
               
                   
                   
                   
                   
                 m), 
                   
               
               
                   
               
               
                 510 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.37 min, MI: 466.20 [M + H] 
                 1H NMR (500 MHz, DMSO) 8.93 (1H, s), 8.11 (1H, d), 8.06 (1H, s), 7.54 (1H, s), 7.41 (1H, d), 6.80 (1H, d), 4.02-3.97 (1H, m, br), 3.79-3.54 (4H, m, br), 2.84 (4H, m, 2.62 1H NMR (500 MHz, DMSO) 8.93 (1H, s), 8.11 (1H, d), 8.06 (1H, s), 7.54 (1H, s), 7.41 (1H, d), 6.80 (1H, d), 4.02-3.97 (1H, m, br), 3.79-3.54 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(4,4- difluoro- cyclohexyl)-amine 
               
               
                   
                   
                   
                   
                 (4H, m, br), 2.84 (4H, m, 2.62-2.59 
                   
               
               
                   
                   
                   
                   
                 (1H, m), 2.10-1.89 (6H, m, br), 
                   
               
               
                   
                   
                   
                   
                 1.59-1.53 (2H, m, br), 1.26-1.22 
                   
               
               
                   
                   
                   
                   
                 (2H, m), 1 
                   
               
               
                   
               
               
                 511 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.31 min, MI: 525 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.00 (1H, s), 8.68 (1H, s), 8.50 (1H, m), 8.45 (1H, m), 8.32 (1H, m), 8.11 (1H, s), 7.89 (1H, d), 7.85 (1H, m), 4.47 (1H, d), 4.38 (1H, d), 4.30 (1H, m), 4.16 (1H, m), 3.32 (1H, m), 3.22 (2H, m), 3.13 (2H, m), 2.62 (1H, m), 1.26-1.24 (2H, m), 1.05-1.03 (2H, 
                 {4-[5-Cyclopropyl- 4-((R)-3-fluorometh- yl-piperazin-1- yl)-pyrido[3,4-d]py- rimidin-2-yl]- pyridin-2-yl}-(4- trifluoromethyl- pyridin-2-yl)- 
               
               
                   
                   
                   
                   
                 m) 
                 amine 
               
               
                   
               
               
                 512 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.31 min, MI: 525 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.00 (1H, s), 8.68 (1H, s), 8.50 (1H, m), 8.45 (1H, m), 8.32 (1H, m), 8.11 (1H, s), 7.89 (1H, d), 7.85 (1H, m), 4.47 (1H, d), 4.38 (1H, d), 4.30 (1H, m), 4.16 (1H, m), 3.32 (1H, m), 3.22 (2H, m), 3.13 (2H, m), 2.62 (1H, m), 
                 {4-[5-Cyclopropyl- 4-((R)-3-fluorometh- yl-piperazin-1- yl)-pyrido[3,4-d]py- rimidin-2-yl]- pyridin-2-yl}-(6- fluoro-pyridin-2- 
               
               
                   
                   
                   
                   
                 1.26-1.24 (2H, m), 1.05-1.03 (2H, 
                 yl)-amine 
               
               
                   
                   
                   
                   
                 m) 
                   
               
               
                   
               
               
                 513 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 455.2 (M + H) 
                 (CDCl 3 ) 9.12 (d, J = 1.6 Hz, 1H), 8.70 (dd, J = 8.0; 1.5 Hz, 1H), 8.40 (d, J = 4.4 Hz, 1H), 8.06 (s, 1H), 7.89 (s, 1H), 7.83 (dd, J = 5.2; 1.3 Hz, 1H), 7.75 (m, 1H), 7.19 (s, 1H), 6.92 (m, 1H), 4.07 (s, 3H), 3.77 (br s, 4H), 3.04 (m, 4H), 2.70 (m, 1H), 1.84 (exch. protos), 1.27 (m, 2H), 1.01 (m, 2H) 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2- methoxy-pyridin-3- yl)-amine 
               
               
                   
               
               
                 514 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 459.1 (M + H) 
                 (dmso-d6) 10.24 (s, 1H), 8.98 (s, 1H), 8.75 (s, 1H), 8.41 (d, J = 5.2 Hz, 1H), 8.10 (s, 1H), 7.88 (m, 1H), 7.82 (m, 1H), 7.74 (m, 1H), 6.97 (d, J = 7.5 Hz, 1H), 3.75 (br m, 4H), 2.86 (br m, 4H), 2.62 (m, 1H), 1.25 (m, 2H), 1.03 (m, 2H) 
                 (6-Chloro-pyridin- 2-yl)-[4-(5-cyclo- propyl-4-piperazin- 1-yl-pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- amine 
               
               
                   
               
               
                 515 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 454.2 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2- methoxy-phenyl)- amine 
               
               
                   
               
               
                 516 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 492.1 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2- trifluoromethyl- phenyl)- amine 
               
               
                   
               
               
                 517 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 468.2 (M + H)+ 
                 (CDCl 3 ) 9.11 (s, 1H), 8.37 (dd, J = 5.3; 0.4 Hz, 1H), 8.04 (s, 1H), 7.96 (s, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.79 (dd, J = 5.3; 1.3 Hz, 1H), 7.72 (br s, 1H), 7.35 (m, 1H), 7.27 (m, 1H), 7.01 (m, 1H), 4.57 (s, 2H), 3.75 (br s, 4H), 3.43 (s, 3H), 3.01 (m, 4H), 2.69 (m, 1H), 2.04 (br s, esch. protons), 1.26 (m, 2H), 1.00 (m, 2H) 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2- methoxymethyl- phenyl)-amine 
               
               
                   
               
               
                 518 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.27 min, MI: 418.17 M + H] 
                 1H NMR (500 MHz, DMSO) 8.93 (1H, s), 8.11 (1H, d), 8.06 (1H, s), 7.56 (1H, s), 7.43 (1H, dd), 7.01 (1H, d), 4.45-4.39 (1H, m), 3.90- 3.53 (4H, s, br), 3.89 (1H, dd), 3.85 (1H, q), 3.75-3.70 (1H, m), 3.55 (1H, dd), 3.15 (2H, d), 2.85 (4H, s, br), 2.62-2.61 (1H, m), 2.20-2.16 (1H, m), 1.85-1.80 (1H, m), 1.26- 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(S)- tetrahydro-furan-3- yl-amine 
               
               
                   
                   
                   
                   
                 1.22 (2H, m), 1.02-1.01 (2H, m) 
                   
               
               
                   
               
               
                 519 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 449.1 (M + H)+ 
                 (CDCl 3 ) 9.14 (m, 2H), 8.42 (d, J = 1.4 Hz, 1H), 8.07 (s, 1H), 7.93 (d, J = 8.1 Hz, 1H), 7.84 (dd, J = 8.1; 5.9 Hz, 1H), 7.68 (m, 2H), 7.39 (m, 2H), 3.82 (m, 4H), 3.05 (m, 4H), 2.71 (m, 1H), 1.7 (br s, exch. H&#39;s), 1.28 (m, 2H), 1.02 (m, 2H) 
                 2-[4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2- ylamino]- benzonitrile 
               
               
                   
               
               
                 520 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.73 min, MI: 404.30 [M + H] 
                 1H NMR (DMSO, 500 MHz) 8.92 (1H, s), 8.07 (2H, dd), 7.56 (1H, s), 7.35 (1H, s), 6.47 (1H, s), 3.75-3.54 (4H, m, br), 2.83 (4H, m, br), 2.62 (1H, m, br), 1.41 (9H, s), 1.24 (2H, m, br), 1.00 (2H, m, br). 
                 tert-Butyl-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)-pyrido-2-yl]- amine 
               
               
                   
               
               
                 521 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.90 min, MI: 460 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.25 (1H, s), 9.05 (1H, s), 8.97 (1H, s, br), 8.39 (1H, d), 8.24 (1H, s), 8.17 (1H, s), 7.78 (1H, d), 7.28 (1H, m), 6.76 (1H, m), 3.96-3.88 (4H, s, br), 3.31 (4H, s, br), 2.65 (1H, m), 1.28-1.25 (2H, m), 1.08-1.05 (2H, m) 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,5- difluoro-phenyl)- amine 
               
               
                   
               
               
                 522 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 4.02 min, MI: 510 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.37 (1H, s), 9.06 (1&#39;H, s), 8.97 (1H, s, br), 8.41 (1H, d), 8.23 (1H, s), 8.18 (1H, s), 7.84 (1H, d), 7.47 (1H, m), 7.32 (1H, m), 3.96-3.88 (4H, s, br), 3.31 (4H, s, br), 2.65 (1H, m), 1.28-1.25 (2H, m), 1.08-1.05 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2- fluoro-5- trifluoromethyl- phenyl)-amine 
               
               
                   
               
               
                 523 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.80 min, MI: 466 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.05 (1H, s), 8.97 (1H, s, br), 8.28 (1H, d), 8.18 (1H, s), 8.05 (1H, s), 7.81 (1H, s), 7.75 (1H, d), 7.23 (1H, d), 6.81 (1H, d), 3.96-3.88 (4H, s, br), 3.31 (4H, s, br), 2.66 (1H, m), 2.27 (3H, s), 1.28-1.25 (2H, m), 1.08- 1.05 (2H, m) 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(5- fluoro-2-methyl- phenyl)- amine 
               
               
                   
               
               
                 524 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 1H NMR (DMSO, 500 MHz) 9.06 (1H, s), 8.96 (1H, s, br), 8.78 (1H, s), 8.36 (1H, s), 8.33 (1H, d), 8.18 (1H, s), 8.06 (1H, s), 7.78 (1H, d), 7.43 (1H, m), 3.96-3.88 (4H, s, br), 3.31 (4H, s, br), 2.68 (1H, m), 2.38 (3H, s), 1.28-1.25 (2H, m), 1.08- 1.05 (2H, m) 
                 3-[4-(5- Cyclopropyl-4- piperaizn-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2- ylamino]-4-methyl- benzonitrile 
               
               
                   
               
               
                 525 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.20 min, MI: 480 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.30 (1H, s), 9.01 (1H, s), 8.32 (1H, d), 8.16 (1H, s), 7.91 (1H, s), 7.75 (1H, d), 7.70 (1H, d,), 7.28 (2H, m), 6.90 (1H, m), 4.43 (4H, m), 4.05 (2H, m), 3.67 (1H, m), 3.48 (1H, m), 3.21 (1H, m), 2.53 (1H, m), 1.28-1.25 (2H, m), 1.3-1.01 (2H, m) 
                 7-[5-Cyclopropyl- 2-(2-phenylamino- pyri- din-4-yl)- pyrido[3,4- d]pyrimidin- 4-yl]-hexahydro- oxazolo[3,4- a]pyrazin-3-one 
               
               
                   
               
               
                 526 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.33 min, MI: 443 [M + H] 
                 1H NMR (DMSO, 500 MHz) 11.53 (1H, s), 9.11 (1H, s), 8.92 (1H, s), 8.55 (1H, d), 8.30 (1H, d), 8.24 (1H, s), 8.21 (1H, dd), 7.98 (1H, m), 7.31 (1H, m), 4.01 (4H, s), 3.30 (4H, s), 2.68 (1H, m), 1.28 (2H, m), 1.10 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin- 2-yl]-(3-fluoro- pyridin-2-yl)- amine 
               
               
                   
               
               
                 527 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 5.3 min, MI: 472 [M + H] 
                 1H NMR (DMSO, 500 MHz, 1IGO538) 9.05 (1H, s), 9.02-8.90 (2H, broad s), 8.19 (1H, s), 8.14 (1H, d), 7.75 (1H, s), 7.69 (1H, d), 7.45 (1H, d), 7.34 (1H, d), 7.27 (1H, m), 3.89 (4H, s), 3.31 (4H, s), 2.67 (1H, m), 1.26 (2H, m), 1.07 (2H, m) 
                 (2-Chloro-6- methyl-phenyl)-[4- (5-cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)-pyridin-2-yl]- amine 
               
               
                   
               
               
                 528 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.68 min, MI: 467 [M + H] 
                 1H NMR (DMSO, 500 MHz, 1IGO539) 9.41 (1H, s), 9.05 (1H, s), 8.98 (1H, d), 8.43 (1H, d), 8.23 (1H, s), 8.18 (1H, s), 7.86 (1H, d), 7.49 (1H, m), 3.94 (4H, s), 3.33 (4H, s), 2.69 (1H, m), 1.26 (2H, m), 1.08 (2H, m). 
                 3-[4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2- ylamino]-4-fluoro- benzonitrile 
               
               
                   
               
               
                 529 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 4.21 min, MI: 514 [M + H] 
                 1H NMR (DMSO, 500 MHz, 1IGO541) 9.06 (1H, s), 9.01-8.90 (2H, broad s), 8.24 (1H, d), 8.19 (1H, s), 8.01 (1H, s), 7.84 (1H, d), 7.75 (1H, dd), 7.48 (1H, d), 7.39 (1H, dd), 3.91 (4H, s), 3.32 (4H, s), 2.68 (1H, m), 1.31 (9H, s), 1.24 (2H, m), 1.08 (2H, m). 
                 (4-tert-Butyl-2- chloro-phenyl)-[4- (5-cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2- yl]-amine 
               
               
                   
               
               
                 530 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.13 min, MI: 482 [M + H] 
                 1H NMR (DMSO, 500 MHz) 10.00 (1H, s), 9.06 (1H, s), 8.61 (1H, s), 8.48 (2H, m), 8.31 (1H, s), 7.93 (1H, d), 7.26 (1H, d), 4.44 (2H, m), 4.06 (2H, m), 3.77 (1H, m), 3.35 (4H, m), 2.68 (1H, m), 1.28-1.25 (2H, m), 1.02-0.99 (2H, m) 
                 2-[4-[5- Cyclopropyl-4- ((R)-3-fluoro methyl-piperazin- 1-yl)-pyrido[3,4-d] pyrimidin-2-yl]- pyridin-2-ylamino}- 
               
               
                   
                   
                   
                   
                   
                 isonicotinonitrile 
               
               
                   
               
               
                 531 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.54 min, MI: 475 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.22 (1H, s), 8.98 (1H, s), 8.86 (1H, m), 8.33 (1H, d), 8.15 (1H, s), 8.13 (1H, s), 8.11 (1H, s), 7.79 (1H, d), 7.74 (1H, d), 7.30 (1H, m), 4.50 (1H, d), 4.40 (1H, d), 4.17 (1H, m), 3.34 (2H, m), 3.21 (2H, m), 2.99 (2H, m), 
                 {4-[5-Cyclopropyl- 4-((R)-3-fluorometh- yl-piperazin-1- yl)-pyrido[3,4-d]pyri- midin-2-yl]- pyridin-2-yl}-(2- fluoro-pyridin-3- 
               
               
                   
                   
                   
                   
                 2.53 (1H, m), 1.26-1.24 (2H, m), 
                 yl)-amine 
               
               
                   
                   
                   
                   
                 1.05-1.03 (2H, m). 
                   
               
               
                   
               
               
                 532 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.75 min, MI: 430.26 [M + H] 
                 1H NMR (DMSO, 500 MHz) 8.94 (1H, s), 8.16 (1H, d), 8.07 (1H, s), 7.8 (1H, s), 7.54 (1H, dd), 7.40 (1H, t), 4.24-4.20 (2H, m), 3.86-3.51 (4H, m, br), 2.84 (4H, m, br), 2.63- 2.57 (1H, m), 1.25-1.23 (2H, m), 1.02-1.01 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- (2,2,2-trifluoro- ethyl)-amine 
               
               
                   
               
               
                 533 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.99 min, MI: 506 [M + H] 
                 1H NMR (DMSO, 500 MHz) 10.00 (1H, s), 9.06 (1H, s), 8.61 (1H, s), 8.48 (2H, m), 8.31 (1H, s), 7.93 (1H, d), 7.26 (1H, d), 4.44 (2H, m), 4.06 (2H, m), 3.77 (1H, m), 3.35 (4H, m), 2.68 (1H, m), 1.28-1.25 (2H, m), 1.02-0.99 (2H, m) 
                 2-{4-[5- Cyclopropyl-4-(3- oxo-tetrahydro- oxazolo[3,4- a]pyrazin-7-yl)-py- rido[3,4- d]pyrimidin-2-yl]- pyridin- 2-ylamino}- 
               
               
                   
                   
                   
                   
                   
                 isonicotinonitrile 
               
               
                   
               
               
                 534 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.4 min, MI: 493 [M + H] 
                   
                 [4-(5-cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(6- trifluoromethyl- pyridin- 2-yl)-amine 
               
               
                   
               
               
                 535 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.81 min, MI: 443 [M + H] 
                 1H NMR (DMSO, 500 MHz, 1IGO528) 9.90 (1H, s), 8.98 (1H, s), 8.59 (1H, t), 8.48-8.44 (1H, td), 8.42 (1H, d), 8.20 (1H, s), 8.07 (1H, d), 7.98 (1H, s), 7.82 (1H, dd), 2.89 (4H, s), 2.63 (1H, m), 1.27 (2H, m), 1.40 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(5- fluoro-pyridin-3- yl)-amine 
               
               
                   
               
               
                 536 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.31 min, MI: 493 [M + H] 
                 1H NMR (DMSO, 500 MHz, 1IGO529) 8.98 (1H, s), 8.83 (1H, s), 8.44 (1H, d), 8.28 (1H, d), 8.20 (1H, d), 8.10 (1H, s), 8.04 (1H, s), 7.75 (1H, d), 7.69-7.66 (1H, q), 3.42 (4H, broad s), 2.87 (1H, s), 2.62 (1H, m), 1.27 (2H, m), 1.04 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2- trifluoromethyl- pyridin-3-yl)- amine 
               
               
                   
               
               
                 537 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 436.1 
                   
                 {4-[5-Cyclopropyl- 4-(2,5-diaza-bicy- clo[4.1.0]hept-2- yl)-pyrido[3,4-d]py- rimidin-2-yl]- pyridin-2-yl}- phenyl-amine 
               
               
                   
               
               
                 538 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 472.1 
                   
                 {4-[5-Cyclopropyl- 4-(2,5-diaza-bicy- clo[4.1.0]hept-2- yl)-pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(2,6- difluoro-phenyl)- amine 
               
               
                   
               
               
                 539 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 492.1 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,6- dichloro-phenyl)- amine 
               
               
                   
               
               
                 540 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 452.2 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,3- dimethyl-phenyl)- amine 
               
               
                   
               
               
                 541 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 452.2 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,6- dimethyl-phenyl)- amine 
               
               
                   
               
               
                 542 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 492.1 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,3- dichloro-phenyl)- amine 
               
               
                   
               
               
                 543 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 466.30 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,3- dichloro-phenyl)- amine 
               
               
                   
               
               
                 544 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 439.20 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2- methyl-pyridin-3- yl)-amine 
               
               
                   
               
               
                 545 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 426.15 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- pyridazin-3-yl- amine 
               
               
                   
               
               
                 546 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 439.20 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(6- methyl-pyridin-3- yl)-amine 
               
               
                   
               
               
                 547 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 455.20 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(6- methoxy-pyridin-3- yl)-amine 
               
               
                   
               
               
                 548 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 461.20 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3,6- difluoro-pyridin-2- yl)-amine 
               
               
                   
               
               
                 549 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 500.20 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-[4- (dimethyl- phosphinoyl)- phenyl]-amine 
               
               
                   
               
               
                 550 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.20 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-[4- (diethyl- phosphinoyl)- phenyl]-amine 
               
               
                   
               
               
                 551 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 468.25 (M + H) 
                   
                 N 5 -[4-(5- Cyclopropyl-4- piperazin- 1-yl-pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- N 2 ,N 2 -dimethyl- pyridine-2,5- diamine 
               
               
                   
               
               
                 552 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.16 min, MI: 456 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.30 (1H, s), 8.98 (1H, s), 8.31 (1H, d), 8.11 (1H, s), 7.90 (1H, s), 7.75 (1H, d), 7.66 (1H, d), 7.27 (2H, m), 6.89 (1H, m), 4.46 (1H, d), 4.38 (1H, d), 4.13 (2H, m), 3.34 (2H, m), 3.00 (3H, m), 2.68 (1H, m), 1.28-1.25 (2H, m), 1.08-1.05 (2H, m) 
                 {4-[5-Cyclopropyl- 4-((R)-3-fluoro- methyl-piperazin-1- yl)-pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}- phenyl-amine 
               
               
                   
               
               
                 553 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.74 min, MI: 468 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.05 (1H, s), 8.91 (1H, s, br), 8.19 (2H, dd), 7.97 (1H, s), 7.72 (1H, d), 7.26 (1H, s), 7.21 (1H, dd), 6.73 (1H, d), 3.99-3.88 (4H, s, br), 3.73 (3H, s), 3.30 (4H, s, br), 2.62 (1H, m, br), 2.19 (3H, s), 2.20 (3H, s), 1.25-1.23 (2H, m), 1.08-1.05 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(5- methoxy-2-methyl- phenyl)- amine 
               
               
                   
               
               
                 554 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.92 min, MI: 405 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.05 (1H, s), 8.98 (1H, s, br), 8.28 (1H, dd), 8.22 (1H, s), 8.18 (1H, s), 8.06 (1H, s), 7.78 (1H, d), 7.49 (1H, d), 7.36 (1H, d), 3.96-3.88 (4H, s, br), 3.30 (4H, s, br), 2.68 (1H, m), 2.37 (3H, s), 1.26-1.23 (2H, m), 1.08- 1.05 (2H, m) 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2- methyl-5- trifluoromethyl- phenyl)-amine 
               
               
                   
               
               
                 555 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.30 min, MI: 526 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.32 (1H, s), 9.05 (1H, s), 8.92 (1H, s, br), 8.62 (1H, m), 8.40 (1H, d), 8.23 (1H, s), 8.18 (1H, s), 8.06 (1H, s), 7.83 (1H, d), 7.49 (1H, d), 7.36 (1H, m), 3.96-3.88 (4H, s, br), 3.33 (4H, s, br), 2.68 (1H, m), 1.26-1.23 (2H, m), 1.08-1.05 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2- fluoro-5- trifluoromethoxy- phenyl)-amine 
               
               
                   
               
               
                 556 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.35 min, MI: 520 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.44 (1H, s), 9.08 (1H, s), 9.04 (1H, s), 8.97 (1H, s, br), 8.43 (1H, dd), 8.24 (1H, s), 8.20 (1H, s), 7.87 (1H, d), 7.56 (1H, d), 3.96-3.88 (4H, s, br), 3.35 (4H, s, br), 3.24 (3H, s), 2.69 (1H, m), 1.28-1.25 (2H, m), 1.08- 1.05 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2- fluoro-5- methanesulfonyl- phenyl)-amine 
               
               
                   
               
               
                 557 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.37 min, MI: 474 [M + H] 
                 H NMR (DMSO, 500 MHz) 9.05 (1H, s), 8.93 (1H, s, br), 8.83 (1H, s), 8.18 (1H, s), 7.82 (1H, s), 7.15 (1H, m), 7.06 (1H, m), 3.87 (4H, s, br), 3.31 (4H, s, br), 2.69 (1H, m), 2.24 (3H, s), 1.26-1.24 (2H, m), 1.07- 1.05 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,6- difluoro-3-methyl- phenyl)-amine 
               
               
                   
               
               
                 558 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 4.08 min, MI: 480 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.02 (1H, s), 8.93 (1H, s, br), 8.17 (2H, dd), 7.90 (1H, s), 7.71 (1H, s), 7.38 (1H, s), 7.23 (1H, dd), 7.02 (1H, m), 4.02-3.88 (4H, s, br), 3.30 (4H, s, br), 2.87 (1H, m, br), 2.63-2.57 (1H, m), 2.20 (3H, s), 1.25-1.23 (2H, m), 1.20 (6H, m), 1.06-1.02 (2H, m) 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(5- isopropyl-2- methyl-phenyl)- amine 
               
               
                   
               
               
                 559 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.01 min, MI: 429 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.45 (1H, s, br), 9.05 (1H, s), 8.90 (1H, s, br), 8.32 (1H, d), 8.18 (1H, s), 7.82 (1H, s), 7.15 (1H, m), 7.06 (1H, m), 3.87 (4H, s, br), 3.31 (4H, s, br), 2.69 (1H, m), 2.24 (3H, s), 1.26-1.24 (2H, m), 1.07-1.05 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-pent- deuterio-phenyl- amine 
               
               
                   
               
               
                 560 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 450.2 (M − OH)+ 
                 (CDCl 3 ) 9.07 (s, 1H), 8.30 (d, J = 5.3 Hz, 1H), 8.00 (br s, 2H), 7.91 (s, 1H), 7.80 (d, J = 7.5 Hz, 1H), 7.75 (dd, J = 5.3; 1.2 Hz, 1H), 7.30 (m, 2H), 7.05 (m, 1H), 5.09 (q, J = 6.6 Hz, 1H), 3.73 (br s, 4H), 2.97 (m, 4H), 2.66 (m, 1H), 2.17 (br s, OH, exch. NH), 1.61 (d, J = 6.6 Hz, 3H), 1.24 (m, 2H), 0.98 (m, 2H) 
                 1-{2-[4-(5- Cyclopropyl-4- piperazin- 1-yl-pyrido[3,4- d]pyimidin-2-yl)- pyridin-2- ylamino]-phenyl}- ethanol 
               
               
                   
               
               
                 561 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 459.25 (M + H)+ 
                 (dmso-d6; note: a minor rotamer also observed) 10.85 (s, 1H), 9.17 (br s, exch. 3H), 9.08 (s, 1H), 8.53 (d, J = 5.2 Hz, 1H), 8.19 (s, 1H), 8.10 (dd, J = 5.2; 1.4 Hz, 1H), 8.04 (br s, 3H), 4.19 (br s, large exch. H&#39;s signal), 3.91 (m, 4H), 3.35 (br s, 4H), 3.08 (m, 1H), 2.70 (m, 1H), 
                 (1R, 2S)-2-Amino- cyclopentane- carboxylic acid [4- (5-cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- 
               
               
                   
                   
                   
                   
                 2.24 (m, 1H), 2.08 (m, 2H), 1.73 
                 amide 
               
               
                   
                   
                   
                   
                 (m, 4H), 1.26 (m, 2H), 1.08 (m, 2H) 
                   
               
               
                   
               
               
                 562 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 — 
                 423.00 (M + H) 
                   
                 1-{4-[2-(2-Chloro- pyridin-4-yl)-5- cyclopropyl- pyrido[3,4- d]pyrimidin-4- yl]-piperazin-2- yl}-cyclopropanol 
               
               
                   
               
               
                 563 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 464.20 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- pyrazolo[1,5- a]pyridin-6-yl- amine 
               
               
                   
               
               
                 564 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 464.15 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- pyrazolo[1,5- a]pyridin-5-yl- amine 
               
               
                   
               
               
                 565 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 494.10 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(5- trifluoromethyl- pyridazin-3-yl)- amine 
               
               
                   
               
               
                 566 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 490 
                 (dmso-d6) 9.11 (br s, 3H, exch. H&#39;s), 9.07 (s, 1H), 8.20 (m, 2H), 7.88 (s, 1H), 7.73 (dd, J = 5.3; 1.4 Hz, 1H), 7.09 (m, 2H), 3.92 (br s, 4H), 3.87 (s, 3H), 3.33 (br s, 4H), 2.69 (m, 1H), 1.26 (m, 2H), 1.09 (m, 2H) 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,6- difluoro-3- methoxy-phenyl)- amine 
               
               
                   
               
               
                 567 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 503.9 
                 (dmso-d6) 9.06 (s, 1H), 9.05 (br s, 3H, exch. H&#39;s), 8.20 (m, 2H), 7.87 (s, 1H), 7.72 (dd, J = 5.4; 1.3 Hz, 1H), 7.07 (m, 2H), 5.40 (br s, exch. H&#39;s), 4.12 (q, J = 7.0 Hz, 2H), 3.93 (br s, 4H), 3.33 (br s, 4H), 2.68 (m, 1H), 1.36 (t, J = 7.0 Hz, 3H), 1.26 (m, 2H), 1.09 (m, 2H) 
                 [4-(5-Cyclopropyl- 4-piperazin--1yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3- ethoxy-2,6- difluoro-phenyl)- amine 
               
               
                   
               
               
                 568 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.46 min, MI: 472 [M + H] 
                 1H NMR (DMSO, 500 MHz), 9.06 (1H, s), 8.26 (1H, d), 8.18 (1H, s), 8.05 (1H, s), 7.84 (1H, d), 7.75 (1H, dd), 7.24 (1H, t), 7.11 (1H, s), 3.91 (4H, s), 3.32 (4H, s), 2.68 (1H, m), 2.39 (3H, s), 1.25 (2H, m), 1.08 (2H, m). 
                 (2-Chloro-3- methyl-phenyl)-[4- (5-cylcopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)-pyridin-2-yl]- amine 
               
               
                   
               
               
                 569 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 4.22 min, MI: 438.28 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.59 (1H, br s), 9.05 (1H, s), 8.99 (1H, br s), 8.31 (1H, d), 8.18 (1H, s), 7.97 (1H, s), 7.73-7.69 (2H, m), 7.32 (2H, t), 6.77 (1H, t), 4.96 (4H, br s), 4.32 (1H, br s), 3.37 (2H, br s), 1.34-1.23 (5H, m), 1.07 (2H, br s). 
                 {4-[5-Cycopropyl- 4-((S)-3-methyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}- phenyl-amine 
               
               
                   
               
               
                 570 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 5.57 min, MI: 476 [M + H] 
                 1H NMR (DMSO, 500 MHz),) 9.07 (1H, s), 8.25 (1H, d), 8.19 (1H, s), 8.01 (1H, s), 7.93 (1H, m), 7.76 (1H, d), 7.54 (1H, dd), 7.26 (1H, m), 3.92 (4H, s), 3.32 (4H, s), 2.68 (1H, m), 1.24 (2H, m), 1.09 (2H, m). 
                 (2-Chloro-4-fluoro- phenyl)-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)-pyridin-2-yl]- amine 
               
               
                   
               
               
                 571 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 5.27 min, MI: 454 [M + H] 
                 1H NMR (DMSO, 500 MHz,) 9.53 (1H, s), 9.06 (1H, s), 8.33 (1H, d), 8.19 (1H, s), 7.98 (1H, s), 7.74 (1H, dd), 7.46 (1H, s), 7.24 (2H, m), 6.56 (1H, d), 3.91 (4H, s), 3.76 (3H, s), 3.33 (4H, s), 2.69 (1H, m), 1.25 (2H, m), 1.08 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3- methoxy-phenyl)- amine 
               
               
                   
               
               
                 572 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 5.77 min, MI: 472 [M + H] 
                 1H NMR (DMSO, 500 MHz,) 9.07 (1H, s), 8.22 (1H, d), 8.19 (1H, s), 8.03 (1H, s), 7.76 (1H, dd), 7.46 (1H, s), 7.74 (1H, d), 7.40 (1H, s), 7.20 (1H, d), 3.93 (4H, s), 3.32 (4H, s), 2.66 (1H, m), 2.33 (3H, s), 1.25 (2H, m), 1.08 (2H, m). 
                 (2-Chloro-4- methyl-phenyl)-[4- (5-cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)-pyridin-2-yl]- amine 
               
               
                   
               
               
                 573 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 452.0 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,4- dimethyl-phenyl)- amine 
               
               
                   
               
               
                 574 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 455.9 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2- fluoro-3-methyl- phenyl)-amine 
               
               
                   
               
               
                 575 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 455.9 (MH)+ 
                   
                 [4-(5-Cylcopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2- fluoro-4-methyl- phenyl)-amine 
               
               
                   
               
               
                 576 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 4.02 min, MI: 476 [M + H] 
                 1H NMR (DMSO, 500 MHz,) 9.07 (1H, s), 8.87 (1H, s), 8.39 (1H, d), 8.23 (2H, m), 8.19 (1H, s), 7.85 (1H, dd), 7.51 (1H, m), 6.88 (1H, m), 3.93 (4H, s), 3.33 (4H, s), 2.69 (1H, m), 1.26 (2H, m), 1.08 (2H, m). 
                 (2-Chloro-5-fluoro- phenyl)-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- Amine 
               
               
                   
               
               
                 577 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.48 min, MI: 472 [M + H] 
                 1H NMR (DMSO, 500 MHz,) 9.07 (1H, s), 8.28 (1H, d), 8.17 (1H, s), 8.05 (1H, s), 7.78 (2H, s), 7.41 (1H, dd), 6.98 (1H, d), 3.92 (4H, s), 3.32 (4H, s), 2.68 (1H, m), 2.32 (3H, s), 1.25 (2H, m), 1.08 (2H, m). 
                 (2-Chloro-5- methyl-phenyl)-[4- (5-cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- Amine 
               
               
                   
               
               
                 578 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 5.25 min, MI: 476 [M + H] 
                 1H NMR (DMSO, 500 MHz,) 9.07 (1H, s), 8.33 (1H, d), 8.19 (1H, s), 8.14 (1H, s), 7.97 (1H, d), 7.82 (1H, dd), 7.37-7.32 (1H, m), 7.10-7.06 (1H, m), 3.93 (4H, s), 3.33 (4H, s). 2.69 (1H, m), 1.26 (2H, m), 1.09 (2H, m). 
                 (2-Chloro-3-fluoro- phenyl)-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)-pyridin-2-yl]- Amine 
               
               
                   
               
               
                 579 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 44 
                   
                 5-Cyclopropyl-2- (6,7-dimethoxy- quinolin-4-yl)-4- piperazin-1-yl- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 580 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 471.9 
                 (CDCl 3 ) 9.12 (s, 1H), 8.41 (dd, J = 5.3; 0.4 Hz, 1H), 8.05 (s, 1H), 7.98 (dd, J = 7.0; 3.1 Hz, 1H), 7.95 (s, 1H), 7.85 (dd, J = 5.3; 1.3 Hz, 1H), 7.02 (dd, J = 10.8; 8.9 Hz, 1H), 6.89 (m, 1H), 6.45 (m, 1H), 3.82 (s, 3H), 3.78 (br s, 4H), 3.03 (m ,4H), 2.70 (m, 1H), 1.87 (br s, exch. H&#39;s), 1.27 (m, 2H), 1.01 (m, 2H) 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2- fluoro-5-methoxy- phenyl)-amine 
               
               
                   
               
               
                 581 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 390.10 (M + H) 
                   
                 N-[4-(5- Cycopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- acetamide 
               
               
                   
               
               
                 582 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 348.05 (M + H) 
                   
                 4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-ylamine 
               
               
                   
               
               
                 583 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 418.15 (M + H) 
                   
                 N-[4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- isobutyramide 
               
               
                   
               
               
                 584 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 416.10 (M + H) 
                   
                 Cyclopropane- carboxylic acid [4- (5-cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- amide 
               
               
                   
               
               
                 585 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 438 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3,3- difluorocyclo- butyl)-amine 
               
               
                   
               
               
                 586 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 452.0 (M + H) 
                 (dmso-d6) 9.14 (br s, exch. H&#39;s), 9.07 (s, 1H), 8.22 (s, 1H), 8.09 (d, J = 6.4 Hz, 1H), 8.02 (br s, 1H), 7.70 (d, J = 6.3 Hz, 1H), 7.47 (m, 2H), 7.40 (m, 2H), 7.30 (m, 1H), 5.10 (m, 1H), 3.90 (br s, 4H), 3.33 (br s, 4H), 2.66 (m, 1H), 1.58 (d, J = 6.7 Hz, 3H), 1.26 (m, 2H), 1.08 (m, 2H) 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-((R)- 1-phenyl-ethyl)- amine 
               
               
                   
               
               
                 587 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 452.0 (M + H) 
                 (dmso-d6) 9.12 (br s, exch. H&#39;s), 9.06 (s, 1H), 8.21 (s, 1H), 8.09 (d, J = 6.4 Hz, 1H), 7.98 (br s, 1H), 7.680 (d, J = 6.3 Hz, 1H), 7.47 (m, 2H), 7.39 (m, 2H), 7.29 (m, 1H), 5.10 (m, 1H), 3.89 (br s, 4H), 3.33 (br s, 4H), 2.65 (m, 1H), 1.57 (d, J = 6.7 Hz, 3H), 1.26 (m, 2H), 1.08 (m, 2H) 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-((S)- 1-phenyl-ethyl)- amine 
               
               
                   
               
               
                 588 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 455.0 (M + H) 
                 (CDCl3) 9.05 (s, 1H), 8.95 (s, 1H), 8.40 (dd, J = 5.2; 0.3 Hz, 1H), 8.05 (s, 1H), 7.89 (dd, J = 5.2; 1.4 Hz, 1H), 7.76 (s, 1H), 7.51 (m, 1H), 6.95 (d, J = 7.8 Hz, 1H), 6.33 (d, J = 7.8 Hz, 1H), 4.10 (s, 3H), 375 (br s, 4H), 3.03 (m, 4H), 2.71 (m, 1H), 1.96 (br s, exch. H&#39;s), 1.27 (m, 2H), 1.01 (m, 2H) 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(6- methoxy-pyridin-2- yl)-amine 
               
               
                   
               
               
                 589 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 472.0 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2- fluoro-3-methoxy- phenyl)-amine 
               
               
                   
               
               
                 590 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 489.9 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,6- difluoro-4- methoxy-phenyl)- amine 
               
               
                   
               
               
                 591 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 468.0 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3- methoxy-2-methyl- phenyl)- amine 
               
               
                   
               
               
                 592 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.59 min, MI: 488 [M + H] 
                 1H NMR (DMSO, 500 MHz,) 9.06 (1H, s), 8.32 (1H, d), 8.19 (1H, s), 8.12 (1H, s), 7.80 (1H, dd), 7.76 (1H, d), 7.41 (1H, d), 6.72 (1H, dd), 3.92 (4H, s), 3.77 (3H, s), 3.33 (4H, s), 2.68 (1H, m), 1.26 (2H, m), 1.08 (2H, m). 
                 (2-Chloro-5- methoxy-phenyl)- [4-(5-cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- amine 
               
               
                   
               
               
                 594 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.19 min, MI: 442 [M + H] 
                 1H NMR (DMSO, 500 MHz), 9.55 (1H, s), 9.06 (1H, s), 8.31 (1H, d), 8.19 (1H, s), 7.93 (1H, s), 7.76-7.72 (3H, m), 7.16 (2H, t), 3.92 (4H, s), 3.33 (4H, s), 2.69 (1H, m), 1.25 (2H, m), 1.09 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(4- fluoro-phenyl)- amine 
               
               
                   
               
               
                 595 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.33 min, MI: 492 [M + H] 
                 1H NMR (DMSO, 500 MHz,) 9.86 (1H, s), 9.07 (1H, s), 8.43 (1H, d), 8.19 (1H, s), 8.02 (1H, s), 7.99 (2H, d), 7.83 (1H, dd), 7.64 (2H, d), 3.94 (4H, s), 3.34 (4H, s), 2.69 (1H, m), 1.27 (2H, m), 1.08 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(4- trifluoromethyl- phenyl)-amine 
               
               
                   
               
               
                 596 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.9 min, MI: 483 [M + H] 
                 1H NMR (DMSO, 500 MHz,) 9.07 (2H, s), 8.71 (1H, d), 8.40 (1H, d), 8.24 (1H, s), 8.19 (1H, s), 7.88 (1H, dd), 7.72 (1H, d), 7.48 (1H, dd), 3.92 (4H, s), 3.34 (4H, s), 2.69 (1H, m), 1.25 (2H, m), 1.08 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(4- trifluoromethyl- phenyl)-amine 
               
               
                   
               
               
                 597 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.41 min, MI: 526 [M + H] 
                 1H NMR (DMSO, 500 MHz,) 9.07 (1H, s), 9.02 (1H, s), 8.69 (1H, d), 8.39 (1H, d), 8.25 (1H, s), 8.19 (1H, s), 7.86 (1H, dd), 7.73 (1H, d), 7.36 (1H, dd), 3.94 (4H, s), 3.34 (4H, s), 2.69 (1H, m), 1.26 (2H, m), 1.08 (2H, m). 
                 (2-Chloro-5- trifluoromethyl- phenyl)- [4-(5-cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- amine 
               
               
                   
               
               
                 598 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 5.48 min, MI: [M + H] 
                 1H NMR (500 MHz, DMSO) 8.93 (1H, s), 8.13 (1H, d), 8.06 (1H, s), 7.74 (1H, s), 7.51 (1H, d), 6.87 (1H, s), 3.77 (4H, m, br), 2.83 (4H, m, br), 2.62-2.61 (1H, m), 1.66 (6H, s), 1.25-1.23 (2H, m), 1.02-1.01 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- (2,2,2-trifluoro-1,1- dimethyl-ethyl)- amine 
               
               
                   
               
               
                 599 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.85 min, MI: 460 [M + H] 
                 1H NMR (DMSO, 500 MHz,) 9.70 (1H, s), 9.06 (1H, s), 8.37 (1H, d), 8.18 (1H, s), 8.12-8.07 (1H, m), 7.94 (1H, s), 7.77 (1H, d), 7.37 (2H, m), 3.94 (4H, s), 3.34 (4H, s), 2.69 (1H, m), 1.27 (2H, m), 1.08 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3,4- difluoro-phenyl)- amine 
               
               
                   
               
               
                 600 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 428 
                 (dmso-d6) 9.39 (s, 1H), 8.97 (s, 1H), 8.37 (s, 1H), 8.25 (d, J = 5.3 Hz, 1H), 8.09 (s, 1H), 7.63 (dd, J = 5.2; 1.4 Hz, 1H), 7.53 (d, J = 2.2 Hz, 1H), 6.34 (d, J = 2.2 Hz, 1H), 3.77 (s, 3H), 3.70 (br s, 4H), 3.30- 3.32 (exch. H&#39;s), 2.85 (br s, 4H), 2.63 (m, 1H), 1.25 (m, 2H), 1.02 (m, 2H) 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(1- methyl-1H- pyrazol-3-yl)- amine 
               
               
                   
               
               
                 601 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.29 min, MI: 448.35 [M + H] 
                 1H NMR (500 MHZ, DMSO) 9.16 (2H, s, br), 9.06 (1H, s), 8.21 (1H, s), 8.08 (1H, d), 8.05 (1H, s), 4.85 (1H, d), 3.96 (4H, m, br), 3.80 (1H, s, br), 3.37-3.32 (4H, m), 2.66-2.62 (1H, m), 2.02-1.98 (2H, m), 1.87- 1.85 (2H, m), 1.73 (1H, t), 1.65-1.61 (3H, m), 1.27-1.23 (2H, m), 1.09- 1.06 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(4- fluorocyclohexyl)- amine 
               
               
                   
               
               
                 602 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.1 (M + H) 
                 (CDCl 3 ) 9.07 (s, 1H), 8.32 (d, J = 5.2 Hz, 1H), 8.08 (br s, 1H), 8.02 (s, 1H), 7.79 (d, J = 5.2 Hz, 1H), 7.24 (dd, J = 8.4 Hz, 1H), 7.06 (br s, 1H), 6.98 (br s, 1H), 6.82 (br d, J = 7.08 Hz, 1H), 6.69 (dd, J = 8.4; 1.9 Hz, 1H), 3.95 (m, 5H), 3.55 (m, br s, 1H), 3.25 (br s, 5H), 2.60 (m, 5H), 2.34 (s, 3H), 1.91 (m, 1H), 1.7 br s (exch. H&#39;s), 1.24 (m, 2H), 0.97 
                 (+/−)-(cis)-1-(5- Cylcopropyl-2-(2- [3-(4-methyl- piperazin-1-yl)- phenylamino]- pyridin-4-yl}- pyrido[3,4- d]pyrimidin-4-yl)- piperidine-3,4-diol 
               
               
                   
                   
                   
                   
                 (m, 2H) 
                   
               
               
                   
               
               
                 603 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 500.0 (MH)+ 
                   
                 (4-Cyclopropyl- 2,6-difluoro- phenyl)-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- amine 
               
               
                   
               
               
                 604 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 473.9 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,6- difluoro-4-methyl- phenyl)-amine 
               
               
                   
               
               
                 605 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 428.0 (M + H) 
                 (CDCl 3 ) 9.13 (s, 1H), 8.37 (d, J = 5.4 Hz, 1H), 8.05 (s, 1H), 7.81 (s, 1H), 7.73 (dd, J = 5.4; 1.3 Hz, 1H), 7.47 (br s, 1H), 7.37 (d, J = 1.5 Hz, 1H), 7.26 (s, 1H, *“shoulder” under solvent&#39;s peak), 3.77 (br s, 4H), 3.71 (s, 3H), 3.03 (m, 4H), 2.70 (m, 1H), 2.93 (br s, exch. H&#39;s), 1.26 (m, 2H), 1.01 (m, 2H) 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(1- methyl-1H- imidazol-4-yl)- amine 
               
               
                   
               
               
                 606 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 468.0 (M + H) 
                 (CDCl 3 ) 9.11 (s, 1H), 8.34 (d, J = 5.2 Hz, 1H), 8.04 (s, 1H), 8.01 (s, 1H), 7.78 (dd, J = 5.2; 1.3 Hz, 1H), 7.45 (m, 2H), 7.35 (m, 2H), 7.17 (br s, 1H), 7.06 (m, 1H), 3.79 (br s, 4H), 3.68 (m, 2H), 3.14 (br s, exch. H&#39;s), 2.63 (m, 5H), 2.60 (m, 2H), 1.26 (m, 2H), 1.0 (m, 2H) 
                 2-{4-[5- Cyclopropyl-2-(2- phenylamino- pyridin-4-yl)- pyrido[3,4- d]pyrimidin-4-yl]- piperazin-1-yl}- ethanol 
               
               
                   
               
               
                 607 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 498.0 (M + H) 
                 (CDCl 3 ) 9.11 (s, 1H), 8.35 (d, J = 5.2 Hz, 1H), 8.04 (s, 1H), 8.00 (s, 1H), 7.78 (dd, J = 5.3; 1.3 Hz, 1H), 7.45 (m, 2H), 7.35 (m, 2H), 7.06 (m, 1H), 6.98 (br s, 1H), 3.87 (m, 1H), 3.79 (m, 5H), 3.54 (d, J = 11.5; 4.4 Hz, 1H), 3.40-2.10 (br signal, —OH&#39;s), 2.78 (m, 2H), 2.64 (m, 2H), 2.58 (m, 2H), 2.40 (dd, J = 12.5 Hz,; 3.7 Hz, 1H), 1.25 (m, 2H), 1.00 (m, 2H) 
                 (S)-3-{4-[5- Cyclopropyl-2-(2- phenylamino- pyridin-4-yl)- pyrido[3,4- d]pyrimidin-4-yl]- piperazin-1-yl}- propane-1,2-diol 
               
               
                   
               
               
                 608 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 498.0 (M + H) 
                 (CDCl 3 ) 9.11 (s, 1H), 8.35 (d, J = 5.2 Hz, 1H), 8.04 (s, 1H), 8.00 (s, 1H), 7.78 (dd, J = 5.3; 1.3 Hz, 1H), 7.45 (m, 2H), 7.35 (m, 2H), 7.09 (br s, 1H), 7.06 (m, 1H), 3.87 (m, 1H), 3.79 (m, 5H), 3.54 (d, J = 11.5; 4.4 Hz, 1H), 3.40-2.10 (br signal, —OH&#39;s), 2.78 (m, 2H), 2.64 (m, 2H), 2.58 (m, 2H), 2.40 (dd, J = 12.5 Hz; 3.7 Hz, 1H), 1.25 (m, 2H), 1.00 (m, 2H) 
                 (R)-3-{4-[5- Cyclopropyl-2-(2- phenylamino- pyridin-4-yl)- pyrido[3,4- d]pyrimidin-4-yl]- piperazin-1-yl}- propane-1,2-diol 
               
               
                   
               
               
                 609 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 468.0 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3- methoxy-4-methyl- phenyl)-amine 
               
               
                   
               
               
                 610 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 484.0 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3,4- dimethoxy- phenyl)-amine 
               
               
                   
               
               
                 611 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 514.0 (MH)+ 
                   
                 [4-(5-Cylcopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- (3,4,5-trimethoxy- phenyl)-amine 
               
               
                   
               
               
                 612 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 466.15 (M + H) 
                   
                 N-[4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-2- phenyl-acetamide 
               
               
                   
               
               
                 613 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 458.15 (M + H) 
                   
                 N-[4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-3,3,3- trifluoro- propionamide 
               
               
                   
               
               
                 614 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.25 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-[4-(1- methyl-4-oxo-4λ 5 - [1,4]azaphos- phinan-4-yl)- phenyl]-amine 
               
               
                   
               
               
                 615 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 — 
                 449.10 (M + H) 
                   
                 2-(2-Chloro- pyridin-4-yl)-5- cyclopropyl-4-[3- (2,2,2-trifluoro- ethyl)-piperazin-1- yl]-pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 616 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.25 min, MI: 476 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.05 (2H, bs), 8.93 (1H, bs), 8.21 (1H, d), 8.17 (1H, s), 7.88 (1H, s), 7.73 (1H, dd), 7.48 (1H, m), 7.25 (1H, m), 4.68 (4H, bs), 3.89 (4H, bs), 2.70 (1H, m), 1.28-1.25 (2H, m), 1.06-1.05 (2H, m). 
                 (2-Chloro-6-fluoro- phenyl)-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- amine 
               
               
                   
               
               
                 617 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.36 min, MI: 490 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.04 (1H, s), 8.80 (1H, bs), 8.17 (1H, s), 8.15 (1H, d), 7.80 (1H, s), 7.67 (1H, d), 7.30 (1H, dd), 7.19 (1H, m), 3.91 (4H, bs), 3.31 (4H, bs), 2.68 (1H, m), 2.24 (3H, s), 1.23 (2H, m), 1.08-1.07 (2H, m). 
                 (6-Chloro-2-fluoro- 3-methyl-phenyl)- [4-(5-cylcopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- amine 
               
               
                   
               
               
                 618 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.62 min, MI: 494 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.05 (1H, s), 8.86 (1H, bs), 8.20 (1H, d), 8.17 (1H, s), 7.88 (1H, s), 7.73 (1H, dd), 7.47 (1H, m), 7.25 (1H, m), 3.89 (4H, bs), 3.31 (4H, bs), 2.68 (1H, m), 1.28-1.25 (2H, m), 1.08-1.07 (2H, m). 
                 (3-Chloro-2,6- difluoro-phenyl)- [4-(5-cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- amine 
               
               
                   
               
               
                 619 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.04 min, MI: 438 [M + H] 
                 NMR:- (1H, d6-dmso, 500 MHz) 9.30 (1H, s), 9.04 (1H, s), 8.69 (1H, s), 8.29 (1H, d), 7.90 (1H, s), 7.74 (2H, d), 7.65 (1H, dd), 7.27 (2H,tr), 6.89 (1H, tr), 4.26-4.20 (1H, m), 3.67 (2H, br s), 3.46 (2H, br s), 2.93 (2H, br s), 2.83 (2H, br s), 2.46-2.43 (2H, m partially hidden by large DMSO peak), 2.21-2.14 (2H, m), 
                 [4-(5-Cyclobutyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- phenyl-amine 
               
               
                   
                   
                   
                   
                 2.10-2.03 (1H, m), 1.92-1.86 (1H, 
                   
               
               
                   
                   
                   
                   
                 m). 
                   
               
               
                   
               
               
                 620 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.39 min, MI: 474 [M + H] 
                 NMR: (1H, d6-dmso, 500 MHz) 9.02 (1H, s), 8.75 (1H, s), 8.68 (1H, s), 8.14 (1H, d), 7.77 (1H, s), 7.63 (1H, dd), 7.29-7.23 (1H, m), 7.15 (2H, t), 4.22 (1H, dq), 3.63 (2H, br s), 3.50 (2H, br s), 2.90 (2H, br s), 2.78 (2H, br s), 2.44-2.42 (2H, m, partially obscured by DMSO peak), 2.20-2.12 (2H, m), 2.10- 
                 [4-(5-Cyclobutyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-2,6- difluoro-phenyl)- amine 
               
               
                   
                   
                   
                   
                 2.01 (1H, m), 1.91-1.86 (1H, m) 
                   
               
               
                   
               
               
                 621 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.24 min, MI: 452.37 [M + H] 
                 1H NMR (500 MHz, DMSO) 8.93 (1H, s), 8.13 (1H, d), 8.06 (1H, s), 7.53 (1H, s), 7.44 (1H, dd), 7.04 (1H, d), 4.42-4.38 (1H, m), 3.75- 3.57 (4H, m, br), 2.84 (4H, m), 2.62-2.58 (2H, m), 2.27-1.97 (4H, m), 1.77-1.69 (1H, m),, 1.26-1.22 (2H, m), 1.01-1.00 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3,3- difluoro- cyclopentyl)-amine 
               
               
                   
               
               
                 622 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 466.30 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3- isopropyl-phenyl)- amine 
               
               
                   
               
               
                 623 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 452.25 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3- ethyl-phenyl)- amine 
               
               
                   
               
               
                 624 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 — 
                 435.10 (M + H) 
                   
                 2-(2-Chloro- pyridin-4-yl)-5- cyclopropyl-4-(3- trifluoromethyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 625 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 599.20 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-[4-(1- ethyl-4-oxo-4λ 5 - [1,4]azaphos- phinan-4-yl)-2- methoxy-phenyl]- amine 
               
               
                   
               
               
                 626 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 472.00 (M + H) 
                   
                 N-(4-{5- Cyclopropyl-4-[3- (2,2,2-trifluoro- ethyl)-piperazin-1- yl]-pyrido[3,4- d]pyrimidin-2-yl}- pyridin-2-yl)- 
               
               
                   
                   
                   
                   
                   
                 acetamide 
               
               
                   
               
               
                 627 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 0.48 min, MI: 472 [M + H] 
                 1H NMR (DMSO, 500 MHz,) 9.62 (1H, s), 9.06 (1H, s), 8.32 (1H, d), 8.19 (1H, s), 7.96 (1H, s), 7.74 (1H, d), 7.62 (1H, dd), 7.28 (1H, m), 7.17-7.13 (1H, m), 3.85 (7H, m), 3.34 (4H, s), 2.68 (1H, m), 1.27 (2H, m), 1.09 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(4- fluoro-3-methoxy- phenyl)-amine 
               
               
                   
               
               
                 628 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.37 min, MI: 490 [M + H] 
                 1H NMR (DMSO, 500 MHz, 1IGO570) 9.27 (1H, s), 9.06 (1H, s), 8.30 (1H, d), 8.18 (1H, s), 8.06 (1H, s), 7.96 (1H, t), 7.78 (1H, dd), 7.39 (1H, t), 3.96 (4H, s), 3.84 (3H, s), 3.33 (4H, s), 2.68 (1H, m), 1.27 (2H, m), 1.08 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,4- difluoro-5- methoxy-phenyl)- amine 
               
               
                   
               
               
                 629 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.16 min, MI: 402.22 [M + H] 
                 1H NMR (500 MHz, CDCl3) 9.07 (1H, s), 8.21 (1H, s), 8.04 (2H, d), 7.65 (1H, d), 4.10-3.74 (8H, m, br), 3.26 (2H, d), 2.66-2.62 (1H, m), 1.28-1.24 (2H, m), 1.15-1.13 (1H, m), 1.09-1.07 (2H, m), 0.57-0.56 (2H, m), 0.32-0.31 (2H, m). 
                 Cyclopropylmethyl- [4-(5-cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- amine 
               
               
                   
               
               
                 630 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 1.61 min, MI: 362.19 [M + H] 
                 1H NMR (500 MHz, DMSO) 8.94 (1H, s), 8.12 (&#39;1H, d), 8.06 (1H, s), 7.48 (1H, s), 7.41 (1H, dd), 6.72 (1H, d), 3.77-3.55 (4H, m), 2.85 (4H, m, br), 2.82 (3H, d), 2.63-2.59 (1H, m), 1.25-1.22 (2H, m), 1.02- 1.00 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- methyl-amine 
               
               
                   
               
               
                 631 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.04 min, MI: 467 [M + H] 
                 1H NMR (DMSO, 500 MHz,) 10.30 (1H, s), 9.06 (1H, s), 8.50 (1H, d), 8.23 (1H, dd), 8.19 (1H, s), 8.05 (1H, s), 7.92 (1H ,dd), 7.75 (1H, t), 7.52 (1H, dd), 3.94 (4H, s), 3.33 (4H, s), 2.68 (1H, m), 1.26 (2H, m), 1.09 (2H, m). 
                 4-[4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2- ylamino]-2-fluoro- benzonitrile 
               
               
                   
               
               
                 632 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 1.96 min, MI: 438 [M + H] 
                 1H NMR (DMSO, 400 MHz, 90° C., 1IGO565_2) 8.99 (1H, s), 8.31 (1H, dd), 8.18 (1H, s), 7.95 (1H, s), 7.72 (1H, dd), 7.70-7.67 (2H, dd), 7.32 (2H, t), 6.97 (1H, t), 4.22 (2H, t), 4.05 (2H, t), 3.50 (2H, t), 3.20 (2H, t), 2.44 (1H, m), 2.11 (2H, quin), 1.27-1.23 (2H, m), 0.97-0.93 (2H, m). 
                 [4-(5-Cyclopropyl- 4-[1,4]diazepan-1- yl-pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- phenyl-amine 
               
               
                   
               
               
                 633 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.02 min, MI: 446.23 [M + H] 
                 1H NMR (500 MHz, DMSO) 8.92 (1H, s), 8.08 (1H, d), 8.06 (1H, s), 7.49 (1H, s), 7.35 (1H, dd), 6.61 (1H, d), 4.53 (1H, d), 3.83-3.67 (5H, m, br), 3.51-3.42 (1H, m), 2.85 (4H, m), 2.61-2.60 (1H, m), 2.53 (2H, m), 1.97-1.95 (2H, m), 1.85-1.83 (2H, m), 1.24-1.20 (6H, m), 1.01- 0.95 (6H, m). 
                 4-[4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2- ylamino]- cyclohexanol 
               
               
                   
               
               
                 634 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.29 min, MI: 506 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.06 (1H, s), 8.83 (1H, bs), 8.17 (1H, s), 8.16 (1H, d), 7.81 (1H, s), 7.67 (1H, dd), 7.25 (1H, t), 7.03 (1H, dd), 4.7 (4H, bs), 3.87 (3H, s), 3.31 (4H, m) 2.68 (1H, m), 1.26-1.23 (2H, m), 1.06-1.05 (2H, m). 
                 (2-Choro-6-fluoro- 3-methoxy- phenyl)-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- amine 
               
               
                   
               
               
                 635 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.53 min, MI: 494 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.05 (1H, s), 9.01 (1H, s), 8.86 (1H, bs), 8.18 (1H, s), 8.17 (1H, d), 7.87 (1H, s), 7.71 (1H, dd), 7.35 (1H, m), 3.89 (4H, bs), 3.31 (4H, m) 2.68 (1H, m), 2.35 (3H, s), 1.25-1.23 (2H, m), 1.08-1.06 (2H, m). 
                 (2-Chloro-3,6- difluoro-phenyl)- [4-(5-cyclopropyl- 4-piperaizn-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- amine 
               
               
                   
               
               
                 636 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 1.36 min, MI: 432 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.05 (1H, s), 9.01 (1H, s), 8.86 (1H, bs), 8.18 (1H, s), 8.17 (1H, d), 7.87 (1H, s), 7.71 (1H, dd), 7.35 (1H, m), 3.89 (4H, bs), 3.31 (4H, m) 2.68 (1H, m), 2.35 (3H, s), 1.25-1.23 (2H, m), 1.08-1.06 (2H, m). 
                 {4-[5-Cyclopropyl- 4-(2,2,3,3,5,5,6,6- octadeuterio- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}- 
               
               
                   
                   
                   
                   
                   
                 phenyl-amine 
               
               
                   
               
               
                 637 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 494.0 (MH)+ 
                   
                 (4-Cyclopropyl-3- methoxy-phenyl)- [4-(5-cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- amine 
               
               
                   
               
               
                 638 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 467.0 (M + H) 
                 (dmso-d6) 9.61 (br s, 1H), 8.95 (s, 1H), 8.21 (d, J = 5.6 Hz, 1H), 8.09 (s, 1H), 7.92 (s, 1H), 7.67 (dd, J = 5.6; 1.1 Hz, 1H), 7.63 (d, J = 7.8 Hz, 2H), 7.29 (dd, J = 7.8; 8.0 Hz, 2H), 6.96 (t, J = 7.2 Hz, 1H), 6.06 (br s, 2H), 3.47-3.95 (br m, 4H), 3.47-3.37 (m, 5H), 2.55 (m, 1H), 1.21 (m, 2H), 0.99 (m, 2H) 
                 4-[5-Cyclopropyl- 2-(2-phenylamino- pyridin-4-yl)- pyrido[3,4- d]pyrimidin-4-yl]- piperazine-1- carboxylic acidamide 
               
               
                   
               
               
                 639 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 502 (M + H) 
                   
                 N-[4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-2- (2,6-difluoro- phenyl)-acetamide 
               
               
                   
               
               
                 640 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 484.20 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2- fluoro-5-propyl- phenyl)-amine 
               
               
                   
               
               
                 641 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 482.15 
                   
                 (4-Cyclopropyl-2- fluoro-phenyl)-[4- (5-cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- amine 
               
               
                   
               
               
                 642 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.10 (M + H) 
                   
                 (4-{5-Cyclopropyl- 4-[3-(2,2,2- trifluoro-ethyl)- piperazin-1-yl]- pyrido[3,4- d]pyrimidin-2-yl}- pyridin-2-yl)-(2,6- 
               
               
                   
                   
                   
                   
                   
                 difluoro-phenyl)- 
               
               
                   
                   
                   
                   
                   
                 amine 
               
               
                   
               
               
                 643 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 506.20 (M + H) 
                   
                 (4-{5-Cyclopropyl- 4-[3-(2,2,2- trifluoro-ethyl)- piperazin-1-yl]- pyrido[3,4- d]pyrimidin-2-yl}- pyridin-2-yl)- 
               
               
                   
                   
                   
                   
                   
                 penyl-amine 
               
               
                   
               
               
                 644 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 470 (M + H) 
                 1H NMR (500 MHz, DMSO) 8.92 (1H, s), 8.05 (1H, s), 8.04 (1H, d), 7.55 (1H, s), 7.40 (1H, dd), 7.35- 7.29 (2H, m), 7.24 (1H, d), 7.21 (1H, d), 6.99 (1H, td), 5.08 (1H, t), 4.09-4.08 (1H, m), 3.78-3.51 (4H, m, br), 2.62-2.58 (1H, m), 1.44 (3H, d), 1.24-1.22 (2H, m), 1.01-1.00 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-[(R)- 1-(3-fluoro- phenyl)-ethyl]- amine 
               
               
                   
               
               
                 645 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.83 min, MI: 449 [M + H] 
                 1H NMR (DMSO, 500 MHz,) 9.98 (1H, s), 9.05 (1H, s), 8.44 (1H, d), 8.18 (1H, s), 8.02 (1H, s), 7.97 (2H, d), 7.85 (1H, dd), 7.72 (2H, d), 3.92 (4H, s), 3.33 (4H, s), 2.68 (1H, m), 1.25 (2H, m), 1.07 (2H, m). 
                 4-[4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2- yalmino]- benzonitrile 
               
               
                   
               
               
                 646 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 4.3 min, MI: 492 [M + H] 
                 1H NMR (DMSO, 500 MHz,) 9.79 (1H, s), 9.06 (1H, s), 8.42 (1H, d), 8.34 (1H, s), 8.18 (1H, s), 7.99 (1H, s), 7.94 (1H, d), 7.80 (1H, dd), 7.52 (1H, t), 7.24 (1H, d), 3.92 (4H, s), 3.34 (4H, s), 2.69 (1H, m), 1.27 (2H, m), 1.09 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3- trifluoromethyl- phenyl)-amine 
               
               
                   
               
               
                 649 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.44 min, MI: 490 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.04 (1H, s), 8.79 (1H, bs), 8.17 (1H, s), 8.15 (1H, d), 7.80 (1H, s), 7.66 (1H, dd), 7.27 (1H, dd), 7.20 (1H, t), 3.88 (4H, bs), 3.31 (4H, m) 2.68 (1H, m), 2.35 (3H, s), 1.26-1.23 (2H, m), 1.08-1.06 (2H, m). 
                 (3-Chloro-2,6- difluoro-phenyl)- [4-(5-cylcopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- amine 
               
               
                   
               
               
                 650 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.26 min, MI: 478 [M + H] 
                 1H NMR (DMSO, 500 MHz,) 9.06 (1H, s), 8.85 (1H, s), 8.18 (2H, s), 7.84 (1H, s), 7.71 (1H, dd), 7.29 (2H, t), 3.90 (4H, s), 3.33 (4H, s), 2.69 (1H, m), 1.25 (2H, m), 1.08 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- (2,4,6-trifluoro- phenyl)-amine 
               
               
                   
               
               
                 651 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.22 min, MI: 460 [M + H] 
                 1H NMR (DMSO, 500 MHz, 1IGO581) 9.13 (1H, s), 9.06 (1H, s), 8.28 (1H, d), 8.18 (1H, s), 8.12-8.07 (1H, m), 8.02 (1H, s), 7.75 (1H, dd), 7.35-7.30 (1H, m), 7.11-7.06 (1H, m), 3.92 (4H, s), 3.33 (4H, s), 2.69 (1H, m), 1.26 (2H, m), 1.08 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,4- difluoro-phenyl)- amine 
               
               
                   
               
               
                 652 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.71 min, MI: 470.37 [M + H] 
                 1H NMR (500 MHz, DMSO) 8.92 (1H, s), 8.05 (1H, s), 8.03 (1H, d), 7.63 (1H, s), 7.42 (2H, dd), 7.39 (1H, dd), 7.26 (1H, d), 7.15 (1H, t), 7.10 (2H, t), 5.06 (1H, 03.77-3.52 (4H, m), 2.83 (4H, m), 2.62-2.58 (1H, m), 1.43 (3H, s), 1.30 (1H, d), 1.24-1.22 (2H, m), 1.01-1.00 (2H, m). 
                 4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-[(R)- 1(4-fluoro- phenyl)-ethyl]- amine 
               
               
                   
               
               
                 653 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 5.46 min, MI: 488.35 [M + H] 
                 1H NMR (500 MHz, DMSO) 8.92 (1H, s), 8.06 (1H, s), 8.04 (1H, d), 7.61 (1H, d), 7.39 (1H, dd), 7.27 (1H, dt), 7.24 (1H, d), 7.00 (2H, t), 5.47 (1H, t), 3.78-3.54 (4H, m), 2.86 (4H, m), 2.63-2.62 (2H, m), 2.37- 2.35 (1H, m), 1.55 (3H, d), 1.24- 1.22 (2H, m), 1.01-1.00 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-[(R)- 1-(2,6-difluoro- phenyl)-ethyl]- amine 
               
               
                   
               
               
                 654 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.31 min, MI: 442.34 [M + H] 
                 1H NMR (500 MHz, DMSO) 9.28 (1H, s), 8.93 (1H, s), 8.24 (1H, d), 8.11 (1H, s), 7.66 (1H, d), 7.62 (2H, d), 7.26 (2H, t), 6.89 (1H, t), 3.68 (4H, s, br), 3.15 (1H, d), 2.82 (4H, s, br), 2.59-2.57 (1H, m), 1.26-1.24 (2H, m), 1.03-1.02 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- 5-fluoro-pyridin-2- yl]-phenyl-amine 
               
               
                   
               
               
                 655 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544 (M + H) 
                   
                 1-{5-Cyclopropyl- 2-[2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidine-4- carboxylic acid isopropylamide 
               
               
                   
               
               
                 656 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 502 (M + H) 
                   
                 1-{5-Cyclopropyl- 2-[2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidine-4- carboxylic acid amide 
               
               
                   
               
               
                 657 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 516 (M + H) 
                   
                 N-(1-{5- Cyclopropyl-2-[2- (2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidin-4-yl)- acetamide 
               
               
                   
               
               
                 658 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 548 (M + H) 
                   
                 1-{5-Cyclopropyl- 2-[2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidine-4- carboxylic acid (2- fluoro-ethyl)-amide 
               
               
                   
               
               
                 659 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 458 
                   
                 N-{4-[5- Cyclopropyl-4- ((S)-3- trifluoromethyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidine-2-yl]- pyridin-2-yl}- acetamide 
               
               
                   
               
               
                 660 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 — 
                 435 
                   
                 2-(2-Chloro- pyridin-4-yl)-5- cyclopropyl-4- ((R)-3- trifluoromethyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 661 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 482 
                   
                 (4-{5-Cyclopropyl- 4-[4-(2-methoxy- ethyl)-piperazin-1- yl]-pyrido[3,4- d]pyrimidin-2-yl}- pyridin-2-yl)- phenyl-amine 
               
               
                   
               
               
                 662 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 500 
                   
                 (4-{5-Cyclopropyl- 4-[4-(2-methoxy- ethyl)-piperazin-1- yl]-pyrido[3,4- d]pyrimidin-2-yl}- pyridin-2-yl)-(4- fluoro-phenyl- amine 
               
               
                   
               
               
                 663 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 530 
                   
                 (4-{5-Cyclopropyl- 4-{4-(2- methanesulfonyl- ethyl)-piperazin-1- yl]-pyrido[3,- d]pyrimidin-2-yl}- pyridin-2-yl)- phenyl-amine 
               
               
                   
               
               
                 664 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 548 
                   
                 (4-{5-Cyclopropyl- 4-[4-(2- methanesulfonyl- ethyl)-piperazin-1- yl]-pyrido[3,4- d]pyrimidin-2-yl}- pyridin-2-yl)-(4- fluoro-phenyl)- amine 
               
               
                   
               
               
                 665 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 522 
                   
                 Cyclopropane- carboxylic acid (4- {5-cyclopropyl-4- [4-(2- methanesulfonyl- ethyl)-piperazin-1- yl]-pyrido[3,4- d]pyrimidin-2-yl}- pyridin-2-yl)- amide 
               
               
                   
               
               
                 666 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 474 
                   
                 Cyclopropane- carboxylic acid (4- {5-cyclopropyl-4- [4-(2-methoxy- ethyl)-piperazin-1- yl]-pyrido[3,4- d]pyrimidin-2-yl}- pyridin-2-yl)- amide 
               
               
                   
               
               
                 667 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 482 
                   
                 (5-Cyclopropyl-2- fluoro-phenyl)-[4- (5-cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- amine 
               
               
                   
               
               
                 668 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 599 (M + H) 
                   
                 1-{5-Cyclopropyl- 2-[2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidine-4- carboxylic acid (2- pyrrolidin-1-yl- ethyl)-amide 
               
               
                   
               
               
                 669 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 516 (M + H) 
                   
                 1-{5-Cyclopropyl- 2-[2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidine-4- carboxylic acid methylamide 
               
               
                   
               
               
                 670 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 461.2 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,4- difluoro-pyridin-3- yl)-amine 
               
               
                   
               
               
                 671 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 461.0 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,6- difluoro-pyridin-3- yl)-amine 
               
               
                   
               
               
                 672 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 443.1 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(6- fluoro-pyridin-3- yl)-amine 
               
               
                   
               
               
                 673 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.41 min, MI: 466.32 [M + H] 
                 1H NMR (500 MHz, DMSO) 9.05 (1H, s), 8.19 (1H, s), 8.10 (1H, d), 7.91 (1H, s, br), 7.64 (1H, d, br), 3.98-3.80 (5H, m), 3.31 (4H, m, br), 2.67-2.62 (1H, m), 2.03-2.01 (2H, m), 1.94-1.79 (3H, m), 1.54-1.51 (1H, m), 1.35-1.32 (1H, m), 1.26- 1.24 (2H, m), 1.07-1.06 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3,3- difluoro- cyclohexyl)-amine 
               
               
                   
               
               
                 674 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 514 (M + H) 
                   
                 1-[2-(2- Cyclohexylamino- pyridin-4-yl)-5- cyclopropyl- pyrido[3,4- d]pyrimidin-4-yl]- piperidine-4- carboxylic acid isopropylamide 
               
               
                   
               
               
                 675 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 455.1 
                 (dmso-d6) 9.84 (br s, 1H), 8.98 (s, 1H), 8.26 (d, J = 5.7 Hz, 1H), 8.12 (s, 1H), 7.99 (s, 1H), 7.74 (dd, J = 5.7; 1.2 Hz, 1H), 7.67 (d, J = 7.8 Hz, 2H), 7.38 (app t, J = 8.00 Hz, 2H), 7.07 (app t, 6.8 Hz, 1H), 4.19 (large br s, exch. H&#39;s), 3.77 (br s, 4H), 3.70-3.47 (m, 2H), 3.47-3.25 
                 (+/−)-(cis)-1-[5- Cyclopropyl-2-(2- phenylamino- pyridin-4-yl- pyrido[3,4- d]pyrimidin-4-yl]- piperidine-3,4-diol 
               
               
                   
                   
                   
                   
                 (m, 1H), 3.13-1.78 (m, 1H), 1.68 (br 
                   
               
               
                   
                   
                   
                   
                 s, 1H), 1.47-1.13 (m, 2H), 1.13-0.87 
                   
               
               
                   
                   
                   
                   
                 (m, 2H) 
               
               
                   
               
            
           
         
       
     
     The following compounds were synthesised according to the general synthesis shown in scheme [B4] 
     
       
         
           
               
               
               
               
               
            
               
                   
               
               
                   
                   
                   
                 Analysis  
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Ex 
                 Amine 1 
                 Amine 2 
                 LCMS 
                 NMR 
                 Name 
               
               
                   
               
               
                 676 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 455.1 (M + H) 
                 NMR (dmso-d6) 9.74 (br s, 1H), 8.98 (s, 1H), 8.27 (d, J = 5.6 Hz, 1H), 8.13 (s, 1H), 7.98 (s, 1H), 7.73 (d, J = 6.4 Hz, 1H), 7.68 (d, J = 8.0 Hz, 2H), 7.36 (app t, J = 8.0 Hz, 2H), 7.04 (app t, J = 7.2 Hz, 
                 (+/−)-(trans)-1-[5- Cyclopropyl-2-(2- phenylamino- pyridin-4-yl)- pyrido[3,4- d]pyrimidin-4-yl]- piperidine-3,4-diol 
               
               
                   
                   
                   
                   
                 1H), 3.80 (large br s, 
                   
               
               
                   
                   
                   
                   
                 exch. H&#39;s - overlapping 
                   
               
               
                   
                   
                   
                   
                 other signals), 3.52 (br s, 
                   
               
               
                   
                   
                   
                   
                 2H), 3.40-3.35 (m, 2H), 
                   
               
               
                   
                   
                   
                   
                 2.23-1.83 (m, 2H), 1.55 
                   
               
               
                   
                   
                   
                   
                 (br s, 1H), 1.49 (br s, 
                   
               
               
                   
                   
                   
                   
                 1H), 1.35 (br s, 1H), 
                   
               
               
                   
                   
                   
                   
                 1.12-0.92 (m, 2H) 
                   
               
               
                   
               
               
                 677 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 481.1 (M + H) 
                 (CDCl 3 ) 10.39 (br s, 1H), 8.97 (br s, 1H), 8.65 (s, 1H), 8.50 (d, J = 4.8 Hz,  1H), 8.46 (d, J = 5.2 Hz,  1H), 8.35 (s, 1H), 8.10 (s, 1H), 7.89 (d, J = 4.9 Hz, 1H), 7.30 (d, J = 4.9 Hz, 1H), 5.25-4.65 
                 (+/−)-2-{4-[5- Cyclopropyl-4- ((trans)-3,4- dihydroxy- piperidin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-ylamino}- 
               
               
                   
                   
                   
                   
                 (m, 2H), 4.40-3.70 (m, 
                 isonicotinonitrile 
               
               
                   
                   
                   
                   
                 4H), 3.52 (br s, 1H), 
                   
               
               
                   
                   
                   
                   
                 2.25-1.85 (m, 1H), 1.65- 
                   
               
               
                   
                   
                   
                   
                 1.50 (m, 1H), 1.50-1.15 
                   
               
               
                   
                   
                   
                   
                 (m, 3H), 1.10-0.90 (m, 2H) 
                   
               
               
                   
               
               
                 678 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.26 (M + H) 
                 (CDCl 3 ) 9.16 (s, 1H), 8.94 (s, 1H), 8.30 (d, J = 5.3 Hz, 1H), 8.08 (s, 1H), 7.91 (s, 1H), 7.66 (dd, J = 5.2; 1.0 Hz, 1H), 7.34 (app t, J = 2.0 Hz, 1H), 7.22 (dd, J = 8.0; 1.1 Hz, 1H), 7.11 (app t, J = 8.1 Hz, 1H), 6.52 (dd, J = 8.2; 1.8 Hz, 1H), 
                 (+/−)-(trans)-1-(5- Cyclopropyl-2-{2- [3-(4-methyl- piperazin-1-yl)- phenylamino]- pyridin-4-yl}- pyrido[3,4d]pyrimidin- 4-yl)-piperidine- 3,4-diol 
               
               
                   
                   
                   
                   
                 5.28-4.67 (m, 2H), 4.28- 
                   
               
               
                   
                   
                   
                   
                 3.71 (m, 2H), 3.50 (br s, 
                   
               
               
                   
                   
                   
                   
                 1H), 3.15-3.11 (m, 4H), 
                   
               
               
                   
                   
                   
                   
                 2.61-2.53 (m, 1H), 2.49- 
                   
               
               
                   
                   
                   
                   
                 2.45 (m, 4H), 2.23 (s, 
                   
               
               
                   
                   
                   
                   
                 3H), 2.18-1.73 (m, 2H), 
                   
               
               
                   
                   
                   
                   
                 1.44-1.11 (m, 3H), 1.10- 
                   
               
               
                   
                   
                   
                   
                 0.90 (m, 2H) 
                   
               
               
                   
               
               
                 679 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 500 (M + H) 
                   
                 1-[2-(2- Cyclopentylamino- pyridin-4-yl)-5- cyclopropyl- pyrido[3,4- d]pyrimidin-4-yl]- piperidine-4- carboxylicacid isopropylamide 
               
               
                   
               
               
                 680 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 479.1 (M + H)+ 
                   1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 9.69 (s, 1 H) 8.98 (s, 1 H) 8.81 (s, 1 H) 8.40 (dd, J = 5.3, 0.8 Hz, 1 H) 8.21- 8.30 (m, 1 H) 8.10 (s, 1 H) 7.92 (dd, J = 5.1, 1.4 Hz,  1 H) 3.77 (d, J = 11.3 Hz,  4 H) 2.85 (br. s., 4 H)  2.59-2.65 (m, 1 H) 
                 4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3,5,6- trifluoro-pyridin-2- yl)-amine 
               
               
                   
                   
                   
                   
                 1.21-1.31 (m, 3 H) 1.00-  
                   
               
               
                   
                   
                   
                   
                 1.07 (m, 2 H) 
                   
               
               
                   
               
               
                 681 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 522.19 (M + H) 
                 1H NMR (400 MHz, DMSO-d6) 9.55 (1 H, s), 9.07 (1 H, s), 8.73-9.00 (2 H, m), 8.38 (1 H, d, J = 5.5 Hz), 8.19 (1 H, s), 7.99 (1 H, s), 7.87 (2 H, d, J = 8.5 Hz), 7.75 (1 H, dd, J = 5.3, 1.3 Hz), 7.60- 7.69 (4 H, m), 7.45 (2 H, t, J = 7.7 Hz), 7.25-7.36 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-[3-(4- methyl-piperazin-1- yl)-phenyl]-amine 
               
               
                   
                   
                   
                   
                 (1 H, m), 3.94 (4 H, br. 
                   
               
               
                   
                   
                   
                   
                 s.), 3.34 (4 H, br. s.), 
                   
               
               
                   
                   
                   
                   
                 2.70 (1 H, br. s.), 1.21- 
                   
               
               
                   
                   
                   
                   
                 1.31 (2 H, m), 1.09 (2 H, 
                   
               
               
                   
                   
                   
                   
                 d, J = 3.5 Hz) 
                   
               
               
                   
               
               
                 682 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 479.1 (M + H)+ 
                 1H NMR (400 MHz, DMSO-d6) 9.82 (1 H, s), 9.07 (1 H, s), 8.69-8.99 (2 H, m), 8.43 (1 H, d, J = 5.3 Hz), 8.19 (1 H, s), 8.03 (1 H, s), 7.88 (4 H, s), 7.82 (1 H, dd, J = 5.3, 1.3 Hz), 3.94 (4 H, br. s.), 3.34 (4 H, br. s.), 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,3,6- trifluoro-pyridin-4- yl)-amine 
               
               
                   
                   
                   
                   
                 2.67-2.75 (1 H, m), 
                   
               
               
                   
                   
                   
                   
                 1.26 (2 H, d, J = 8.5 Hz), 
                   
               
               
                   
                   
                   
                   
                 1.09 (2 H, d, J = 5.5 Hz) 
                   
               
               
                   
               
               
                 683 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 500 (M + H) 
                   
                 Biphenyl-4-yl-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
               
               
                 684 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 468 (M + H) 
                   
                 4-[4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-ylamino]- benzoic acid 
               
               
                   
               
               
                 685 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 546 (M + H) 
                   
                 1-{5-Cyclopropyl-2- [2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidine-4- carboxylic acid (2- hydroxy-ethyl)- amide 
               
               
                   
               
               
                 686 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 530 (M + H) 
                   
                 1-{5-Cyclopropyl-2- [2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidine-4- carboxylic acid dimethylamide 
               
               
                   
               
               
                 687 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 565.18 (M + H) 
                 (dmso-d6) 9.99 (br s, 1H), 9.87 (s, 1H), 9.02 (s, 1H), 8.26 (d, J = 5.8 Hz,  1H), 8.16 (s, 1H), 8.02 (s, 1H), 7.76 (dd,  J = 5.8; 1.4 Hz, 1H), 7.37 (s, 1H), 7.27 (app t, J = 8.1 Hz, 1H), 7.15 (d, J = 8.1 Hz, 1H), 6.75 (dd, J =  8.2; 1.6 Hz, 1H), 6.13 
                 4-(5-Cyclopropyl-2- {2-[3-(4-methyl- piperazin-1-yl)- phenylamino]- pyridin-4-yl}- pyrido[3,4- d]pyrimidin-4-yl)- piperazine-1- carboxylic acid amide 
               
               
                   
                   
                   
                   
                 (br s, 1H), 4.56 (br s, 
                   
               
               
                   
                   
                   
                   
                 exchangeable H&#39;s), 3.87- 
                   
               
               
                   
                   
                   
                   
                 3.81 (m, 4H), 3.67 (br s, 
                   
               
               
                   
                   
                   
                   
                 2H), 3.60-3.50 (m, 7H), 
                   
               
               
                   
                   
                   
                   
                 3.19 (br s, 2H), 3.01 (app 
                   
               
               
                   
                   
                   
                   
                 t, J = 12.2 Hz, 2H), 2.89 
                   
               
               
                   
                   
                   
                   
                 (s, 3H), 2.65-2.60 (m, 
                   
               
               
                   
                   
                   
                   
                 1H), 1.31-1.26 (m, 2H), 
                   
               
               
                   
                   
                   
                   
                 1.09-1.04 (m, 2H) 
                   
               
               
                   
               
               
                 688 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 537.3 (M + H) 
                 (dmso-d6) 9.17 (s, 1H), 8.96 (s, 1H), 8.30 (d, J = 5.3 Hz, 1H), 8.09 (s, 1H), 7.92 (s, 1H), 7.66 (dd, J = 5.3; 1.4 Hz, 1H), 7.34 (app t, J = 2.0 Hz, 1H), 7.22 (dd, J = 8.0; 1.2 Hz, 1H), 7.11 (app t, J = 8.0 Hz, 1H), 6.52 (dd, J = 8.2 Hz; 1.8 Hz, 
                 1-(5-Cyclopropyl-2- {2-[3-(4-methyl- piperazin-1-yl)- phenylamino]- pyridin-4-yl}- pyrido[3,4- d]pyrimidin-4-yl)- piperidin-4-ol 
               
               
                   
                   
                   
                   
                 1H), 4.82 (br s, 1H), 4.1- 
                   
               
               
                   
                   
                   
                   
                 4.06 (m, 2H), 3.79 (br s, 
                   
               
               
                   
                   
                   
                   
                 1H), 3.51 (br s, 2H), 
                   
               
               
                   
                   
                   
                   
                 3.15-3.11 (m, 4H), 2.50 
                   
               
               
                   
                   
                   
                   
                 (br s, 1H), 2.50-2.45 (m, 
                   
               
               
                   
                   
                   
                   
                 4H), 2.23 (s, 3H), 1.91- 
                   
               
               
                   
                   
                   
                   
                 1.87 (m, 2H), 1.54 (br s, 
                   
               
               
                   
                   
                   
                   
                 2H), 1.27-1.24 (m, 2H), 
                   
               
               
                   
                   
                   
                   
                 1.04-1.02 (m, 2H) 
                   
               
               
                   
               
               
                 689 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 — 
                 method 5:  RT: 2.86 min, MI: 351.25 [M + H] 
                 1H NMR (500 MHz, DMSO) 8.98 (1H, s), 8.41 (1H, d), 8.26 (1H, d), 8.11 (1H, s), 7.95 (1H, d), 3.79-3.61 (4H, m), 2.83 (4H, m), 2.65- 2.57 (1H, m), 1.26-1.24 (2H, m), 1.03-1.01 (2H, m). 
                 5-Cyclopropyl-2-(2- fluoro-pyridin-4-yl)- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 690 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 474 (M + H) 
                   
                 {4-[4-(4-Amino- piperidin-1-yl)-5- cyclopropyl- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(2,6- difluoro-phenyl)- amine 
               
               
                   
               
               
                 691 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.43 min, MI: 456 [M + H] 
                 1H NMR (DMSO, 400 MHz, 1IG0596, 90° C.) 9.06 (1H, s), 8.32 (1H, dd), 8.22 (1H, s), 8.10-8.05 (1H, td), 7.98 (1H, s), 7.75 (1H, dd), 7.25-7.15 (2H, m), 7.09-7.03 (1H, m), 4.30 
                 {4-[5-Cyclopropyl- 4-((S)-3-methyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(2- fluoro-phenyl)- amine 
               
               
                   
                   
                   
                   
                 (2H, m), 3.55 (2H, m), 
                   
               
               
                   
                   
                   
                   
                 3.42 (1H, m), 3.36-3.23 
                   
               
               
                   
                   
                   
                   
                 (2H, m), 2.66 (1H, m), 
                   
               
               
                   
                   
                   
                   
                 1.32 (3H, d), 1.26 (2H, 
                   
               
               
                   
                   
                   
                   
                 m), 1.05 (2H, m). 
                   
               
               
                   
               
               
                 692 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.42 min, MI: 474 [M + H] 
                 1H NMR (DMSO, 500 MHz, 1IG0593) 9.06 (1H, s), 8.22 (2H, m), 7.76 (1H, s), 7.71 (1H, dd), 7.32-7.25 (1H, m), 7.16 (2H, m), 2.67 (1H, m), 1.31 (3H, d), 1.26 (2H, m), 1.05 (2H, m). 
                 {4-[5-Cyclopropyl- 4-((S)-3-methyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(2,6- difluoro-phenyl)- amine 
               
               
                   
                   
                   
                   
                 [methyl piperazine side 
                   
               
               
                   
                   
                   
                   
                 chain peaks not 
                   
               
               
                   
                   
                   
                   
                 integrated). 
                   
               
               
                   
               
               
                 693 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.27 min, MI: 456 [M + H] 
                 1H NMR (DMSO, 400 MHz, 1IG0594, 90° C.) 9.07 (1H, s), 8.32 (1H, dd), 8.22 (1H, s), 7.90 (1H, s), 7.70 (3H, m), 7.11 (2H, m), 4.34 (2H, m), 3.55 (2H, m), 3.43 (1H, m), 3.30 (2H, 
                 {4-[5-Cyclopropyl- 4-((S)-3-methyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(4- fluoro-phenyl)- amine 
               
               
                   
                   
                   
                   
                 m), 2.67 (1H, m), 1.32 
                   
               
               
                   
                   
                   
                   
                 (3H, d), 1.24 (2H, m), 
                   
               
               
                   
                   
                   
                   
                 1.04 (2H, m). 
                   
               
               
                   
               
               
                 694 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT:  2.65 min, MI: 475 [M + H] 
                 1H NMR (DMSO, 400 MHz, 1IG0595, 90° C.) 9.08 (1H, s), 8.94 (1H, m), 8.46 (1H, dd), 8.23 (1H, s), 8.00 (1H, dd), 7.83-7.77 (1H, m), 6.69-6.65 (1H, m), 4.36 (2H, m), 3.58 (2H, m), 
                 {4-[5-Cyclopropyl- 4-((S)-3-methyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(3,6- difluoro-pyridin-2- yl)-amine 
               
               
                   
                   
                   
                   
                 3.46-3.27 (3H, m), 2.67 
                   
               
               
                   
                   
                   
                   
                 (1H, m), 1.31 (3H, d), 
                   
               
               
                   
                   
                   
                   
                 1.27 (2H, m), 1.05 (2H, m). 
                   
               
               
                   
               
               
                 695 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 442 (M + H) 
                   
                 (+/−)- (1RS,2RS,4SR)- Bicyclo[2.2.1]hept- 2-yl-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
               
               
                 696 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 488 (M + H) 
                 1H NMR (400 MHz, DMSO-d6) 9.07 (1 H, s), 8.93 (2 H, br. s.), 8.22 (1 H,  s), 8.07 (1 H, d, J = 6.3 Hz),  7.80-8.03 (1 H, m), 7.65 (1H, br. s.), 3.91-4.00 (2 H, m), 3.61- 3.65 (4 H, m), 3.27 -3.34 (4 H, m), 2.62- 2.67(1 H, m), 
                 {4-[4-(4- Aminomethyl- piperidin-1-yl)-5- cyclopropyl- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(2,6- difluoro-phenyl)- amine 
               
               
                   
                   
                   
                   
                 2.30 (1 H, br. s.), 1.85 (1 H,  
                   
               
               
                   
                   
                   
                   
                 br. s.), 1.41-1.64 (4 H,  
                   
               
               
                   
                   
                   
                   
                 m), 1.12-1.38 (6 H, 
                   
               
               
                   
                   
                   
                   
                 m), 1.01-1.12 (2 H, m) 
                   
               
               
                   
               
               
                 697 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 438.1 (MH)+ 
                   
                 [5-Cyclopropyl-2- (2-phenylamino- pyridin-4-yl)- pyrido[3,4- d]pyrimidin-4-yl]- (S)-1-pyrrolidin-2- ylmethyl-amine 
               
               
                   
               
               
                 698 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 474.3 (MH)+ 
                   
                 {5-Cyclopropyl-2- [2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- (S)-1-pyrrolidin-2- 
               
               
                   
                   
                   
                   
                   
                 ylmethyl-amine 
               
               
                   
               
               
                 699 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.19 min, MI: 456 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.49 (1H, s), 8.96 (1H, s), 8.30 (1H, d), 8.14 (1H, s), 7.91 (1H, s), 7.76 (2H, m), 7.71 (1H, dd), 7.17 (2H, m), 4.17 (2H, m), 4.01 (2H, m), 3.49 (2H, m), 3.16 
                 [4-(5-Cyclopropyl- 4-[1,4]diazepan-1- yl-pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(4- fluoro-phenyl)- amine 
               
               
                   
                   
                   
                   
                 (2H, m), 2.35 (1H, m), 
                   
               
               
                   
                   
                   
                   
                 2.06 (2H, m), 1.24 (2H, 
                   
               
               
                   
                   
                   
                   
                 m), 0.97 (2H, m). 
                   
               
               
                   
               
               
                 700 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.59 min, MI: 414.29 [M + H] 
                 1H NMR (500 MHz, DMSO) 8.94 (1H, s), 8.18 (1H, d), 8.06 (1H, s), 7.58 (1H, s), 7.46 (1H, dd), 7.39 (1H, s), 3.74-3.63 (4H, m), 2.88 (4H, m), 2.62-2.60 (2H, m), 2.09 (6H, s), 1.24- 1.22 (2H, m), 1.01-0.99 
                 Bicyclo[1.1.1]pent- 1-yl-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
                   
                   
                   
                 (4H, m). 
                   
               
               
                   
               
               
                 701 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.76 min, MI: 442.33 [M + H] 
                 1H NMR (500 MHz, DMSO) 8.98 (1H, d), 8.94 (1H, s), 8.11 (1H, s), 8.06 (1H, d), 7.81 (2H, d), 7.42 (1H, t), 7.28 (2H, t), 6.95 (1H, t), 3.73 (4H, s, br), 2.82 (4H, s, br), 2.63-2.57 (1H, m), 1.27-1.25 (2H, 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)-3- fluoro-pyridin-2-yl]- phenyl-amine 
               
               
                   
                   
                   
                   
                 m), 1.03-1.02 (2H, m). 
                   
               
               
                   
               
               
                 702 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.35 min, MI: 474 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.04 (1H, s), 8.98 (1H, s), 8.18 (1H, d), 8.15 (1H, s), 7.84 (1H, s), 7.71 (1H, dd), 7.31 (1H, m), 7.19 (2H, t), 4.18 (2H, m), 4.01 (2H, 
                 [4-(5-Cyclopropyl- 4-[1,4]diazepan-1- yl-pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,6- difluoro-phenyl)- amine 
               
               
                   
                   
                   
                   
                 m), 3.47 (2H, m), 3.16 
                   
               
               
                   
                   
                   
                   
                 (2H, m), 2.35 (1H, m), 
                   
               
               
                   
                   
                   
                   
                 2.06 (2H, m), 1.26 (2H, 
                   
               
               
                   
                   
                   
                   
                 m), 0.98 (2H, m). 
                   
               
               
                   
               
               
                 703 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.19 min, MI: 420.29 [M + H] 
                 1H NMR (500 MHz, DMSO) 8.93 (1H, s), 8.11 (1H, d), 9.06 (1H, s), 7.48 (1H, s), 7.44 (1H, dd), 7.14 (1H, d), 5.34-5.20 (1H, m), 4.85 (1H, m, br), 3.77-3.56 (5H, m, br), 2.84 (4H, s), 2.62-2.59 (2H, m), 2.36- 
                 (+/−)cis-[4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d] pyrimidin-2-yl)- pyridin-2-yl]-(3- fluoro-cyclobutyl)- amine 
               
               
                   
                   
                   
                   
                 2.27 (2H, m), 1.26-1.23 
                   
               
               
                   
                   
                   
                   
                 (2H, m), 1.03-1.00 (2H, m). 
                   
               
               
                   
               
               
                 704 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 461.54 
                   1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 9.39 (s, 1 H) 8.98 (s, 1 H) 8.67 (s, 1 H) 8.35 (d, J = 5.3 Hz, 1 H) 8.22 (d, J = 2.5 Hz, 1 H) 8.10 (s,  1 H) 7.94 (ddd, J = 10.7, 8.3, 2.6 Hz, 1 H) 7.84 (dd, J = 5.1, 1.4 Hz, 1 H) 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3,5- difluoro-pyridin-2- yl)-amine 
               
               
                   
                   
                   
                   
                 3.58-3.86 (m, 4 H) 2.85 
                   
               
               
                   
                   
                   
                   
                 (br. s., 4 H) 2.73-52 (m, 
                   
               
               
                   
                   
                   
                   
                 1H) 1.22-1.31 (m, 2 H) 
                   
               
               
                   
                   
                   
                   
                 0.99-1.07 (m, 2 H) 
                   
               
               
                   
               
               
                 705 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 461.63 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3,5- difluoro-pyridin-4- yl)-amine 
               
               
                   
               
               
                 706 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 506.53 (M + H) 
                 (dmso-d6) 9.05 (s, 1H), 8.99 (br s, 1H), 8.22- 8.16 (m, 2H), 8.13 (d, J =  10.0 Hz, 1H), 7.89 (s, 1H), 7.65 (app d, J =  7.2 Hz, 2H), 7.61 (dd, J = 5.4; 1.4 Hz, 1H), 7.48- 7.35 (m, 3H), 6.23 (quint, J = 9.2 Hz, 1H), 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,2,2- trifluoro-1-phenyl- ethyl)-amine 
               
               
                   
                   
                   
                   
                 4.51 (br s, exch. H&#39;s), 
                   
               
               
                   
                   
                   
                   
                 3.91 (br s, 6H), 2.74- 
                   
               
               
                   
                   
                   
                   
                 2.64 (m, 1H), 1.30-1.22 
                   
               
               
                   
                   
                   
                   
                 (m, 2H), 1.12-1.04 (m, 2H) 
                   
               
               
                   
               
               
                 707 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 516 (M + H) 
                   
                 1-{5-Cyclopropyl-2- [2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidine-3- carboxylic acid 
               
               
                   
                   
                   
                   
                   
                 methyl amide 
               
               
                   
               
               
                 708 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 460 (M + H) 
                   
                 {4-[4-(3-Amino- pyrrolidin-1-yl)-5- cyclopropyl- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(2,6- difluoro-phenyl)- amine 
               
               
                   
               
               
                 709 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 482 (M + H) 
                 1H NMR (400 MHz, DMSO-d6) 9.52 (1 H, br. s.), 9.06 (1 H, s), 8.76- 9.04 (2 H, m), 8.31 (1 H,  d, J = 5.3 Hz), 8.19 (1 H,  s), 7.97 (1 H, s), 7.72 (1H, dd, J = 5.5, 1.3 Hz), 7.65 (2 H, d, J = 8.5 Hz), 7.21 (2 H, d, J = 8.5 Hz), 3.78-3.99 (4 H, m), 3.52 (2 H, s), 3.33 (4 H, br. s.), 2.65-2.78 (1 H, 
                 {4-[4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-ylamino]- phenyl}-acetic acid 
               
               
                   
                   
                   
                   
                 m), 1.19-1.34 (2 H, m), 
                   
               
               
                   
                   
                   
                   
                 0.99-1.14 (2 H, m) 
                   
               
               
                   
               
               
                 710 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 521.78 
                 (CDCl 3 ) 9.06 (s, 1H), 8.35 (d, J = 5.2 Hz, 1H), 8.07 (s, 1H), 8.01 (s, 1H), 7.79 (dd, J = 5.2; 1.3 Hz, 1H), 7.23 (app t, J = 8.0 Hz, 1H), 7.05- 7.02 (m, 1H), 7.00-6.98 (m, 1H), 6.93 (dd, J = 8.0; 1.6 Hz, 1H), 6.65 (dd, J = 8.0; 2.0 Hz, 1H), 
                 [4-(5-Cyclopropyl- 4-piperidin-1-yl- pyrido[3,4d]pyrimidin- 2-yl)-pyridin-2- yl]-[3-(4-methyl- piperazin-1-yl)- phenyl]-amine 
               
               
                   
                   
                   
                   
                 3.70 (br s, 4H), 3.28- 
                   
               
               
                   
                   
                   
                   
                 3.24 (m, 4H), 2.66-2.62 
                   
               
               
                   
                   
                   
                   
                 (m, 1H), 2.61-2.56 (m, 
                   
               
               
                   
                   
                   
                   
                 4H), 2.35 (s, 3H), 1.69 br 
                   
               
               
                   
                   
                   
                   
                 s, 6H), 1.26-1.18 (m, 
                   
               
               
                   
                   
                   
                   
                 2H), 1.00-0.95 (m, 2H) 
                   
               
               
                   
               
               
                 711 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 480.59 
                   
                 3-{4-[5- Cyclopropyl-4- ((3R,4S)-3,4- dihydroxy- piperidin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-ylamino}- 
               
               
                   
                   
                   
                   
                   
                 benzonitrile 
               
               
                   
               
               
                 712 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 480 (M + H) 
                 1H NMR (400 MHz, DMSO-d6) 9.06 (1H, s), 8.88 (2 H, br. s.), 8.13- 8.25 (2 H, m), 7.89 (1 H, br. s.), 7.63 (1 H, br. s.), 7.33 (1 H, d, J = 7.3 Hz), 7.23 (1 H, t, J = 7.5 Hz), 6.92 (1 H, t, J = 7.3 Hz), 6.86 (1H, d, J = 8.3 Hz), 
                 Chroman-4-yl-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
                   
                   
                   
                 5.21 (1 H, br. s.), 4.18- 
                   
               
               
                   
                   
                   
                   
                 4.31 (3 H, m), 3.83- 
                   
               
               
                   
                   
                   
                   
                 3.94 (4 H, m), 3.31 (4 H, 
                   
               
               
                   
                   
                   
                   
                 br. s.), 2.64-2.72 (1 H, 
                   
               
               
                   
                   
                   
                   
                 m), 2.13-2.26 (1 H, m), 
                   
               
               
                   
                   
                   
                   
                 2.00-2.13 (1 H, m), 
                   
               
               
                   
                   
                   
                   
                 1.20-1.33 (2 H, m), 
                   
               
               
                   
                   
                   
                   
                 1.01-1.12 (2 H, m) 
                   
               
               
                   
               
               
                 713 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 502 (M + H) 
                   
                 N-(1-{5- Cyclopropyl-2-[2- (2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- pyrrolidin-3-yl)- 
               
               
                   
                   
                   
                   
                   
                 acetamide 
               
               
                   
               
               
                 714 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 484.25 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2- fluoro-4-isopropyl- phenyl)-amine 
               
               
                   
               
               
                 715 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 470 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(5- ethyl-2-fluoro- phenyl)-amine 
               
               
                   
               
               
                 716 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 484.2 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2- fluoro-5-isopropyl- phenyl)-amine 
               
               
                   
               
               
                 717 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 470.2 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(4- ethyl-2-fluoro- phenyl)-amine 
               
               
                   
               
               
                 718 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 488 (M + H) 
                 1H NMR (500 MHz, DMSO) 8.92 (1H, s), 8.75 (1H, s), 8.15 (1H, d), 8.08 (1H, s), 7.74 (1H, s), 7.64 (1H, dd), 7.34-7.24 (1H, m), 7.16 (2H, t), 3.91-3.52 (4H, m, br), 2.85 (2H, s), 
                 {4-[5-Cyclopropyl- 4-(3,3-dimethyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(2,6- difluoro-phenyl)- amine 
               
               
                   
                   
                   
                   
                 2.50-2.45 (1H, m), 1.23- 
                   
               
               
                   
                   
                   
                   
                 1.22 (2H, m), 1.08-0.98 
                   
               
               
                   
                   
                   
                   
                 (6H, m), 0.78 (2H, s, br). 
                   
               
               
                   
               
               
                 719 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 470 (M + H) 
                 1H NMR (500 MHz, DMSO) 9.32 (1H, s), 8.93 (1H, s), 8.28 (1H, d), 8.08 (1H, s), 7.85 (1H, s), 7.76-7.73 (2H, m), 7.66 (1H, d), 7.11 (2H, t), 3.95-3.55 (4H, m), 2.87 (2H, m, br), 
                 {4-[5-Cyclopropyl- 4-(3,3-dimethyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(4- fluoro-phenyl)- amine 
               
               
                   
                   
                   
                   
                 2.53 (1H, m), 1.24-1.22 
                   
               
               
                   
                   
                   
                   
                 (2H, m), 1.06-0.78 (9H, m). 
                   
               
               
                   
               
               
                 720 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 537.67 
                   
                 (R)-1-(5- Cyclopropyl-2-{2- [3-(4-methyl- piperazin-1-yl)- phenylamino]- pyridin-4-yl}- pyrido[3,4- d]pyrimidin-4-yl)- piperidin-3-ol 
               
               
                   
               
               
                 721 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 537.71 
                   
                 [(R)-1-(5- Cyclopropyl-2-{2- [3-(4-methyl- piperazin-1-yl)- phenylamino]- pyridin-4-yl}- pyrido[3,4- d]pyrimidin-4-yl)- pyrrolidin-3-yl]- methanol 
               
               
                   
               
               
                 722 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 537.7 
                   
                 [(S)-1-(5- Cyclopropyl-2-{2- [3-(4-methyl- piperazin-1-yl)- phenylamino]- pyridin-4-yl}- pyrido[3,4- d]pyrimidin-4-yl)- pyrrolidin-3-yl]- methanol 
               
               
                   
               
               
                 723 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 530 (M + H) 
                   
                 1-{5-Cyclopropyl-2- [2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidine-4- carboxylic acid ethylamide 
               
               
                   
               
               
                 724 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 501.57 (MH)+ 
                   
                 (6-Cyclopropyl-2,4- difluoro-pyridin-3- yl)-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-amine; bis-trifluoroacetic salt 
               
               
                   
               
               
                 725 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 483.61 (MH)+ 
                   
                 (6-Cyclopropyl-2- fluoro-pyridin-3-yl)- [4-(5-cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-amine; bis-trifluoroacetic acid salt 
               
               
                   
               
               
                 726 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 502 (M + H) 
                   
                 1-{5-Cyclopropyl-2- [2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- pyrrolidine-3- carboxylic acid methylamide 
               
               
                   
               
               
                 727 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 523.66 (M + H)+ 
                   
                 (S)-1-(5- Cyclopropyl-2-{2- [3-(4-methyl- piperazin-1-yl)- phenylamino]- pyridin-4-yl}- pyrido[3,4- d]pyrimidin-4-yl)- pyrrolidin-3-ol 
               
               
                   
               
               
                 728 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 537.73 (M + H)+ 
                   
                 1-(3-{4-[5- Cyclopropyl-4-(4- methyl-piperazin-1- yl)-pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-ylamino}- phenyl)-piperidin-4- ol 
               
               
                   
               
               
                 729 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 523.70 (M + H)+ 
                   
                 1-{5-Cyclopropyl-2- [2-(3-piperazin-1-yl- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidin-4-ol 
               
               
                   
               
               
                 730 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 456 (M + H) 
                 1H NMR (400 MHz, DMSO-d6) 9.08 (4 H, s), 8.22(1 H, s), 8.08 (1 H, d, J = 6.5 Hz), 8.04 (1 H, br. s.), 7.75 (1 H, s), 7.70 (1 H, dd, J = 6.5, 1.3 Hz), 7.49 (1 H, s), 5.06 (1 H, br. s.), 3.6-3.9 (8 H, m), 3.32 (4 H, br. s.), 2.62- 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-[1-(1- methyl-1H-pyrazol- 4-yl)-ethyl]-amine 
               
               
                   
                   
                   
                   
                 2.68 (1H, m), 1.55 (3 H, 
                   
               
               
                   
                   
                   
                   
                 d, J = 6.8 Hz), 1.21-1.31 
                   
               
               
                   
                   
                   
                   
                 (2 H, m), 1.05-1.12 (2 H,  
                   
               
               
                   
                   
                   
                   
                 m) 
                   
               
               
                   
               
               
                 731 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.63 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2- fluoro-6-morpholin- 4-yl-pyridin-3-yl)- amine 
               
               
                   
               
               
                 732 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 526 
                   
                 1-{5-Cyclopropyl-2- [2-(1-piperidin-4- ylmethyl-1H- pyrazol-4-ylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidin-4-ol 
               
               
                   
               
               
                 733 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 — 
                 487.15 
                   
                 4-((R)-3- Benzyloxymethyl- piperazin-1-yl)-2-(2- chloro-pyridin-4- yl)-5-cyclopropyl- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 734 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 464.2 
                   
                 (3-Cyclopropyl- phenyl)-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
               
               
                 735 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 585 (M + H) 
                   
                 (1-{5-Cyclopropyl- 2-[2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidin-4-yl)-(4- methyl-piperazin-1- yl)-methanone 
               
               
                   
               
               
                 736 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573 (M + H) 
                   
                 1-{5-Cyclopropyl-2- [2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidine-4- carboxylic acid (2- dimethylamino- ethyl)-amide 
               
               
                   
               
               
                 737 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 537.72 (M + H) 
                   
                 (S)-1-(5- Cyclopropyl-2-{2- [3-(4-methyl- piperazin-1-yl)- phenylamino]- pyridin-4-yl}- pyrido[3,4- d]pyrimidin-4-yl)- piperidin-3-ol 
               
               
                   
               
               
                 738 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 523.68 (M + H)+ 
                   
                 (R)-1-(5- Cyclopropyl-2-{2- [3-(4-methyl- piperazin-1-yl)- phenylamino]- pyridin-4-yl}- pyrido[3,4- d]pyrimidin-4-yl)- pyrrolidin-3-ol 
               
               
                   
               
               
                 739 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560 (M + H) 
                   
                 1-{5-Cyclopropyl-2- [2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidine-4- carboxylic acid (2- methoxy-ethyl)- amide 
               
               
                   
               
               
                 740 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 485 (M + H) 
                 1H NMR (400 MHz, DMSO-d6) 9.13 (1 H, s), 9.02-9.09 (1 H, m), 8.75 - 8.98 (2 H, m), 8.39 (1 H, br. s.), 8.17- 8.31 (2 H, m), 7.74- 8.06 (2 H, m), 3.84- 4.04 (4 H, m), 3.36 (4 H, br. s.), 2.71 (1 H, br. s.), 1.19-1.33 (2 H, m), 1.04-1.16 (2 H, m) 
                 4-[4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-ylamino]- 3,5-difluoro- benzonitrile 
               
               
                   
               
               
                 741 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 571 (M + H) 
                   
                 (1-{5-Cyclopropyl- 2-[2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidin-4-yl)- piperazin-1-yl- methanone 
               
               
                   
               
               
                 742 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 467 (M + H) 
                 1H NMR (400 MHz, DMSO-d6) 9.72 (1 H, s), 9.07 (1 H, s), 8.78-9.03 (2 H, m), 8.41 (1 H, d, J = 5.3 Hz), 8.19 (1 H, s), 8.01 (1 H, s), 7.69-7.89 (6 H, m), 7.14 (1 H, br. s.), 3.94 (4 H, br. s.), 3.34 (4 H, br. s.), 2.64- 2.77 (1 H, m), 1.20- 
                 4-[4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-ylamino]- benzamide 
               
               
                   
                   
                   
                   
                 1.32 (2 H, m), 1.01- 
                   
               
               
                   
                   
                   
                   
                 1.13 (2 H, m) 
                   
               
               
                   
               
               
                 743 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 465.56 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- [1,2,4]triazolo[1,5- a]pyridin-2-yl- amine 
               
               
                   
               
               
                 744 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559 (M + H) 
                   
                 1-{5-Cyclopropyl-2- [2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidine-4- carboxylic acid (2- methylamino-ethyl)- amide 
               
               
                   
               
               
                 745 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 481.53 
                   
                 6-{4-[5- Cyclopropyl-4- ((cis)-3,4- dihydroxy- piperidin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-ylamino}- pyridine-2- 
               
               
                   
                   
                   
                   
                   
                 carbonitrile 
               
               
                   
               
               
                 746 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 450.55 (M + H)+ 
                   
                 6-[4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-ylamino]- pyridine-2- carbonitrile 
               
               
                   
               
               
                 747 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 589.70 (M + H)+ 
                   
                 1-(5-Cyclopropyl-2- {2-[3-(4-methyl- piperazin-1-yl)- phenylamino]- pyridin-4-yl}- pyrido[3,4- d]pyrimidin-4-yl)- 3,3-difluoro- piperidine-4,4-diol 
               
               
                   
               
               
                 748 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 461.51 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(4,6- difluoro-pyridin-3- yl)-amine 
               
               
                   
               
               
                 749 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 461.50 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(2,5- difluoro-pyridin-3- yl)-amine 
               
               
                   
               
               
                 750 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 425.54 (M + H)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- pyridin-2-yl-amine 
               
               
                   
               
               
                 751 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.28 
                 (CDCl 3 ) 9.07 (s, 1H), 8.32 (d, J = 5.2 Hz, 1H), 8.08 (br s, 1H), 8.02 (s, 1H), 7.79 (d, J = 5.2 Hz, 1H), 7.24 (dd, J = 8.4 Hz,  1H)), 7.06 (br s, 1H), 6.98 (br s, 1H), 6.82 (br d, J = 7.08 Hz, 1H), 6.69 (dd, J = 8.4; 1.9 Hz, 1H), 3.95 (m, 5H), 3.55 (m, br 
                 (3R,4S or 3R,4S)-1- (5-Cyclopropyl-2- {2-[3-(4-methyl- piperazin-1-yl)- phenylamino]- pyridin-4-yl}- pyrido[3,4- d]pyrimidin-4-yl)- piperidine-3,4-diol Single enantiomer, 
               
               
                   
                   
                   
                   
                 s, 1H), 3.25 (br s, 5H), 
                 unassigned 
               
               
                   
                   
                   
                   
                 2.60 (m, 5H), 2.34 (s, 
                   
               
               
                   
                   
                   
                   
                 3H), 1.91 (m, 1H), 1.7 br 
                   
               
               
                   
                   
                   
                   
                 s (exch. H&#39;s), 1.24 (m, 
                   
               
               
                   
                   
                   
                   
                 2H), 0.97 (m, 2H) 
                   
               
               
                   
               
               
                 752 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.29 
                 (CDCl 3 ) 9.07 (s, 1H), 8.32 (d, J = 5.2 Hz, 1H), 8.08 (br s, 1H), 8.02 (s, 1H), 7.79 (d, J = 5.2 Hz, 1H), 7.24 (dd, J = 8.4 Hz,  1H)), 7.06 (br s, 1H), 6.98 (br s, 1H), 6.82 (br d, J = 7.08 Hz, 1H), 6.69 (dd, J = 8.4; 1.9 Hz, 1H), 3.95 (m, 5H), 3.55 (m, br 
                 (3R,4S or 3R,4S)-1- (5-Cyclopropyl-2- {2-[3-(4-methyl- piperazin-1-yl)- phenylamino]- pyridin-4-yl}- pyrido[3,4- d]pyrimidin-4-yl)- piperidine-3,4-diol Single enantiomer, 
               
               
                   
                   
                   
                   
                 s, 1H), 3.25 (br s, 5H), 
                 unassigned 
               
               
                   
                   
                   
                   
                 2.60 (m, 5H), 2.34 (s, 
                   
               
               
                   
                   
                   
                   
                 3H), 1.91 (m, 1H), 1.7 br 
                   
               
               
                   
                   
                   
                   
                 s (exch. H&#39;s), 1.24 (m, 
                   
               
               
                   
                   
                   
                   
                 2H), 0.97 (m, 2H) 
                   
               
               
                   
               
               
                 753 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.3 
                 (CDCl 3 ) 9.16 (s, 1H), 8.94 (s, 1H), 8.30 (d, J = 5.3 Hz, 1H), 8.08 (s, 1H), 7.91 (s, 1H), 7.66 (dd, J = 5.2; 1.0 Hz, 1H), 7.34 (app t, J = 2.0 Hz, 1H), 7.22 (dd, J = 8.0; 1.1 Hz, 1H), 7.11 (app t, J = 8.1 Hz, 1H), 6.52 (dd, J = 8.2; 1.8 Hz, 1H), 
                 (3S,4S or 3R,4R)-1- (5-Cyclopropyl-2- {2-[3-(4-methyl- piperazin-1-yl)- phenylamino]- pyridin-4-yl}- pyrido[3,4- d]pyrimidin-4-yl)- piperidine-3,4-diol Single enantiomer, 
               
               
                   
                   
                   
                   
                 5.28-4.67 (m, 2H), 4.28- 
                 unassigned 
               
               
                   
                   
                   
                   
                 3.71 (m, 2H), 3.50 (br s, 
                   
               
               
                   
                   
                   
                   
                 1H), 3.15-3.11 (m, 4H), 
                   
               
               
                   
                   
                   
                   
                 2.61-2.53 (m, 1H), 2.49- 
                   
               
               
                   
                   
                   
                   
                 2.45 (m, 4H), 2.23 (s, 
                   
               
               
                   
                   
                   
                   
                 3H), 2.18-1.73 (m, 2H), 
                   
               
               
                   
                   
                   
                   
                 1.44-1.11 (m, 3H), 1.10- 
                   
               
               
                   
                   
                   
                   
                 0.90 (m, 2H) 
                   
               
               
                   
               
               
                 754 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.3 
                 (CDCl 3 ) 9.16 (s, 1H), 8.94 (s, 1H), 8.30 (d, J = 5.3 Hz, 1H), 8.08 (s, 1H), 7.91 (s, 1H), 7.66 (dd, J = 5.2; 1.0 Hz, 1H), 7.34 (app t, J = 2.0 Hz, 1H), 7.22 (dd, J = 8.0; 1.1 Hz, 1H), 7.11 (app t, J = 8.1 Hz, 1H), 6.52 (dd, J = 8.2; 1.8 Hz, 1H), 
                 (3S,4S or 3R,4R)-1- (5-Cyclopropyl-2- {2-[3-(4-methyl- piperazin-1-yl)- phenylamino]- pyridin-4-yl}- pyrido[3,4- d]pyrimidin-4-yl)- piperidine-3,4-diol Single enantiomer, 
               
               
                   
                   
                   
                   
                 5.28-4.67 (m, 2H), 4.28- 
                 unassigned 
               
               
                   
                   
                   
                   
                 3.71 (m, 2H), 3.50 (br s, 
                   
               
               
                   
                   
                   
                   
                 1H), 3.15-3.11 (m, 4H), 
                   
               
               
                   
                   
                   
                   
                 2.61-2.53 (m, 1H), 2.49- 
                   
               
               
                   
                   
                   
                   
                 2.45 (m, 4H), 2.23 (s, 
                   
               
               
                   
                   
                   
                   
                 3H), 2.18-1.73 (m, 2H), 
                   
               
               
                   
                   
                   
                   
                 1.44-1.11 (m, 3H), 1.10- 
                   
               
               
                   
                   
                   
                   
                 0.90 (m, 2H) 
                   
               
               
                   
               
               
                 755 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 449 (M + H) 
                   
                 {4-[5-Cyclopropyl- 4-(2-methylamino- ethoxy)-pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(2,6- difluoro-phenyl)- amine 
               
               
                   
               
               
                 756 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 443 (M + H)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(4- fluoro-pyridin-2-yl)- amine 
               
               
                   
               
               
                 757 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 475 (M + H) 
                   
                 {4-[5-Cyclopropyl- 4-(piperidin-4- yloxy)-pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(2,6- difluoro-phenyl)- amine 
               
               
                   
               
               
                 758 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 442 (M + H) 
                 1H NMR (400 MHz, DMSO-d6) 9.08 (1 H, s), 8.78-9.01 (2 H, m), 8.22 (1 H, s), 8.11 (1 H, d, J = 6.3 Hz), 7.90-8.05 (1 H, m), 7.76 (1 H, s), 7.68 (1 H, d, J = 6.8 Hz), 7.50 (1 H, s), 4.45 (2 H, br. s.), 3.88 (4 H, br. s.), 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(1- methyl-1H-pyrazol- 4-ylmethyl)-amine 
               
               
                   
                   
                   
                   
                 3.83 (3 H, s), 3.31 (4 H, 
                   
               
               
                   
                   
                   
                   
                 br. s.), 2.63-2.70 (1 H, 
                   
               
               
                   
                   
                   
                   
                 m), 1.19-1.34 (2 H, m), 
                   
               
               
                   
                   
                   
                   
                 1.02-1.15 (2 H, m) 
                   
               
               
                   
               
               
                 759 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.56 min, MI: 452 [M + H] 
                 1H NMR (DMSO, 500 MHz) 8.99 (1H, s), 8.17 (4H, m), 7.55 (1H, m), 7.44 (1H, m), 7.28 (4H, m), 7.20 (1H, m), 6.89 (1H, m), 3.75 (4H, s), 3.56 (6H, m), 2.88 (2H, m), 2.66 (1H, m), 1.25 (2H, m), 1.03 (2H, m). 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- phenethyl-amine 
               
               
                   
               
               
                 760 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 507.35 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-pyrrolidin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-[3-(4- methyl-piperazin-1- yl)-phenyl]-amine 
               
               
                   
               
               
                 761 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 493.39 (M + H) 
                   
                 [4-(4-Azetidin-1-yl- 5-cyclopropyl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-[3-(4- methyl-piperazin-1- yl)-phenyl]-amine 
               
               
                   
               
               
                 762 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.12 min, MI: 473 [M + H] 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3- fluoro-6-methoxy- pyridin-2-yl)-amine 
               
               
                   
               
               
                 763 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.03 min, MI: 489 [M + H] 
                   
                 {4-[5-Cyclopropyl- 4-(3,5-dimethyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(3,6- difluoro-pyridin-2- yl)-amine 
               
               
                   
               
               
                 764 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 4.20 min, MI: 478.39 [M + H] 
                 1H NMR (500 MHz, DMSO) 8.93 (1H, s), 8.75 (1H, s), 8.11 (1H, d), 8.10 (1H, s), 7.50 (1H, d), 7.26-7.23 (1H, m), 7.15 (2H, t), 4.09- 4.08 (2H, m), 3.67 (4H, s, br), 2.80 (4H, s, br), 2.58-2.54 (1H, m), 1.26- 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)-5- fluoro-pyridin-2-yl]- (2,6-difluoro- phenyl)-amine 
               
               
                   
                   
                   
                   
                 1.24 (2H, m), 1.03-1.01 
                   
               
               
                   
                   
                   
                   
                 (2H, m). 
                   
               
               
                   
               
               
                 765 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 4.58 min, MI: 460.40 [M + H] 
                 1H NMR (500 MHz, DMSO) 9.31 (1H, s), 8.94 (1H, s), 8.23 (1H, d), 8.18 (1H, s), 8.12 (1H, s), 7.67 (2H, dd), 7.58 (1H, 7.11 (2H, t), 3.69 (4H, s, br), 2.88 (4H, s, br), 2.60-2.56 (1H, m), 1.26-1.24 (2H, 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)-5- fluoro-pyridin-2-yl]- (4-fluoro-phenyl)- amine 
               
               
                   
                   
                   
                   
                 m), 1.03-1.02 (2H, m). 
                   
               
               
                   
               
               
                 766 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 493.39 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-pyrrolidin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3- piperazin-1-yl- phenyl)-amine 
               
               
                   
               
               
                 767 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 479.29 (M + H) 
                   
                 [4-(4-Azetidin-1-yl- 5-cyclopropyl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3- piperazin-1-yl- phenyl)-amine 
               
               
                   
               
               
                 768 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 510.25 
                   
                 N-{4-[4-((R)-3- Benzyloxymethyl- piperazin-1-yl)-5- cyclopropyl- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}- acetamide 
               
               
                   
               
               
                 769 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 516 
                   
                 {4-[5-Cyclopropyl- 4-((R)-3- methanesulfonyl- methyl-piperazin-1- yl)-pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}- phenyl-amine 
               
               
                   
               
               
                 770 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 482 
                   
                 N-{4-[5- Cyclopropyl-4-((R)- 3-methanesulfonyl- methyl-piperazin-1- yl)-pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}- 
               
               
                   
                   
                   
                   
                   
                 acetamide 
               
               
                   
               
               
                 771 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 534.2 
                   
                 {4-[5-Cyclopropyl- 4-((R)-3- methanesulfonyl- methyl-piperazin-1- yl)-pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(4- 
               
               
                   
                   
                   
                   
                   
                 fluoro-phenyl)- 
               
               
                   
                   
                   
                   
                   
                 amine 
               
               
                   
               
               
                 772 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 552.2 
                   
                 {4-[5-Cyclopropyl- 4-((R)-3- methanesulfonyl- methyl-piperazin-1- yl)-pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(2,6- 
               
               
                   
                   
                   
                   
                   
                 difluoro-phenyl)- 
               
               
                   
                   
                   
                   
                   
                 amine 
               
               
                   
               
               
                 773 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 508.2 
                   
                 Cyclopropanecar- boxylic acid {4-[5- cyclopropyl-4-((R)- 3-methanesulfonyl- methyl-piperazin-1- yl)-pyrido[3,4- d]pyrimidin-2-yl]- 
               
               
                   
                   
                   
                   
                   
                 pyridin-2-yl}-amide 
               
               
                   
               
               
                 774 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 479 (M + H)+ 
                   1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 10.08 (s, 1 H) 8.96-9.02 (m, 1 H)  8.89-9.13 (m, 3 H) 8.43-8.53 (m, 1 H) 8.19 (s, 1 H) 8.00 (dd, J = 5.1, 1.4 Hz, 1 H) 7.01 (dt, J = 9.3, 3.0 Hz, 1 H) 3.77- 4.13 (m, 4 H) 3.28- 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3,4,6- trifluoro-pyridin-2- yl)-amine 
               
               
                   
                   
                   
                   
                 3.41 (m, 4 H) 2.63-2.74 
                   
               
               
                   
                   
                   
                   
                 (m, 1 H) 1.20-1.33 (m, 
                   
               
               
                   
                   
                   
                   
                 2 H) 1.04-1.13 (m, 2 H) 
                   
               
               
                   
               
               
                 775 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 448 (M + H) 
                   
                 N-{5-Cyclopropyl- 2-[2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- N′-methyl-ethane- 
               
               
                   
                   
                   
                   
                   
                 1,2-diamine 
               
               
                   
               
               
                 776 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 462 (M + H) 
                   
                 N-{5-Cyclopropyl- 2-[2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- N′,N′-dimethyl- 
               
               
                   
                   
                   
                   
                   
                 ethane-1,2-diamine 
               
               
                   
               
               
                 777 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 509.26 (M + H) 
                   
                 1-(5-Cyclopropyl-2- {2-[3-(4-methyl- piperazin-1-yl)- phenylamino]- pyridin-4-yl}- pyrido[3,4- d]pyrimidin-4-yl)- azetidin-3-ol 
               
               
                   
               
               
                 778 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 495.29 (M + H) 
                   
                 1-{5-Cyclopropyl-2- [2-(3-piperazin-1-yl- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- azetidin-3-ol 
               
               
                   
               
               
                 779 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 456.22 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(1- isopropyl-1H- pyrazol-3-yl)-amine 
               
               
                   
               
               
                 780 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 456.24 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(1- ethyl-5-methyl-1H- pyrazol-3-yl)-amine 
               
               
                   
               
               
                 781 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 538.36 (M + H) 
                   
                 (R)-1-(5- Cyclopropyl-2-{2- [6-(4-methyl- piperazin-1-yl)- pyridin-2-ylamino]- pyridin-4-yl}- pyrido[3,4- d]pyrimidin-4-yl)- piperidin-3-ol 
               
               
                   
               
               
                 782 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 523.66 (M + H) 
                   
                 [4-(5-Cyclopropyl- 4-piperidin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-[6-(4- methyl-piperazin-1- yl)-pyridin-2-yl]- amine 
               
               
                   
               
               
                 783 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 475.19 (MH)+ 
                   
                 [4-(5-Cyclobutyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3,5- difluoro-pyridin-2- yl)-amine 
               
               
                   
               
               
                 784 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 457.25 (MH)+ 
                   
                 [4-(5-Cyclobutyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3- fluoro-pyridin-2-yl)- amine 
               
               
                   
               
               
                 785 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 457.29 (M + H)+ 
                   
                 [4-(5-Cyclobutyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(4- fluoro-pyridin-2-yl)- amine 
               
               
                   
               
               
                 786 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 593.28 (M + H)+ 
                   1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 10.09 (s, 1 H) 9.15 (s, 1 H) 8.79-8.96 (m, 3 H) 8.48 (d, J = 5.3 Hz, 1 H) 8.00 (dd, J = 5.1, 1.4 Hz, 1 H) 7.02 (dt, J = 9.5, 3.0 Hz,  1 H) 4.17-4.32 (m, 1 H) 3.81-3.92 (m, 4 H) 3.19- 
                 [4-(5-Cyclobutyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3,4,6- trifluoro-pyridin-2- yl)-amine 
               
               
                   
                   
                   
                   
                 3.39 (m, 4 H) 1.86- 
                   
               
               
                   
                   
                   
                   
                 2.44 (m, 6 H) 
                   
               
               
                   
               
               
                 787 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.09 min, MI: 488 [M + H] 
                   
                 {4-[5-Cyclopropyl- 4-(3,5-dimethyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(2,6- difluoro-phenyl)- amine 
               
               
                   
               
               
                 788 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 4.07 min, MI: 485 [M + H] 
                   
                 (R)-4-{5- Cyclopropyl-2-[2- (2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperazine-2- 
               
               
                   
                   
                   
                   
                   
                 carbonitrile 
               
               
                   
               
               
                 789 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 457 (M + H) 
                   
                 {4-[5-Cyclopropyl- 4-(1,2,3,6- tetrahydro-pyridin- 4-yl)-pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(2,6- difluoro-phenyl)- amine 
               
               
                   
               
               
                 790 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 474 (M + H) 
                   
                 {5-Cyclopropyl-2- [2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidin-4-yl-amine 
               
               
                   
               
               
                 791 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 491 (M + H) 
                   
                 {4-[5-Cyclopropyl- 4-(piperidin-4- ylsulfanyl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(2,6- difluoro-phenyl)- 
               
               
                   
                   
                   
                   
                   
                 amine 
               
               
                   
               
               
                 792 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 491 (M + H) 
                   
                 {4-[5-Cyclopropyl- 4-(piperidin-4- ylsulfanyl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(2,6- difluoro-phenyl)- amine 
               
               
                   
               
               
                 793 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 539.5 (M + H) 
                   
                 (3S,4S)-1-(5- Cyclopropyl-2-{2- [3-(4-methyl- piperazin-1-yl)- phenylamino]- pyridin-4-yl}- pyrido[3,4- d]pyrimidin-4-yl)- pyrrolidine-3,4-diol 
               
               
                   
               
               
                 794 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 454.25 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(1- cyclopropyl-1H- pyrazol-4-yl)-amine 
               
               
                   
               
               
                 795 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 498.25 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-[1- (tetrahydro-pyran-4- yl)-1H-pyrazol-4- yl]-amine 
               
               
                   
               
               
                 796 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 482.2 
                   
                 (1-Cyclopentyl-1H- pyrazol-4-yl)-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
               
               
                 797 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 476 (M + H) 
                   
                 N-{5-Cyclopropyl- 2-[2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- N,N′,N′-trimethyl- ethane-1,2-diamine 
               
               
                   
               
               
                 798 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method: 5, RT: 2.78 min, MI: 489 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.70 (1H, s), 9.17 (1H, s, br), 9.11 (1H, s), 8.69 (1H, s), 8.46 (1H, m), 7.98 (1H, m), 7.85 (1H, m), 6.71 (1H, m), 4.28 (1H, m), 4.26 (1H, m), 4.06 (1H, m), 
                 {4-[5-Cyclobutyl-4- ((S)-3-methyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(3,6- difluoro-pyridin-2- yl)-amine 
               
               
                   
                   
                   
                   
                 3.91 (1H, m), 3.79 
                   
               
               
                   
                   
                   
                   
                 (1H, m), 3.65 (1H, m), 
                   
               
               
                   
                   
                   
                   
                 3.23 (1H, m), 3.06 
                   
               
               
                   
                   
                   
                   
                 (1H, m), 2.52 (3H, s), 
                   
               
               
                   
                   
                   
                   
                 2.16 (2H, m), 2.21 (2H, 
                   
               
               
                   
                   
                   
                   
                 m), 2.09 (1H, m), 1.91 
                   
               
               
                   
                   
                   
                   
                 (1H, m). 
                   
               
               
                   
               
               
                 799 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.72 min, MI: 475 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.70 (1 H, s), 9.14 (1H, s, br), 9.02 (1H, s), 8.80 (1H, d), 8.46 (1H, m), 7.97 (1H, m), 7.86 (1H, m), 6.71 (1H, m), 4.25 (1H, m), 3.86 (4H, m), 3.58 (4H, m), 2.80 (2H, m), 2.21 (2H, 
                 [4-(5-Cyclobutyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3,6- difluoro-pyridin-2- yl)-amine 
               
               
                   
                   
                   
                   
                 m), 2.08 (1H, m), 1.93 
                   
               
               
                   
                   
                   
                   
                 (1H, m). 
                   
               
               
                   
               
               
                 800 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 1.62 min, MI: 457 [M + H] 
                   
                 {4-[5-Cyclopropyl- 4-((S)-3-methyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(3- fluoro-pyridin-2-yl)- amine 
               
               
                   
               
               
                 801 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.59 min, MI: 477 [M + H] 
                   
                 (6-Chloro-3-fluoro- pyridin-2-yl)-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
               
               
                 802 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.57 min, MI: 489.49 [M + H] 
                 1H NMR (500 MHz, DMSO) 8.93 (1H, s), 8.06 (1H, s), 8.01 (1H, d), 7.92-7.84 (1H, m), 7.66 (1H, s), 7.39 (1H, d), , 7.33 (1H, d), 7.12- 7.07 (1H, m), 5.42 (1H, t, br), 3.83-3.57 (4H, m, br), 3.16 (1H, s, br), 2.84 (4H, s, br), 2.61 (1H, m, br), 1.45 (3H, d), 1.25- 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-[(R)-1- (3,6-difluoro- pyridin-2-yl)-ethyl]- amine 
               
               
                   
                   
                   
                   
                 1.22 (2H, m), 1.03-1.01 
                   
               
               
                   
                   
                   
                   
                 (2H, m). 
                   
               
               
                   
               
               
                 803 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 490 (M + H) 
                   
                 N-{5-Cyclopropyl- 2-[2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- N′,N′-dimethyl- butane-1,4-diamine 
               
               
                   
               
               
                 804 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 535.50 (M + H) 
                   
                 [4-(4-Azepan-1-yl- 5-cyclopropyl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-[3-(4- methyl-piperazin-1- yl)-phenyl]-amine 
               
               
                   
               
               
                 805 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 458.36 (M + H) 
                   
                 1-{5-Cyclopropyl-2- [2-(6-fluoro-pyridin- 2-ylamino)-pyridin- 4-yl]-pyrido[3,4- d]pyrimidin-4-yl}- piperidin-4-ol 
               
               
                   
               
               
                 806 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 458.20 (M + H) 
                   
                 (R)-1-{5- Cyclopropyl-2-[2- (6-fluoro-pyridin-2- ylamino)-pyridin-4- yl]-pyrido[3,4- d]pyrimidin-4-yl}- piperidin-3-ol 
               
               
                   
               
               
                 807 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.88 min, MI: 493 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.74 (1H, s), 9.13 (1H, s, br), 8.80 (2H, dd), 8.42 (1H, d), 8.26 (1H, m), 7.94 (1H, d), 4.23 (1H, m), 3.84 (4H, m), 3.25 (4H, m), 2.38 (2H, m), 2.21 (2H, m), 2.10 (1H, 
                 [4-(5-Cyclobutyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(3,5,6- trifluoro-pyridin-2- yl)-amine 
               
               
                   
                   
                   
                   
                 m), 1.89 (1H, m). 
                   
               
               
                   
               
               
                 808 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.90 min, MI: 506 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.76 (1H, s), 9.17 (1H, s, br), 9.11 (1H, s), 8.70 (1H, s), 8.44 (1H, m), 8.28 (1H, m), 7.95 (1H, m), 4.27 (1H, m), 4.26 (1H, m), 4.06 (1H, m), 3.91 (1H, m), 3.79 (1H, m), 3.65 
                 {4-[5-Cyclobutyl-4- ((S)-3-methyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(3,5,6- trifluoro-pyridin-2- yl)-amine 
               
               
                   
                   
                   
                   
                 (1H, m), 3.23 (1H, m), 
                   
               
               
                   
                   
                   
                   
                 3.06 (1H, m), 2.53 
                   
               
               
                   
                   
                   
                   
                 (3H, s), 2.16 (2H, m), 2.16 
                   
               
               
                   
                   
                   
                   
                 (2H, m), 2.07 (1H, m), 
                   
               
               
                   
                   
                   
                   
                 1.89 (1H, m). 
                   
               
               
                   
               
               
                 809 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 507.19 (MH)+ 
                   
                 [4-(5-Cyclobutyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(5- trifluoromethyl- pyridin-2-yl)-amine 
               
               
                   
               
               
                 810 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 416.26 (M + H) 
                   
                 ((R)-1-Cyclopropyl- ethyl)-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
               
               
                 811 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 458.29 (M + H) 
                   
                 ((R)-1-Cyclohexyl- ethyl)-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
               
               
                 812 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 483.21 (MH)+ 
                   
                 (5-Cyclopropyl-3- fluoro-pyridin-2-yl)- [4-(5-cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
               
               
                 813 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.60 min, MI: 515.51 [M + H] 
                 1H NMR (500 MHz, DMSO, 90° C.) 9.07 (1H, s), 8.23 (1H, s), 8.13 (1H, d), 7.76 (1H, s), 7.57 (1H, dd), 4.22-4.19 (2H, m), 4.11-4.06 (1H, m), 3.97 (4H, t, br), 3.35 (4H, t, br), 3.15-3.08 (2H, m), 2.70-2.66 (1H, 
                 1-{4-[4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-ylamino]- piperidin-1-yl}-2,2- dimethyl-propan-1- one 
               
               
                   
                   
                   
                   
                 m), 2.05-2.03 (2H, m), 
                   
               
               
                   
                   
                   
                   
                 1.52-1.42 (2H, m), 1.29- 
                   
               
               
                   
                   
                   
                   
                 1.27 (2H, m), 1.26 (9H, 
                   
               
               
                   
                   
                   
                   
                 s), 1.05-1.03 (2H, m). 
                   
               
               
                   
               
               
                 814 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.43 min, MI: 513.41 [M + H] 
                 1H NMR (500 MHz, DMSO, 90° C.) 9.07 (1H, s), 8.23 (1H, s), 8.10 (1H, d), 7.81 (1H, s), 7.58 (1H, dd), 3.97 (4H, t, br), 3.86-3.81 (1H, m), 3.34 (4H, t, br), 3.20 (2H, q), 3.01-2.98 (2H, m), 2.70-2.67 (1H, m), 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-[1- (2,2,2-trifluoro- ethyl)-piperidin-4- yl]-amine 
               
               
                   
                   
                   
                   
                 2.61 (2H, t), 2.00-1.97 
                   
               
               
                   
                   
                   
                   
                 (2H, m), 1.66-1.57 (2H, 
                   
               
               
                   
                   
                   
                   
                 m), 1.30-1.25 (2H, m), 
                   
               
               
                   
                   
                   
                   
                 1.05-1.03 (2H, m). 
                   
               
               
                   
               
               
                 815 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.71 min, MI: 507.41 [M + H] 
                 1H NMR (500 MHz, DMSO, 90° C.) 9.07 (1H, s), 8.71 (1H, s), 8.43 (1H, d), 8.26 (1H, s), 8.12 (1H, q), 7.98 (1H, dd), 4.02 (2H, t, br), 3.95 (2H, s), 3.38 (2H, t), 2.56-2.54 (1H, m), 1.31 
                 {4-[5-Cyclopropyl- 4-(3,3-dimethyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(3,5,6- trifluoro-pyridin-2- yl)-amine 
               
               
                   
                   
                   
                   
                 (6H, s), 1.30-1.27 (2H, 
                   
               
               
                   
                   
                   
                   
                 m), 1.02 (2H, dd). 
                   
               
               
                   
               
               
                 816 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.06 min, MI: 509.44 [M + H] 
                 1H NMR (500 MHz, DMSO, 90° C.) 9.07 (1H, s), 8.22 (1H, s), 8.14 (1H, d), 7.74 (1H, s), 7.57 (1H, dd), 3.97 (4H, t, br), 3.65-3.60 (2H, m), 3.35 (4H, t, br), 3.04- 2.97 (2H, m), 2.90 (3H, s), 2.71-2.65 (1H, m), 
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(1- methanesulfonyl- piperidin-4-yl)- amine 
               
               
                   
                   
                   
                   
                 2.12-2.07 (2H, m), 1.68- 
                   
               
               
                   
                   
                   
                   
                 1.59 (2H, m), 1.29-1.26 
                   
               
               
                   
                   
                   
                   
                 (2H, m), 1.05-1.03 (2H, m). 
                   
               
               
                   
               
               
                 817 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 508.05 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-[1-(2- fluoro-phenyl)-1H- pyrazol-4-yl]-amine 
               
               
                   
               
               
                 818 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 526.2 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-[1- (2,6-difluoro- phenyl)-1H-pyrazol- 4-yl]-amine 
               
               
                   
               
               
                 820 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.2 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-[1- (2,4,6-trifluoro- phenyl)-1H-pyrazol- 4-yl]-amine 
               
               
                   
               
               
                 821 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 494.25 (M + H) 
                   
                 1-{5-Cyclopropyl-2- [2-(2-methyl-2,3- dihydro-1H- isoindol-5-ylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidin-4-ol 
               
               
                   
               
               
                 822 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 486 (M + H − NH3) 
                 1H NMR (400 MHz, DMSO-d6) 9.10 (1 H, s), 8.93 (3 H, d, J = 7.8 Hz), 8.45-8.51 (1 H, m), 8.22 (1H, s), 8.03 (1 H, dd, J = 7.7, 1.9 Hz), 7.97 (1 H, ddd, J = 10.6, 8.8, 2.9 Hz), 7.86 (1 H, dt, J = 8.5, 1.5 Hz), 4.00 (4 H,  br. s.), 3.40 (4 H, br.  
                 4-[4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-ylamino]- 3,5-difluoro- benzamide 
               
               
                   
                   
                   
                   
                 s.), 2.65-2.78 (1 H, m), 
                   
               
               
                   
                   
                   
                   
                 1.26-1.36 (2 H, m), 
                   
               
               
                   
                   
                   
                   
                 1.07-1.16 (2 H, m) 
                   
               
               
                   
               
               
                 823 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 442 (M + H) 
                 1H NMR (400 MHz, DMSO-d6) 9.10 (1 H, s), 8.97 (2 H, br. s.), 8.25 (1 H,  s), 8.08 (2 H, d, J = 6.3 Hz),  7.70 (1 H, d, J = 5.8 Hz),  4.19-4.47 (4 H, m), 3.66 (2 H, br. s.), 3.34 (4 H, br. s.), 2.65- 2.76 (1 H, m), 2.32- 
                 (1S,2S,4R)- Bicyclo[2.2.1]hept- 2-yl-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
                   
                   
                   
                 2.39 (2 H, m), 1.85- 
                   
               
               
                   
                   
                   
                   
                 1.96 (1H, m), 1.43- 
                   
               
               
                   
                   
                   
                   
                 1.69 (4H, m), 1.05- 
                   
               
               
                   
                   
                   
                   
                 1.41 (8 H, m) 
                   
               
               
                   
               
               
                 824 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 442 (M + H) 
                 1H NMR (400 MHz, DMSO-d6) 9.09 (1 H, s), 8.82-9.05 (2 H, m), 8.24 (1 H, s), 8.08 (2 H, d, J = 6.8 Hz), 7.63-7.74 (1 H, m), 4.02-4.30 (4 H,  m), 3.63-3.67 (2 H, m), 3.34 (4 H, br. s.), 2.66-2.71 (1 H, m), 
                 (1R,2R,4S)- Bicyclo[2.2.1]hept- 2-yl-[4-(5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
                   
                   
                   
                 2.26-2.41 (2 H, m), 
                   
               
               
                   
                   
                   
                   
                 1.90 (1 H, m), 1.54 (4 H, 
                   
               
               
                   
                   
                   
                   
                 br. s.), 1.06-1.42 (8 H, m) 
                   
               
               
                   
               
               
                 825 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 505.24 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(5- cyclopropyl- [1,2,4]triazolo[1,5- a]pyridin-2-yl)- amine 
               
               
                   
               
               
                 826 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 463 (M + H) 
                   
                 {4-[5-Cyclopropyl- 4-(2- dimethylamino- ethoxy)-pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(2,6- difluoro-phenyl)- 
               
               
                   
                   
                   
                   
                   
                 amine 
               
               
                   
               
               
                 827 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 493.19 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(5- trifluoromethyl- pyridin-2-yl)-amine 
               
               
                   
               
               
                 828 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.69 min, MI: 507 [M + H] 
                 1H NMR (DMSO, 400 MHz, 90° C.) 9.08 (1H, s), 8.67 (1H, s), 8.43 (1H, dd), 8.23 (1H, s), 8.12 (1H, m), 7.97 (1H, m), 4.39 (2H, m), 
                 {4-[5-Cyclopropyl- 4-((3R,5S)-3,5- dimethyl-piperazin- 1-yl)-pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(3,5,6- 
               
               
                   
                   
                   
                   
                 3.23 (2H, m), 2.67 (1H, 
                 trifluoro-pyridin-2- 
               
               
                   
                   
                   
                   
                 m), 1.34 (6H, m), 1.26 
                 yl)-amine 
               
               
                   
                   
                   
                   
                 (2H, m), 1.15 (2H, m), 
                   
               
               
                   
                   
                   
                   
                 1.06 (2H, m). 
                   
               
               
                   
               
               
                 829 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5; RT: 3.32 min, MI: 486.42 [M + H] 
                 1H NMR (500 MHz, DMSO, 90° C.) 9.05 (1H, s), 8.23 (1H, s), 8.20 (1H, d), 7.76 (1H, s), 7.69 (1H, dd), 7.32-7.27 (2H, m), 7.14 (2H, t), 4.04 (2H, t), 3.96 (2H, s), 3.67-3.60 (1H, m), 
                 {4-[5-Cyclopropyl- 4-(4,7-diaza- spiro[2.5]oct-7-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(2,6- difluoro-phenyl)- amine 
               
               
                   
                   
                   
                   
                 3.42 (2H, t), 2.64-2.60 
                   
               
               
                   
                   
                   
                   
                 (1H, m), 1.28-1.24 (2H, 
                   
               
               
                   
                   
                   
                   
                 m), 1.03-1.00 (4H, m), 
                   
               
               
                   
                   
                   
                   
                 0.82 (2H, t). 
                   
               
               
                   
               
               
                 830 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.66 min, MI: 493 [M + H] 
                 1H NMR (DMSO, 500 MHz) 9.81 (1H, s), 9.07 (1H, s), 8.43 (1H, d), 8.28 (1H, m), 8.20 (1H, s), 7.97 (1H, m), 4.25 (2H, m), 2.54 (1H, m), 1.23 (3H, m), 1.16 (2H, m), 1.09 (3H, m). 
                 {4-[5-Cyclopropyl- 4-((S)-3-methyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(3,5,6- trifluoro-pyridin-2- yl)-amine 
               
               
                   
                   
                   
                   
                 (Piperazine aliphatic 
                   
               
               
                   
                   
                   
                   
                 protons under the water 
                   
               
               
                   
                   
                   
                   
                 peak at 3.33 ppm, 
                   
               
               
                   
                   
                   
                   
                 therefore not integrated). 
                   
               
               
                   
               
               
                 831 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 505.27 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(7- cyclopropyl- [1,2,4]triazolo[1,5- a]pyridin-2-yl)- amine 
               
               
                   
               
               
                 832 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 456.27 (M + H) 
                   
                 {4-[5-Cyclopropyl- 4-(3,3-dimethyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(1- methyl-1H- pyrazol-3-yl)- 
               
               
                   
                   
                   
                   
                   
                 amine 
               
               
                   
               
               
                 833 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 488 (M + H) 
                   
                 {5-Cyclopropyl-2- [2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- methyl-piperidin-4- 
               
               
                   
                   
                   
                   
                   
                 yl-amine 
               
               
                   
               
               
                 834 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 524.26 
                   
                 1-{5-Cyclopropyl-2- [2-(3-morpholin- 4-yl-phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidin-4-ol 
               
               
                   
               
               
                 835 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 486.33 
                   
                 ((R)-1-Cyclohexyl- ethyl)-{4-[5- cyclopropyl-4-(3,3- dimethyl-piperazin-1- yl)-pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-amine 
               
               
                   
               
               
                 836 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 461.18 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(4,6- difluoro-pyridin-2- yl)-amine 
               
               
                   
               
               
                 837 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 460 (M + H) 
                   
                 {5-Cyclopropyl-2- [2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- pyrrolidin-3-yl- 
               
               
                   
                   
                   
                   
                   
                 amine 
               
               
                   
               
               
                 838 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.52 min, MI: 489.41 [M + H] 
                 1H NMR (500 MHz, DMSO, 90° C.) 8.97 (1H, s), 8.90 (1H, s), 8.42 (1H, d), 8.14 (1H, s), 7.97 (1H, dd), 7.81-7.75 (1H, m), 6.67-6.63 (1H, m), 3.81 (2H, s, br), 3.68 (2H, s), 2.95 (2H, s), 
                 {4-[5-Cyclopropyl- 4-(3,3-dimethyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(3,6- difluoro-pyridin-2- yl)-amine 
               
               
                   
                   
                   
                   
                 1.25 (2H, dd), 0.99-0.96 
                   
               
               
                   
                   
                   
                   
                 (8H, m). 
                   
               
               
                   
               
               
                 839 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.39 min, MI: 507 [M + H] 
                 1H NMR (DMSO, 500 MHz) 10.91 (1H, s), 9.09 (1H, s), 9.03 (1H, s), 8.78 (1H, s), 8.65 (1H, s), 8.49 (1H, d), 8.20 (1H, s), 8.09 (1H, dd), 7.99 (1H, dd), 7.92 (1H, m), 4.34 (2H, m), 
                 {4-[5-Cyclopropyl- 4-((S)-3-methyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(5- trifluoromethyl- pyridin-2-yl)-amine 
               
               
                   
                   
                   
                   
                 3.71 (1H, m), 3.42 (4H, 
                   
               
               
                   
                   
                   
                   
                 m), 3.06 (1H, m), 1.30 
                   
               
               
                   
                   
                   
                   
                 (5H, m), 1.08 (2H, m). 
                   
               
               
                   
               
               
                 840 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.50 min, MI: 471.42 [M + H] 
                 1H NMR (500 MHz, DMSO, 90° C.) 8.97 (2H, s), 8.64 (1H, s, br), 8.39 (1H, d d), 8.15 (1H, dd), 8.13 (1H, s), 7.89 (1H, dd), 7.65-7.60 (1H, m), 7.07-7.02 (1H, m), 3.79 (2H, t, br), 3.67 (2H, s), 
                 {4-[5-Cyclopropyl- 4-(3,3-dimethyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(3- fluoro-pyridin-2-yl)- amine 
               
               
                   
                   
                   
                   
                 2.95 (2H, s), 1.25 (2H, 
                   
               
               
                   
                   
                   
                   
                 dd), 0.99-0.96 (8H, m). 
                   
               
               
                   
               
               
                 841 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.13 min, MI: 481.47 [M + H] 
                 1H NMR (500 MHz, DMSO, 90° C.) 9.08 (1H, s), 8.40 (1H, dd), 8.23 (1H, s), 8.01 (1H, s), 7.85 (1H, s, br), 7.79- 7.78 (5H, m), 3.99-3.97 (4H, m), 3.37-3.35 (4H, m), 2.82 (3H, s), 2.72- 2.68 (1H, m), 1.29-1.27 
                 -[4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-ylamino]- N-methyl- benzamide 
               
               
                   
                   
                   
                   
                 (2H, m), 1.06-1.04 (2H, m). 
                   
               
               
                   
               
               
                 842 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 474 (M + H) 
                   
                 {5-Cyclopropyl-2- [2-(2,6-difluoro- phenylamino)- pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidin-3-yl- amine 
               
               
                   
               
               
                 843 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 2.36 min, MI: 488 [M + H] 
                 1H NMR (DMSO, 400 MHz, 90° C.) 9.06 (1H, s), 8.22 (2H, m), 7.74 (1H, s), 7.71 (1H, dd), 7.29 (1H, m), 7.13 (2H, t), 4.30 (2H, m), 3.53 (2H, m), 3.21 (2H, 
                 {4-[5-Cyclopropyl- 4-((3R,5S)-3,5- dimethyl-piperazin- 1-yl)-pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(2,6- difluoro-phenyl)- 
               
               
                   
                   
                   
                   
                 m), 2.66 (1H, m), 1.33 
                 amine 
               
               
                   
                   
                   
                   
                 (6H, d), 1.93 (2H, m), 
                   
               
               
                   
                   
                   
                   
                 1.04 (2H, m). 
                   
               
               
                   
               
               
                 844 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 1H NMR (500 MHz, DMSO) 9.09 (1H, s), 8.83 (1H, d), 8.64 (1H, s), 8.51 (1H, d), 8.29 (1H, dd), 8.21 (1H, s), 8.12 (1H, s), 8.07 (1H, d), 7.63 (1H, d), 7.54 (1H, s), 3.96 (4H, s, br), 3.34 (4H, s), 2.72-2.67 
                 6-[4-(5- Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-ylamino]- nicotinamide 
               
               
                   
                   
                   
                   
                 (1H, m), 1.27-1.24 (2H, 
                   
               
               
                   
                   
                   
                   
                 m), 1.09-1.08 (2H, m). 
                   
               
               
                   
               
               
                 845 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.87 min, MI: 507.41 [M + H] 
                 1H NMR (500 MH, DMSO) 10.07 (1H, s), 9.05 (1H, s), 8.85 (1H, s), 8.47 (1H, d), 8.20 (1H, s), 8.02 (1H, d), 7.01 (1H, dd), 3.91 (4H, s, br), 3.35 (2H, s, br), 2.55 (2H, s, br), 1.32- 
                 {4-[5-Cyclopropyl- 4-(3,3-dimethyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(3,4,6- trifluoro-pyridin-2- yl)-amine 
               
               
                   
                   
                   
                   
                 1.02 (13H, m). 
                   
               
               
                   
               
               
                 846 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 505.25 (MH)+ 
                   
                 [4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(8- cyclopropyl- [1,2,4]triazolo[1,5- a]pyridin-2-yl)- amine 
               
               
                   
               
            
           
         
       
     
     General synthesis of substituted substituted 2-morpholin-4-yl-pyrido[3,4-d]pyrimidine derivatives of general formula [H-006] Scheme C1 
     Amino-isonicotinamide derivatives of general formula [H-002] were prepared by reaction of a substituted amino-isonicotinamide derivative of general formula [H-001] with di-tert-butyl dicarbonate and ammonium carbonate in a polar aprotic solvent such as DMA, DMF, NMP with a base pyridine. Substituted 2-mercapto-3H-pyrido[3,4-d]pyrimidin-4-one derivatives of general formula [H-003] were prepared by cyclisation of a Amino-isonicotinamide derivatives of general formula [H-002] with carbon disulfide in a polar aprotic solvent such as DMA, DMF, NMP with a hindered base such as DBU. 2-Chloro-pyrido[3,4-d]pyrimidin-4-ol derivatives of general formula [H-004] were prepared by reaction of a Substituted 2-mercapto-3H-pyrido[3,4-d]pyrimidin-4-one derivatives of general formula [H-003] with thiophosgene in a polar aprotic solvent such as 1,4-dioxane. The 2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-ol derivatives of general formula [H-005] were prepared by the reaction of a 2-Chloro-pyrido[3,4-d]pyrimidin-4-ol derivative of general formula [H-004] with a substituted morpholine derivative of general formula [H-007] in a polar aprotic solvent such as DMA, DMF, NMP at high temperature either by heating thermally or using a microwave reactor. 2-morpholin-4-yl-pyrido[3,4-d]pyrimidine derivatives of general formula [H-006] were prepared by the reaction of a 2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-ol derivatives of general formula [H-005] with 2,4,6-triisopropylbenzenesulfonyl chloride in a polar aprotic solvent such as DMA, DMF, NMP with a tertiary alkylamine base such as Et 3 N, DIPEA or NMM and a catalytic amount of DMAP. The intermediate 6,7-substituted-(2,4,6-triisopropyl-benzenesulfonic acid)-2-morphol-4-yl-pyrido[3,4-d]pyrimidin-4-yl ester was then reacted with a primary or secondary amino derivative, of general formula [H-008], in a polar aprotic solvent such as DMA, DMF, NMP in the presence of a tertiary amine base such as Et 3 N, DIPEA or NMM at ambient temperature. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, TCA, methanesulfonic acid, HCl or H 2 SO 4  in a solvent such as DCM, DCE, THF, EtOH or MeOH and the crude reaction product was purified by reverse phase preparative HPLC. 
     
       
         
         
             
             
         
       
     
     Synthesis of 4-((S)-3-Benzyl-piperazin-1-yl)-2-morpholin-4-yl-pyrido[3,4-d]pyrimidine [1000] 
     
       
         
         
             
             
         
       
     
     3-Amino-isonicotinamide [C001] 
     A slurry of 3-aminoisonicotinic acid (1.00 g, 7.24 mmol) and CDI (1.76 g, 10.85 mmol) in DMF (15 mL) was heated to 40° C. for 0.5 h then cooled. Concentrated aqueous ammonia (50 mL) was added and the mixture was stirred for 15 min then extracted with ethyl acetate. Removal of the solvent gave a solid which was dissolved in EtOAc. The organic phase was washed with water and brine, dried over MgSO 4 , filtered and then concentrated under reduced pressure to give the title compound [C001](780 mg, 79%) LCMS method: 5, RT: 0.54 min, MI 138 [M+H]. 
     
       
         
         
             
             
         
       
     
     2-Mercapto-3H-pyrido[3,4-d]pyrimidin-4-one hydrochloride [C002] 
     3-Amino-isonicotinamide [C001](5 g, 36.46 mmol) was dissolved in DMF (40 mL). Carbon disulfide (11 mL, 183 mmol) and DBU (10.9 mL, 73 mmol) were added and the reaction heated to 60° C. for 2 hours. 2M HCl (40 mL) was added and the precipitate was collected, washed with water and dried under vacuum, to yield the title compound [C002] as a white solid which was was used without further purification: LCMS method: 5, RT: 1.55 min, MI 180 [M+H]. 
     
       
         
         
             
             
         
       
     
     2-Chloro-3H-pyrido[3,4-d]pyrimidin-4-one hydrochloride [C003] 
     To a mixture of 2-Mercapto-pyrido[3,4-d]pyrimidin-4-ol [C002](5.45 g, 30.41 mmol) in dioxine (100 mL) was added thiophosgene (3.5 mL, 45.6 mmol) dropwise and the mixture was heated at 100° C. for 3 h. The mixture was allowed to cool to room temperature and the resulting solid was diluted with Et 2 O (100 mL) and the precipitate was collected by filtration and the solid was washed with Et 2 O to yield the title compound which was used without further purification: LCMS method: 5, RT: 2.61 min, MI 182 [M+H]. 
     
       
         
         
             
             
         
       
     
     2-Morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-ol [C004] 
     In a microwave vial, a solution of 2-Chloro-pyrido[3,4-d]pyrimidin-4-ol hydrochloride (300 mg, 1.38 mmol) and morpholine (0.22 mL, 2.48 mmol) in DMA (4 mL) was heated under microwave irradiation to 150° C. for 20 min. The solvent was removed under reduced pressure and the resulting solid was washed with ether and collected to give the title compound [C004] which was used without further purification. LCMS method: 5, RT: 2.20 min, MI 232 [M+H]. 
     
       
         
         
             
             
         
       
     
     4-((S)-3-Benzyl-piperazin-1-yl)-2-morpholin-4-yl-pyrido[3,4-d]pyrimidine [1000] 
     To a solution of 2-Morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-ol [C004](100 mg, 0.43 mmol) in DMA (3 mL), 2,4,6-Triisopropylbenzenesulfonyl chloride (143 mg, 0.47 mmol), NEt 3  (0.12 mL, 0.86 mmol) and DMAP (10 mg) were added successively. The mixture was stirred at rt for 1 h and (S)-1-Boc-2-benzylpiperazine (154 mg, 0.56 mmol) was added. The reaction was stirred overnight and the solvent was removed under reduced pressure. The mixture was purified by column chromatography on silica gel eluting with CH 2 Cl 2  containing 0-10% MeOH. The appropriate fractions were combined and the solvent removed by rotary evaporation. The residue was dissolved in CH 2 Cl 2  (2 mL) and TFA (0.5 mL) was added. The solution was stirred for 3 h and then loaded onto a SCX-2 cartridge, washing with MeOH (6 mL) and eluting with 2 M ammonia in MeOH. The solvent was removed from the ammonia fraction to give the title compound [1000]: LCMS method: 5, RT: 2.33 min, MI 391 [M+H]; NMR: (1H, 300 MHz, CDCl 3 ); 8.88 (1H, s), 8.10 (1H, d), 7.35-7.21 (7H, m), 4.31-4.21 (2H, m), 3.78-3.71 (8H, m), 3.39-3.30 (1H, m), 3.18-3.08 (2H, m), 2.98-2.90 (2H, m), 2.76 (2H, d). 
     Synthesis of 2-Chloro-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol hydrochloride [C-005] 
     
       
         
         
             
             
         
       
     
     3-amino-5-methoxy-isonicotinamide [C-006] 
     A stirred suspension of 3-Amino-5-methoxy-isonicotinic acid (1.00 g, 5.947 mmol) in anhydrous dioxane (10 mL) was prepared under nitrogen at room temperature. Pyridine (0.53 mL, 6.542 mmol) was added followed by di-tert-butyl dicarbonate (1.43 g, 6.542 mmol) and ammonium carbonate (1.26 g, 13.083 mmol). The reaction mixture was stirred at room temperature for 5 hours then diluted with diethyl ether (50 mL) and the suspension stirred at room temperature for 18 hours. The suspension was filtered and the solid washed with diethyl ether (50 mL) then dissolved in methanol and filtered to remove the inorganic salts. The filtrate was concentrated by rotary evaporation to give the title compound [C-006](690 mg, 70%) as a cream coloured solid. LCMS method: 5, RT 1.27 min, MI 168 [M+H]; NMR: (1H, 300 MHz, d6-dmso) 7.77 (s, 1H), 7.65 (br. S, 1H), 7.58 (br. S, 1H), 7.57 (s, 1H), 6.30 (s, 2H), 3.85 (s, 3H). 
     
       
         
         
             
             
         
       
     
     2-Mercapto-5-methoxy-3H-pyrido[3,4-d]pyrimidin-4-one [C-007] 
     A suspension of 3-Amino-5-methoxy-isonicotinamide [C-006](1.10 g, 6.58 mmol) in anhydrous DMF (10 mL) was prepared under nitrogen. Carbon disulfide (1.97 mL, 32.90 mmol) was added followed by drop-wise addition of DBU (1.96 mL, 13.16 mmol) and the reaction mixture heated to 60° C. for 2.5 hours. The reaction mixture was cooled to room temperature and diluted with 2M HCl, the precipitate was filtered and washed with water. The precipitate was suspended in toluene (40 mL), the toluene was decanted and this was repeated once more. The precipitate was then suspended in toluene (30 mL) and concentrated by rotary evaporation to yield the title compound [C-007](1.05 g, 65%) as a yellow solid. LCMS method: 5, RT 2.33 min, MI 210 [M+H]; NMR: (1H, 500 MHz, d6-dmso) 12.71 (1H, s), 12.38 (1H, s), 8.30 (1H, s), 8.22 (1H, s), 3.95 (3H, s). 
     
       
         
         
             
             
         
       
     
     2-Chloro-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol hydrochloride [C-005] 
     A suspension of 2-Mercapto-5-methoxy-3H-pyrido[3,4-d]pyrimidin-4-one hydrochloride [C-007](1.145 g, 4.660 mmol) in anhydrous dioxane (20 mL) was prepared under nitrogen. Thiophosgene (0.54 mL, 6.990 mmol) was added drop-wise. The reaction mixture was stirred at room temperature for 10 min and then heated to 95° C. for 4 hours. A further portion of thiophosgene (0.09 mL, 1.165 mmol) was added and heating continued for a further 1.5 hours before stirring at room temperature overnight. The reaction mixture was diluted with diethyl ether and the precipitate was filtered, washed with diethyl ether and dried under vacuum to give the title compound [C-003](1.16 g, 100%) as a pale yellow solid. LCMS method: 5, RT 2.71 min, MI 212 [M+H]; NMR: (1H, 500 MHz, d6-dmso) 8.53 (1H, s), 8.40 (1H, s), 3.98 (3H, s). 
     Synthesis of [2-(2-Benzyl-morpholin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-(R)-pyrrolidin-3-yl-amine [1001] 
     
       
         
         
             
             
         
       
     
     2-(2-Benzyl-morpholin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol [C008] 
     Following the procedure described in Scheme C1, 2-Chloro-pyrido[3,4-d]pyrimidin-4-ol hydrochloride (100 mg, 0.459 mmol) was reacted with 2-Benzyl-morpholine (146 mg, 0.825 mmol) to give the title compound [C008](114 mg, 64%) following column chromatography on silica, eluting with CH 2 Cl 2  containing 0-10% MeOH. LCMS method: 5, RT 2.37 min, MI 323.24 [M+H]. 
     
       
         
         
             
             
         
       
     
     (R)-3-[2-(2-Benzyl-morpholin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester [C009] 
     To a stirred solution of 2-(2-Benzyl-morpholin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol [C008](70 mg, 0.21 mmol), NEt 3  (90 mL, 0.63 mmol) and DMAP (3 mg, 0.02 mmol) in DMA (1 mL) was added 2,4,6-triisopropylbenzenesulfonyl chloride (77 mg, 0.25 mmol). After 4 h (R)-(+)-1-Boc-3-aminopyrrolidine (43 mL, 0.25 mmol) was added and stirred overnight at RT. The reaction mixture was partitioned between CH 2 Cl 2  and H 2 O and the organic phase separated and evaporated. The residue was purified by column chromatography on silica, eluting with CH2Cl2 containing 0-5% MeOH. The appropriate fractions were combined and evaporated to give the title compound [C009](43 mg, 33%) as an off-white solid. LCMS method: 5, RT 3.59 min, MI 491.33 [M+H]. 
     
       
         
         
             
             
         
       
     
     [2-(2-Benzyl-morpholin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-(R)-pyrrolidin-3-yl-amine [1001] 
     (R)-3-[2-(2-Benzyl-morpholin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester [C009](34 mg, 0.069 mmol) was stirred in 4N HCl in dioxane (2 mL) for 1 h. The reaction mixture was diluted with MeOH and loaded onto a SCX-cartridge, washing with MeOH and eluting with ammonia in methanol. The ammonia phase was evaporated to give the title compound [1001](21 mg, 78%). LCMS method: 5, RT 1.97 min, MI 391.21 [M+H]; NMR: (1H, 300 MHz, d4-MeOD) 8.66 (1H, s), 8.14 (1H, dd), 7.83 (1H, ddd), 7.35-7.22 (5H, m), 4.66-4.59 (2H, m), 4.50-4.48 (1H, m), 3.98 (1H, dd), 3.71-3.55 (2H, m), 3.44-3.41 (1H, m), 3.16-3.07 (2H, m), 2.99-2.91 (1H, m), 2.85-2.74 (3H, m), 2.34-2.13 (3H, m). 
     General synthesis of substituted substituted 2-morpholin-4-yl-pyrido[3,4-d]pyrimidine derivatives of general formula [H-006] Scheme C2 
     The 2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl derivatives of general formula [H-009] were prepared by the reaction of a 2-Chloro-pyrido[3,4-d]pyrimidin-4-ol derivative of general formula [H-004] with a chlorinatation agent such as phosphorous oxychloride and then reacted with primary or secondary amino derivative of general formula [H-008], in a polar aprotic solvent such as DMA, DMF, NMP in the presence of a tertiary amine base such as Et 3 N, DIPEA or NMM at ambient temperature. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the 2-morpholin-4-yl-pyrido[3,4-d]pyrimidine derivatives of general formula [H-009] were reacted with a substituted morpholine derivative of general formula [H-007] in a polar aprotic solvent such as DMA, DMF, NMP at high temperature either by heating thermally or using a microwave reactor. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, TCA, methanesulfonic acid, HCl or H 2 SO 4  in a solvent such as DCM, DCE, THF, EtOH or MeOH and the crude reaction product was purified by reverse phase preparative HPLC. 
     
       
         
         
             
             
         
       
     
     Synthesis of (S)—N 1 -(5-Methoxy-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-3-phenyl-propane-1,2-diamine [1002] 
     
       
         
         
             
             
         
       
     
     (S)-2-Benzyl-4-(2-chloro-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [C010] 
     A solution of 2-Chloro-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol [C005](1.04 g, 4.911 mmol) in DCE (50 mL) was prepared under nitrogen. DIPEA (1.72 mL 9.822 mmol) and POCl 3  (0.46 mL, 4.911 mmol) were added and the reaction mixture stirred at room temperature for 2 hours. The reaction mixture was evapourated under reduced pressure and the residue used directly in the next step. A solution of 2,4-Dichloro-5-methoxy-pyrido[3,4-d]pyrimidine (280 mg of crude residue, 1.228 mmol assuming complete conversion) in DCM (15 mL) was prepared under nitrogen. Triethylamine (0.34 mL, 2.456 mmol) was added followed by (S)-2-Benzyl-piperazine-1-carboxylicacidtert-butylester (170 mg, 0.614 mmol). The reaction mixture was stirred at room temperature over night. The reaction mixture was evapourated under reduced pressure and the residue purified by chromatography on silica, eluting with DCM containing 0-10% MeOH to yield the title compound [C-010](110 mg, 19%): LCMS method: 5, RT 2.55 min, MI 263 [M+H]; NMR: (1H, 500 MHz, d6-dmso) 8.69 (1H, d, J=3.7 Hz), 8.39 (1H, d, J=3.7 Hz), 4.10 (3H, s), 3.63 (4H, broad s), 3.54 (4H, broad s), 1.47 (9H, s). 
     
       
         
         
             
             
         
       
     
     (S)—N 1 -(5-Methoxy-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-3-phenyl-propane-1,2-diamine [1002] 
     A solution of (S)-2-Benzyl-4-(2-chloro-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [C010](100 mg, 0.213 mmol) in anhydrous DMA (2 mL) was prepared. Morpholine (19 mg, 0.213 mmol) and DIPEA (0.04 mL, 0.213 mmol) were added and the mixture heated to 150° C. for 20 min in the microwave. The reaction mixture was evapourated under reduced pressure and the crude residue was purified by chromatography on silica eluting with DCM containing 0-10% MeOH. The product was stirred in 4M HCl in dioxane at room temperature for 1 hour and the reaction mixture was evapourated under reduced pressure and loaded onto an SCX cartridge, washing with methanol and eluting with 7N ammonia in methanol. The ammonia eluent was evapourated under reduced pressure to the title compound [1001](46 mg, 51%) as a yellow solid: LCMS method: 5, RT 2.51 min, MI 421 [M+H]; NMR: (1H, 500 MHz, d6-dmso) 8.34 (1H, s), 7.82 (1H, s), 7.35-7.32 (2H, m), 7.28-7.25 (3H, m), 4.0-3.97 (1H, m), 3.80 (4H, broad s), 3.62-3.61 (8H, broad m), 3.08-3.03 (1H, m), 2.98-2.91 (1H, m), 2.76-2.57 (6H, m). 
     Synthesis of 5-Methoxy-2-morpholin-4-yl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine [1003] 
     
       
         
         
             
             
         
       
     
     4-(2-Chloro-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [C011] 
     A stirred suspension of 2-Chloro-5-methoxy-pyrido[3,4-d]pyrimidin-4-ol hydrochloride [C005](200 mg, 0.806 mmol) in DCE (10 mL) was prepared under nitrogen. DIPEA (0.31 mL, 1.773 mmol) was added followed by drop-wise addition of POCl 3  (0.08 mL, 0.887 mmol). The reaction mixture was stirred at room temperature for 2 hours. A further portion of DIPEA (0.31 mL, 1.773 mmol) and POCL3 (0.08 mL, 0.887 mmol) were added and stirring continued at room temperature for 3 hours. The reaction mixture was evapourated under reduced pressure and the residue partitioned between CH 2 Cl 2  (30 mL) and sat. NaHCO 3  (aq) (30 mL). The organic phase was separated and the aqueous extracted with CH 2 Cl 2  (2×10 mL). The combined organic portions were dried (phase separator) and evapourated under reduced pressure to give a crude residue containing 2,4-Dichloro-5-methoxy-pyrido[3,4-d]pyrimidine (assumed 185 mg, 100%) which was used without further purification. A solution containing crude 2,4-Dichloro-5-methoxy-pyrido[3,4-d]pyrimidine (assumed 185 mg, 0.806 mmol) in CH 2 Cl 2  (10 mL) was prepared under nitrogen. Triethylamine (0.17 mL, 1.209 mmol) was added followed by piperazine-1-carboxylic acid tert-butyl ester (120 mg, 0.645 mmol) and the reaction mixture stirred at room temperature overnight. The reaction mixture was evapourated under reduced pressure and the residue purified by chromatography on silica eluting with CH 2 Cl 2  containing 0-10% MeOH. The appropriate fractions were combined and concentrated to yield the title compound [1003](177 mg, 58%) as a yellow solid. LCMS method: 5, RT 5.44 min, MI 380 [M+H]; NMR: (1H, 500 MHz, d6-dmso) 8.65 (s, 1H), 8.34 (s, 1H), 4.06 (s, 3H), 3.59 (br. m, 4H), 3.49 (br. m, 4H), 1.42 (s, 9H). 
     
       
         
         
             
             
         
       
     
     5-Methoxy-2-morpholin-4-yl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine [C012] 
     To a solution of 2,4-Dichloro-5-methoxy-pyrido[3,4-d]pyrimidine [C011](70 mg, 0.19 mmol) in DMA (2 mL) was added morpholine (20 mg, 0.228 mmol) and DIPEA (0.04 mL, 0.228 mmol). The reaction mixture was heated to 150° C. for 20 min in a microwave. The reaction mixture was concentrated under reduced pressure and the crude residue was purified by chromatography on silica (eluting with CH2C12 containing 0-10% MeOH) to give the title compound [C012] LCMS method: 5, RT 4.01 min, MI 431 [M+H]. 
     
       
         
         
             
             
         
       
     
     5-Methoxy-2-morpholin-4-yl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine [1003] 
     5-Methoxy-2-morpholin-4-yl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine [C012] was stirred in 4M HCl in dioxane (2 mL) at room temperature for 2 hours. The reaction mixture was diluted with methanol (to dissolved precipitate) and loaded onto a SCX cartridge, washing with methanol and eluting with 7M ammonia in methanol. The ammonia fraction was evapourated under reduced pressure and dried under vacuum to give the title compound [1003](48 mg, 83%): LCMS method: 5, RT 3.54 min, MI 331 [M+H]; NMR: (1H, 500 MHz, d6-dmso) 8.33 (1H, broad d, J=0.9 Hz), 7.88 (1H, s), 3.95 (3H, s), 3.73-3.71 (4H, m), 3.64-3.62 (4H, m), 3.38 (4H, broad m), 2.82-2.80 (4H, broad t, J=4.5 Hz). 
     The following intermediate compounds were synthesised according to the general synthesis shown in scheme [C2] 
     
       
         
           
               
               
               
               
               
            
               
                   
               
               
                   
                   
                   
                 Analysis 
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Int 
                 SM 
                 Amine 
                 LCMS 
                 NMR 
                 Name 
               
               
                   
               
               
                 [C013] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 522 min, MI: 350 [M + H] 
                   
                 4-(2-Chloro-5- methoxy- pyrido[3,4- d]pyrimidin-4-yl)- piperazine-1- carboxylic acid tert-butyl ester 
               
               
                   
               
               
                 [C014] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 6.18 min, MI: 470 [M + H] 
                   
                 (S)-2-Benzyl-4- (2-chloro-4- methoxy- pyrido[3,4- d]pyrimidin-4-yl)- piperazine-1- carboxylic acid tert-butyl ester 
               
               
                   
               
               
                 [C015] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 2.99 min, MI: 386 [M + H] 
                 (1H, 500 MHz, CDCl 3 ): 8.82 (1H, s), 8.18 (1H, s), 7.31-7.28 (2H, m), 6.98 (1H, t, J = 7.4), 6.90 (2H, d, J = 7.9 Hz), 4.27- 4.24 (1H, br. d, J = 12.1 Hz), 4.15-4.10 (1H, m), 4.06 (3H, 
                 2-Chloro-5- methoxy-4-((R)- 3-phenoxymethyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
                   
                   
                   
                 s), 4.03-4.00 (1H, 
                   
               
               
                   
                   
                   
                   
                 m), 3.98-3.94 (1H, 
                   
               
               
                   
                   
                   
                   
                 m), 3.39-3.34 (1H, 
                   
               
               
                   
                   
                   
                   
                 br. s), 3.27-3.18 
                   
               
               
                   
                   
                   
                   
                 (2H, m), 3.11-3.02 
                   
               
               
                   
                   
                   
                   
                 (2H, m). 
                   
               
               
                   
               
               
                 [C016] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 5.40 min, MI: 370 [M + H] 
                 (1H, 500 MHz, d6- dmso): 8.61 (1H, s), 8.29 (1H, s), 7.06 (2H, t, J = 7.6 Hz), 6.77 (1H, br. d, J = 7.3 Hz), 6.51 (1H, t, J = 7.3 Hz), 5.61 (1H, d, J = 7.2 Hz), 4.48 (1H, br. s), 4.03 
                 [(S)-1-(2-Chloro- 5-methoxy- pyrido[3,4- d]pyrimidin-4-yl)- piperidin-3-yl]- phenyl-amine 
               
               
                   
                   
                   
                   
                 (3H, s), 3.85 (1H, 
                   
               
               
                   
                   
                   
                   
                 br, d, J = 12.7 Hz), 
                   
               
               
                   
                   
                   
                   
                 3.46-3.40 (1H, br. 
                   
               
               
                   
                   
                   
                   
                 m), 3.55-3.30 (1H, 
                   
               
               
                   
                   
                   
                   
                 br. m), 2.83 (1H, t, J = 
                   
               
               
                   
                   
                   
                   
                 10.7 Hz), 1.99 
                   
               
               
                   
                   
                   
                   
                 (1H, br. s), 1.79- 
                   
               
               
                   
                   
                   
                   
                 1.78 (1H, br. m), 
                   
               
               
                   
                   
                   
                   
                 1.57-1.49 (2H, br. 
                   
               
               
                   
                   
                   
                   
                 m). 
                   
               
               
                   
               
               
                 [C017] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.00 min, MI: 404 [M + H] 
                 (1H, 500 MHz, d6- dmso) 8.62 (1H, s), 8.32 (1H, s), 7.21-7.16 (2H, m), 7.11 (1H, t, J = 7.9 Hz), 6.96- 6.93 (1H, m), 4.15- 4.13 (1H, br. m), 4.05-3.97 (3H, m), 4.02 (3H, s), 3.19- 
                 2-Chloro-4-[(R)- 3-(2-fluoro- phenoxymethyl)- piperazin-1-yl]-5- methoxy- pyrido[3,4- d]pyrimidine 
               
               
                   
                   
                   
                   
                 3.18 (1H, br. m), 
                   
               
               
                   
                   
                   
                   
                 3.12-3.03 (2H, m), 
                   
               
               
                   
                   
                   
                   
                 2.99-2.95 (1H, m), 
                   
               
               
                   
                   
                   
                   
                 2.84-2.79 (1H, br. 
                   
               
               
                   
                   
                   
                   
                 m). 
                   
               
               
                   
               
               
                 [C018] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.13 min, MI: 404 [M + H] 
                 (1H, 500 MHz, d6- dmso) 8.63 (1H, s), 8.34 (1H, s), 7.14-7.10 (2H, m), 6.98-6.95 (2H, m), 4.16-4.12 (1H, br m), 4.04 (3H, s), 4.04-3.99 (1H, br m), 3.93 (2H, d), 3.16-3.09 (3H, m), 2.98-2.94 (1H, m), 2.84-2.79 
                 2-Chloro-4-[(R)- 3-(4-fluoro- phenoxymethyl)- piperazin-1-yl]-5- methoxy- pyrido[3,4- d]pyrimidine 
               
               
                   
                   
                   
                   
                 (1H, m). 
                   
               
               
                   
               
               
                 [C019] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 5.45 min, MI: 423 [M + H] 
                 (1H, 500 MHz, d6- dmso) 8.64 (1H, s), 8.34 (1H, s), 4.26 (1H, br. s), 4.20 (1H, br. d, J = 13.2 Hz), 4.06 (3H, s), 3.92 (1H, br. d, J = 8 Hz), 3.82- 3.80 (1H, br. m), 3.39-3.35 (1H, br. m), 3.31-3.24 (2H, m), 3.21-3.19 (2H, 
                 (R)-4-(2-Chloro- 5-methoxy- pyrido[3, 4-d]pyrimidin-4- yl)-2- methoxymethyl- piperazine-1- carboxylic acid tert-butyl ester 
               
               
                   
                   
                   
                   
                 m), 3.10 (3H, br. s), 
                   
               
               
                   
                   
                   
                   
                 1.40 (9H, s). 
                   
               
               
                   
               
               
                 [C020] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 4.89 min, MI: 410 [M + H] 
                 (1H, 500 MHz, d6- dmso) 1.40 (s, 9H), 3.17 (t, 1H), 3.22-3.33 (m, 1H), 3.33-3.39 (m, 2H), 3.72-3.82 (m, 1H), 3.87-3.92 (m, 1H), 4.05n (s, 3H), 4.02-4.10 (m, 1H), 4.18-4.24 (m, 1H), 4.76-4.78 (m, 1H), 8.33 (s, 1H), 
                 (R)-4-(2-Chloro- 5-methoxy- pyrido[3, 4-d]pyrimidin-4- yl)-2- hydroxymethyl- piperazine-1- carboxylic acid tert-butyl ester 
               
               
                   
                   
                   
                   
                 8.63 (s, 1H). 
                   
               
               
                   
               
               
                 [C021] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 4.10 min, MI: 350 [M + H] 
                   
                 (2-Chloro-5- methoxy- pyrido[3,4-d]py- rimidin-4-yl)-(R)- pyrrolidin-3-yl- amine 
               
               
                   
               
            
           
         
       
     
     The following compounds were synthesised according to the general synthesis shown in scheme [C2] 
     
       
         
           
               
               
               
               
               
            
               
                   
               
               
                   
                   
                   
                 Analysis 
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Ex 
                 Precursor 
                 Amine 
                 LCMS 
                 NMR 
                 Name 
               
               
                   
               
               
                 1004 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 2.74 min, MI: 437 [M + H] 
                 (1H, 500 MHz, d6- dmso) 8.39 (1H, s), 7.94 (1H, s), 7.36-7.32 (2H, m), 7.03-6.97 (3H, m), 4.70 (1H, broad, d, J = 12.8 Hz), 4.53 (1H, broad d, J = 13.1 Hz), 4.16-4.10 (2H, m), 4.04-4.00 (1H, m), 4.00 (3H, s), 3.86-3.81 (1H, m), 3.63-3.57 (1H, m), 3.44-3.43 (4H, broad m), 3.20 (1H, d, J = 6 Hz), 3.11- 3.06+ (1H, m), 2.99- 2.94 (1H, m), 2.86 (4H, 
                 5-Methoxy-2-(2- phenoxymethyl- morpholin-4-yl)- 4-piperazin-1- yl-pyrido[3,4- d]pyrimidine 
               
               
                   
                   
                   
                   
                 broad t, J = 4.7 Hz) 
                   
               
               
                   
               
               
                 1005 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.49 min, MI: 3.61 (M + H] 
                 (1H, 500 MHz, d6- dmso) 8.34 (1H, s), 7.90 (1H, s), 4.66 (1H, br t, J = 5.1 Hz), 3.98-3.94 (1H, m), 3.95 (3H, s), 3.86 (1H, br d, J = 11.8 Hz), 3.74-3.73 (4H, m), 3.66-3.44 (4H, m), 3.40-3.33 (2H, m), 2.97-2.88 (2H, m), 2.81-2.75 (2H, m), 2.62-2.57 (1H, m). 
                 [(R)-4-(5- Methoxy-2- morpholin-4-yl- pyrido[3,4- d]pyrimidin-4- yl)-piperazin-2- yl]-methanol 
               
               
                   
               
               
                 1006 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 5.02 min, MI: 4.37 [M + H] 
                 (1H, 500 MHz, d6- dmso) 8.34 (1H, s), 7.90 (1H, s), 7.30-7.27 (2H, m), 6.94-6.93 (3H, m), 4.90 (1H, br. d, J = 11.9 Hz), 3.96-3.90 (2H, m), 3.94 (3H, s), 3.84 (1H, br. d, J = 11.8 Hz), 3.72-3.70 (4H, m), 3.63-3.61 (4H, m), 3.19 (1H, br. s), 3.02- 2.98 (2H, br. m), 2.81- 2.74 (2H, br. m). 
                 5-Methoxy-2- morpholin-4-yl- 4-((R)-3- phenoxymethyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1007 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.12 min, MI: 421 [M + H] 
                 (1H, 500 MHz, CDCl 3 ) 8.54 (1H, s), 7.83 (1H, s), 7.17-7.14 (2H, m), 6.69 (1H, br. t, J = 7.3 Hz), 6.62 (2H, br. d, J = 7.5 Hz), 4.02-3.97 (1H, br. m), 4.00 (3H, s), 3.87-3.86 (4H, m), 3.77-3.75 (4H, m), 3.69 (1H, br. s), 3.59- 3.55 (1H, br. m), 3.36- 3.27 (2H, br. m), 2.04- 1.97 (1H, br. m), 1.89- 1.84 (1H, br. m), 1.71- 
                 [(S)-1-(5- Methoxy-2- morpholine-4-yl- pyrido[3,4- d[pyrimidin-4- yl)-piperidin-3- yl]-phenyl- amine 
               
               
                   
                   
                   
                   
                 1.65 (2H, br. m). 
                   
               
               
                   
               
               
                 1008 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 2.54 min, MI: 455 [M + H] 
                 (1H, 500 MHz, d6- dmso): 8.33 (1H, s), 7.89 (1H, s), 7.22-7.16 (2H, m), 7.11 (1H, br. t, J = 7.5 Hz), 6.96-6.92 (1H, m), 4.14 (1H, br. d, J = 12.3 Hz), 4.05-4.02 (1H, m), 3.97-3.93 (1H, m), 3.93 (3H, s), 3.83-3.80 (1H, m), 3.72-3.70 (4H, m), 3.63-3.61 (4H, m), 3.20 (1H, br. s), 3.03- 2.96 (2H, m), 2.78- 2.73 (2H, m). 
                 4-[(R)-3-(2- Fluoro- phenxoymethyl)- piperazin-1-yl]- 5-methoxy-2- morpholin-4-yl- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1009 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 1.26 min, MI: 375 [M + H] 
                 (1H, 500 MHz, d6- dmso): 8.34 (1H, s), 7.90 (1H, s), 3.95 (3H, s), 3.91 (1H, br. d, J = 12.4 Hz), 3.84 (1H, br. d, J = 12.5 Hz), 3.74-3.72 (4H, m), 3.66-3.64 (4H, m), 3.28 (2H, d, J = 5.9 Hz), 3.26 (3H, s), 2.98-2.93 (3H, m), 2.78-2.74 (1H, m), 2.66-2.61 (1H, m). 
                 5-Methoxy-4- ((R)-3- methoxymethyl- piperazin-1-yl)- 2-morpholin-4- yl-pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1010 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 2.62 min, MI: 455 [M + H] 
                 (1H, 500 MHz, d6- dmso): 8.35 (1H, s), 7.91 (1H, s), 7.14-7.10 (2H, m), 6.97-6.95 (2H, m), 4.07 (1H, br. d, J = 12.2 Hz), 3.95 (3H, s), 3.92- 3.90 (2H, m), 3.84 (1H, br. d, J = 12.2 Hz), 3.73- 3.71 (4H, m), 3.64- 3.62 (4H, m), 3.17- 3.16 (1H, br. m), 3.01- 2.97 (2H, br. m), 2.80- 2.73 (2H, br. m). 
                 4-[(R)-3-(4- Fluoro- phenoxymethyl)- piperazin-1-yl]- 5-methoxy-2- morpholin-4-yl- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1011 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 0.54 min, MI: 301 [M + H] 
                 1H NMR (CDCl 3 , 500 MHz) 8.83 (s, 1H), 8.19 (d, 1H), 7.49 (d, 1H), 6.74 (d, 1H), 4.85- 4.75 (m, 1H), 3.92-3.87 (m, 4H), 3.80-3.75 (m, 4H), 3.31-3.06 (m, 4H), 2.38-2.22 (m, 2H). 
                 (2-Morpholin-4- yl-pyrido[3,4- d]pyrimidin-4- yl)-(R)- pyrrolidin-3-yl- amine 
               
               
                   
               
            
           
         
       
     
     Synthesis of [2-Morpholin-4-yl-8-(2H-pyrazol-3-yl)-pyrido[3,4-d]pyrimidin-4-yl]-(R)-pyrrolidin-3-yl-amine [1012] 
     
       
         
         
             
             
         
       
     
     2,8-Dichloro-pyrido[3,4-d]pyrimidin-4-ol [C022] 
     To a suspension of 3-Amino-2-chloro-isonicotinamide (2.00 g, 11.65 mmol) in dioxane (30 mL), thiophosgene (2.25 mL, 29.13 mmol) was added dropwise and the suspension was stirred 15 min. The reaction was then heated at 100° C. for 3 h then cooled down to room temperature and diluted with Et 2 O. The resulting solid was collected and dried to give the title compound [C022](2.41 g, 96%) which was used without further purification. LCMS method: 5, RT 3.51 min, MI 216 [M+H]. 
     
       
         
         
             
             
         
       
     
     8-Chloro-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-ol [C023] 
     To a solution of 2,8-Dichloro-pyrido[3,4-d]pyrimidin-4-ol [C022](200 mg, 0.926 mmol) in DMA (2 mL), morpholine (0.1 mL, 1.20 mmol) was added. The solution was stirred at room temperature for 30 min then heated to 40° C. for 3 h. The solvent was removed under reduced pressure, a minimum amount of CH 2 Cl 2  was added to dissolve the crude residue and Et 2 O was added. The resulting solid was collected and dried to give the title compound [C022](200 mg, 80%) which was used without further purification. LCMS method: 5, RT 3.95 min, MI 267 [M+H]. 
     
       
         
         
             
             
         
       
     
     (R)-3-(8-Chloro-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester [C024] 
     To a solution of 8-Chloro-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-ol [C022](500 mg, 1.87 mmol) in DMA (10 mL), 2,4,6-Triisopropylbenzenesulfonyl chloride (690 mg, 2.25 mmol), NEt 3  (0.52 mL, 3.75 mmol) and DMAP (50 mg, 0.41 mmol) were added successively. The mixture was stirred at 40° C. for 1 h and then (R)-3-Amino-pyrrolidine-1-carboxylic acid tert-butyl ester (460 mg, 2.44 mmol). The reaction was stirred overnight at room temperature then the solvent was removed under reduced pressure. The mixture was purified by column chromatography on silica eluting with CH 2 Cl 2  containing 0-10% MeOH. The appropriate fractions were combined and evapourated under reduced pressure to give the title compound [C023](310 mg, 38%). LCMS method: 5, RT 5.77 min, MI 435 [M+H]. 
     
       
         
         
             
             
         
       
     
     [2-Morpholin-4-yl-8-(2H-pyrazol-3-yl)-pyrido[3,4-d]pyrimidin-4-yl]-(R)-pyrrolidin-3-yl-amine [1012] 
     A microwave vial was charged with (R)-3-(8-Chloro-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester [C024](100 mg, 0.23 mmol), 1H-Pyrazole-5-boronic acid (38 mg, 0.35 mmol), Pd(Ph 3 P) 4  (27 mg, 0.023 mmol), a solution of K 3 PO 4  (0.92 mL of a 0.5M in H 2 O, 0.46 mmol) and DMA (3.5 mL). The mixture was heated under microwave irradiation to 150° C. for 10 min. The solvent was removed under reduced pressure and the residue purified by chromatography on silica, eluting with CH 2 Cl 2  containing 0-10% MeOH. The appropriate fractions were combined and the solvent evaporated under reduced pressure to give the Boc-protected intermediate which was dissolved in CH 2 Cl 2  (2 mL) and TFA (0.5 mL) was added. The solution was stirred for 3 h and then loaded onto a SCX-2 cartridge, washing with MeOH and eluting with 2N ammonia in MeOH solution. The solvent was removed from the ammonia fraction under reduced pressure to yield the title compound [1012]: LCMS method: 5, RT 4.39 min, MI 367 [M+H]; NMR: (1H, 300 MHz, d6-dmso) 8.28 (d, 1H), 7.96 (d, 1H), 7.60 (d, 1H), 7.33 (d, 1H), 4.61-4.68 (m, 1H), 3.78-3.81 (m, 4H), 3.68-3.74 (m, 4H), 3.33-3.40 (m, 2H), 3.18-3.23 (m, 1H), 3.02-3.07 (m, 1H), 2.15-2.24 (m, 1H), 1.98-2.04 (m, 1H). 
     Synthesis of N 4 —((S)-2-Amino-3-phenyl-propyl)-2-morpholin-4-yl-pyrido[3,4-d]pyrimidine-4,8-diamine [1013] 
     
       
         
         
             
             
         
       
     
     [(S)-1-Benzyl-2-(8-chloro-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-ylamino)-ethyl]-carbamic acid tert-butyl ester [C025] 
     Following the procedure described above, 8-Chloro-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-o [C023]1 (500 mg, 1.87 mmol) was reacted with ((S)-1-Aminomethyl-2-phenyl-ethyl)-carbamic acid tert-butyl ester (600 mg, 2.44 mmol) to give the title compound [C024](350 mg, 38%). LCMS method: 5, RT 5.90 min, MI 499 [M+H]. 
     
       
         
         
             
             
         
       
     
     N 4 —((S)-2-Amino-3-phenyl-propyl)-2-morpholin-4-yl-pyrido[3,4-d]pyrimidine-4,8-diamine 
     A microwave vial was charged with [(S)-1-Benzyl-2-(8-chloro-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-ylamino)-ethyl]-carbamic acid tert-butyl ester [C025](100 mg, 0.20 mmol), EtOH (2 mL) and NH 4 OH (2 mL). The reaction mixture was heated under microwave irradiation to 150° C. for 1 h. This was repeated until reasonable conversion to the desired product was identified by LCMS analysis. The solvent was then removed under reduced pressure and the BOC protected compounds were diluted in CH 2 Cl 2  (2 mL) and TFA (0.5 mL) was added. The solution was stirred for 3 h and then loaded onto a SCX-2 cartridge, washing with MeOH and eluting with 2M ammonia in MeOH solution. The solvent was removed from the ammonia fraction and the residue was purified by preparative HPLC (method A) to yield the title compound [1013] LCMS method: 5, RT 2.11 min, MI 380 [M+H]; NMR: (1H, 300 MHz, d6-dmso) 8.30-8.35 (m, 1H), 8.27 (br s, 1H), 7.49 (d, 1H), 7.22-7.33 (m, 4H), 6.97 (d, 1H), 6.34 (br s, 2H), 3.68-3.78 (m, 1H), 3.61-3.65 (m, 1H), 3.37-3.54 (m, 8H), 3.25-3.35 (m, 2H), 2.91 (dd, 1H), 2.73 (dd, 1H). 
     Synthesis of (S)—N 1 -(2-Morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-3-phenyl-propane-1,2-diamine [1014] 
     
       
         
         
             
             
         
       
     
     2-Chloro-pyrido[3,4-d]pyrimidin-4-ol [C003](1.50 g, 8.26 mmol) was suspended in DMA (30 mL). Triethylamine (2.3 mL, 16.52 mmol) was added and the reaction mixture stirred at room temperature. 2,4,6-Triisopropylbenzenesulfonyl chloride (2.75 g, 9.09 mmol) and DMAP (50 mg, 0.41 mmol) were both added and the mixture was stirred at room temperature for 6 hours. ((S)-1-Aminomethyl-2-phenyl-ethyl)-carbamic acid tert-butyl ester (3.10 g, 12.39 mmol) was added to the reaction mixture and stirring continued at room temperature for 18 hours. To the crude solution was added morpholine (1 mL) and the mixture sealed and heated under microwave irradiation to 150° C. for 20 min. The mixture was taken up in DCM and washed with water and brine. The layers were separated and the organic layer was dried over MgSO 4 . The solvent was removed under reduced pressure and the crude mixture purified by flash column chromatography; eluting with a 5% methanol in CH 2 Cl 2 . The appropriate fractions were combined and concentrated and the residue stirred in 4M HCl in dioxane for 18 hours. The mixture was concentrated under reduced pressure and the residue loaded onto a SCX cartridge, washing with MeOH and eluting with 2M ammonia in methanol. The solvent was removed from the ammonia fraction under reduced pressure to give the title compound [1014](150 mg, 22%). LCMS method: 5, RT 1.79 min, MI 365 [M+H]; NMR: (1H, 300 MHz, d6-dmso) 8.73 (1H, br s), 8.64 (1H, s), 8.29 (2H, br s), 8.20 (1H, d), 8.00 (1H, d), 7.38-7.28 (5H, m), 3.90-3.83 (1H, m), 3.62-3.34 (10H overlapping br m), 3.13-3.07 (1H, m), 2.88-2.81 (1H, m). 
     General synthesis of substituted substituted 2-morpholin-4-yl-pyrido[3,4-d]pyrimidine derivatives of general formula [H-006] Scheme C3 
     3-halo-N-(imino-morpholin-4-yl-methyl)-isonicotinamide derivatives of general formula [H-011] were prepared by coupling of a ortho-halo-isonicotinic acid derivative of general formula [H-010] with an appropriately substituted 4-carbamimidoyl-morpholine of general formula [H-004] with a suitable coupling agent such as O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) in a polar aprotic solvent such as DMA or DMF. The isonicotinoyl-amidine derivative of general formula [H-011] were cyclised to displace the relevant halogen group to yield the desired morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-ol derivatives of general formula [H-005]. The 2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl derivatives of general formula [H-006] were prepared by the reaction of a morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-ol derivatives of general formula [H-005] with a chlorinatation agent such as phosphorous oxychloride or a triflating agent such as N-Phenyl-bis(trifluoromethanesulfonimide and then reacted with primary or secondary amino derivative of general formula [H-008], in a polar aprotic solvent such as DMA, DMF, NMP in the presence of a tertiary amine base such as Et 3 N, DIPEA or NMM at ambient temperature. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, TCA, methanesulfonic acid, HCl or H 2 SO 4  in a solvent such as DCM, DCE, THF, EtOH or MeOH and the crude reaction product was purified by reverse phase preparative HPLC. 
     
       
         
         
             
             
         
       
     
     Synthesis of 5-Bromo-2-morpholin-4-yl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine [1015] 
     
       
         
         
             
             
         
       
     
     3-Bromo-5-fluoro-N-(imino-morpholin-4-yl-methyl)-isonicotinamide [C026] 
     A stirred solution of 3-Bromo-5-fluoro-isonicotinic acid hydrochloride (800 mg, 3.119 mmol) and DIPEA (1.91 mL, 10.917 mmol) in DMF (11 mL) was prepared. HATU (1.186 g, 3.119 mmol) was added and the reaction mixture stirred at room temperature for 1 hour, during which time reaction mixture turned slowly brown. 4-Morpholinylformamidine hydrobromide (655 mg, 3.119 mmol) was added and stirring continued at room temperature for 2 hours. The reaction mixture was diluted with water (30 mL) and stirred at room temperature for 10 mins. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organics dried and evapourated under reduced pressure to give the title compound [C026] a brown gum (1.15 g, 87%) which was used without purification in the next step: LCMS method: 5, RT 2.86 min, MI 331 [M+H]. 
     
       
         
         
             
             
         
       
     
     5-Bromo-2-morpholin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [C027] 
     A solution of 3-Bromo-5-fluoro-N-(imino-morpholin-4-yl-methyl)-isonicotinamide [C025](crude product containing 1.03 g, 3.119 mmol starting material assuming 100% conversion) in anhydrous DMA (10 mL) was prepared and potassium carbonate (453 mg, 3.275 mmol) was added. The reaction mixture was heated to 150° C. for 1 hour in the microwave. The reaction mixture was poured into water (20 mL) and acidified with acetic acid. The resulting beige precipitate was filtered, washed with water and dried in the vac. oven over night to give the title compound [C027](400 mg, 41%): LCMS method: 5, RT 1.42 min, MI 313 [M+H]. 
     
       
         
         
             
             
         
       
     
     5-Bromo-2-morpholin-4-yl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine [1015] 
     A solution of 5-Bromo-2-morpholin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one (50 mg, 0.161 mmol) in anhydrous DMF (2 mL) was prepared under nitrogen. N-Phenyl-bis(trifluoromethanesulfonimide) (60 mg, 0.169 mmol) was added followed by DIPEA (0.06 mL, 0.354 mmol) and the reaction mixture stirred at room overnight. Piperazine-1-carboxylic acid tert-butyl ester (60 mg, 0.322 mmol) was added and stirring continued at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the residue diluted with EtOAc (10 mL) and washed with water (3×5 mL). The organic phase was dried, filtered and concentrated by rotary evaporation. The residue was purified by chromatography on silica, eluting with cyclohexane containing 5-50% EtOAc. The appropriate fractions were combined and concentrated to give 4-(5-Bromo-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [C027](35 mg, 45%) as a yellow solid. LCMS method: 5, RT 5.92 min, MI 479 [M+H]; NMR: (1H, 500 MHz, d6-dmso) 8.67 (1H, s), 8.29 (1H, s), 3.78-3.76 (4H, m), 3.66-3.62 (4H, m), 3.62 (2H, very broad s), 3.52-3.47 (4H, very broad m), 3.24 (2H, very broad s), 1.40 (9H, s). 
     The Boc protected intermediate [C026] was taken up in 4M HCl in dioxane (2 mL) and stirred at room temperature 2 hours. The reaction mixture was concentrated by rotary evaporation and the residue loaded onto a SCX-2 cartridge, washing with MeOH and eluting with 7N ammonia in MeOH. The ammonia fraction was concentrated under reduced pressure to give the title compound [1015](24 mg, 86%) as a yellow solid. LCMS method: 5, RT 2.24 min, MI 379 [M+H]; NMR: (1H, 500 MHz, CDCl 3 ) 8.76 (1H, s), 8.28 (s, 1H), 3.89-3.87 (4H, m), 3.78-3.76 (4H, m), 3.70 (2H, br. s), 3.33 (2H, br. s), 3.09 (2H, br. s), 3.00 (2H, br. s). 
     Synthesis of 5-Cyclopropyl-2-morpholin-4-yl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine 
     
       
         
         
             
             
         
       
     
     A solution of 4-(5-Bromo-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [C028](110 mg, 0.229 mmol) in anhydrous dioxane (2.5 mL) was prepared in a microwave vial. potassium phosphate (tribasic) (ground, 145 mg, 0.687 mmol) and cyclopropyl boronic acid (30 mg, 0.344 mmol) were added. The reaction mixture was purged with argon (vacuum/argon balloon) 3 times and then Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (9 mg, 0.011 mmol) was added and the vial sealed and heated to 95° C. for 5 hours. The reaction mixture was cooled to room temperature and allowed to stand overnight. The reaction mixture was evaporated onto silica and purified by chromatography on silica, eluting with CH 2 Cl 2  containing 0-8% MeOH. The product was not purified with this solvent system and so the appropriate fractions were concentrated and purification repeated, eluting with cyclo-hexane containing 50-100% EtOAc. The appropriate fractions were combined and concentrated to give 4-(5-Cyclopropyl-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (53 mg, 52%) as a yellow glassy solid. LCMS method: 5, RT 4.09 min, MI 441 [M+H]; NMR: (1H, 500 MHz, d6-dmso) 8.50 (1H, s), 7.68 (1H, s), 3.79-3.19 (8H, very broad set of signals), 3.79-3.74 (4H, m), 3.66-3.64 (4H, m), 2.62-2.59 (1H, m), 1.40 (9H, s), 1.18-1.14 (2H, m), 0.93-0.90 (2H, m). The Boc-protected intermediate was stirred in 4M HCl in dioxane (2 mL) at room temperature for 2 hours. The reaction mixture was concentrated by rotary evaporation and loaded onto a SCX cartridge, washing with MeOH and eluting with 7N ammonia in MeOH. The ammonia fraction was concentrated by rotary evaporation to give the title compound [1016](37 mg, 90%) as a pale yellow solid. LCMS method: 5, RT 4.41 min, MI 341 [M+H]; NMR: (1H, 500 MHz, d6-dmso) 8.48 (1H, s), 7.65 (1H, s), 3.75-3.73 (4H, m), 3.66-3.62 (overlapping 4H m and 2H very broad s), 3.19 (2H, very broad s), 2.80 (4H, br. m), 2.63-2.58 (1H, m), 1.17-1.14 (2H, m), 0.93-0.90 (2H, m). 
     Synthesis of 4-((S)-3-Benzyl-piperazin-1-yl)-5-cyclopropyl-2-morpholin-4-yl-pyrido[3,4-d]pyrimidine [1017] 
     
       
         
         
             
             
         
       
     
     (S)-2-Benzyl-4-(5-bromo-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [C029] 
     Following the procedure described in Scheme C3,5-Bromo-2-morpholin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [C027](200 mg, 0.64 mmol) was reacted with (S)-2-Benzyl-piperazine-1-carboxylicacidtert-butylester (355 mg, 1.28 mmol) to give (S)-2-Benzyl-4-(5-bromo-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [C028](139 mg, 38%). LCMS method: 5, RT: 5.64 min, MI: 569/571 [M+1]. 
     
       
         
         
             
             
         
       
     
     4-((S)-3-Benzyl-piperazin-1-yl)-5-cyclopropyl-2-morpholin-4-yl-pyrido[3,4-d]pyrimidine 
     Following the procedure described in Scheme C3, (S)-2-Benzyl-4-(5-bromo-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [C029](135 mg, 0.24 mmol) was reacted with cyclopropyl boronic acid (31 mg, 0.36 mmol) to give 4-((S)-3-Benzyl-piperazin-1-yl)-5-cyclopropyl-2-morpholin-4-yl-pyrido[3,4-d]pyrimidine [1017](62 mg, 61%) s a yellow solid. LCMS method: 5, RT 2.74 min, MI 431 [M+H]; NMR: (1H, 500 MHz, CDCl 3 ) 8.66 (1H, s), 7.65 (1H, s), 7.33-7.19 (5H, m), 4.35-2.42 (18H, very broad overlapping multiplets), 1.16-1.08 (2H, br m), 0.90-0.82 (2H, br m). 
     Synthesis of [(S)-4-(5-Cyclopropyl-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazin-2-yl]-acetonitrile [1018] 
     
       
         
         
             
             
         
       
     
     3-Cyclopropyl-5-fluoro-N-(imino-morpholin-4-yl-methyl)-isonicotinamide [C030] 
     Following the procedure described in Scheme C3, trifluoro-acetate 4-carboxy-3-cyclopropyl-5-fluoro-pyridinium (1.51 g, 5.10 mmol) was reacted with 4-Morpholinylformamidine hydrobromide (1.56 g, 5.10 mmol) to give 3-Cyclopropyl-5-fluoro-N-(imino-morpholin-4-yl-methyl)-isonicotinamide [C029](1.23 g, 84%) which was used without purification in the next step. LCMS method: 5, RT 2.35 min, MI 293 [M+H]. 
     
       
         
         
             
             
         
       
     
     Step 2: 5-Cyclopropyl-2-morpholin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [C031] 
     Following the procedure described in Scheme C3,3-Cyclopropyl-5-fluoro-N-(imino-morpholin-4-yl-methyl)-isonicotinamide (1.26 g, 4.30 mmol) was treated with K 2 CO 3  under microwave irradiation to 5-Cyclopropyl-2-morpholin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [C030](402 mg, 34%). LCMS method: 5, RT 3.41 min, MI 273 [M+H]. 
     
       
         
         
             
             
         
       
     
     [(S)-4-(5-Cyclopropyl-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazin-2-yl]-acetonitrile [1018] 
     A stirred solution of 5-Cyclopropyl-2-morpholin-4-yl-3H-pyrido[3,4-d]pyrimidin-4-one [C031](50 mg, 0.184 mmol) in DMF (5 mL) was prepared at room temperature under nitrogen. Triethylamine (0.03 mL, 0.193 mmol) was added followed by 2,4,6-triisopropylbenzenesulfonyl chloride (56 mg, 0.186 mmol). The reaction mixture was stirred at room temperature for 2 hours then (S)-Piperazin-2-yl-acetonitrile (23 mg, 0.184 mmol) was added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the residue purified by chromatography on silica, eluting with CH 2 Cl 2  containing 0-10% MeOH. The appropriate fractions were combined and concentrated to give the title compound [1018](30 mg, 43%) as a yellow solid. LCMS method: 5, RT 5.76 min, MI 380 [M+H]; NMR: (1H, 500 MHz, CDCl 3 ) 8.69 (1H, s), 7.70 (1H, s), 4.46-4.29 (1H, br s), 3.95-3.93 (1H, br m), 3.88 (4H, t), 3.78 (4H, t), 3.32-3.27 (1H, m), 3.20-2.66 (5H, br m), 2.50 (2H, br s), 1.80 (1H, br s), 1.16 (2H, br s), 0.95 (2H, br s). 
     4PPAZ Compounds 
     Several methods for the chemical synthesis of 4-substituted-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-azaquinazoline compounds (for convenience, collectively referred to herein as “4PPAZ compounds”) of the present application are described herein, of general formula [I-001]. These and/or other well known methods may be modified and/or adapted in known ways in order to facilitate the synthesis of additional compounds within the scope of the present application. 
     
       
         
         
             
             
         
       
     
     General synthesis of substituted substituted 4-substituted-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-azaquinazoline derivatives of general formula [I-001] Scheme D1 
     The 4-substituted-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-azaquinazoline derivatives of general formula [I-003] were prepared by the reaction of a 2-Chloro-pyrido[3,4-d]pyrimidine derivative of general formula [I-002], prepared in scheme C2, in a Suzuki type palladium catalysed cross coupling reaction with boronic acid or boronate ester derivative of general formula [I-004] a palladium catalyst such as Pd(PPh 3 ) 4 , a base such as K 2 PO 4  in a polar aprotic solvent such as DMA or DMF at elevated temperature either by heating thermally or using a microwave reactor, to yield 4PPAZ derivative of general formula [I-003]. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the intermediate was purified by column chromatography. The intermediate arylsulphonate protected derivative of general formula [I-003] was then subjected to a deprotection reaction in the presence of a base such as sodium hydroxide in a polar protic solvent such as ethanol. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the intermediate was purified by column chromatography and the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, HCl in a solvent such as DCM, DCE or 1,4-dioxane or by catch and release sulfonic acidic resins such as polymer supported toluene sulfonic acid and the crude reaction product was purified by normal phase chromatography or reverse phase preparative HPLC. 
     
       
         
         
             
             
         
       
     
     Synthesis of 5-Methoxy-4-piperazin-1-yl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine [1200] 
     
       
         
         
             
             
         
       
     
     4-{5-Methoxy-2-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperazine-1-carboxylic acid tert-butyl ester [D001] 
     A solution of 4-(2-Chloro-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester [C011 prepared in scheme C2](250 mg, 0.671 mmol) in DMA (7.5 mL) was prepared. 4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine [D002](374 mg, 0.940 mmol), Pd(PPh 3 ) 4 (77 mg, 0.067 mmol) and K 3 PO 4  (2.68 mL of a 0.5 M solution in water) were added. The reaction mixture was heated to 150° C. in the microwave for 10 min. The reaction mixture was concentrated by rotovap and purified by column chromatography on silica, eluting with cyclohexane containing 0-100% EtOAc. The appropriate fractions were combined and concentrated to give the title compound [D001]](115 mg, 28%) as a yellow solid. LCMS method: 5, RT 5.13 min, MI 616 [M+H]; NMR: (1H, 500 MHz, d6-dmso) 8.92 (s, 1H), 8.53 (d, 1H), 8.37 (s, 1H), 8.26 (d, 1H), 8.05 (d, 1H), 8.02 (d, 1H), 7.77 (d, 1H), 7.64-7.60 (m, 1H), 7.57-7.53 (m, 1H), 7.43 (d, 2H), 4.09 (s, 3H), 3.67 (br. m, 4H), 3.56 (br. m, 4H), 1.43 (s, 9H). 
     
       
         
         
             
             
         
       
     
     5-Methoxy-4-piperazin-1-yl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine 
     A solution of 4-{5-Methoxy-2-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperazine-1-carboxylic acid tert-butyl ester [D001](100 mg, 0.162 mmol) in ethanol (4 mL) was prepared and NaOH (1 mL of a 5 M solution) was added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated by rotary evaporation and the residue dissolved in DCM (10 mL) and water (10 mL). The pH was adjusted to approx 7 by addition of ammonium chloride and the mixture extracted with DCM (3×10 mL). The combined organic extracts were dried (phase separator) and concentrated by rotary evaporation. The residue was purified by column chromatography on silica, eluting with cyclohexane containing 75-100% EtOAc. The appropriate fractions were combined and concentrated to give intermediate 4-[5-Methoxy-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester which was stirred in 4M HCl in dioxane (2 mL) at room temperature for 1 hour. The reaction mixture was concentrated by rotary evaporation, loaded onto a SCX cartridge, washed with methanol and eluted with 7N ammonia in methanol. The ammonia fraction was concentrated by rotary evaporation to give the title compound [1200](29 mg, 49%) as a yellow solid. LCMS method: 5, RT 2.23 min, MI 362 [M+H]; NMR: (1H, 500 MHz, d6-dmso) 11.81 (1H, s), 8.89 (1H, s), 8.37 (1H, d, J=5.0 Hz), 8.31 (1H, s), 8.09 (1H, d, J=5.0 Hz), 7.63-7.62 (1H, m), 7.43 (1H, dd, J=3.3, 1.8 Hz), 4.07 (3H, s), 3.66-3.64 (4H, m), 2.91-2.89 (4H, m). 
     General Synthesis of Substituted Boronic Acid or Boronate Ester Derivative of General Formula [I-004] Scheme D2 
     The substituted boronic acid or boronate ester derivatives of general formula [I-004] were prepared by the reaction of a 4-Bromo-1H-pyrrolo[2,3-b]pyridine derivative of general formula [I-005] with an arylsuphonyl chloride derivative of general formula [I-008] with a base such as NaH in a polar aprotic solvent such as THF at low temperature. The 1-arylsulfonyl-4-bromo-1H-pyrrolo[2,3-b]pyridine derivative of general formula [I-006] was then reacted with a strong base such as LDA, in a polar aprotic solvent such as THF at low temperature and a alkyl halide derivative of general formula [I-009]. The C2 substituted 4-bromo-1H-pyrrolo[2,3-b]pyridine derivative of general formula [I-007] was then reacted in a palladium catalysed cross coupling reaction with a palladium catalyst such as PdCl 2  dppf, a boron agent such as bispinocolatodiboron, potassium acetate in a polar aprotic solvent such as dioxane at elevated temperature either by heating thermally or using a microwave reactor, to yield the substituted boronate ester derivative of general formula [I-004] which after reaction work up, typically by a liquid-liquid extraction was purified by column chromatography. 
     
       
         
         
             
             
         
       
     
     Synthesis of 4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine [D002] 
     
       
         
         
             
             
         
       
     
     4-Bromo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine [D003] 
     4-Bromo-7-azaindole (3 g, 15.22 mmol) was weighed into a round bottom flask and dissolved in THF (50 mL) under nitrogen. The reaction mixture was cooled to 0° C. and treated portionwise with sodium hydride (60% in mineral oil, 0.67 g, 16.75 mmol), the addition was accompanied by fizzing. After the addition the reaction mixture was allowed to stir for 30 minutes at room temperature and then treated with benzenesulfonyl chloride (2.14 mL, 16.75 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 2 hours. The reaction mixture was evaporated under reduced pressure and dissolved in DCM 30 mL, the organics were washed with 2×30 mL portions of 2M sodium carbonate, dried with MgSO4, filtered and evaporated to an orange oil. Purified by flash column chromatography eluting with 1:9 ethyl acetate:cyclohexane to provide the title compound as an off white solid (92%). LCMS method: 5, RT 5.36 min, MI 337 [M+H]; NMR: (1H, 500 MHz, CDCl 3 ) 8.22 (d, 1H), 8.18 (d, 2H), 7.78 (d, 1H), 7.58 (t, 1H), 7.48 (t, 2H), 7.35 (d, 1H), 6.63 (d, 1H). 
     
       
         
         
             
             
         
       
     
     4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine [D002] 
     4-Bromo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine (1.57 g, 4.47 mmol), Bis(pinacolato)diboron [D003](2.71 g, 10.72 mmol), PdCl2.dppf CH2C12 adduct (0.365 g, 0.45 mmol) and potassium acetate (0.876 g, 8.94 mmol) were weighed into a microwave vial. Dioxane (30 mL) was added and the reaction mixture was capped and heated at 130 OC in a microwave reactor for 30 minutes. The solvent was removed under reduced pressure and the residue was partitioned between ammonium chloride 20 mL and ethyl acetate 20 mL. The organics were dried with MgSO4, filtered and evaporated under reduced pressure to a brown oil. This was passed through a short column of silica eluting with 1:4 ethyl acetate:cyclohexane. The fractions were pooled and evaporated to yield the title compound [D002] as a pale yellow solid: LCMS method: 5, RT 4.77 min, MI 317 [M+H for boronic acid intermediate] 
     Synthesis of Benzenesulfonyl-2-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine [D004] 
     
       
         
         
             
             
         
       
     
     1-Benzenesulfonyl-4-bromo-1H-pyrrolo[2,3-b]pyridine [D005] 
     4-Bromo-7-azaindole (3 g, 15.22 mmol) was weighed into a round bottom flask and dissolved in THF (50 mL) under nitrogen. The reaction mixture was cooled to 0° C. and treated portionwise with sodium hydride (60% in mineral oil, 0.67 g, 16.75 mmol), the addition was accompanied by fizzing. After the addition the reaction mixture was allowed to stir for 30 minutes at room temperature and then treated with benzenesulfonyl chloride (2.14 mL, 16.75 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 2 hours. The reaction mixture was evaporated under reduced pressure and dissolved in DCM 30 mL, the organics were washed with 2×30 mL portions of 2M sodium carbonate, dried with MgSO4, filtered and evaporated to an orange oil. Purified by flash column chromatography eluting with 1:9 ethyl acetate: cyclohexane to provide the title compound [D005] as an off white solid (92%): LCMS method: 5, RT 5.36 min, MI 337 [M+H]; NMR: (1H, 500 MHz, CDCl 3 ) 8.22 (d, 1H), 8.18 (d, 2H), 7.78 (d, 1H), 7.58 (t, 1H), 7.48 (t, 2H), 7.35 (d, 1H), 6.63 (d, 1H). 
     
       
         
         
             
             
         
       
     
     1-Benzenesulfonyl-4-bromo-2-methyl-1H-pyrrolo[2,3-b]pyridine [D006] 
     To a solution of 1-Benzenesulfonyl-4-bromo-1H-pyrrolo[2,3-b]pyridine [D005](2 g, 5.93 mmol) in THF (50 mL) at −78° C., LDA (2M, 5.9 mL, 11.86 mmol) was added dropwise. The solution was stirred 30 min. The temperature was allowed to warm to 0° C. and Methyl iodide (3.67 mL, 59 mmol) was then added dropwise and the solution was stirred 3 h at 0° C. and was allowed to stir to room temperature overnight. The reaction was quenched with aqueous ammonium chloride solution and extracted with DCM. The combined organic layers were dried over MgSO4 and concentrated in vacuo. The crude was purified by SP1 (eluent, gradient: Cyclohexane/AcOEt: 1/0 to 8/2). The fractions were collected and concentrated under reduced pressure to yield the title compound [D006] a white solid (87%). LCMS method: 5, RT 5.80 min, MI 351 [M+H]; NMR: (1H, 500 MHz, CDCl 3 ) 8.12-8.15 (m, 3H), 7.56 (t, 1H), 7.47 (t, 2H), 7.29 (d, 1H), 6.34 (s, 1H), 2.74 (s, 3H). 
     
       
         
         
             
             
         
       
     
     Benzenesulfonyl-2-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine [D004] 
     Following the procedure described in scheme D2 replacing 1-Benzenesulfonyl-4-bromo-1H-pyrrolo[2,3-b]pyridine with 1-Benzenesulfonyl-4-bromo-2-methyl-1H-pyrrolo[2,3-b]pyridine gave the title compound [D004](72%%) as a pale yellow solid. LCMS method: 5, RT 6.19 min, MI 399 [M+H]; NMR: (1H, 500 MHz, CDCl 3 ) 8.34 (d, 1H), 8.07 (d, 2H), 7.50 (t, 1H), 7.46 (d, 1H), 7.41 (t, 2H), 6.70 (s, 1H), 2.73 (s, 3H), 1.33 (s, 12H). 
     The following compounds were prepared according to Scheme D2: 
     1-Benzenesulfonyl-2-benzyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine [D007] 
     
       
         
         
             
             
         
       
     
     1-Benzenesulfonyl-2-benzyl-4-bromo-1H-pyrrolo[2,3-b]pyridine [D008] 
     Following the procedure described in scheme D2,1-Benzenesulfonyl-4-bromo-1H-pyrrolo[2,3-b]pyridine was reacted with benzyl bromide to give the title compound [D008] which was used crude in the next step. LCMS method: 5, RT 6.62 min, MI 427 [M+H]. 
     
       
         
         
             
             
         
       
     
     1-Benzenesulfonyl-2-benzyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine [D007] 
     Following the procedure described in scheme D2 replacing 1-Benzenesulfonyl-4-bromo-1H-pyrrolo[2,3-b]pyridine with 1-Benzenesulfonyl-2-benzyl-4-bromo-1H-pyrrolo[2,3-b]pyridine gave the title compound [D007] as a pale yellow solid: LCMS method: 5, RT 5.59 min, MI 392 [M+H, Boronic ester hydrolysed into the corresponding boronic acid in the LCMS conditions]; NMR: (1H, 500 MHz, d6-dmso) 8.38 (d, 1H), 7.70 (dd, 1H), 7.49 (d, 1H), 7.42 (t, 1H), 7.23-7.30 (m, 7H), 6.75 (s, 1H), 4.54 (d, 2H), 1.34 (s, 12H). 
     Synthesis of 1-Benzenesulfonyl-2-(2-fluoro-benzyl)-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine [D009] 
     
       
         
         
             
             
         
       
     
     Step 1: 1-Benzenesulfonyl-4-bromo-2-(2-fluoro-benzyl)-1H-pyrrolo[2,3-b]pyridine [D010] 
     Following the procedure described in scheme D2,1-Benzenesulfonyl-4-bromo-1H-pyrrolo[2,3-b]pyridine was reacted with 2-fluorobenzylbromide to give the title compound [D010](75%): LCMS method: 5, RT 6.45 min, MI 445 [M+H]. 
     
       
         
         
             
             
         
       
     
     Step 2: 1-Benzenesulfonyl-2-(2-fluoro-benzyl)-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine [D009] 
     Following the procedure described in scheme D2 replacing 1-Benzenesulfonyl-4-bromo-1H-pyrrolo[2,3-b]pyridine with 1-Benzenesulfonyl-4-bromo-2-(2-fluoro-benzyl)-1H-pyrrolo[2,3-b]pyridine gave the title compound [D009] as a white solid. LCMS method: 5, RT 5.50 min, MI 411 [M+1, hydrolysed boronic ester to its corresponding boronic acid]. 
     Synthesis of 1-Benzenesulfonyl-2-ethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine [D011] 
     
       
         
         
             
             
         
       
     
     1-Benzenesulfonyl-4-bromo-2-ethyl-1H-pyrrolo[2,3-b]pyridine [D012] 
     Following the procedure described in scheme D 2,1-Benzenesulfonyl-4-bromo-1H-pyrrolo[2,3-b]pyridine was reacted with iodoethane to give the title compound [D012] as a white solid: LCMS method: 5, RT 6.01 min, MI 351 [M+H]; NMR: (1H, 500 MHz, d6-dmso) 8.11-8.15 (m, 3H), 7.56 (d, 1H), 7.45-7.48 (m, 2H), 7.30 (d, 1H), 6.39 (s, 1H), 3.19 (q, 2H), 1.42 (t, 3H). 
     
       
         
         
             
             
         
       
     
     1-Benzenesulfonyl-2-ethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine [D011] 
     Following the procedure described in scheme D 2 replacing 1-Benzenesulfonyl-4-bromo-1H-pyrrolo[2,3-b]pyridine with 1-Benzenesulfonyl-4-bromo-2-ethyl-1H-pyrrolo[2,3-b]pyridine gave the title compound [D011] as a pale yellow solid. LCMS method: 5, RT 6.42 min, MI 413 [M+H]; LCMS Method 1LCMS5, 6.42 min, MI: 413 [M+1]. 
     The following compounds were synthesised according to the general synthesis shown in scheme [D1] 
     
       
         
           
               
               
               
               
               
            
               
                   
               
               
                   
                   
                   
                 Analysis 
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Ex 
                 Precursor 
                 Boronic ester 
                 LCMS 
                 NMR 
                 Name 
               
               
                   
               
               
                 1201 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 2.39 min, MI: 376 [M + H] 
                 (1H, 500 MHz, d6- dmso) 3.44 (brs, 4H), 3.86- (brs, 4H), 4.10 (s, 3H), 7.16 (s, 1H), 8.06 (d, 1H), 8.25 (d, 1H), 8.39 (s, 1H), 8.92 (brs, 2H), 8.98 (s, 1H), 11.77 (brs, 1H). 
                 5-Methoxy-2- (2-methyl-1H- pyrrolo[2,3- b]pyridin-4- yl)-4- piperazin-1-yl- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1202 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.49 min, MI: 452 [M + H] 
                 (1H, 500 MHz, d6- dmso) 3.19-3.39 (m, 3H), +H2O), 3.77-3.83 (m, 4H), 4.08 (s, 3H), 4.16 (s, 2H), 7.08 (s, 1H), 7.24 (t, 1H), 7.32-7.40 (m, 4H), 8.05 (d, 1H), 8.26 (d, 1H), 8.36 (s, 1H), 8.90 (s, 1H), 8.97 (brs, 2H), 11.86 (s, 1H). 
                 2-(2-Benzyl- 1H- pyrrolo[2,3- b]pyridin-4- yl)-5-methoxy- 4-piperazin-1- yl-pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1203 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.39 min, MI: 470 [M + H] 
                 (1H, 500 MHz, d6- dmso) 2.96 (brs, 4H), 3.60 (brs, 4H), 4.05 (s, 3H), 4.18 (s, 2H), 6.96 (s, 1H), 7.19-7.23 (m, 2H), 7.32-7.44 (m, 2H), 8.03 (s, 1H), 8.27 (d, 1H), 8.29 (s, 1H), 8.79 (s, 1H), 11.87 (brs, 1H). 
                 2-[2-(2- Fluoro- benzyl)-1H- pyrrolo[2,3- b]pyridin-4- yl]-5-methoxy- 4-piperazin-1- yl-pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1204 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                   
                 2-(2-Ethyl-1H- pyrrolo[2,3- b]pyridin-4- yl)-5methoxy- 4-piperazin-1- yl-pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1205 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 2.53 min, MI: 406 [M + H] 
                   
                 5-Methoxy-4- ((R)-3- methoxymethyl- piperazin-1- yl)-2-(1H- pyrrolo[2,3- b]pyridin-4- yl)-pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1206 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 2.36 min, MI: 392 [M + H] 
                 (1H, 500 MHz, d6- dmso) 2.86-2.96 (m, 3H), 3.10 (d, 1H), 3.15-3.19 (m, 1H), 3.39-3.45 (m, 2H), 4.06 (s, 3H), 4.15- 4.24 (m, 2H), 7.43-7.44 (m, 1H), 7.60-7.61 (m, 1H), 8.08 (d, 1H), 8.19 (s, 1H), 8.32 (s, 1H), 8.35 (d, 1H), 8.89 (s, 1H), 11.89 (brs, 1H). 
                 {(R)-4-[5- Methoxy-2- (1H- pyrrolo[2,3- b]pyridin-4- yl)-pyrido[3,4- d]pyrimidin-4- yl]piperazin- 2-yl}- methanol 
               
               
                   
               
               
                 1207 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 1.99 min, MI: 332 [M + H] 
                 (1H, 500 MHz, d6- dmso) 2.94-2.97 (m, 4H), 3.89-3.93 (m, 4H), 7.45 (t, 1H), 7.63 (t, 1H), 7.90 (d, 1H), 8.11 (d, 1H), 8.37 (d, 1H), 8.57 (d, 1H), 9.32 (s, 1H), 11.83 (brs, 1H). 
                 4-Piperazin-1- yl-2-(1H- pyrrolo[2,3- b]pyridin-4- yl)-pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1208 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 1.91 min, MI: 332 [M + H] 
                 (1H, 500 MHz, d6- dmso) 2.21-2.28 (m, 1H), 2.34-2.44 (m, 1H), 3.33-3.50 (m, 3H), 3.67-3.74 (m, 2H), 4.95-5.04 (m, 1H), 7.50 (d, 1H), 7.63 (t, 1H), 8.15 (d, 1H), 8.25 (d, 1H), 8.38 (d, 1H), 8.64 (d, 1H), 8.70 (d, 1H), 9.30 (s, 1H), 11.86 (s, 1H) 
                 (R)-Pyrrolidin- 3-yl-[2-(1H- pyrrolo[2,3- b]pyridin-4- yl)-pyrido[3,4- d]pyrimidin-4- yl]-amine 
               
               
                   
               
            
           
         
       
     
     General synthesis of substituted substituted 4-substituted-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-azaquinazoline derivatives of general formula [I-001] Scheme D3 
     The 4-substituted-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-azaquinazoline derivatives of general formula [I-001] were prepared by the reaction of a halogenated pyridine derivative of general formula [I-010] with a strong base such as LDA, in a polar aprotic solvent such as THF, a symmetrical anhydride such as Di-tert-butyl dicarbonate at low temperature to yield halo-substituted-isonicotinic acid tert-butly ester derivatives of general formula [I-011]. After reaction work up, typically by a liquid-liquid extraction the intermediate was purified by column chromatography. The halo-substituted-isonicotinic acid tert-butly ester derivative of general formula [I-011] was then subjected to a Suzuki type palladium catalysed cross coupling reaction with boronic acid or boronate ester derivative of general formula [I-018] a palladium catalyst such as Pd(PPh 3 ) 4 , a base such as K 2 PO 4  in a polar aprotic solvent such as DMA or DMF at elevated temperature either by heating thermally or using a microwave reactor, to yield the substituted-isonicotinic acid tert-butly ester derivative of general formula [I-012]. After reaction work up, typically by a liquid-liquid extraction the intermediate was purified by column chromatography. The t-butylester inter intermediate [I-012] was then subjected to a deprotection reaction in the presence of a base such as sodium hydroxide in a polar protic solvent such as ethanol to yield the substituted-isonicotinic acid derivative of general formula [I-013], which was then subjected to a coupling reaction with a substituted 1H-pyrrolo[2,3-b]pyridine-4-carboxamidine derivative of general formula [I-014], with a suitable coupling agent such as O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) in a polar aprotic solvent such as DMA or DMF. The isonicotinoyl-amidine derivative of general formula [I-015] can then be cyclised to displace the relevant halogen group to yield the desired 2-(1H-pyrrolo[2,3-b]pyridine-4-yl)-pyrido[3,4-d]pyrimidin-4-ol derivative of general formula [I-016]. The 4-substituted-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-azaquinazoline derivatives of general formula [I-001] were prepared by the reaction of a 2-(1H-pyrrolo[2,3-b]pyridine-4-yl)-pyrido[3,4-d]pyrimidin-4-ol derivative of general formula [I-016] with a chlorinatation agent such as phosphorous oxychloride to give compounds of general formula and the intermediate 4-chloro derivative was then further reacted with primary or secondary amino derivative of general formula [I-017], in a polar aprotic solvent such as DMA, DMF, NMP in the presence of a tertiary amine base such as Et 3 N, DIPEA or NMM at ambient temperature [method A]. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, TCA, methanesulfonic acid, HCl or H 2 SO 4  in a solvent such as DCM, DCE, THF, EtOH or MeOH and the crude reaction product was purified by normal phase silica gel chromatography or reverse phase preparative HPLC. 4-substituted-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-azaquinazoline derivatives of general formula [I-001] were prepared by the reaction of a -(1H-pyrrolo[2,3-b]pyridine-4-yl)-pyrido[3,4-d]pyrimidin-4-ol derivative of general formula [I-016] with 2,4,6-triisopropylbenzenesulfonyl chloride in a polar aprotic solvent such as DMA, DMF, NMP with a tertiary alkylamine base such as Et 3 N, DIPEA or NMM and a catalytic amount of DMAP [method B]. The intermediate 6,7-substituted-(2,4,6-triisopropyl-benzenesulfonic acid)-(1H-pyrrolo[2,3-b]pyridine-4-yl)-pyrido[3,4-d]pyrimidin-4-yl ester was then reacted with a primary or secondary amino derivative, of general formula [G-117], in a polar aprotic solvent such as DMA, DMF, NMP in the presence of a tertiary amine base such as Et 3 N, DIPEA or NMM at ambient temperature. After reaction work up, typically by a liquid-liquid extraction or purification by acidic ion exchange catch-release, the N-Boc derivatives were deprotected under acidic conditions with a strong acid such as TFA, TCA, methanesulfonic acid, HCl or H 2 SO 4  in a solvent such as DCM, DCE, THF, EtOH or MeOH and the crude reaction product was purified by reverse phase preparative HPLC. 
     
       
         
         
             
             
         
       
     
     Synthesis of 5-Cyclopropyl-4-piperazin-1-yl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine [1209] 
     
       
         
         
             
             
         
       
     
     3-Bromo-5-fluoro-isonicotinic acid tert-butyl ester [D013] 
     To a solution of LDA (2M, 72 mL, 144 mmol) in THF (100 mL) at −78° C. was added dropwise via cannula a solution of 3-bromo-5-fluoropyridine (21.12 g, 120 mmol) in THF (50 mL) pre-cooled at −78° C. During the addition the internal temperature did not rise above −65° C. The dark red-brown solution was stirred for 1 hour. Di-tert-butyldicarbonate (52.4 g, 240 mmol) in THF (50 mL) was cooled to −10° C. in a methanol/ice bath then added dropwise via cannula to the dark red-brown solution. The mixture was stirred for 2 hours then allowed to warm to room temperature and stir for 1 hour. Saturated aqueous ammonium chloride (100 mL) was added slowly and then water (200 mL) and EtOAc (200 mL) and the mixture was vigorously stirred for 45 minutes. The mixture was transferred to a separatory funnel and the layers were separated. The aqueous layer was extracted with EtOAc (200 mL). The THF and EtOAc layers were combined, dried over magnesium sulfate, filtered and evaporated. The recovered dark red-brown oil was purified by column chromatography (Cyclohexane/AcOEt: 1/0 to 97/3). Fractions containing desired material were concentrated in vacuo (14 g, 85%). LCMS method: 5, RT 5.44 min, MI 277 [M+H]; NMR: (1H, 500 MHz, CDCl3) 8.56 (s, 1H), 8.43 (s, 1H), 1.62 (s, 9H). 
     3-Cyclopropyl-5-fluoro-isonicotinic acid tert-butyl ester [D014] 
     A solution containing 3-Bromo-5-fluoro-isonicotinic acid tert-butyl ester [D013](5.52 g, 20 mmol), potassium phosphate tribasic (12.74 g, 60 mmol) and cyclopropyl boronic acid (2.58 g, 30 mmol), in dioxane (100 mL) was subjected to vacuum/argon balloon (three times). Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.408 g, 0.5 mmol) was added and the reaction heated at 96° C. overnight under positive pressure of nitrogen. The mixture was cooled to room temperature and was filtered through a pad of 200 g silica and washed with EtOAc (1 L). The filtrate was concentrated in vacuo and the crude was purified by column chromatography (Cyclohexane/AcOEt: 98:2 to 96:4). The combined fractions were concentrated under reduced pressure to give the title compound [D014] as a colourless oil (3.42 g, 72%). LCMS method: 5, RT 5.36 min, MI 238 [M+H]; NMR: (1H, 500 MHz, CDCl3) 8.33 (s, 1H), 8.15 (s, 1H), 2.05-2.00 (m, 1H), 1.62 (s, 9H), 1.04-1.00 9 m, 2H), 0.82-0.78 (m, 2H). 
     3-Cyclopropyl-5-fluoro-isonicotinic acid [D015] 
     In a microwave vial, 3-cyclopropyl-5-fluoro-isonicotinic acid tert-butyl ester [D014](1.186 g, 5 mmol) was dissolved in methanol and then heated in microwave at 140° C. for 1 hr. The reaction was concentrated in vacuo to yield the title compound [D015] 0.84 g (92%) of white crystalline solid. LC-MS: 1NJM406_1_28Jul2011; 1.51 min, 87%; 182+; 1LCMS5. 
     3-Cyclopropyl-5-fluoro-N-[imino-(1H-pyrrolo[2,3-b]pyridin-4-yl)-methyl]-isonicotinamide [D016] 
     3-Cyclopropyl-5-fluoro-isonicotinic acid [D015](0.681 g, 3.76 mmol), HATU (1.43 g, 3.76 mmol) and diisopropyethylamine (2.29 mL, 13.16 mmol) were stirred in DMF (5 mL). After 1 hr, 1H-Pyrrolo[2,3-b]pyridine-4-carboxamidine; acetic acid salt (0.92 g, 3.76 mmol) was added. Having stirred for 18 hr the mixture was poured into water (180 ml), stirred for 2 hours and then a white solid collected by filtration and washed with H 2 O to yield the title compound [D016] as a white solid (1.17 g) was used without further purification. LCMS method: 5, RT 3.22 min, MI 324 [M+H]. 
     5-Cyclopropyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ol [D017] 
     A mixture of N-[(2-Chloro-pyridin-4-yl)-imino-methyl]-3-cyclopropyl-5-fluoro-isonicotinamide [D016](1.164 g, 3.6 mmol) and Cs2CO3 (1.18 g, 3.60 mmol) in DMA (12 mL) was heated thermally at 90° C. overnight. The reaction mixture was poured into H 2 O (20 ml) and acidified with dropwise addition of acetic acid at 0 OC. The beige precipitate (0.474, 43%) was collected by filtration and washed with H 2 O to yield the title compound [D017] which was used without further purification. LCMS method: 5, RT 4.58 min, MI 304 [M+H]; NMR: (1H, 500 MHz, d6-dmso) 12.12 (brs, 1H), 9.09 (s, 1H), 8.54 (d, 1H), 8.37 (s, 1H), 7.90 (d, 1H), 7.83 (s, 1H), 7.36 (s, 1H), 3.56-3.64 (m, 1H), 1.24-1.30 (m, 2H), 1.08-1.14 (m, 2H). 
     4-[5-Cyclopropyl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [D018] 
     To a solution of 5-Cyclopropyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-o [D017]1 (0.47 g, 1.55 mmol) in DMF (25 mL) was added DIPEA (0.809 mL, 4.65 mmol) and DMAP (5 mg). 2,4,6-Triisopropylbenzenesulfonyl chloride (0.563 g, 1.86 mmol) was then added and the mixture was stirred 2 hours. N-Boc-Piperazine (0.318 g, 1.705 mmol) was then added and the mixture was the stirred overnight. Water was added water (60-70 mL) and the solution was stirred at RT for 15 mins. The resulting solid was collected and washed twice with water. The solid was dissolved in DCM and purified by column chromatography (eluent: DCM/MeOH gradient 0% to 10% MeOH) to yield the title compound [D018] as a dark brown gum (0.6 g, 82%) was used without further purification in the next step. LCMS method: 5, RT 5.85 min, MI 472 [M+H]. 
     5-Cyclopropyl-4-piperazin-1-yl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine 
     To a solution of 4-[5-Cyclopropyl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [D018](0.6 g, 1.27 mmol) in DCM (15 mL) was added HCl (4N, dioxane, 2 mL) and the resultant bright yellow suspension was stirred at RT for 90 mins. The solution was concentrated under reduced pressure and dissolved in MeOH and added to SCX-2 cartridge (10 g), washed with MeOH/DCM (1:1, 40 mL) and MeOH (20 mL). Then the SCX-2 cartridge was washed with ammonia (7N in MeOH, 30 mL). The ammonia washes were concentrated in vacuo and the material purified on the column chromatography (eluent DCM/MeOH gradient 0-20% MeOH/DCM). The fractions were combined and concentrated under reduced pressure to yield the title compound [1009]: LCMS method: 5, RT 2.65 min, MI 372 [M+H]; NMR: (1H, 500 MHz, d6-dmso) 11.82 (brs, 1H), 9.13 (s, 1H), 8.36 (d, 1H), 8.10 (d, 1H), 7.62 (t, 1H), 7.45 (dd, 1H), 3.50-3.90 (m, 4H), 2.88-2.91 (m, 4H), 2.66-2.69 (m, 1H), 1.22-1.27 (m, 2H), 1.02-1.06 
     Synthesis of 8-Chloro-5-cyclopropyl-4-piperazin-1-yl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine [1210] 
     
       
         
         
             
             
         
       
     
     5-Bromo-2-chloro-3-fluoro-isonicotinic acid tert-butyl ester [D019] 
     Following the procedure described in scheme D3 1,5-Bromo-2-chloro-3-fluoro-isonicotinic acid tert-butyl ester was prepared [D019] as a colourless oil by reaction of 5-bromo-2-chloro-3-fluoropyridine, LDA (2M), Di-tert-butyldicarbonate, and THF. LCMS method: 5, RT 6.25 min, MI 311 [M+H]. 
     S2-Chloro-5-cyclopropyl-3-fluoro-isonicotinic acid tert-butyl ester [D020] 
     Following the procedure described in scheme D3,5-Bromo-2-chloro-3-fluoro-isonicotinic acid tert-butyl ester was reacted with cyclopropyl boronic acid to give 2-Chloro-5-cyclopropyl-3-fluoro-isonicotinic acid tert-butyl ester [D020]. LCMS method: 5, RT 6.19 min, MI 272 [M+H]. 
     2-Chloro-5-cyclopropyl-3-fluoro-isonicotinic acid [D021] 
     2-Chloro-5-cyclopropyl-3-fluoro-isonicotinic acid tert-butyl ester [D020](815 mg, 3.00 mmol) was suspended in 2-propanol (9 mL) and HCl (5 mL of a 4M solution in dioxane) was added. The reaction mixture was heated to 50° C. overnight. The reaction mixture was concentrated under reduced pressure to the title compound [D021](530 mg, 82%) as a white crystalline solid which was used without purification. LCMS method: 5, RT 0.91 min, MI 216 [M+H]. 
     2-Chloro-5-cyclopropyl-3-fluoro-N-[imino-(1H-pyrrolo[2,3-b]pyridin-4-yl)-methyl]-isonicotinamide [D022] 
     Following the procedure described in scheme D3,2-chloro-5-cyclopropyl-3-fluoro-isonicotinic acid [D021] was reacted with 1H-Pyrrolo[2,3-b]pyridine-4-carboxamidine to give the title compound [D022]. LCMS method: 5, RT 4.45 min, MI 358 [M+H]. 
     8-Chloro-5-cyclopropyl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol [D023] 
     Following the procedure described in scheme D3,2-Chloro-5-cyclopropyl-3-fluoro-N-[imino-(1H-pyrrolo[2,3-b]pyridin-4-yl)-methyl]-isonicotinamide [D022] was reacted with Cs 2 CO 3  to give the title compound [D023]. LCMS method: 5, RT 4.87 min, MI 306 [M+H]. 
     4-[8-Chloro-5-cyclopropyl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [D024] 
     Following the procedure described in scheme D3,8-Chloro-5-cyclopropyl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol [D023] was reacted with 1-Boc-piperazine to give the title compound [D024]. LCMS method: 5, RT 6.05 min, MI 506 [M+H]. 
     8-Chloro-5-cyclopropyl-4-piperazin-1-yl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine [1210] 
     Following the procedure described in scheme D3, 8 4-[8-Chloro-5-cyclopropyl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [D024] was reacted with 4N HCl in dioxane to give the title compound [1210]: LCMS method: 5, RT 3.22 min, MI 406 [M+H]. 
     Synthesis of -Isopropyl-4-piperazin-1-yl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine [1211] 
     
       
         
         
             
             
         
       
     
     3-Fluoro-5-isopropenyl-isonicotinic acid tert-butyl ester [D025] 
     Following the procedure described scheme D3,3-Bromo-5-fluoro-isonicotinic acid tert-butyl ester [D013] was reacted with isopropenylboronic acid pinacol ester (contains phenothiazine as stabilizer), with dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct as catalyst to give 3-Fluoro-5-isopropenyl-isonicotinic acid tert-butyl ester [D025]. LCMS method: 5, RT 5.41 min, MI 238 [M+H]. 
     3-Fluoro-5-isopropyl-isonicotinic acid tert-butyl ester [D026] 
     To a solution of 3-Fluoro-5-isopropenyl-isonicotinic acid tert-butyl ester [D025] in EtOH was added ammonium formate and palladium on charcoal (5% wt/wt) and the mixture was heated at 60° C. overnight. More ammonium formate was added and the mixture was stirred for a further 45 min at 60° C. then was allowed to cool down to room temperature and was stirred overnight. The mixture was filtered through a celite pad and washed with EtOAc. Water was added to the filtrate and the layers were separated. The organic was dried over MgSO4 and concentrated in vacuo. The crude was purified by column chromatography (gradient Cyclohexane/AcOEt: 1:0 to 92:8). The combined fractions were concentrated under reduced pressure to led the title compound [D026] as a pale yellow oil (0.34 g, 37%). LCMS method: 5, RT 5.55 min, MI 240 [M+H]; NMR: (1H, 500 MHz, CDCl3) 8.42 (1H, s), 8.35 (1H, s), 3.09 (1H, sept), 1.60 (9H, s), 1.33 (6H, d). 
     3-Fluoro-5-isopropyl-isonicotinic acid [D027] 
     To a solution of 3-Fluoro-5-isopropyl-isonicotinic acid tert-butyl ester [D026](0.335 g, 1.4 mmol) in isopropyl alcohol (5 mL), a solution of HCl (4N in dioxane, 1 mL) was added and the solution was warmed to 50° C. overnight. LC-MS implies some progress but not complete. HCl (4N in dioxane, 1 mL) was added again and left at 50° C. overnight. The reaction is still not complete so more HCl (4N in dioxane, 1 mL) was added and left through the day (˜6-7 hrs). The solution was concentrated in vacuo to yield the title compound [D027] an off-white solid which was used without further purification and analysis. 
     3-Fluoro-N-[imino-(1H-pyrrolo[2,3-b]pyridin-4-yl)-methyl]-5-isopropyl-isonicotinamide [D028] 
     Following the procedure described in scheme D3,3-Fluoro-5-isopropyl-isonicotinic acid was reacted [D027] with, 1H-Pyrrolo[2,3-b]pyridine-4-carboxamidine to give 3-Fluoro-N-[imino-(1H-pyrrolo[2,3-b]pyridin-4-yl)-methyl]-5-isopropyl-isonicotinamide [D028]. LCMS method: 5, RT 3.67 min, MI 326 [M+H]. 
     5-Isopropyl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol [D029] 
     Following the procedure described in scheme D3, 3-Fluoro-N-[imino-(1H-pyrrolo[2,3-b]pyridin-4-yl)-methyl]-5-isopropyl-isonicotinamide [D028] was treated with Cs 2 CO 3  to give 5-Isopropyl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol [D029] as a brown solid. LCMS method: 5, RT 4.87 min, MI 306 [M+H]. 
     4-[5-Isopropyl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [D030] 
     Following the procedure described in scheme D3, 5-Isopropyl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol [D029] was treated with 1-Boc-piperazine to give the title compound [D030] as a brown solid. LCMS method: 5, RT 5.78 min, MI 474 [M+H]. 
     5-Isopropyl-4-piperazin-1-yl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine 
     Following the procedure described in scheme D3, 4-[5-Isopropyl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester [D030] was treated with 4N HCl to give the title compound [1211] as a brown solid. LCMS method: 5, RT 2.82 min, MI 374 [M+H], NMR: (1H, 500 MHz, CDCl3) 9.28 (1H, s), 9.0 (1H, br s), 8.61 (1H, s), 8.46 (1H, s), 8.23 (1H, d), 7.63 (1H, s), 7.47 (1H, s), 4.07 (1H, m), 3.86 (2H, m), 3.49 (2H, m), 3.11 (4H, m), 1.25 (6H, d). 
     General synthesis of substituted 1H-pyrrolo[2,3-b]pyridine-4-carboxamidine derivative of general formula [I-012] Scheme D4 
     The substituted 1H-pyrrolo[2,3-b]pyridine-4-carboxamidine derivatives of general formula [I-012] were prepared by the reaction of 2-methyl pyridine-2-yl carbamic acid tert butyl ester derivative of general formula [I-019] with a strong base such as nBuLi, in a polar aprotic solvent such as THF, and a substituted Weinreb amide derivative of general formula [I-025] at low temperature followed by reaction with a mineral acid such as hydrochloric acid at elevated temperature to yield the 1-H-pyrrolo[2,3-b]pyridine derivative of general formula [I-020], after reaction work up, typically by a liquid-liquid extraction the intermediate was purified by column chromatography. The 1-H-pyrrolo[2,3-b]pyridine derivative of general formula [I-020] was then subjected to a pyridine N-oxidation reaction with an oxidising reagent such as mCPBA in a solvent such as DCM. The intermediate 1-H-pyrrolo[2,3-b]pyridine-7-oxide derivative of general formula [I-021] was then reacted with a chlorinating agent such as methansulfonyl chloride, in a polar aprotic solvent such as DMF at elevated temperature, after reaction work up, typically by a liquid-liquid extraction the intermediate was purified by column chromatography. The intermediate 4-chloro-1H-pyrrolo[2,3-b]pyridine derivative of general formula [I-022] was then submitted to a palladium catalysed cross coupling reaction with a cyanide species such as zinc cyanide, a palladium catalyst such as dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct, zinc dust, in a polar aprotic solvent such as DMF at elevated temperature, after reaction work up, typically by a liquid-liquid extraction the intermediate was purified by column chromatography. The intermediate 1H-pyrrolo[2,3-b]pyridine-4-carbonitrile derivative of general formula [I-023] was then reacted with hydroxylamine (50% wt/wt in water) and a polar protic solvent such as EtOH at elevated temperature. The intermediate N-hydroxy-1H-pyrrolo[2,3-b]pyridine-4-carboxamide of general formula [I-024] was then subjected to a hydrogenolysis reaction with acetic anhydride in a polar protic solvent such as methanol a palladium catalyst such as palladium on activated charcoal under a atmosphere of hydrogen gas, to yield the substituted 1H-pyrrolo[2,3-b]pyridine-4-carboxamidine derivative of general formula [I-012] Scheme D4. 
     
       
         
         
             
             
         
       
     
     Synthesis of 2-Trifluoromethyl-1H-pyrrolo[2,3-b]pyridine-4-carboxamidine; acetic acid salt [D036] 
     
       
         
         
             
             
         
       
     
     Step 1: 2-Trifluoromethyl-1H-pyrrolo[2,3-b]pyridine [D031] 
     To a solution of (3-Methyl-pyridin-2-yl)-carbamic acid tert-butyl ester (5 g, 24 mmol) in THF (50 mL) at −30° C. was added BuLi (2.5M, 28.5 mL, 72 mmol) and the reaction mixture was warmed to 0° C. and stirred for 90 min. A solution of 2,2,2-Trifluoro-N-methoxy-N-methyl-acetamide (2.9 mL, 24 mmol) in THF (10 mL) was slowly added and the reaction was stirred at 0° C. for 3 h. The reaction mixture was slowly treated with HCl (30 mL, 6M) followed by heating at 60° C. for 18 h. The reaction mixture was cooled, the layers were separated and the aqueous layer was made basic with NaOH (5M) and extracted twice with AcOEt. The combined organic layers (plus the one from the first extraction) were dried over MgSO4, concentrated and the residue was purified by Column chromatography (eluent Cyclohexane/AcOEt 1/0 to 8/2) to afford the title compound [D031] as a yellow solid (1.2 g, 27%): LCMS method: 5, RT 4.44 min, MI 187 [M+H], NMR: (1H, 500 MHz, d6-dmso) 14.33 (brs, 1H), 8.49 (d, 1H), 8.09 (d, 1H), 7.27 (dd, 1H), 6.90 (s, 1H). 
     2-Trifluoromethyl-1H-pyrrolo[2,3-b]pyridine 7-oxide [D032] 
     To a solution of 2-Trifluoromethyl-1H-pyrrolo[2,3-b]pyridine [D031](1.2 g, 6.45 mmol) in DCM (10 mL), 3-Chloroperoxybenzoic acid (1.22 g, 7.09 mmol) was added and the mixture was stirred overnight. A saturated solution of NaHCO3 was added and the layers were separated. The organic was dried over MgSO4 and concentrated under reduced pressure. To yield the title compound [D032] as yellow solid (0.82 g, 63%) was used without further purification. LCMS method: 5, RT 3.43 min, MI 203 [M+H], NMR: (1H, 500 MHz, d6-dmso) 8.34 (d, 1H), 7.76 (d, 1H), 7.19 (d, 1H), 7.18 (s, 1H), 
     4-Chloro-2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridine [D033] 
     To a solution of 2-Trifluoromethyl-1H-pyrrolo[2,3-b]pyridine 7-oxide [D032](0.82 g, 4.05 mmol) in DMF (10 mL) at 50° C., methane sulfonyl chloride (1.57 mL, 20.28 mmol) was added dropwise. The solution was stirred 3 h at 50° C. The reaction was then cooled to room temperature and water (5 mL) was added. A solution of 5M NaOH was added and the solid was collected, dried using an azeotrope with toluene to yield the title compound [D032] which was used without further purification. LCMS: 1LCMS5 5.77 min, 221-223 [M+1, Cl pattern]. 
     2-Trifluoromethyl-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile [D034] 
     A sealable vial was charged with 4-Chloro-2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridine [D033](0.6 g, 2.72 mmol), Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.222 g, 0.27 mmol), zinc cyanide (0.958 g, 8.16 mmol), zinc (dust, 0.036 g, 0.54 mmol) and DMF (15 mL). The vial was capped and heated at 900° C. overnight. The reaction was poured in water and extracted with AcOEt. The aqueous layer was extracted again with AcOEt and the organics were combined, washed with water and brine and dried over MgSO4 to yield the title compound [D043] which was used without further purification: LCMS method: 5, RT 4.98 min, MI 212 [M+H]. 
     N-Hydroxy-2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridine-4-carboxamidine [D035] 
     A mixture of 2-Trifluoromethyl-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile [D034](0.68 g, 3.22 mmol) and hydroxylamine (50% wt/wt in water, 0.205 mL, 6.44 mmol) and EtOH (5 mL) was heated at 80° C. overnight. Solvent was then evaporated and the mixture azeotroped twice with toluene under vacuum. To yield the title compound [D035] as a yellow solid (0.78 g, 99%) which was used in the next step without further purification: LCMS method: 5, RT 2.22 min, MI 245 [M+H], NMR: (1H, 500 MHz, d6-dmso): 13.14 (brs, 1H), 10.40 (s, 1H), 8.70 (s, 1H), 7.70 (s, 1H), 7.56 (d, 1H), 6.27 (s, 2H). 
     2-Trifluoromethyl-1H-pyrrolo[2,3-b]pyridine-4-carboxamidine; compound with acetic acid [D036] 
     To a suspension of N-Hydroxy-2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridine-4-carboxamidine [D035](0.43 g, 1.76 mmol) in MeOH (10 mL) was added dropwise acetic anhydride (0.175 mL, 1.85 mmol) at room temperature. The suspension was stirred 15 min and palladium on charcoal (5% wt/wt, 0.1 g) was added. The vessel was seal and hydrogen (balloon) was bubble in the mixture for 10 min and left stirring at RT under hydrogen atmosphere overnight. The mixture was filtered through celite and concentrated in vacuo to yield the title compound [D036] as a yellow solid (0.51 g, 100%) which was used without further purification. LCMS method: 5, RT 4.45 min, MI 229 [M+H], NMR: (1H, 500 MHz, d6-dmso) 1.79 (s, 3H, CH 3 CO 2 H), 8.50 (s, 1H), 7.35 (s, 1H), 7.03 (s, 1H). 
     Synthesis of 2-Thiophen-2-yl-1H-pyrrolo[2,3-b]pyridine-4-carboxamidine acetic acid salt [D042] 
     
       
         
         
             
             
         
       
     
     2-Thiophen-2-yl-1H-pyrrolo[2,3-b]pyridine [D037] 
     Was prepared, following the procedure described in scheme D4, step 1, by reaction of (3-Methyl-pyridin-2-yl)-carbamic acid tert-butyl ester, thiophene-2-carboxylic acid methoxy-methyl-amide, BuLi and THF to give the title compound as a yellow solid. LCMS method: 5, RT 4.79 min, MI 201 [M+H]. 
     2-Thiophen-2-yl-1H-pyrrolo[2,3-b]pyridine 7-oxide [D038] 
     Was prepared, following the procedure described in scheme D4, step 2, by reaction of 2-Thiophen-2-yl-1H-pyrrolo[2,3-b]pyridine [D037], m-CPBA and DCM to give the title compound as a yellow solid. LCMS method: 5, RT 3.38 min, MI 217 [M+H]. 
     4-Chloro-2-thiophen-2-yl-1H-pyrrolo[2,3-b]pyridine [D039] 
     Was prepared, following the procedure described in scheme D4, step 3, by reaction of 2-Thiophen-2-yl-1H-pyrrolo[2,3-b]pyridine 7-oxide [D038], methane sulfonyl chloride and DMF to give the title compound as a yellow solid. LCMS method: 5, RT 6.05 min, MI 235 [M+H]. 
     2-Thiophen-2-yl-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile [D040] 
     Was prepared, following the procedure described in scheme D4, step 4, by reaction of 4-Chloro-2-thiophen-2-yl-1H-pyrrolo[2,3-b]pyridine [D039], PdCl2dppf:CH2C12, Zinc cyanide, zinc dust and DMA to give the title compound as a yellow solid. LCMS method: 5, RT 5.28 min, MI 226 [M+H]. 
     N-Hydroxy-2-thiophen-2-yl-1H-pyrrolo[2,3-b]pyridine-4-carboxamidine [D041] 
     Was prepared, following the procedure described in scheme D4, step 5, by reaction of 2-thiophen-2-yl-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile [D040], hydroxylamine and EtOH to give the title compound as a yellow solid. LCMS method: 5, RT 2.38 min, MI 259 [M+H]. 
     2-Thiophen-2-yl-1H-pyrrolo[2,3-b]pyridine-4-carboxamidine acetic acid salt [D042] 
     Was prepared, following the procedure described in scheme D4, step 6, by reaction of N-Hydroxy-2-thiophen-2-yl-1H-pyrrolo[2,3-b]pyridine-4-carboxamidineacetic anhydride [D041], Pd/C, hydrogen and MeOH to give the title compound as a yellow solid. LCMS method: 5, RT 4.45 min, MI 243 [M+H]. 
     Synthesis of 2-methyl-1H-pyrrolo[2,3-b]pyridine-4-carboxamidine acetic acid salt [D045] 
     
       
         
         
             
             
         
       
     
     2-Methyl-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile [D043] 
     Was prepared, following the procedure described in scheme D4, step 4, by reaction of 4-Chloro-2-methyl-1H-pyrrolo[2,3-b]pyridine, PdCl2dppf:CH2Cl2, Zinc cyanide, zinc dust and DMA to give the title compound as a white solid. LCMS method: 5, RT 4.17 min, MI 158 [M+H]. 
     N-Hydroxy-2-methyl-1H-pyrrolo[2,3-b]pyridine-4-carboxamidine [D044] 
     Was prepared, following the procedure described in scheme D4, step 5, by reaction of 2-Methyl-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile [D043], hydroxylamine and EtOH to give the title compound as a yellow solid. LCMS method: 5, RT 1.92 min, MI 191 [M+H]. 
     2-methyl-1H-pyrrolo[2,3-b]pyridine-4-carboxamidine acetic acid salt [D045] 
     Was prepared, following the procedure described in scheme D4, step 6, by reaction of N-Hydroxy-2-methyl-1H-pyrrolo[2,3-b]pyridine-4-carboxamidine [D044], acetic anhydride, Pd/C, hydrogen and MeOH to give the title compound as a yellow solid. LCMS method: 5, RT 2.44 min, MI 175 [M+H]. 
     For example Synthesis of 21H-pyrrolo[2,3-b]pyridine-4-carboxamidine acetic acid salt [D047] 
     
       
         
         
             
             
         
       
     
     N-Hydroxy-1H-pyrrolo[2,3-b]pyridine-4-carboxamidine [D047] 
     Was prepared, following the procedure described in scheme D4, step 5, by reaction of 1H-pyrrolo[2,3-b]pyridine-4-carbonitrile, hydroxylamine and EtOH to give the title compound as a yellow solid. LCMS method: 5, RT 1.24 min, MI 162 [M+H]. 
     2-1H-pyrrolo[2,3-b]pyridine-4-carboxamidine acetic acid salt [D047] 
     Was prepared, following the procedure described in scheme D4, step 6, by reaction of N-Hydroxy-1H-pyrrolo[2,3-b]pyridine-4-carboxamidine [D047], acetic anhydride, Pd/C, hydrogen and MeOH to give the title compound as a yellow solid. LCMS method: 5, RT 1.23 min, MI 161 [M+H], NMR: (1H, 500 MHz, d6-dmso) 8.38 (1H, d), 7.71 (1H, d), 7.30 (1H, d), 6.58 (1H, d), 1.80 (8H, s) 
     Following the procedures described in Example AZA-9, the following compounds were prepared from 3-Cyclopropyl-5-fluoro-isonicotinic acid: 
     
       
         
           
               
               
               
               
               
               
            
               
                   
               
               
                   
                 SM 
                 Amidine 
                 Amine 
                 Analysis 
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Ex 
                 [I-013] 
                 [I-014] 
                 [I-017] 
                 LCMS 
                 NMR 
                 Name 
               
               
                   
               
               
                 1212 
                 [D015] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.59 min, MI: 440 [M + H] 
                 1H NMR (DMSO, 500 MHz) 13.17 (s, 1H), 9.19 (s, 1H), 8.63 (d, 1H), 8.25 (d, 1H), 8.19 (s, 1H), 7.95 (s, 1H), 4.10- 3.77 (m, 8H), 2.75- 2.69 (m, 1H), 1.28- 1.22 (m, 2H), 1.13- 1.07 (m, 2H). 
                 [5-Cyclopropyl- 4-piperazin-1- yl-2-(2- trifluoromethyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1213 
                 [D015] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 5.02 min, MI: 440 [M + H] 
                 1H NMR (400 MHz, d6-DMSO, 90° C.) 11.49 (1H, br. s), 9.10 (1H, s), 8.39 (1H, d, J = 5.0 Hz), 8.16 (1H, s), 8.10 (1H, d, J = 5 Hz), 7.57 (1H, t, J = 2.9 Hz), 7.46 (1H, dd, J = 3.3, 1.9 Hz) 4.43 (1H, br. d, J = 12.8 Hz), 
                 5-Cyclopropyl- 2-(1H- pyrrolo[2,3- b]pyridin-4-yl)- 4-((R)-3- trifluoro- methyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
                   
                   
                   
                   
                 4.01-3.96 (1H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 3.77-3.72 (1H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 3.48-3.38 (2H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 3.10-3.07 (1H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 2.93-2.85 (1H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 2.75-2.70 (1H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 1.34-1.20 (2H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 1.08-0.96 (2H, m). 
                   
               
               
                   
               
               
                 1214 
                 [D015] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 5.03 min, MI: 440 [M + H] 
                 (1H, 400 MHz, d6- dmso 90° C.) 11.49 (1H, brs), 9.10 (1H, s), 8.39 (1H, d), 8.16 (1H, s), 8.10 (1H, d), 7.57 (1H, t), 7.46 (1H, dd) 4.43 (1H, br. d), 4.01-3.96 (1H, m), 3.77-3.72 (1H, m), 3.48-3.38 (2H, m), 3.10-3.07 (1H, 
                 5-Cyclopropyl- 2-(1H- pyrrolo[2,3- b]pyridin-4-yl)- 4-((S)-3- trifluoro- methyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
                   
                   
                   
                   
                 m), 2.93-2.85 (1H, 
                   
               
               
                   
                   
                   
                   
                   
                 m), 2.75-2.70 (1H, 
                   
               
               
                   
                   
                   
                   
                   
                 m), 1.34-1.20 (2H, 
                   
               
               
                   
                   
                   
                   
                   
                 m), 1.08-0.96 (2H, 
                   
               
               
                   
                   
                   
                   
                   
                 m). 
                   
               
               
                   
               
               
                 1215 
                 [D015] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 5.27 min, MI: 454 [M + H] 
                 1H NMR (DMSO, 500 MHz), 11.67 (brs, 1H), 9.07 (brs, 1H), 8.24 (d, 1H), 8.10 (s, 1H), 8.03 (d, 1H), 7.16 (s, 1H), 4.72- 4.18 (m, 1H), 4.05- 3.88 (m, 1H), 3.85- 3.61 (m, 1H), 3.31 (s, 3H), 3.18-2.72 (m, 4H), 1.33-1.14 (m, 
                 5-Cyclopropyl- 2-(2-methyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- 4-(3-trifluoro- methyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
                   
                   
                   
                   
                 2H), 1.06-0.95 (m, 
                   
               
               
                   
                   
                   
                   
                   
                 1H). 
                   
               
               
                   
               
               
                 1216 
                 [D015] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.20 min, MI: 426 [M + H] 
                 1H NMR (DMSO, 500 MHz) 11.68 (brs, 1H), 9.07 (brs, 1H), 8.24 (d, 1H), 8.13 (d, 1H), 8.11 (d, 1H), 7.17 (s, 1H), 4.34- 4.08 (m, 2H), 3.60- 3.46 (m, 2H), 3.18- 2.84 (m, 2H), 3.01 (s, 3H), 1.04-0.88 (m, 3H), 0.60-0.25 (m, 
                 5-Cyclopropyl- 4-((S)-3- cyclopropyl- piperazin-1-yl)- 2-(2-methyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
                   
                   
                   
                   
                 5H). 
                   
               
               
                   
               
               
                 1217 
                 [D015] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 2.80 min, MI: 386 [M + H] 
                 (1H, 500 MHz, d6- dmso) 11.64 (s, 1H), 9.03 (s, 1H), 8.22 (d, 1H), 8.06 (s, 1H), 8.02 (d, 1H), 7.15 (s, 1H), 3.08 (very broad m, 4H), 2.87-2.92 (m, 4H), 2.65-2.70 (m, 1H), 2.47 (s, 3H), 1.22-1.26 (m, 2H), 
                 5-Cyclopropyl- 2-(2-methyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- 4-piperazin-1- yl-pyrido[3,4- d]pyrimidine 
               
               
                   
                   
                   
                   
                   
                 1.02-1.07 (m, 2H), 
                   
               
               
                   
               
               
                 1218 
                 [D015] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 5.03 min, MI: 440 [M + H] 
                 1H NMR (400 MHz, d6-DMSO, 90° C.) 11.49 (1H, br. s), 9.10 (1H, s), 8.39 (1H, d, J = 5.0 Hz), 8.16 (1H, s), 8.10 (1H, d, J = 5 Hz), 7.57 (1H, t, J = 2.9 Hz), 7.46 (1H, dd, J = 3.3, 1.9 Hz) 4.43 (1H, br. d, J = 12.8 Hz), 
                 5-Cyclopropyl- 2-(1H- pyrrolo[2,3- b]pyridin-4-yl)- 4-(3- trifluoromethyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
                   
                   
                   
                   
                 4.01-3.96 (1H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 3.77-3.72 (1H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 3.48-3.38 (2H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 3.10-3.07 (1H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 2.93-2.85 (1H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 2.75-2.70 (1H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 1.34-1.20 (2H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 1.08-0.96 (2H, m). 
                   
               
               
                   
               
               
                 1219 
                 [D015] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.53 min, MI: 462 [M + H] 
                 (1H, 500 MHz, d6- dmso) 11.47 (1H, brs), 9.05 (1H, s), 8.35 (1H, d), 8.06 (1H, s), 7.95 (1H, d), 7.56-7.55 (1H, br. m), 7.43 (1H, d), 7.34-7.30 (2H, m), 7.27-7.24 (3H, m), 4.27 (1H, dr. d), 4.20-4.17 (1H, m), 
                 4-((S)-3- Benzyl- piperazin-1-yl)- 5-cyclopropyl- 2-(1H- pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
                   
                   
                   
                   
                 3.39-3.33 (1H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 3.21-3.17 (1H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 3.14-3.04 (2H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 2.96-2.82 (2H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 2.77-2.72 (1H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 2.63-2.56 (1H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 1.23-1.15 (2H, m), 
                   
               
               
                   
                   
                   
                   
                   
                 0.94-0.87 (2H, m). 
                   
               
               
                   
               
               
                 1220 
                 [D015] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 3.09 min, MI: 412 [M + H] 
                 (1H, 500 MHz, d6- dmso) 11.52 (1H, s, brs), 9.13 (1H, s), 8.41 (1H, d), 8.20 (1H, s), 8.11 (1H, d), 7.60 (1H, d), 7.47 (1H, d), 4.44-4.41 (1H, br. m), 4.28-4.24 (1H, br. m), 3.74-3.68 (1H, br. m), 3.60- 
                 5-Cyclopropyl- 4-((S)-3- cyclopropyl- piperazin-1-yl)- 2-(1H- pyrrolo[2,3-b] pyridin-4-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
                   
                   
                   
                   
                 3.53 (1H, m), 3.36- 
                   
               
               
                   
                   
                   
                   
                   
                 3.33 (1H, m), 3.14- 
                   
               
               
                   
                   
                   
                   
                   
                 3.07 (1H, m), 2.80- 
                   
               
               
                   
                   
                   
                   
                   
                 2.68 (2H, m), 1.30- 
                   
               
               
                   
                   
                   
                   
                   
                 1.24 (2H, m), 1.12- 
                   
               
               
                   
                   
                   
                   
                   
                 1.04 (2H, m), 1.02- 
                   
               
               
                   
                   
                   
                   
                   
                 0.97 (1H, m), 0.66- 
                   
               
               
                   
                   
                   
                   
                   
                 0.59 (3H, m), 0.46- 
                   
               
               
                   
                   
                   
                   
                   
                 0.41 (1H, m). 
                   
               
               
                   
               
               
                 1221 
                 [D015] 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Method 5: RT: 2.94 min, MI: 411 [M + H] 
                 (1H, 400 MHz, d6- dmso 90° C.) 11.46 (1H, brs), 9.08 (1H, s), 8.38 (1H, d), 8.15 (1H, s), 8.13 (1H, d), 7.57-7.55 (1H, m), 7.48 (1H, dd), 4.34- 4.32 (1H, m), 4.13- 4.10 (1H, m), 3.31- 3.25 (1H, m), 3.21- 3.16 (1H, m), 3.11- 
                 {(S)-4-[5- Cyclopropyl-2- (1H- pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidin-4- yl]-piperazin-2- yl}-acetonitrile 
               
               
                   
                   
                   
                   
                   
                 3.01 (2H, m), 2.95- 
                   
               
               
                   
                   
                   
                   
                   
                 2.86 (2H, m), 2.72- 
                   
               
               
                   
                   
                   
                   
                   
                 2.69 (1H, m), 2.61- 
                   
               
               
                   
                   
                   
                   
                   
                 2.58 (1H, m), 1.30- 
                   
               
               
                   
                   
                   
                   
                   
                 1.23 (2H, m), 1.03- 
                   
               
               
                   
                   
                   
                   
                   
                 0.98 (2H, m). 
               
               
                   
               
            
           
         
       
     
     The following compounds were synthesised according to the general synthesis shown in scheme [B4] 
     
       
         
           
               
               
               
               
               
            
               
                   
               
               
                   
                   
                   
                 Analysis 
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Ex 
                 Amine 1 
                 Amidine 2 
                 LCMS 
                 NMR 
                 Name 
               
               
                   
               
               
                 1222 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT 3.59 min, MI: 454 [MH+] 
                 NHM, CDCl3, 500 MHz, 12.06 (brs, 1H), 9.12 (s, 1H), 8.47 (d, 1H), 8.23 (d, 1H), 8.06 (s, 1H), 7.80 (s, 1H), 7.57 (d, 1H), 7.39 (d, 1H), 7.19 (dd, 1H), 4.02-3.61 (m, 4H), 3.12- 3.06 (m, 4H), 2.80-2.74 (m, 1H), 1.30-1.26 (m, 2H), 1.05- 1.01 
                 5-Cyclopropyl-4- piperazin-1-yl-2- (2-thiophen-2-yl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1223 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT 3.21 min, MI: 412 [MH+] 
                 1H NMR (400 MHz, 90° C., d6-DMSO) 11.27 (1H, br s), 9.04 (1H, s), 8.23 (1H, d, J = 5.1 Hz), 8.11 (1H, s), 8.02 (1H, d, J = 5.1 Hz), 7.10 (1H, s), 3.74-3.72 (4H, m), 2.95- 2.92 (4H, m, overlapping with water signal), 2.74-2.67 (1H, m), 2.18-2.12 (1H, m), 1.28- 
                 5-Cyclopropyl-2- (2-cyclopropyl-1H- pyrrolo[2,3- b]pyridin-4-yl)-4- piperazin-1-yl- pyrido[3,4- d]primidine 
               
               
                   
                   
                   
                   
                 1.23 (2H, m), 1.09-1.04 (2H, 
                   
               
               
                   
                   
                   
                   
                 m), 1.00-0.96 (2H, m), 0.95- 
                   
               
               
                   
                   
                   
                   
                 0.91 (2H, m). 
                   
               
               
                   
               
               
                 1224 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT 4.98 min, MI: 412 [MH+] 
                 NMR 1H DMSO 13.11 (brs, 1H), 9.12 (s, 1H), 8.60 (d, 1H), 8.23 (d, 1H), 8.14 (s, 1H), 7.94 (s, 1H), 40.08-4.05 (m, 1H), 3.95-3.55 (m, 8H), 1.26-1.17 (m, 2H), 1.56-1.00 (m, 2H) 
                 4-[5-Cyclopropyl- 2-(2- trifluoromethyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidin-4-yl]- piperazine-1- carboxylic acid ethyl ester 
               
               
                   
               
               
                 1225 
                 — 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT 5.77 min, MI: 372 [MH+] 
                 NMR 1H DMSO 8.97 (s, 1H), 8.62 (d, 1H), 8.24 (s, 1H), 7.88 (d, 1H), 7.67 (s, 1H), 3.45- 3.39 (m, 1H), 1.12-1.08 (m, 2H), 0.97-0.92 (m, 2H). 
                 5-Cyclopropyl-2- (2-trifluoromethyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidin-4-ol 
               
               
                   
               
               
                 1226 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT 2.10 min, MI: 390 [MH+] 
                 1H NMR (500 MHz, d6- DMSO) 11.92 (1H, s), 8.98 (1H, s), 8.32 (1H, d, J = 3.5 Hz), 8.12 (1H, s), 7.65 (1H, t, J = 2.9 Hz), 6.94 (1H, dd, J = 3.4, 2.0 Hz), 3.84-3.49 (4H, br m), 2.85 (4H, br s), 2.67- 2.62 (1H, m), 1.29-1.26 (2H, m), 1.07-1.04 (2H, m). 
                 5-Cyclopropyl-2- (5-fluoro-1H- pyrrolo[2,3- b]pyridin-4-yl)-4- piperazin-1-yl- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1227 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT 6.01 min, MI: 441 [MH+] 
                 NMR 1H DMSO 13.11 (s, 1H), 9.12 (s, 1H), 8.62 (s, 1H), 8.22 (d, 1H), 8.13 (s, 1H), 7.93 (s, 1H), 3.80-3.60 (m, 8H), 2.72-2.67 (m, 1H), 1.28- 1.23 (m, 2H), 1.06-1.03 (m, 2H). 
                 5-Cyclopropyl-4- morpholin-4-yl-2- (2-trifluoromethyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1228 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT 2.16 min, MI: 389 [MH+] 
                 1H NMR (400 MHz, d6- DMSO, 90° C.) 11.28 (1H, s), 9.04 (1H, s), 8.24 (1H, d, J = 5.2 Hz), 8.11 (1H, s), 8.03 (1H, d, J = 5.2 Hz), 7.16 (1H, d, J = 1.5 Hz), 3.74-3.72 (4H, m), 2.95-2.93 (4H, m, overlapping with water signal), 2.74-2.69 (1H, m), 
                 5-Cyclopropyl-4- piperazin-1-yl-2- (2- triduteriomethyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
                   
                   
                   
                 1.28-1.23 (2H, m), 1.01- 
                   
               
               
                   
                   
                   
                   
                 0.97 (2H, m). 
                   
               
               
                   
               
               
                 1229 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT 3.44 min, MI: 462 [MH+] 
                 1H NMR (d6-DMSO, 500 MH), 11.87 (1H, s), 8.94 (1H, s), 8.22 (1H, s), 8.11 (1H, s), 3.75-3.55 (4H, m), 2.82 (4H, br s), 2.64-2.59 (1H, m), 1.27 (2H, ddd), 1.05 (2H, ddd) 
                 2-(2-tert-Butyl-5- chloro-1H- pyrrolo[2,3- b]pyridin-4-yl)-5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1230 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 4.02 min, MI: 466 [M + H] 
                 1H NMR (400 MHz, d6- DMSO, 90° C.) 9.13 (1H, s), 8.38 (1H, d, J = 5.1 Hz), 8.14 (1H, s), 8.11 (1H, d, J = 5.1 Hz), 8.07-8.03 (2H, m), 7.84 (1H, s), 7.32 (2H, t, J = 8.9 Hz), 3.78-3.76 (4H, m), 2.97- 2.94 (4H, m, overlapping with water signal), 2.77-2.70 
                 5-Cyclopropyl-2- [2-(4-fluoro- phenyl)-1H- pyrrolo[2,3- b]pyridin-4-yl]-4- piperazin-1-yl- pyrido[3,4- d]pyrimidine 
               
               
                   
                   
                   
                   
                 (1H, m), 1.30-1.25 (2H, m), 
                   
               
               
                   
                   
                   
                   
                 1.02-0.98 (2H, m). 
                   
               
               
                   
               
               
                 1231 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.51 min, MI: 428 [M + H] 
                 NMR: (1H, d6-DMSO, 500 MHz) 11.71 (1H, br s), 9.03 (1H, s), 8.26 (1H, d), 8.07 (1H, s), 8.02 (1H, d), 7.18 (1H, d), 3.81 (2H, v br s), 3.62 (2H, v br s), 2.90 (4H, br s), 2.70-2.65 (1H, m), 1.41 (9H, s), 1.28-1.22 (2H, m), 1.04- 1.01 (2H, dt). 
                 2-(2-tert-Butyl-1H- pyrrolo[2,3- b]pyridin-4-yl)-5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1232  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT 2.48 min, MI: 458 [MH+] 
                 1H NMR (400 MHz, d6- DMSO, 90° C.) 9.02 (1H, s), 8.54 (1H, d, J = 3.6 Hz), 8.18 (1H, s), 7.51-7.49 (1H, m), 3.74-3.72 (4H, m), 2.92- 2.89 (4H, m), 2.68-2.62 (1H, m), 1.31-1.26 (2H, m), 1.04- 1.01 (2H, m). 
                 5-Cyclopropyl-2- (5-fluoro-2- trifluoromethyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)-4- piperazin-1-yl- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1233 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.63 min, MI = 454 [M + H] 
                   
                 5-Cyclopropyl-4- ((S)-3-methyl- piperazin-1-yl)-2- (2-trifluoromethyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1234 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 471.1 (M + H) 
                 (CDCl 3 ) 13.11 (br s, 1H), 9.06 (s, 1H), 8.62 (d, J = 5.0 Hz, 1H), 8.25 (d, J = 5.0 Hz, 1H), 8.10 (s, 1H), 7.98 (d, J = 1.0 Hz, 1H), 5.09-4.67 (m, 1H), 4.67-4.17 (m, 2H), 4.03-3.68 (m, 4H), 3.68-3.38 (m, 2H), 2.63-2.53 (m, 1H), 2.06 (br s, 1H), 1.70 (br s, water), 1.49- 
                 (+/−)-(cis)-1-[5- Cyclopropyl-2-(2- trifluoromethyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidin-4-yl]- piperidine-3,4-diol 
               
               
                   
                   
                   
                   
                 0.80 (m, 4H) 
                   
               
               
                   
               
               
                 1235 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 471.1 (M + H) 
                 (CDCl 3 ): 13.09 (br s, 1H), 9.07 (s, 1H), 8.62 (d, J = 5.0 Hz, 1H), 8.25 (d, J = 5.0 Hz, 1H), 8.11 (s, 1H), 7.98 (d, J = 1.0 Hz, 1H), 5.22-4.71 (m, 2H), 4.22-3.74 (m, 3H), 3.62- 3.34 (m, 3H), 2.60-2.53 (m, 1H), 2.30-1.81 (m, 1H), 1.71- 1.13 (m, 3H), 1.12-0.95 (m, 
                 (+/−)-(trans)-1-[5- Cyclopropyl-2-(2- trifluoromethyl- 1H-pyrrolo[2,3- b]pyridin-4-l)- pyrido[3,4- d]pyrimidin-4-yl]- piperidine-3,4-diol 
               
               
                   
                   
                   
                   
                 2H) 
                   
               
               
                   
               
               
                 1236 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 4.74 min, MI 508 [M + H] 
                 1H NMR (DMSO, 500 MHz) 13.14 (s, 1H), 9.12 (s, 1H), 8.61 (d, 1H), 8.21 (d, 1H), 8.14 (s, 1H), 7.91 (s, 1H), 4.70-4.21 (m, 1H), 4.04-3.96 (m, 1H), 3.87-3.46 (m, 2H), 3.19-2.96 (m, 3H), 1.37-1.17 (m, 2H), 1.14-0.96 (m, 2H). 
                 5-Cyclopropyl-4- (3-trifluoromethyl- piperazin-1-yl)-2- (2-trifluoromethyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1237 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 439.49 
                   
                 5-Cyclopropyl-4- piperidin-1-yl-2-(2- trifluoromethyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1238 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 5.31 min, MI 480 [M + H] 
                 1H NMR (400 MHz, d6- DMSO, 90° C.) 11.66 (1H, br s), 9.04 (1H, s), 8.39 (1H, d, J = 5.0 Hz), 8.13 (1H, s), 8.10 (1H, d, J = 5.0 Hz), 7.55 (1H, s), 3.76-3.73 (4H, m), 2.94- 2.91 (4H, m, partly obscured by water signal), 2.73-2.66 (1H, m), 1.49-1.48 (2H, m), 
                 5-Cyclopropyl-4- piperazin-1-yl-2- [2-(1- trifluoromethyl- cyclopropyl)-1H- pyrrolo[2,3- b]pyridin-4-yl]- pyrido[3,4- d]pyrimidine 
               
               
                   
                   
                   
                   
                 1.47-1.46 (2H, m), 1.29- 
                   
               
               
                   
                   
                   
                   
                 1.24 (2H, m), 1.01-0.97 (2H, 
                   
               
               
                   
                   
                   
                   
                 m). 
                   
               
               
                   
               
               
                 1239 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT 6.34 min, MI = 455 [M + H] 
                 NMR 1H DMSO 13.12 (s, 1 H), 9.08 (s, 1H), 8.61 (d, 1H), 8.23 (d, 1H), 8.10 (s, 1H), 7.96 (s, 1H), 4.84-4.70 (m, 1H), 4.14-4.04 (m, 1H), 3.88-3.75 (m, 1H), 3.68-3.40 (m, 2H), 1.95-1.84 (m, 1H), 1.67-1.39 (m, 2H), 1.31-1.20 (m, 2H), 1.17-0.99 (m, 4H). 
                 1-[5-Cyclopropyl- 2-(2- trifluoromethyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidin-4-yl]- piperidin-4-ol 
               
               
                   
               
               
                 1240 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.82 min, MI: 488 [M + H] 
                 1H NMR (400 MHz, d6- DMSO, 90°) 11.28 (1H, br s), 8.96 (1H, s), 8.27 (1H, d, J = 5.1 Hz), 8.09 (1H, s), 8.05 1H, d, J = 5.1 Hz), 7.45-7.43 (2H, m), 7.38-7.34 (2H, m), 7.29- 7.26 (1H, m), 7.02 (1H, m), 3.63-3.60 (4H, m), 2.88- 2.85 (4H, m), 2.70-2.64 (1H, 
                 5-Cyclopropyl-2- [2-(1-phenyl- cyclopropyl)-1H- pyrrolo[2,3- b]pyridin-4-yl]-4- piperazin-1-yl- pyrido[3,4- d]pyrimidine 
               
               
                   
                   
                   
                   
                 m), 1.60-1.57 (2H, m), 1.40- 
                   
               
               
                   
                   
                   
                   
                 1.37 (2H, m), 1.27-1.22 (2H, 
                   
               
               
                   
                   
                   
                   
                 m), 1.00-0.96 (2H, m). 
                   
               
               
                   
               
               
                 1241 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT 5.38 min, MI = 464 [M + H] 
                 NMR 1H DMSO, 90°C.,, 12.78 (brs, 1H), 9.12 (s, 1H), 8.62 (d, 1H), 8.24 (d, 1H), 8.18 (s, 1H), 7.95 (d, 1H), 4.04-3.98 (m, 2H), 3.72-3.66 (m, 2H), 3.22-3.15 (m, 1H), 2.72-2.65 (m, 1H), 2.15-2.08 (m, 2H), 2.00-1.91 (m, 2H), 1.31-1.26 (m, 2H), 1.03-0.99 
                 1-[5-Cyclopropyl- 2-(2- trifluoromethyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidin-4-yl]- piperidine-4- carbonitrile 
               
               
                   
                   
                   
                   
                 (m, 2H). 
                   
               
               
                   
               
               
                 1242 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 5.29 min, MI = 469 [M + H] 
                 NMR 1H DMSO, 90°C., 12.76 (brs, 1H), 9.08 (s, 1H), 8.61 (d, 1H), 8.25 (d, 1H), 8.16 (s, 1H), 7.96 (d, 1H), 4.38-4.35 (m, 2H), 4.12 (t, 1H), 3.37- 3.28 (m, 4H), 2.69-2.62 (m, 1H), 1.91-1.73 (m, 3H), 1.46- 1.34 (m, 2H), 1.29-1.25 (m, 2H), 1.02-0.98 (m, 2H). 
                 {1-[5-Cyclopropyl- 2-(2- trifluoromethyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidin-4-yl]- piperidin-4-yl}- methanol 
               
               
                   
               
               
                 1243 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT 4.57 min, MI: 441 [M + H] 
                 NMR 1H DMSO, 90° C., 9.03 (s, 1H), 8.60 (d, 1H), 8.26 (d, 1H)m, 8.19 (s, 1H), 7.96 (d, 1H), 4.53 (t, 2H), 4.26 (dd, 2H), 3.62 (d, 2H), 3.00-2.87 (m, 2H), 1.32-1.28 (m, 2H), 0.97-0.93 (m, 2H). 
                 {1-[5-Cyclopropyl- 2-(2- trifluoromethyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidin-4-yl]- azetidin-3-yl}- methanol 
               
               
                   
               
               
                 1244 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT = 5.05 min, MI: 503 [M + H] 
                 1H NMR (400 MHz, d6- DMSO, 90° C.) 11.27 (1H, s), 8.95 (1H, s), 8.26 (1H, d, J = 5.1 Hz), 8.09 (1H, s), 8.05 (1H, d, J = 5.1 Hz), 7.45-7.42 (2H, m), 7.37-7.34 (2H, m), 7.29-7.25 (1H, m), 7.05 (1H, d, J = 2.2 Hz), 4.40 (1H, d, J = 4.3 Hz), 4.01-3.95 (2H, m), 
                 1-[5-Cyclopropyl- 2-[2-(1-phenyl- cyclopropyl)-1H- pyrrolo[2,3- b]pyridin-4-yl]- pyrido[3,4- d]pyrimidin-4-yl}- piperidin-4-ol 
               
               
                   
                   
                   
                   
                 3.83-3.77 (1H, m), 3.45- 
                   
               
               
                   
                   
                   
                   
                 3.38 (2H, m), 2.66-2.61 (1H, 
                   
               
               
                   
                   
                   
                   
                 m), 1.90-1.83 (2H, m), 1.59- 
                   
               
               
                   
                   
                   
                   
                 1 .49 (4H, q and m 
                   
               
               
                   
                   
                   
                   
                 overlapping), 1.39-1.37 (2H, 
                   
               
               
                   
                   
                   
                   
                 m), 1.26-1.21 (2H, m), 0.99- 
                   
               
               
                   
                   
                   
                   
                 0.95 (2H, m). 
                   
               
               
                   
               
               
                 1245 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT 4.51 min, MI: 489 [M + H] 
                 1H NMR (DMSO, 500 MHz) 13.15 (s, 1H), 9.19 (s, 1H), 8.63 (d, 1H), 8.25 (d, 1H), 8.16 (s, 1H), 7.97 (s, 1H), 4.41-4.01 (m, 4H), 3.41-3.34 (m, 4H), 2.73-2.66 (m, 1H), 1.32-1.23 (m, 2H), 1.09-1.02 (m, 2H). 
                 5-Cyclopropyl-4- (1,1-dioxo-1λ 6 - thiomorpholin-4- yl)-2-(2- trifluoromethyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1246 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT 5.95 min, MI = 457 [M + H] 
                 1H NMR (DMSO, 500 MHz) 13.12 (s, 1H), 9.10 (s, 1H), 8.61 (d, 1H), 8.22 (d, 1H), 8.11 (s, 1H), 7.94 (s, 1H), 4.09-4.01 (m, 4H), 2.83-2.73 (m, 4H), 2.63-2.57 (m, 1H), 1.31-1.23 (m, 2H), 1.06-0.98 (m, 2H). 
                 5-Cyclopropyl-4- thiomorpholin-4- yl-2-(2- trifluoromethyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1247 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 5.61 min, MI: 443 [M + H] 
                 1H NMR (400 MHz, d6- DMSO, 90° C.) 11.31 (1H, br s), 9.03 (1H, s), 8.27 (1H, d, J = 5.2 Hz), 8.11 (1H, s), 8.06 (1H, d, J = 5.2 Hz), 7.24-7.23 (1H, m), 4.42 (1H, d, J = 4.1 Hz), 4.18-4.08 (2H, m), 3.88- 3.83 (1H, m), 360-3.53 (2H, m), 2.71-2.65 (1H, m), 
                 1-[2-(2-tert-Butyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)-5- cyclopropyl- pyrido[3,4- d]pyrimidin-4-yl]- piperidin-4-ol 
               
               
                   
                   
                   
                   
                 1.95-1.91 (2H, m), 1.65- 
                   
               
               
                   
                   
                   
                   
                 1.57 (2H, m), 1.46 (9H, s), 
                   
               
               
                   
                   
                   
                   
                 1.28-1.23 (2H, m), 1.00- 
                   
               
               
                   
                   
                   
                   
                 0.96 (2H, m). 
                   
               
               
                   
               
               
                 1248 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 5.62 min, MI: 411 [M + H] 
                 1H NMR (DMSO, 500 MHz) 13.09 (brs, 1H), 9.02 (s, 1H), 8.59 (d, 1H), 8.24 (d, 1H), 8.13 (s, 1H), 7.95 (s, 1H), 7.47 (t, 4H), 2.43-2.33 (m, 3H), 1.31-1.24 (m, 2H), 0.99-0.92 (m, 2H). 
                 4-Azetidin-1-yl-5- cyclopropyl-2-(2- trifluoromethyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1249 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 1.76 min, MI: 456 [M + H] 
                 1H NMR (400 MHz, d6- DMSO, 90° C.) 11.31 (1H, s), 9.05 (1H, s), 8.28 (1H, d, J = 5.0 Hz), 8.15 (1H, s), 8.06 (1H, d, J = 5.0 Hz), 7.29-7.26 (1H, m), 7.19 (1H, d, J = 2.3 Hz), 4.03-4.00 (2H, m), 3.96- 3.94 (2H, m), 3.39-3.35 (2H, m), 2.77-2.74 (2H, m), 
                 1-[2-(2-tert-Butyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)-5- cyclopropyl- pyrido[3,4- d]pyrimidin-4-yl]- [1,4]diazepan-5- one 
               
               
                   
                   
                   
                   
                 2.65-2.58 (1H, m), 1.47 (9H, 
                   
               
               
                   
                   
                   
                   
                 s), 1.28-1.23 (2H, m), 0.99- 
                   
               
               
                   
                   
                   
                   
                 0.95 (2H, m). 
                   
               
               
                   
               
               
                 1250 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 4.78 min, MI: 429 [M + H] 
                 1H NMR (500 MHz, d6- DMSO), 11.67 (1H, br d, J = 1.8 Hz), 8.92 (1H, s), 8.25 (1H, d, J = 5.2 Hz), 8.07 (1H, s), 8.06 (1H, d, J = 5.2 Hz), 7.22 (1H, d ,J = 2.3 Hz), 4.95 (1H, br, J = 2.9 Hz), 4.35 (1H, br s), 4.19-4.13 (1H, m), 4.09- 
                 (R)-1-[2-(2-tert- Butyl-1H- pyrrolo[2,3- b]pyridin-4-yl)-5- cyclopropyl- pyrido[3,4- d]pyrimidin-4-yl]- pyrrolidin-3-ol 
               
               
                   
                   
                   
                   
                 4.04 (1H, s), 3.77-3.72 (1H, 
                   
               
               
                   
                   
                   
                   
                 m), 3.48 (1H, d, J = 11.3 Hz), 
                   
               
               
                   
                   
                   
                   
                 2.35-2.28 (1H, m), 2.05- 
                   
               
               
                   
                   
                   
                   
                 1.98 (1H, m), 1.90-1.86 (1H, 
                   
               
               
                   
                   
                   
                   
                 m), 1.34-1.29 (1H, m), 1.20- 
                   
               
               
                   
                   
                   
                   
                 1.14 (1H, m), 1.20-1.14 (1H, 
                   
               
               
                   
                   
                   
                   
                 m), 1.04-0.99 (1H, m), 0.94- 
                   
               
               
                   
                   
                   
                   
                 0.89 (1H, m). 
                   
               
               
                   
               
               
                 1251 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 method 5: RT: 3.79 min, MI: 468 [M + H] 
                 1H NMR (DMSO, 500 MHz) 13.10 (brs, 1H), 9.06 (s, 1H), 8.61 (d, 1H), 8.23 (d, 1H), 8.11 (s, 1H), 7.96 (s, 1H), 4.02-3.75 (m, 1H), 3.70-3.53 (m, 2H), 3.38-3.25 (m, 2H), 2.98-2.85 (m, 2H), 1.29-0.70 (m, 10H). 
                 5-Cyclopropyl-4- (3,3-dimethyl- piperazin-1-yl)-2- (2-trifluoromethyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)- pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 1252 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 442 
                 1H NMR (400 MHz, d6- DMSO, 90° C.) 8.96 (1H, s), 8.10 (1H, s), 7.82 (1H, d, J = 5.5 Hz), 7.34 (1H, d, J = 5.5 Hz), 6.42 (1H, s), 3.70-3.67 (2H, m), 3.09-3.106 (2H, m), 2.90-2.88 (2H, m), 2.70- 2.66 (3H, m), 1.73-1.58 (7H, m), 1.55-1.45 (4H, m), 1.28- 
                 4-(5-cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2- yl)spiro[1,3- dihydropyrrolo[2,3- b]pyridine-2,1′- cyclohexane] 
               
               
                   
                   
                   
                   
                 1.20 (3H, m), 0.99-0.95 (2H, 
                   
               
               
                   
                   
                   
                   
                 m). 
                   
               
               
                   
               
               
                 1253 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 422 (M + H) 
                   1 H-NMR (DMSO-d 6 , 400 MHz): δ 12.08 (s, 1H), 9.17 (s, 1H), 8.83 (br s, 1H), 8.68 (d, 1H, J = 8.4 Hz), 8.59 (d, 1H, J = 5.1 Hz), 8.26 (s, 1H), 7.89 (d, 1H, J = 5.1 Hz), 7.55 (d, 1H, J = 7.9 Hz), 7.49 (m, 1H), 7.18 (m, 1lH), 3.68 (br s, 4H), 3.34 (br s, 4H), 2.77 (m, 1H), 
                 4-(5-Cyclopropyl- 4-piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)- 9H-pyrido[2,3- b]indole 
               
               
                   
                   
                   
                   
                 1.30 (m, 2H), 1.14 (m ,2H). 
                   
               
               
                   
               
               
                 1254 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 437 (M + H) 
                   1 H-NMR (DMSO-d 6 , 400 MHz): δ 12.12 (s, 1H), 9.07 (s, 1H), 8.60 (d, 1H, J = 5.0 Hz) 8.54 (d, 1H, J = 8.1 Hz), 8.22 (s, 1H), 7.84 (d, 1H, J = 5.0 Hz), 7.56 (d, 1H, J = 8.0 Hz), 7.49 (m, 1H), 7.17 (m, 1H), 4.11 (m, 3H), 3.58 (br s, 2H), 2.61 (m, 1H), 1.89 (m, 2H), 
                 1-[5-Cyclopropyl- 2-(9H-pyrido[2,3- b]indol-4-yl)- pyrido[3,4- d]pyrimidine-4-yl]- piperidin-4-ol 
               
               
                   
                   
                   
                   
                 1.55 (m, 2H), 1.92 (m, 2H), 
                   
               
               
                   
                   
                   
                   
                 1.21 (m, 2H). 
                   
               
               
                   
               
               
                 1255 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 450 (M + H) 
                   1 H-NMR (DMSO-d 6 , 400 MHz): δ 12.09 (s, 1H), 9.17 (s, 1H), 9.05 (br s, 2H), 8.67 (d, 1H, J = 8.1 Hz), 8.60 (d, 1H, J = 5.1 Hz), 8.29 (s, 1H), 7.93 (d, 1H, J = 5.1 Hz) 7.55 (d, 1H, J = 7.9 Hz), 7.49 (m, 1H), 7.18 (m, 1H), 3.93 (m, 4H), 3.39 (m, 2H), 2.61 (m,1H), 
                 4-[5-Cyclopropyl- 4-(3,3-dimethyl- piperazin-1-yl)- pyrido[3,4- d]pyrimidin-2-yl]- 9H-pyrido[2,3- b]indole 
               
               
                   
                   
                   
                   
                 1.01-1.48 (m, 10H). 
               
               
                   
               
            
           
         
       
     
     Example 1253. 4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-9H-pyrido[2,3-b]indole trifluoroacetic acid salt 
     1253a) A mixture of azeotropically dried (xylene) 4-chloro-9H-pyrido[2,3-b]indole (1.31 g, 6.46 mmol), zinc cyanide (1.21 g, 10.3 mmol), zinc (0.145 g, 2.22 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.479 g, 0.523 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (0.375 g, 0.676 mmol) in N,N-dimethylformamide (27 mL) was vacuum degassed then heated at 100 OC under an atmosphere of argon overnight. The mixture is cooled and poured into water:ethyl acetate (2:1, 150 mL). The layers were separated, the aqueous extracted with ethyl acetate (2×50 mL) and the combined organic extracts are diluted with hexane (15 mL) and brine (100 mL). The fine suspension of solids was removed by filtration of the aqueous layer through Celite, washing with methanol and ethyl acetate. The organic extracts and aqueous/organic rinsate were combined, separated and the organic layer washed with additional brine (100 mL), dried over magnesium sulfate, filtered and concentrated in vacuo onto silica gel (12 g) prior to purification on silica gel (80 g, 5-35% ethyl acetate:hexane). 9H-Pyrido[2,3-b]indole-4-carbonitrile was isolated as a yellow solid (0.830 g, 66% yield). LCMS (ESI): 194 (M+H) + ;  1 H-NMR (DMSO-d 6 , 400 MHz): δ 12.45 (s, 1H), 8.63 (d, 1H, J=5.0 Hz), 8.32 (d, 1H, J=8.0 Hz), 7.68 (d, 1H, J=5.0 Hz), 7.64 (m, 2H), 7.40 (m, 1H);  13 C-NMR (DMSO-d 6 , 100 MHz): δ 151.6, 146.2, 139.7, 128.6, 121.1, 120.5, 117.9, 116.9, 116.7, 114.1, 112.0, 109.8. 
     1253b) Lithium hexamethyldisilazide in tetrahydrofuran (1.0 M, 7.0 mL, 7.0 mmol) was added to a suspension of 9H-pyrido[2,3-b]indole-4-carbonitrile (0.422 g, 2.18 mmol) in tetrahydrofuran (12.0 mL, 148 mmol) at room temperature under an atmosphere of nitrogen. Additional lithium hexamethyldisilazide in tetrahydrofuran (1.0 M, 7 mL) was added at 48 h to drive the reaction to completion. After stirring a total of 72 h, the mixture was diluted with water (50 mL) and the resultant solids were collected by filtration, washed with water and dried on a Buchner funnel and in vacuo. 9H-Pyrido[2,3-b]indole-4-carboxamidine was isolated as beige solids (0.297 g, 65% yield) and was used without further purification. LCMS (ESI): 211 (M+H) + . 
     1253c) 9H-Pyrido[2,3-b]indole-4-carboxamidine (0.295 g, 1.40 mmol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (0.806 g, 2.12 mmol), 3-cyclopropyl-5-fluoro-isonicotinic acid (0.320 g, 1.76 mmol) and N,N-diisopropylethylamine (0.750 mL, 4.30 mmol) were combined in N,N-dimethylformamide (8.0 mL) and stirred for 90 min. The mixture was poured into ethyl acetate (50 mL) and washed with water (2×5 mL). The combined aqueous wash was extracted with ethyl acetate (3×15 mL) which was combined with the first organic extract, washed with brine (30 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude 3-cyclopropyl-5-fluoro-N-[imino-(9H-pyrido[2,3-b]indol-4-yl)-methyl]-isonicotinamide was combined with cesium carbonate (0.914 g, 2.81 mmol) in N,N-dimethylformamide (14.0 mL) and was heated at 90 OC under an atmosphere of nitrogen overnight. The mixture was concentrated in vacuo onto silica gel (4.5 g) then purified (silica gel 40 g, 0-10% MeOH:DCM) to afford 5-cyclopropyl-2-(9H-pyrido[2,3-b]indol-4-yl)-3H-pyrido[3,4-d]pyrimidin-4-one (0.230 g; Yield=46.4%). LCMS (ESI): 354 (M+H) + . 
     1253d) 5-Cyclopropyl-2-(9H-pyrido[2,3-b]indol-4-yl)-3H-pyrido[3,4-d]pyrimidin-4-one (18 mg, 0.051 mmol), 2,4,6-triisopropylbenzenesulfonyl chloride (17.5 mg, 0.0578 mmol), 4-dimethylaminopyridine (1.0 mg, 0.0082 mmol) and triethylamine (35.0 μL, 0.251 mmol) in N,N-dimethylformamide (1.00 mL) was stirred under an atmosphere of nitrogen at room temperature for 1 h, then a solution of piperazine (74.0 mg, 0.859 mmol) in N,N-dimethylformamide (1.0 mL) was added and stirring was continued for 3 h. The mixture was concentrated in vacuo and purified by preparative HPLC (0-45% acetonitrile:water, 0.1% trifluoracetic acid) to afford 4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-9H-pyrido[2,3-b]indole trifluoroacetic acid salt (10.0 mg; Yield=37%) as a yellow lyophilate. LCMS (ESI): 422 (M+H);  1 H-NMR (DMSO-d 6 , 400 MHz): δ 12.08 (s, 1H), 9.17 (s, 1H), 8.83 (br s, 1H), 8.68 (d, 1H, J=8.4 Hz), 8.59 (d, 1H, J=5.1 Hz), 8.26 (s, 1H), 7.89 (d, 1H, J=5.1 Hz), 7.55 (d, 1H, J=7.9 Hz), 7.49 (m, 1H), 7.18 (m, 1H), 3.68 (br s, 4H), 3.34 (br s, 4H), 2.77 (m, 1H), 1.30 (m, 2H), 1.14 (m, 2H). 
     Example 1254. 1-[5-cyclopropyl-2-(9H-pyrido[2,3-b]indol-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-ol trifluoroacetic acid salt 
     Analogous to Example 1253d, 5-cyclopropyl-2-(9H-pyrido[2,3-b]indol-4-yl)-3H-pyrido[3,4-d]pyrimidin-4-one (44.0 mg, 0.124 mmol) was reacted with piperidin-4-ol (34.0 mg, 0.336 mmol) to afford 1-[5-cyclopropyl-2-(9H-pyrido[2,3-b]indol-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-ol trifluoroacetic acid salt (32 mg; Yield=47%) as a yellow lyophilate. LCMS (ESI): 437 (M+H);  1 H-NMR (DMSO-d 6 , 400 MHz): δ 12.12 (s, 1H), 9.07 (s, 1H), 8.60 (d, 1H, J=5.0 Hz) 8.54 (d, 1H, J=8.1 Hz), 8.22 (s, 1H), 7.84 (d, 1H, J=5.0 Hz), 7.56 (d, 1H, J=8.0 Hz), 7.49 (m, 1H), 7.17 (m, 1H), 4.11 (m, 3H), 3.58 (br s, 2H), 2.61 (m, 1H), 1.89 (m, 2H), 1.55 (m, 2H), 1.92 (m, 2H), 1.21 (m, 2H). 
     Example 1255. 4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-9H-pyrido[2,3-b]indole trifluoroacetic acid salt 
     Analogous to Example 1253d, 5-cyclopropyl-2-(9H-pyrido[2,3-b]indol-4-yl)-3H-pyrido[3,4-d]pyrimidin-4-one (52.5 mg, 0.148 mmol) was reacted with 2,2-dimethylpiperazine (31.4 mg, 0.275 mmol) to afford 4-[5-cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-9H-pyrido[2,3-b]indole trifluoroacetic acid salt (17.5 mg; Yield=21%) as a yellow lyophilate. LCMS (ESI): 450 (M+H);  1 H-NMR (DMSO-d6, 400 MHz): δ 12.09 (s, 1H), 9.17 (s, 1H), 9.05 (br s, 2H), 8.67 (d, 1H, J=8.1 Hz), 8.60 (d, 1H, J=5.1 Hz), 8.29 (s, 1H), 7.93 (d, 1H, J=5.1 Hz) 7.55 (d, 1H, J=7.9 Hz), 7.49 (m, 1H), 7.18 (m, 1H), 3.93 (m, 4H), 3.39 (m, 2H), 2.61 (m, 1H), 1.01-1.48 (m, 10H). 
     The following compounds were synthesized according to the general syntheses shown in any of the Scheme(s) provided above using analogous procedures, starting materials and intermediates. 
     
       
         
           
               
               
               
               
               
            
               
                   
               
               
                   
                   
                   
                 Analysis 
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Ex 
                 Structure 
                 Scheme 
                 LCMS 
                   1 H-NMR 
                 Name 
               
               
                   
               
               
                 2001 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 3.66 min, MI: 442 [M + H] 
                 (400 MHz, d6-DMSO,  90° C.) 11.32 (1H, s), 9.03 (1H, s), 8.27 (1H, d, J = 5.1 Hz), 8.11 (1H, s), 8.04 (1H, d,  J = 5.1 Hz), 7.21 (1H, d, J = 2.2 Hz), 4.21-4.16 (2H, m), 3.23-3.16 (1H, m), 3.06- 3.01 (1H, m), 2.94-2.82 (3H, m), 2.74-7.66 (1H, m), 1.28-1.23 (2H, m), 1.07 (3H, d, J = 6.0 Hz), 1.02-0.98 (2H, m). 
                 2-(2-tert-Butyl-1H- pyrrolo[2,3-b]pyridin- 4-yl)- 5-cyclopropyl-4-((S)-3- methyl-piperazin-1-yl)- pyrido[3,4-d]pyrimidine 
               
               
                   
               
               
                 2002 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 3.75 min, MI: 456 [M + H] 
                 (400 MHz, d6-DMSO,  90° C.) 11.38 (1H, br s), 9.11 (1H, s), 8.30 (1H, d, J = 5.0 Hz), 8.21 (1H, s), 8.07 (1H, d, J = 5.0 Hz), 7.19 (1H, d,  J = 2.3 Hz) 3.97-3.94 (2H, m), 3.89 (2H, s), 3.35-3.32 (2H, m), 2.67-2.60 (1H, m), 1.31-1.26 (8 H, m), 1.05-1.00 (2H, m). 
                 2-(2-tert-Butyl-1H- pyrrolo[2,3-b]pyridin- 4-yl)- 5-cyclopropyl-4-(3,3- dimethyl-piperazin-1-yl)- pyrido[3,4-d]pyrimidine 
               
               
                   
               
               
                 2003 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 Method 5: RT: 3.05 min, MI: 495.42 [M + H] 
                 (500 MHz, DMSO) 9.06 (1H, s), 8.37 (1H, d), 8.17 (1H, s), 7.98 (1H, s), 7.82 (1H, s), 7.80 (1H, s), 7.76 (1H, dd), 7.38 (2H, d), 3.92 (4H, s, br), 3.32 (4H, s, br), 2.97 (6H, s), 2.70-2.66 (1H, m), 1.26-1.24 (2H, m),  1.08-1.07 (2H, m). 
                 4-[4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido [3,4-d]pyrimidin-2-yl)- pyridin-2- ylamino]-N,N-dimethyl- benzamide 
               
               
                   
               
               
                 2004 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 Method 5: RT: 2.74 min, MI: 493 [M + H] 
                 (DMSO, 500 MHz) 10.13 (1H, s), 9.07 (1H, s), 8.93 (2H, s), 8.48 (1H, s), 8.19 (1H, s), 8.02 (1H, s), 7.02 (1H, m), 4.34 (2H, m), 3.72 (1H, m), 3.48 (4H, m), 3.09 (1H, m), 1.25 (5H, m), 1.09 (2H, m). 
                 {4-[5-Cyclopropyl- 4-((S)-3- methyl-piperaizn-1-yl)- pyrido[3,4-d]pyrimidin-2- yl]-pyridin-2-yl}-(3,4,6- trifluoro-pyridin-2-yl)- amine 
               
               
                   
               
               
                 2005 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 90% RT: min, MI: 540.289 978 
                 (CDCl 3 ): 9.06 (s, 1H), 8.31 (br d, J = 4.4 Hz, 1H), 8.03 (br s, 2H), 7.76 (dd, J = 5.3; 1.3 Hz, 1H), 7.06 (app t, J = 2.0 Hz, 1H), 6.91 (br s, 2H), 6.65 (dd, J = 8.2; 2.0 Hz, 1H), 4.59-3.90 (br m, 4H), 3.89-3.84 (m, 4H), 3.84- 3.51 (br s, 2H), 3.22-3.16 (m, 4H), 2.62-2.51 (m, 1H), 1.90-1.50 (br m, 3H), 1.27- 1.21 (m, 2H), 0.99-0.95 (m, 2H) 
                 (+/−)-cis-1-{5- Cyclopropyl-2- [2-(3-morpholin-4-yl- phenylamino)-pyridin- 4-yl]- pyrido[3,4-d]pyrimidin-4- yl}-piperidine-3,4-diol 
               
               
                   
               
               
                 2006 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 92% RT: min, MI: 444.28 (M + H) 
                 (dmso-d6) 9.08 (br s, 2H), 8.83 (br s, 1H), 8.81 (s, 1H), 8.00 (s, 1H), 7.83 (br s, 1H), 7.77 (d, J = 6.7 Hz, 1H), 7.47 (dd, J = 6.7; 1.5 Hz, 1H), 5.98 (br s, exch. H&#39;s), 3.69 (br s, 4H), 3.26 (br s, 1H), 3.09 (br s, 2H), 2.25- 2.17 (m, 1H), 1.12 (br s, 2H), 1.05 (d, J = 6.4 Hz, 3H), 1.05-0.95 (m, 4H), 0.94-0.70 (m, 5H), 0.40- 0.35 (m, 3H), 0.05-(−0.03) (m, 1H). 
                 {4-[5-Cyclopropyl- 4-(3,3- dimethyl-piperazin-1-yl)- pyrido[3,4-d]pyrimidin-2- yl]-pyridin-2-yl}-((R)-1- cyclopropyl-ethyl)-amine 
               
               
                   
               
               
                 2007 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 94%, RT: min, MI: 480.28 (M + H) 
                 (dmso-d6) 9.39 (br s, 3H), 9.09 (s, 1H), 8.28 (s, 1H), 8.13 (d, J = 6.5 Hz, 1H), 8.10 (br s, 1H), 7.79 (d, J = 6.5 Hz, 1H), 7.51 (d, J = 7.4 Hz, 2H), 7.44 (app t, J = 7.4 Hz, 2H), 7.33 (app t, J = 7.4 Hz, 1H), 5.17 (br s, 1H), 4.20-3.80 (m, 4H), 3.38 (br s, 2H), 2.52-2.47 (m, 1H), 1.63 (d, J = 6.7 Hz, 3H), 1.60-1.00 (m, 10H) 
                 {4-[5-Cyclopropyl- 4-(3,3- dimethyl-piperazin-1-yl)- pyrido[3,4-d[pyrimidin- 2-yl]-pyridin-2-yl}- ((R)-1-phenyl- ethyl)-amine 
               
               
                   
               
               
                 2008 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 3.98 min, MI: 456.43 [M + H] 
                 (d6-DMSO, 400 MHz,  90° C.) 11.34 (1H, s), 9.11 (1H, s), 8.67 (1H, s), 8.28 (1H, d), 8.05 (1H, d), 7.20 (1H, s), 4.36 (1H, m), 3.98 (2H, m), 3.10 (1H, m), 3.02 (2H, m), 2.96 (2H, m), 2.54 (2H, s), 2.22 (2H, m), 2.17 (1H, m), 1.97 (1H, m), 1.47 (9H, s), 1.07 (3H, d). 
                 2-(2-tert-Butyl-1H- pyrrolo[2,3-b]pyridin- 4-yl)- 5-cyclobutyl-4-((S)-3- methyl-piperazin-1-yl)- pyrido[3,4-d]pyrimidine 
               
               
                   
               
               
                 2009 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 3.99 min, MI: 506 [M + H] 
                 (400 MHz, d6-DMSO,  90° C.) 11.18 (1H, br s), 8.90 (1H, s), 8.25 (1H, d, J = 5.1 Hz), 8.08 (1H, s), 8.04 (1H, d, J = 5.1 Hz), 7.61 (1H, dt, J = 7.7, 1.8 Hz), 7.43-7.38 (1H, m), 7.25 (1H, dt, J = 7.5, 1.2 Hz), 7.21-7.16 (1H, m), 6.88 (1H, s), 3.60- 3.57 (4H, m), 2.89-2.86 (4H, m), 2.68-2.64 (1H, m), 1.69-1.66 (2H, m), 1.40-1.37 (2H, m), 1.26- 1.21 (2H, m), 0.98-0.95 
                 5-Cyclopropyl-2-{2-[1- (2-fluoro-phenyl)- cyclopropyl]-1H- pyrrolo[2,3-b]pyridin-4- yl}-4-piperazin-1-yl- pyrido[3,4-d]pyrimidine 
               
               
                   
                   
                   
                   
                 (2H, m). 
                   
               
               
                   
               
               
                 2010 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 3.90 min, MI: 442.48 [M + H] 
                 (d6-DMSO,  500 MHz) 11.71 (1H, s), 9.07 (1H, s), 8.65 (1H, s), 8.26 (1H, d), 8.04 (1H, d), 7.17 (1H, s), 4.24 (1H, m), 3.84 (1H, m), 3.56 (1H, m), 3.38 (1H, m), 3.36 (1H, m), 2.94 (2H, s), 2.41 (2H, m), 2.15 (2H, m), 2.12 (1H, m), 2.04 (1H, m), 1.41 (9H, s), 1.10 (3H, s), 0.75 (3H, s). 
                 2-(2-tert-Butyl-1H- pyrrolo[2,3-b]pyridin- 4-yl)-5-cyclobutyl- 4-piperazin-1-yl- pyrido[3,4-d]pyrimidine 
               
               
                   
               
               
                 2011 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 97%, RT: min, MI: 475.19 (MH)+, 
                 (400 MHz, d6-DMSO, δ): 10.45 (s, 1H), 9.15 (s, 1H), 8.90-8.75 (m, 3H), 8.62 (s, 1H), 8.47 (d, J = 5.3 Hz,  1H), 7.92 (dd, J = 5.2,  1.3 Hz, 1H), 7.80 (dd, J = 11.2, 1.6 Hz, 1H), 6.69 (dt, J = 8.5, 1.6 Hz, 1H), 4.25 (pent, J = 8.8 Hz, 1H), 3.89-3.84 (m, 4H), 3.40-3.17 (m, 4H), 2.52- 2.42 (m, 2H), 2.28-2.03 (m, 3H), 1.97-1.87 (m, 1H). 
                 [4-(5-Cyclobutyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidin- 2-yl)-pyridin-2-yl]- (4,6-difluoro-pyridin-2- yl)-amine 
               
               
                   
               
               
                 2012 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 96%, RT: min, MI: 505.25 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 10.63 (br s, 1H), 9.15 (s, 1H), 9.12 (s, 1H), 8.89 (br s, 2H), 8.68 (s, 1H), 8.45 (d, J = 5.8 Hz, 1H),  8.21 (s, 1H), 7.94 (dd, J = 5.4, 1.3 Hz,  1H), 7.60 (d, J = 9.0 Hz,  1H), 7.42 (dd, J = 9.2, 1.7 Hz, 1H), 3.96 (br s, 4H), 3.36 (br s, 4H), 2.76-2.68 (m, 1H), 2.12- 2.05 (m, 1H), 1.30-1.24 (m, 2H), 1.12-1.07 (m ,2H), 1.04-0.98 (m, 2H), 0.85- 0.80 (m, 2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d] pyrimidin-2-yl)-pyridin- 2-yl]-(6-cyclopropyl- [1,2,4]triazolo[1,5-a] pyridin-2-yl)-amine 
               
               
                   
               
               
                 2013 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 97%, RT: min, MI: 497.24 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 10.26 (br s, 1H), 9.10 (s, 1H), 8.90 (br s, 2H), 8.83  (s, 1H), 8.44 (d, J =  5.7 Hz, 1H), 8.22 (s, 1H), 8.07 (d, J = 1.5 Hz, 1H), 8.01 (d, J = 5.6 Hz, 1H), 7.83 (d, J = 11.2 Hz, 1H), 3.94 (br s, 4H), 3.61 (pent, J = 8.7 Hz, 1H), 3.34 (br s, 4H), 2.72-2.65 (m, 1H), 2.37-2.28 (m, 2H), 2.22-2.11 (m, 2H), 2.08- 1.95 (m, 1H), 1.91-1.82 (m, 1H), 1.30-1.24 (m, 2H), 1.12-1.07 (m, 2H). 
                 (5-Cyclobutyl-3-fluoro- pyridin-2-yl)-[4-(5- cyclopropyl-4-piperazin- 1-yl-pyrido[3,4-d] pyrimidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
               
               
                 2014 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 507 (M + H) 
                 1H-NMR DMSO 9.69 (br s, 1H), 8.93 (s, 1H), 8.60 (s, 1H), 8.40 (m, 1H), 8.27 (m, 1H), 8.12 (s, 1H), 7.91 (m, 1H), 4.62 (br m, 1H), 3.13 (s, 3H), 3.08 (m, 2H), 2.66 (m, 2H), 2.43 (m, 1H), 1.79 (br m, 4H), 1.22 (m, 3H), 0.96 (m, 2H) 
                 {5-Cyclopropyl-2-[2- (3,5,6-trifluoro- pyridin-2-ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}- methyl-piperidin-4- yl-amine 
               
               
                   
               
               
                 2015 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 476.21 (M + H) 
                 (dmso-d6) 9.91 (br s, 1H), 9.13 (br s, 1H), 9.10 (s, 2H), 8.38-8.32 (m, 2H), 8.24 (s, 1H), 8.15 (s, 1H), 7.90 (dd, J = 5.8; 1.1 Hz, 1H), 5.25 (br s, exch. H&#39;s), 4.19 (q, J = 7.2 Hz, 2H), 3.96 (br s, 4H), 3.67 (br s, 4H), 2.90-2.60 (m, 1H), 1.47 (t, J = 7.2 Hz, 3H), 1.34-1.25 (m, 2H), 1.41-1.08 (m, 2H) 
                 (4-Chloro-1-ethyl-1H- pyrazol-3-yl)-[4-(5- cyclopropyl-4- piperazin-1-yl-pyrido [3,4-d]pyrimidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
               
               
                 2016 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 96%, RT: min, MI: 496.20 (M + H) 
                 (dmso-d6) 10.68 (br s, 1H), 9.09 (br s, 3H), 8.44 (s, 1H), 8.38 (d, J = 5.8 Hz, 1H), 8.22 (s, 1H), 7.87 (d, J = 5.5 Hz, 2H), 6.50 (d, J = 2.4 Hz, 1H), 5.86 (br s, exch. H&#39;s), 5.12 (q, J (CH2—CF3) =  9.0 Hz, 2H), 3.96 (br s, 4H), 3.35 (br s, 4H), 2.73-2.65 (m, 1H), 1.32-1.23 (m, 2H), 1.14-1.06 (m, 2H) 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido [3,4-d]pyrimidin- 2-yl)-pyridin-2-yl]- [1-(2,2,2-trifluoro-ethyl)- 1H-pyrazol-3-yl]-amine 
               
               
                   
               
               
                 2017 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 524.24 (M + H) 
                 (dmso-d6) 10.79 (br s, 1H), 9.32 (br s, 2H), 9.10 (s, 1H), 8.42-8.36 (m, 2H), 8.26 (s, 1H), 7.93-7.87 (m, 2H), 6.58 (d, J = 2.3 Hz, 1H), 5.56 (br s, exch. H&#39;s), 5.14 (q, J(CH2CF3) = 9.0 Hz, 2H), 3.99 (br s, 4H), 3.38 (br s, 2H), 2.58-2.50 (m, overlapping solvent signal, 1H), 1.70-1.00 (m, 10H) 
                 {4-[5-Cyclopropyl- 4-(3,3- dimethyl-piperazin-1-yl)- pyrido[3,4-d]pyrimidin-2- yl]-pyridin-2-yl}- [1-(2,2,2-trifluoro- ethyl)-1H-pyrazol- 3-yl]-amine 
               
               
                   
               
               
                 2018 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 97%, RT: min, MI: 484.28 (M + H) 
                 (dmso-d6) 11.37 (br s, 1H), 9.34 (br s, 2H), 9.10 (s, 1H), 8.44 (d, J = 6.3 Hz, 1H), 8.42 (s, 1H), 8.28 (s, 1H), 7.97 (d, J = 6.3 Hz, 1H), 7.88 (d, J = 2.2 Hz, 1H), 6.32 (d, J = 2.3 Hz, 1H), 4.94 (br s, exch. H&#39;s), 4.59 (hept, J = 6.6 Hz, 1H), 3.99 (br s, 4H), 3.38 (br s, 2H), 2.55-2.48 (m, partially overlaped by solvent peak, 1H), 1.53 (d, J = 6.6 Hz, 6H), 1.52-1.00 (m, 10H) 
                 {4-[5-Cyclopropyl- 4-(3,3- dimethyl-piperazin-1-yl)- pyrido[3,4-d]pyrimidin- 2-yl]-pyridin- 2-yl}-(1-isopropyl- 1H-pyrazol-3-yl)-amine 
               
               
                   
               
               
                 2019 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity 92%, RT: min, MI: 507 (M + H) 
                 1H-NMR: DMSO 10.03 (br s, 1H), 8.93 (s, 1H), 8.73 (s, 1H), 8.45 (m, 1H), 8.12 (s, 1H), 7.97 (m, 1H), 7.01 (m, 1H), 4.59 (br m, 1H), 3.12 (s, 3H), 3.00 (m, 2H), 2.67 (m, 2H), 2.42 (m, 1H), 1.72 (br m, 4H), 1.23 (m, 3H), 0.96 (m, 2H) 
                 {5-Cyclopropyl-2-[2- (3,4,6-trifluoro-pyridin-2- ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-methyl- piperidin-4-yl-amine 
               
               
                   
               
               
                 2020 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 479 (M + H): 
                 1H-NMR: DMSO 9.66 (br s, 1H), 9.02 (s, 1H), 8.75 (s, 1H), 8.45 (s, 1H), 8.39 (m, 1H), 8.26 (m, 1H), 7.95 (m, 2H), 4.85 (m, 1H), 3.20 (m, 1H), 3.04 (m, 1H), 2.95 (m, 1H), 2.87 (m, 1H), 2.56 (m, 1H), 2.26 (m, 1H), 1.85 (m, 1H), 1.19 (m, 3H), 1.08 (m, 2H) 
                 {5-Cyclopropyl-2-[2- (3,5,6-trifluoro-pyridin-2- ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}- pyrrolidin-3-yl-amine 
               
               
                   
               
               
                 2021 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 479 (M + H) 
                 1H-NMR: DMSO 10.07 (s, 1H), 9.08 (s, 1H), 9.03 (br s, 1H), 8.95 (br s, 1H), 8.82 (s, 1H), 8.48 (m, 2H), 8.03 (m, 1H), 7.89 (m, 1H), 7.00 (m, 1H), 5.03 (m, 1H), 3.69 (m, 1H), 3.48 (m, 2H), 3.34 (m, 1H), 2.62 (m, 1H), 2.52 (m, 2H), 2.26 (m, 1H), 1.22 (m, 2H), 1.07 (m, 2H) 
                 {5-Cyclopropyl-2- [2-(3,4,6-trifluoro- pyridin-2-ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}- pyrrolidin-3-yl-amine 
               
               
                   
               
               
                 2022 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 479.25 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 10.50 (br s, 1H), 9.22 (s, 1H), 9.18 (s, 1H), 8.95-8.75 (m, 4H), 8.44 (d, J = 5.3 Hz, 1H), 7.91 (dd, J = 5.4, 1.4  Hz, 1H), 7.71-7.63 (m, 2H), 7.14 (dt, J = 6.5,  2.0 Hz, 1H), 4.32-4.23 (m, 1H), 3.87 (br s, 4H), 3.41-3.23 (m, 4H), 2.51-2.43 (m, 2H), 2.29- 2.05 (m, 3H), 1.98-1.88 (m, 1H). 
                 [4-(5-Cyclobutyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)-pyridin- 2-yl]-[1,2,4]triazolo[1,5- a]pyridin-2-yl-amine  
               
               
                   
               
               
                 2023 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 93%, RT: min, MI: 509.3 (M + H) 
                 (dmso-d6) 9.93 (br s, 1H), 9.50-8.5 (broad signal - in the noise), 9.12 (br s, 1H), 9.11 (s, 1H), 8.29 (d, J = 5.8 Hz, 1H), 8.24 (s, 1H), 8.09 (s, 1H), 7.80 (dd, J = 5.8; 1.3 Hz, 1H), 7.33 (br s, 1H), 7.28 (qpp t, J = 8.1 Hz, 1H), 7.15 (d, J = 8.1 Hz, 1H), 6.75 (d, J = 8.1 Hz, 1H), 3.97 (br s, 4H), 3.82-3.78 (m, 4H), 3.37 (br s, 4H), 3.21-3.16 (m, 4H), 2.75- 2.68 (m, 1H), 1.33-1.26 (m, 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)-pyridin- 2-yl]-(3-morpholin-4-yl- phenyl)-amine 
               
               
                   
                   
                   
                   
                 2H), 1.16-1.10 (m, 2H) 
                   
               
               
                   
               
               
                 2024 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 3.93 min, MI: 455.38 [M + H] 
                 (500 MHz, DMSO) 13.20 (1H, s), 8.99 (1H, s, br), 8.88 (1H, s, br), 8.81 (1H, s), 8.69 (1H, d), 8.25 (1H, d), 7.95 (1H, s), 4.30-4.24 (1H, 3.86-3.81 (4H, m), 3.35-3.29 (4H, m),  2.50.2.45 (2H, m), 2.26-2.08 (3H, m), 1.96-1.90 (1H, m). 
                 5-Cyclobutyl-4- piperazin-1-yl-2- (2-trifluoromethyl-1H- pyrrolo[2,3-b]pyridin-4- yl)-pyrido[3,4-d] pyrimidine 
               
               
                   
               
               
                 2025 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 474 (M + H) 
                 1H-NMR: DMSO 9.02 (s, 1H), 8.93 (br m, 2H), 8.89 (s, 1H), 8.21 (m, 2H), 7.84 (s, 1H), 7.71 (m, 1H), 7.29 (m, 1H), 7.16 (m, 2H), 5.13 (br m, 1H), 3.79 (m, 1H), 3.45 (m, 1H), 3.29 (br m, 2H), 3.12 (s, 3H), 2.54 (m, 1H), 2.40 (m, 1H), 2.25 (br m, 1H), 1.26 (br m, 2H), 1.01 (m, 2H) 
                 {5-Cyclopropyl-2-[2-(2,6- difluoro-phenylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-methyl- pyrrolidin-3-yl-amine 
               
               
                   
               
               
                 2026 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 446 (M + H) 
                 1H-NMR: DMSO 9.07 (s, 1H), 8.90 (br s, 3H),  8.51 (s, 1H), 8.25 (d, 1H, J = 4.6 Hz), 8.17 (d, 1H, J = 5.6 Hz), 7.78 (s, 1H), 7.66 (m, 1H), 7.30 (m, 1H), 7.18 (m, 2H), 5.11 (m, 1H), 4.44 (m, 2H), 4.25 (m, 2H), 2.64 (m, 1H), 2.54 (m, 1H), 1.27 (m, 2H), 1.05 (m, 2H) 
                 Azetidin-3-yl-{5- cyclopropyl-2-[2-(2,6- difluoro-phenylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-amine 
               
               
                   
               
               
                 2027 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D3] 
                 LCMS: Purity: 95%, RT: min, MI: 458 (M + H)+ 
                 1H-NMR (DMSO-d6, 400 MHz): 9.05 (s, 1H),  8.85 (br s, 2H), 8.69 (d, 1H, J = 4.1 Hz), 8.24 (s, 1H), 7.53 (d, 1H, J = 4.9 Hz), 7.34 (m, 1H), 6.78 (m, 1H), 3.73 (m, 4H), 3.25 (m, 4H), 2.77 (m, 1H), 1.29 (m, 2H), 1.14 (m, 2H) 
                 4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)-5,8- difluoro-9H-pyrido[2,3- b]indole 
               
               
                   
               
               
                 2028 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 4.03 min, MI: 470.45 [M + H] 
                 (d6-DMSO,  500 MHz) 11.71 (1H, s), 9.07 (1H, s), 8.65 (1H, s), 8.26 (1H, d), 8.04 (1H, d), 7.17 (1H, s), 4.24 (1H, m), 3.84 (1H, m), 3.56 (1H, m), 3.38 (1H, m), 3.36 (1H, m), 2.94 (2H, s), 2.41 (2H, m), 2.15 (2H, m), 2.12 (1H, m), 2.04 (1H, m), 1.41 (9H, s), 1.10 (3H, s), 0.75 (3H, s). 
                 2-(2-tert-Butyl-1H- pyrrolo[2,3-b]pyridin-4- yl)-5-cyclobutyl-4-(3,3- dimethyl-piperazin-1-yl)- pyrido[3,4-d]pyrimidine 
               
               
                   
               
               
                 2029 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;90%, RT: min, MI: 460 (M + H) 
                 (d6-DMSO) 9.04 (s, 1H), 8.88 (s, 1H), 8.85 (br s,  2H), 8.24 (s, 1H),  8.19 (d, 1H, J = 5.3 Hz), 7.73 (s, 1H), 7.61 (m, 1H), 7.29 (m, 1H), 7.18 (m, 2H), 4.74 (m, 1H),  4.24-4.35 (br m, 4H), 3.11 (s, 3H), 2.70 (m, 1H), 1.30 (br m, 2H), 1.07 (m, 2H) 
                 Azetidin-3-yl-{5- cyclopropyl-2-[2-(2,6- difluoro-phenylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-methyl- amine 
               
               
                   
               
               
                 2030 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 96%, RT: min, MI: 530.15 (M + H) 
                 (dmso-d6) 9.36 (br s, 1H), 9.09 (s, 1H), 9.02 (br s, 2H), 8.35 (d, J = 5.4 Hz, 1H), 8.27 (s, 1H), 8.22 (s, 1H), 8.20 (s, 1H), 7.85 (d, J = 5.4 Hz, 1H), 5.16 (q, J(H, F) = 9.0 Hz, 2H), 3.94 (br s, 4H), 3.36 (br s, 4H), 2.77-2.66 (m, 1H), 1.33-1.25 (m ,2H), 1.15-1.07 (m, 2H) 
                 [4-Chloro-1-(2,2,2- trifluoro-ethyl)-1H- pyrazol-3-yl]-[4-(5- cyclopropyl-4-piperazin- 1-yl-pyrido[3,4-d] pyrimidin-2-yl)-pyridin- 2-yl]-amine 
               
               
                   
               
               
                 2031 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D3] 
                 LCMS: Purity: 95%, RT: min, MI: 440 (M + H)+ 
                 1H-NMR (DMSO-d6, 400 MHz): 12.60 (s, 1H), 9.18 (s, 1H), 8.88 (br s, 2H), 8.66 (d, 1H, J = 5.1 Hz), 8.53 (d, 1H, J = 8.1 Hz), 8.27 (s, 1H), 7.95 (d, 1H, J = 5.1 Hz), 7.38 (m, 1H), 7.16 (ddd, 1H, J = 5.1, 8.1, 8.1 Hz), 3.92 (br s, 4H), 3.34 (br s, 4H), 2.76 (m, 1H), 1.30 (m, 2H), 1.14 (m, 2H) 
                 4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)- 8-fluoro-9H-pyrido [2,3-b]indole 
               
               
                   
               
               
                 2032 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 99%, RT: min, MI: 483.21 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 10.62 (s, 1H), 9.27 (s, 1H), 9.13 (s, 1H), 8.90 (br s, 2H), 8.76 (dd, J = 6.7,  0.7 Hz, 1H), 8.46 (dd, J = 5.2, 0.4 Hz, 1H), 8.20 (s, 1H), 7.94 (dd, J = 5.2, 1.4 Hz, 1H), 7.65- 7.59 (m, 1H), 7.14-7.08 (m, 1H), 3.97 (br s, 4H), 3.36 (br s, 4H), 2.75-2.68 (m, 1H), 1.30-1.24 (m, 2H), 1.12-1.07 (m, 2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(8-fluoro- [1,2,4]triazolo[1,5-a] pyridin-2-yl)-amine 
               
               
                   
               
               
                 2033 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 98%, RT: min, MI: 483.19 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 10.50 (s, 1H), 9.17 (s, 1H), 9.15 (s, 1H), 8.93 (dd, J = 7.4, 5.5 Hz, 1H), 8.87 (br s, 2H), 8.45 (dd, J = 5.2, 0.5 Hz, 1H), 8.21 (s, 1H), 7.92 (dd, J = 5.3, 1.4 Hz, 1H),  7.60 (dd, J = 9.4, 2.7 Hz, 1H), 7.15 (dt, J = 7.6, 2.8 Hz, 1H), 3.95 (br s, 4H), 3.36 (br s, 4H), 2.75-2.69 (m, 1H), 1.30- 1.24 (m, 2H), 1.12-1.07 (m, 2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)-pyridin- 2-yl]-(7-fluoro- [1,2,4]triazolo[1,5-a] pyridin-2-yl)-amine 
               
               
                   
               
               
                 2034 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 460 (M + H) 
                 1H-NMR: DMSO 9.07 (s, 1H), 9.00 (br s, 2H), 8.90 (s, 1H), 8.50 (s, 1H), 8.19 (d, 1H, J = 4.9 Hz), 7.85 (m, 2H), 7.72 (m, 1H), 7.32 (m, 1H), 7.18 (m, 2H), 4.98 (m, 1H), 3.70 (m, 1H), 3.45 (m, 2H), 3.37 (m, 1H), 2.62 (m, 1H), 2.45 (m, 1H), 2.24 (m, 1H), 1.21 (m, 2H), 1.06 (m, 2H) 
                 {5-Cyclopropyl-2-[2-(2,6- difluoro-phenylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-(S)- pyrrolidin-3-yl-amine 
               
               
                   
               
               
                 2035 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 460 (M + H) 
                 1H-NMR: DMSO 9.07 (s, 1H), 9.01 (br m, 2H), 8.94 (s, 1H), 8.50 (s, 1H), 8.18 (d, 1H, J = 5.2 Hz), 7.85 (m, 2H), 7.73 (m, 1H), 7.30 (m, 1H), 7.19 (m, 2H), 4.97 (m, 1H), 3.70 (m, 1H), 3.44 (m, 3H), 2.61 (m, 1H), 2.47 (m, 1), 2.24 (m, 1H), 1.21 (m, 2H), 1.06 (m, 2H) 
                 {5-Cyclopropyl-2-[2-(2,6- difluoro-phenylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl]-(R)- pyrrolidin-3-yl-amine 
               
               
                   
               
               
                 2036 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D3] 
                 LCMS: Purity: 95%, RT: min, MI: 458 (M + H)+ 
                 1H-NMR (DMSO-d6, 400 MHz): 12.84 (s, 1H), 9.20 (s, 1H), 8.87 (br s, 2H), 8.70 (dd, 1H, J = 4.4, 8.8 Hz), 8.65 (d, 1H, J = 5.1 Hz), 8.26 (s, 1H), 8.01 (d, 1H,  J = 5.1 Hz), 7.23 (m, 1H), 3.90 (m, 4H), 3.34 (m, 4H), 2.75 (m, 1H), 1.29 (m, 2H), 1.13 (m, 2H) 
                 4-(5-Cyclopropyl-4- piperaizn-1-yl-pyrido[3,4- d]pyrimidin-2-yl)-7,8- difluoro-9H-pyrido[2,3- b]indole 
               
               
                   
               
               
                 2037 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 Method 5: RT: 2.76 min, MI: 507 [M + H] 
                 (DMSO, 500 MHz) 10.02 (1H, s), 8.98 (1H, s), 8.89 (1H, m), 8.45 (1H, d), 8.10 (1H, s), 7.98 (1H, s), 7.01 (1H, m), 4.09 (2H, m), 3.04 (2H, m), 2.69 (1H, m), 1.22 (4H, m), 1.06 (6H, m), unidentified 2 × CH  protons. Peaks are too broad. 
                 {4-[5-Cyclopropyl- 4-((cis)-3,5-dimethyl- piperazin-1-yl)-pyrido [3,4-d]pyrimidin-2-yl]- pyridin-2-yl}-(3,4,6- trifluoro-pyridin-2-yl)- amine 
               
               
                   
               
               
                 2038 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 97%, RT: 2.76 min, MI: 507 (MH)+ 
                 1H-NMR: DMSO 9.04 (s, 1H), 8.81 (br s, 2H), 8.54 (m, 1H), 8.48 (s, 1H), 8.18 (d, 1H, J = 5.2 Hz), 7.78 (s, 1H), 7.72 (m, 2H), 7.29 (m, 1H), 7.18 (m, 2H), 4.71 (m, 1H), 3.35 (m, 2H), 2.62 (m, 1H), 2.32 (m, 1H), 2.23 (m, 1H), 1.72 (m, 2H), 1.48 (s, 3H), 1.39 (s, 3H), 1.16 (m, 2H), 1.05 (m, 2H) 
                 {5-Cyclopropyl-2-[2-(2,6- difluoro-phenylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-(2,2- dimethyl-piperidin-4-yl)- amine 
               
               
                   
               
               
                 2039 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 97%, RT: 2.76 min, MI: 507 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 10.51 (br s, 1H), 9.23-9.20 (m, 1H), 9.18 (s, 1H), 9.16 (s, 1H), 8.86 (br s, 2H), 8.45 (d, J = 5.2 Hz, 1H), 8.21 (s, 1H), 7.92 (d, J = 5.2 Hz,  1H), 7.80-7.70 (m, 2H), 3.96 (br s, 4H), 3.36 (br s, 4H), 2.76- 2.67 (m, 1H), 1.30-1.24 (m, 2H), 1.12-1.07 (m, 2H). 
                 [4-(5-Cyclopropyl--4 piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)-pyridin- 2-yl]-(6-fluoro- [1,2,4]triazolo[1,5-a] pyridin-2-yl)-amine 
               
               
                   
               
               
                 2040 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 97%, RT: 2.76 min, MI: 507 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 10.61 (s, 1H), 9.24 (s, 1H), 9.20-9.17 (m, 1H), 9.14 (s, 1H), 8.87 (br s, 2H), 8.46 (dd, J = 5.1, 0.6 Hz,  1H), 8.20 (s, 1H), 8.04-7.97 (m, 1H), 7.93 (dd, J = 5.2, 1.4 Hz, 1H), 3.96 (br s, 4H), 3.35 (br s, 4H), 2.75-2.67 (m, 1H), 1.30-1.24 (m, 2H), 1.12- 1.07 (m, 2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)-pyridin- 2-yl]-6,8-difluoro- [1,2,4]triazolo[1,5-a] pyridin-2-yl)-amine 
               
               
                   
               
               
                 2041 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 97%, RT: 2.76 min, MI: 507 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 10.61 (s, 1H), 9.31 (s, 1H), 9.10 (s, 1H), 8.90 (br s, 2H), 8.46 (d, J = 5.3 Hz, 1H),  8.20 (s, 1H), 7.95 (dd, J = 5.2, 1.3 Hz, 1H), 7.77-7.70 (m, 1H), 7.56 (dd, J = 8.8,  0.6 Hz, 1H), 7.10-7.05 (m ,1H), 3.97 (br s, 4H), 3.36 (br s, 4H),  2.76-2.67 (m, 1H), 1.30-1.24 (m, 2H), 1.12-1.07 (m, 2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)-pyridin- 2-yl]-(5-fluoro- [1,2,4]triazolo[1,5-a] pyridin-2-yl)-amine 
               
               
                   
               
               
                 2042 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 97%, RT: 2.76 min, MI: 507 (MH)+ 
                 (dmso-d6) 9.17 (s, 1H), 9.10 (br s, 3H), 8.86 (s, 1H), 8.12 (d, J = 6.3 Hz, 1H), 7.99 (br s, 1H), 7.69 (d, J = 6.3 Hz, 1H), 7.50 (app d, J = 7.3 Hz, 2H), 7.42 (app t, J = 7.3 Hz, 2H), 7.32 (app t, J = 7.3 Hz, 1H), 5.17-5.12 (m, 1H), 4.32-4.20 (m, 1H), 3.90- 3.78 (m, 4H), 3.38 (br s, 2H), 3.26 (br s, 2H), 2.51- 2.44 (m, 2H), 2.35-2.05 (m, 3H), 2.00-1.92 (m, 1H), 1.60 (d, J = 6.8 Hz, 3H) 
                 [4-(5-Cyclobutyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-((R)-1- phenyl-ethyl)-amine 
               
               
                   
               
               
                 2043 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 97%, RT: 2.76 min, MI: 507 (MH)+ 
                 (dmso-d6) 9.83 (br s, 1H), 9.26 (br s, 2H), 9.08 (s, 1H), 8.34 (d, J = 5.8 Hz, 1H), 8.26 (s, 1H), 8.23 (br s, 1H), 8.15 (s, 1H), 7.90 (d, J = 5.8 Hz, 1H), 4.18 (q, J = 7.2 Hz, 2H), 3.96 (br s, 4H), 3.38 (br s, 2H), 2.58-2.49 (m, overlapped w/ solvent signals, 1H), 1.47 (t, J = 7.2 Hz, 3H), 1.49-1.06 (m, 10H) 
                 (4-Chloro-1-ethyl-1H- pyrazol-3-yl)-{4-[5- cyclopropyl-4-(3,3- dimethyl-piperazin- 1-yl)-pyrido[3,4- d]pyrimidin-2-yl]-pyridin- 2-yl}-amine 
               
               
                   
               
               
                 2044 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 97%, RT: 2.76 min, MI: 507 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 11.50 (br s, 1H), 9.38 (s, 1H), 9.14 (s, 1H), 8.87 (br s, 2H), 8.53 (d, J = 5.3 Hz,  1H), 8.21 (s, 1H), 8.03 (dd, J = 5.2, 1.4 Hz, 1H), 7.59- 7.55 (m, 2H), 7.30 (dt, J = 7.6, 1.1 Hz, 1H),  7.21 (dt, J = 7.8, 1.1 Hz, 1H), 3.98 (br s, 4H), 3.38 (br s, 4H), 2.76- 2.68 (m ,1H), 1.30-1.24 (m, 2H), 1.12-1.07 (m, 2H). 
                 Benzooxazol-2-yl-[4-(5- cyclopropyl-4-piperazin- 1-yl-pyrido [3,4-d]pyrimidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
               
               
                 2045 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 97%, RT: 2.76 min, MI: 507 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 11.75 (br s, 1H), 9.10 (s, 1H), 8.86 (br s, 2H),  8.55 (d, J = 5.8 Hz, 1H), 8.31 (s, 1H), 8.20 (s, 1H), 7.97 (dd, J = 5.3, 1.4 Hz, 1H), 7.92  (d, J = 7.5 Hz, 1H), 7.66 (d, J = 8.1 Hz, 1H), 7.42-7.37 (m, 1H), 7.25-7.20 (m, 1H), 3.95 (br s, 4H), 3.34 (br s, 4H), 2.73-2.65 (m, 1H), 1.29-1.24 (m, 2H), 1.12- 1.06 (m, 2H). 
                 Benzothiazol-2-yl-[4-(5- cyclopropyl-4-piperazin- 1-yl-pyrido [3,4-d][primidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
               
               
                 2046 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 97%, RT: 2.76 min, MI: 507 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 13.68 (br s, 1H),  11.71 (br s, 1 H), 9.10 (s, 1H), 8.93 (br s, 2H), 8.75-8.62 (m, 1H), 8.60-8.45 (m, 1H), 8.27- 8.20 (m, 2H), 7.85-7.65 (m, 2H), 4.15-3.80 (m, 7H), 3.35 (m ,4H), 2.73-2.65 (m, 1H), 1.30-1.24 (m ,2H), 1.13-1.07 (m, 2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)-pyridin- 2-yl]-(1-methyl-1H- benzoimidazol-2-yl)- amine 
               
               
                   
               
               
                 2047 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 Method 5: RT: 2.77 min, MI: 501 [M + H] 
                 (DMSO, 400 MHz, 90° C.) 8.98 (1H, s), 8.85 (1H, s), 8.38 (1H, d), 8.13 (1H, s), 7.91 (1H, dd), 7.46 (1H, m), 3.77 (4H, t), 2.91 (4H, t), 2.66 (1H, m), 1.96 (1H, m), 1.27 (2H, m), 0.98 (4H, m), 0.79 (2H, m). 
                 (5-Cyclopropyl-3,6- difluoro-pyridin-2-yl)- [4-(5-cyclopropyl- 4-piperazin-1-yl-pyrido [3,4-d]pyrimidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
               
               
                 2048 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 3.03 min, MI: 506 [M + H] 
                 (400 MHz, d6-DMSO,  90° C.) 11.30 (1H, s), 8.96 (1H, s), 8.27 (1H, d, J = 5.0 Hz), 8.09 (1H, s), 8.05 (1H, d,  J = 5.0 Hz), 7.50-7.46 (2H, m), 7.17-7.13 (2H, m), 7.00 (1H, s), 3.62 (4H, m), 2.88-2.85 (4H, m), 2.70- 2.67 (1H, m), 1.60-1.57 (2H, m), 1.39-1.36 (2H, m), 1.28-1.23 (2H, m), 1.00-0.96 (2H, m). 
                 5-Cyclopropyl-2- {2-[1-(4-fluoro-phenyl)- cyclopropyl]-1H-pyrrolo [2,3-b]pyridin-4- yl}-4-piperazin-1-yl- pyrido[3,4-d]pyimidine 
               
               
                   
               
               
                 2049 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 Method 5: RT: 1.68 min, MI: 527 [M + H] 
                 (DMSO, 500 MHz) 8.95 (1H, s), 8.11 (1H, d), 8.08 (1H, s), 7.52 (1H, s), 7.40 (1H, d), 6.72 (1H, d), 4.17 (2H, s), 3.76 (1H, m), 3.32 (2H, s), 3.16 (3H, m), 2.91 (3H, m), 2.86 (2H, m), 2.46 (1H, m), 1.90 (2H, m), 1.48 (2H, m), 1.23 (2H, m), 1.10 (2H, m), 1.08 (4H, m). 
                 {4-[5-Cyclopropyl- 4-((S)-3-methyl- piperazin-1-yl)-pyrido [3,4-d]pyrimidin-2-yl]- pyridin-2-yl}-[1-(2,2,2- trifluoro-ethyl)-piperidin- 4-yl]-amine 
               
               
                   
               
               
                 2050 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 100%, RT: 1.68 min, MI: 527  (MH)+ 
                 (400 MHz, D6-DMSO, δ): 9.67 (s, 1H), 9.08 (s, 1H), 8.88 (br s, 2H), 8.53 (d, J = 1.6 Hz, 1H), 8.44 (d, J = 5.3 Hz, 1H), 8.19 (s,  1H), 8.05 (s, 1H), 7.86-7.76 (m, 4H), 7.67 (dd, J = 8.9, 2.1 Hz, 1H), 7.47-7.42 (m, 1H), 7.36-7.31 (m, 1H), 3.93 (br s, 4H), 3.34 (br s,  4H), 2.74-2.66 (m, 1H), 1.29-1.23 (m, 2H), 1.12-1.06 (m ,2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)-pyridin- 2-yl]-naphthalen-2-yl- amine 
               
               
                   
               
               
                 2051 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 100%:, RT: 1.68 min, MI: 527  (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.52 (s, 1H), 9.07 (s, 1H), 8.86 (br s, 2H), 8.37 (d, J = 5.4 Hz, 1H),  8.19 (s, 1H), 8.06 (t, J = 1.8 Hz, 1H), 8.00 (s, 1H), 7.78-7.73 (m, 2H), 7.67-7.64 (m, 2H), 7.52- 7.47 (m, 2H), 7.42-7.36 (m, 2H), 7.22 (d, J = 7.9 Hz,  1H), 3.94 (br s, 4H), 3.32  (br s, 4H), 2.73-2.65 (m,  1H), 1.29-1.23 (m, 2H),  1.11-1.06 (m, 2H). 
                 Biphenyl-3-yl-[4-(5- cyclopropyl-4- piperazin-1-yl-pyrido [3,4-d]pyrimidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
               
               
                 2052 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 100%, RT: 1.68 min, MI: 527  (MH)+ 
                 (dmso-d6) 9.86 (br s, 1H), 9.57 (br s, 1H), 9.08 (s, 1H), 8.33 (d, J = 5.5 Hz, 1H), 8.20 (s, 1H), 7.97 (s, 1H), 7.72 (br d, J = 5.0 Hz, 1H), 7.44 (s, 1H), 7.24-7.21 (m, 2H), 6.70-6.66 (m, 1H), 5.25 (br signal, exchangeable protons), 4.80-4.20 (m, 2H), 4.20- 3.90 (m, 2H), 3.85-3.79 (m, 2H), 3.59-3.54 (m, 2H), 3.40-3.10 (m, 4H), 3.00 (app t, J = 12.5 Hz, 2H), 2.90 (s, 3H), 2.70 (br s, 1H), 1.33-1.22 (m, 2H), 1.14- 1.06 (m, 2H) 
                 {4-[5-Cyclopropyl- 4-((R)-3-trifluoromethyl- piperazin-1-yl)- pyrido[3,4-d]pyrimidin-2- yl]-pyridin-2-yl}-[3-(4- methyl-piperazin-1-yl)- phenyl]-amine 
               
               
                   
               
               
                 2053 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 100%, RT: 1.68 min, MI: 527  (MH)+ 
                 (dmso-d6) 11.25 (br s, 1H), 9.09 (s, 1H), 8.37 (d, J = 6.4  Hz, 1H), 8.34 (s, 1H), 8.21 (s, 1H), 7.88 (d, J = 5.2 Hz, 1H), 7.78 (d, J = 2.0 Hz, 1H), 6.23 (d, J = 2.4 Hz, 1H), 4.70-3.95 (m, 3H), 3.89 (s, 3H), 3.89 (overlapped m, 1H), 3.72 (br s, 1H), 3.25 (br s, 3H), 2.73 (br s, 1H), 1.35-1.20 (m, 2H), 1.15-1.00 (m, 2H) 
                 {4-[5-Cyclopropyl- 4-((R)-3-trifluoromethyl- piperazin-1-yl)- pyrido[3,4-d]pyrimidin-2- yl]-pyridin-2-yl}-(1- methyl-1H-pyrazol-3-yl)- amine 
               
               
                   
               
               
                 2054 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, MI: 479 (MH)+ 
                 1H-NMR: DMSO 10.08 (s, 1H), 9.08 (br s, 2H), 9.00 (br s, 1H), 8.82 (s, 1H), 8.51 (s, 1H), 8.48 (d, 1H, J = 5.2 Hz), 8.03 (m, 1H), 7.90 (m, 1H), 7.02 (m, 1H), 5.04 (m, 1H), 3.69 (m, 1H), 3.49 (m, 2H), 3.36 (m, 1H), 2.62 (m, 1H), 2.52 (m, 1H), 2.26 (m, 1H), 1.24 (m, 2H), 1.07 (m, 2H) 
                 {5-Cyclopropyl- 2-[2-(3,4,6-trifluoro- pyridin-2-ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-(R)- pyrrolidin-3-yl-amine 
               
               
                   
               
               
                 2055 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 99.7399 98%, RT: min, MI: 522 
                   
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2- yl]-[2-fluoro-4-(2-methyl- 2H-pyrazol-3-yl)-phenyl]- amine 
               
               
                   
               
               
                 2056 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 98% RT: min, MI: 465.19 (MH)+ 
                 1H-NMR: DMSO 9.78 (s, 1H), 9.08 (br s, 2H), 8.97 (br s, 1H), 8.73 (s, 1H), 8.51 (s, 1H), 8.43 (d, 1H, J = 5.2 Hz), 8.29 (m, 1H), 7.98 (m, 1H), 7.90 (m, 1H), 5.04 (m, 1H), 3.72 (m, 1H), 3.48 (m, 2H), 3.37 (m, 1H), 2.62 (m, 1H), 2.52 (m, 1H), 2.26 (m, 1H), 1.24 (m, 2H), 1.06 (m, 2H) 
                 {5-Cyclopropyl-2- [2-(3,5,6-trifluoro- pyridin-2-ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-(R)- pyrrolidin-3-yl-amine 
               
               
                   
               
               
                 2057 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 474 (MH)+ 
                 1H-NMR: DMSO 9.02 (s, 1H), 8.88 (br s, 2H), 8.84 (s, 1H), 8.20 (m, 2H), 7.83 (s, 1H), 7.70 (d, 1H, J = 5.2 Hz), 7.29 (m, 1H), 7.17 (m, 2H), 5.12 (br m, 1H), 3.78 (m, 1H), 3.45 (m, 1H), 3.29 (m, 2H), 3.11 (s, 3H), 2.54 (m, 1H), 2.40 (m, 1H), 2.25 (m, 1H), 1.26 (m, 2H), 1.01 (m, 2H) 
                 {5-Cyclopropyl-2-[2-(2,6- difluoro-phenylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-methyl- (R)-pyrrolidin-3-yl-amine 
               
               
                   
               
               
                 2058 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 100%, RT: min, MI: 465.19 (MH)+ 
                 1H-NMR: DMSO 9.03 (s, 1H), 8.90 (s, 1H), 8.69 (br s, 2H), 8.48 (s, 1H), 8.19 (d, 1H, J = 5.2 Hz), 7.86 (m, 1H), 7.80 (s, 1H), 7.72 (m, 1H), 7.33 (m, 1H), 7.19 (m, 2H), 4.58 (m, 1H), 3.35 (m, 4H), 2.60 (m, 1H), 2.32 (m, 2H), 2.14 (m, 1H), 1.94 (m, 3H), 1.22 (m, 2H), 1.11 (m, 1H), 1.05 (m, 1H) 
                 Azepan-4-yl-{5- cyclopropyl- 2-[2-(2,6-difluoro- phenylamino)-pyridin- 4-yl]-pyrido [3,4-d]pyrimidin-4- yl}-amine 
               
               
                   
               
               
                 2059 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 101%, RT: min, MI: 465.19 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.72 (br s, 1H), 9.06 (s, 1H), 8.89 (br s, 2H), 8.23-8.16 (m, 3H), 8.08 (s, 1H), 8.02- 7.98 (m, 1H),  7.90 (d, J = 7.3 Hz, 1H), 7.80 (d, J = 7.5 Hz, 1H), 7.76 (d, J = 5.5 Hz, 1H), 7.61-7.53 (m, 3H), 3.88 (br s, 4H), 3.30 (br s,  4H), 2.71- 2.63 (m, 1H), 1.28-1.23 (m, 2H), 1.11-1.06 (m, 2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido [3,4-d]pyrimidin- 2-yl)-pyridin-2- yl]-naphthalen-1-yl-amine 
               
               
                   
               
               
                 2060 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 102%, RT: min, MI: 465.19 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 10.69 (br s, 1H), 9.19 (s, 1H), 9.10 (s, 1H),  8.89 (br s, 2H), 8.49 (d, J = 5.6 Hz, 1H), 8.46 (s, 1H), 8.32 (br s, 1H), 8.21 (s, 1H), 8.09 (d, J =  8.1 Hz, 1H), 7.94- 7.87 (m, 2H), 7.71 (t, J = 7.5 Hz, 1H), 7.49 (t, J = 7.4 Hz, 1H), 3.97 (br s, 4H), 3.34 (br s, 4H), 2.73- 2.65 (m, 1H), 1.30-1.24 (m, 2H), 1.12-1.07 (m, 2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido [3,4-d]pyrimidin- 2-yl)-pyridin-2-yl]- iso[D4], [D3]uinolin-3- yl-amine 
               
               
                   
               
               
                 2061 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 103%, RT: min, MI: 465.19 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 10.60 (br s, 1H), 9.11 (s, 1H), 9.05-8.80 (m, 3H), 8.41 (d, J = 5.5 Hz, 1H), 8.21 (s, 1H), 8.07 (d, J = 8.1 Hz, 1H), 7.91 (d, J = 5.4 Hz, 1H), 7.61 (d, J = 8.6 Hz, 1H), 7.49-7.44 (m, 1H), 7.13 (t, J = 7.5 Hz, 1H), 4.05 (s, 3H), 3.59 (br s, 4H), 3.36 (br s, 4H), 2.75-2.67 (m, 1H), 1.30-1.24 (m, 2H), 1.12- 1.07 (m, 2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-(1- methyl-1H-indazol-3- yl)-amine 
               
               
                   
               
               
                 2062 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 104%, RT: min, MI: 465.19 (MH)+ 
                 (d6-DMSO) 10.06 (s, 1H), 9.06 (s, 1H), 8.73 (s, 1H), 8.70 (br s, 1H), 8.50 (s, 1H), 8.45 (m, 1H), 8.37 (br m, 1H), 8.02 (m, 1H), 7.82 (m, 1H), 6.99 (m, 1H), 4.59 (m, 1H), 3.40 (m, 2H), 3.13 (m, 2H), 2.66 (m, 1H), 2.34 (m, 2H), 1.90 (m, 2H), 1.19 (m, 2H), 1.07 (m, 2H) 
                 {5-Cyclopropyl-2- [2-(3,4,6-trifluoro- pyridin-2-ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}- piperidin-4-yl-amine 
               
               
                   
               
               
                 2063 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 2.75 min, MI: 482 [M + H] 
                 (500 MHz, d6-DMSO) 12.09 (brs, 1H), 9.15 (s, 1H), 8.42 (d, 1H), 8.17 (s, 1H), 8.13 (d, 1H), 7.48 (d, 1H), 4.10-3.71 (m, 4H), 3.41-3.31 (m, 4H), 2.77- 2.71 (m, 1H), 1.69 (s, 6H), 1.28-1.21 (m, 2H), 1.10- 1.05 (m, 2H). 
                 5-Cyclopropyl- 4-piperazin-1-yl-2- [2-(2,2,2-trifluoro-1,1- dimethyl-ethyl)-1H- pyrrolo[2,3-b]pyridin-4- yl]-pyrido[3,4-d] pyrimidine 
               
               
                   
               
               
                 2064 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 3.05 min, MI: 502 [M + H] 
                 (500 Mhz, d6-DMSO) 11.88 (brs, 1H), 9.12 (s, 1H), 8.29 (d, 1H), 8.16 (s, 1H), 8.07 (d, 1H), 7.44 (dd, 2H), 7.33 (t, 2H), 7.23 (d, 1H), 7.19 (t, 1H), 4.08-3.66 (m, 4H), 3.36-3.27 (m, 4H), 2.94-2.86 (m, 2H), 2.75- 2.68 (m, 3H), 2.10-2.00 (m, 1H), 1.96-1.86 (m, 1H), 1.28-1.21 (m, 2H), 1.11- 1.03 (m, 2H). 
                 5-Cyclopropyl-2-[2-(1- phenyl-cyclobutyl)-1H- pyrrolo[2,3-b]pyridin- 4-yl]-4-piperazin- 1-yl-pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 2065 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 105%, RT: min, MI: 465.19 (MH)+ 
                 (d6-DMSO) 9.76 (s, 1H), 9.05 (s, 1H), 8.76 (br m, 1H), 8.63 (s, 1H), 8.50 (s, 1H), 8.40 (br m, 2H), 8.29 (m, 1H), 7.98 (m, 1H), 7.80 (m, 1H), 4.60 (m, 1H), 3.38 (m, 2H), 3.15 (m, 2H), 2.66 (m, 1H), 2.32 (m, 2H), 1.94 (m, 2H), 1.19 (m, 2H), 1.08 (m, 2H) 
                 {5-Cyclopropyl- 2-[2-(3,5,6-trifluoro- pyridin-2-ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}- piperidin-4-yl-amine 
               
               
                   
               
               
                 2066 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;90%, RT: min, MI: 465.19 (MH)+ 
                 (dmso-d6) 9.16 (br s, 3H), 9.10 (s, 1H), 8.24 (s, 1H), 8.10-8.07 (m, 2H), 7.72 (dd, J = 6.7; 1.3 Hz, 1H), 4.10- 3.85 (m, 5H), 3.85-3.75 (m, 1H), 3.70-3.60 (m, 1H), 3.55-3.20 (m, 2H), 3.34 (br s, 4H), 2.67 (m, 1H), 2.10- 1.95 (m, 1H), 1.95-1.75 (m, 4H), 1.55-1.45 (m, 1H), 1.30-1.25 (m, 2H), 1.20- 1.05 (m, 2H) 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido [3,4-d]pyrimidin- 2-yl)-pyridin-2- yl]-[1-(tetrahydro-furan- 2-yl)-ethyl]-amine 
               
               
                   
               
               
                 2067 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 107%, RT: min, MI: 465.19 (MH)+ 
                 (dmso-d6) 9.18 (br s, 2H), 9.06 (s, 1H), 8.21 (s, 1H), 8.10 (d, J = 6.4 Hz, 1H), 7.98 (br s, 1H), 7.68 (d, J = 5.4 Hz, 1H), 7.51-7.46 (m, 1H), 7.38-7.30 (m, 1H), 7.30-7.17 (m ,2H), 5.33 (br s, 2H), 3.91 (br s, 4H), 3.33 (br s, 4H), 2.70-2.62 (m, 1H), 1.58 (d, J = 6.8 Hz, 3H), 1.30-1.20 (m, 2H), 1.10-1.05 (m, 2H) 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- [(R)-1-(2-fluoro-phenyl)- ethyl]-amine 
               
               
                   
               
               
                 2068 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 454 (M + H), 
                 (d6-DMSO) 13.13 (s, 1H), 9.18 (s, 1H), 8.70 (br m, 1H), 8.63 (d, 1H, J = 4.9 Hz), 8.51 (s, 1H), 8.37 (br m, 1H), 8.30 (m, 1H), 7.96 (s, 1H), 7.83 (m, 1H), 4.62 (m, 1H), 3.43 (m, 2H), 3.20 (m, 2H), 2.67 (m, 1H), 2.35 (m, 2H), 1.94 (m, 2H), 1.20 (m, 2H), 1.08 (m, 2H) 
                 [5-Cyclopropyl-2-(2- trifluoromethyl-1H- pyrrolo[2,3-b]pyridin- 4-yl)-pyrido[3,4-d] pyrimidin-4-yl]- piperidin-4-yl-amine 
               
               
                   
               
               
                 2069 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 440 (M + H) 
                 1H-NMR: DMSO 13.15 (s, 1H), 9.22 (s, 1H), 8.99 (br m, 2H), 8.64 (d, 1H, J = 4.9 Hz), 8.52 (s, 1H), 8.28 (m, 1H), 7.99 (s, 1H), 7.89 (m, 1H), 5.08 (m, 1H), 3.73 (m, 1H), 3.45 (m, 4H), 2.63 (m, 1H), 2.26 (m, 1H), 1.23 (m, 2H), 1.10 (m, 2H) 
                 [5-Cyclopropyl-2-(2- trifluoromethyl-1H- pyrrolo[2,3-b] pyridin-4-yl)-pyrido [3,4-d]pyrimidin-4-yl]- (R)-pyrrolidin-3-yl-amine 
               
               
                   
               
               
                 2070 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 468 (M + H) 
                 1H-NMR: DMSO 13.14 (s, 1H), 9.11 (s, 1H), 8.69 (br m, 1H), 8.63 (d, 1H, J = 4.9 Hz), 8.32 (br m, 1H), 8.28 (m, 1H), 8.19 (s, 1H), 7.97 (s, 1H), 4.88 (m, 1H), 3.46 (m, 2H), 3.12 (m, 5H), 2.07- 2.32 (br m, 5H), 1.23 (m, 2H), 0.98 (m, 2H) 
                 [5-Cyclopropyl-2-(2- trifluoromethyl-1H- pyrrolo[2,3-b] pyridin-4-yl)-pyrido [3,4-d]pyrimidin-4-yl]- methyl-piperidin-4-yl- amine 
               
               
                   
               
               
                 2071 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 99%, RT: min, MI: 474 (M + H 
                 1H-NMR (DMSO-d6, 400 MHz): 13.21 (s, 1H), 8.94 (br s, 1H), 8.82 (br s, 1H), 8.67 (d, 1H, J = 4.9 Hz), 8.32 (d, 1H, J = 4.9 Hz), 8.20 (s, 1H), 7.99 (s, 1H), 3.99 (br s, 4H), 3.33 (br s, 4H), 2.64 (m, 1H), 1.26 (m, 2H), 1.07 (m, 2H) 
                 8-Chloro-5-cyclopropyl- 4-piperazin-1-yl-2-(2- trifluoromethyl-1H- pyrrolo[2,3-b]pyridin-4- yl)-pyrido[3,4-d] pyrimidine 
               
               
                   
               
               
                 2072 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;90%, RT: min, MI: 464 (M + H)+ 
                 1H NMR (400 MHz, DMSO-d6) δ ppm 10.48 (br. s, 1 H) 9.11 (s, 1 H) 8.94 (br. s, 2 H) 8.54 (dd, J = 6.8, 0.8 Hz, 1 H) 8.46 (s, 1 H) 8.41 (d, J = 5.5 Hz, 1 H) 8.20 (s, 1 H) 7.84 (d, J = 5.5 Hz, 1 H) 7.58 (d, J = 8.8 Hz, 1 H) 7.12-7.30 (m, 1 H) 6.68- 6.85 (m, 2 H) 3.95 (br. s., 4 H) 3.35 (br. s., 4 H) 2.60- 2.79 (m, 1 H) 1.21-1.32 (m, 2 H) 0.98-1.16 (m, 2 H) 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- pyrazolo[1,5-a]pyridin-2- yl-amine 
               
               
                   
               
               
                 2073 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 Method 5: RT: 1.7 min, MI: 541 [M + H] 
                 (DMSO, 400 MHz, 90° C.) 8.96 (1H, s), 8.12 (2H, m), 7.51 (1H, s), 7.43 (1H, dd), 4.26 (2H, m), 3.76 (1H, m), 3.16 (3H, m), 2.92 (2H, m), 2.71 (1H, m), 2.46 (1H, m), 1.90 (2H, m), 1.49 (3H, m), 1.08 (9H, m). 
                 {4-[5-Cyclopropyl-4- ((cis)-3,5-dimethyl- piperazin-1-yl)-pyrido [3,4-d]pyrimidin-2-yl]- pyridin-2-yl}-[1-(2,2,2- trifluoro-ethyl)-piperidin- 4-yl]-amine 
               
               
                   
               
               
                 2074 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3], [D5] 
                 Method 5: RT: 3.29 min, MI: 406 [M + H] 
                 (400 MHz, d6-DMSO,  90° C.) 9.06 (1H, s), 8.37 (1H, d, J = 4.9 Hz), 8.13-8.11 (2H, m), 7.42 (1H, s), 3.74- 3.71 (4H, m), 2.94-2.91 (4H, m), 2.72-2.66 (1H, m), 1.28-1.24 (2H, m), 1.01-0.97 (2H, m). 
                 2-(2-Chloro-1H-pyrrolo [2,3-b]pyridin-4-yl)-5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidine 
               
               
                   
               
               
                 2075 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 93%, RT: min, MI: 416.22 (M + H) 
                 (dmso-d6) 12.00 (br s, 1H), 9.17 (s, 1H), 8.92 (br s, 2H), 8.40 (d, J = 5.1 Hz, 1H), 8.20 (s, 1H), 8.15 (d, J = 5.1 Hz, 1H), 7.44 (br s, 1H), 4.66 (s, 2H), 3.92 (br s, 4H), 3.39 (br s, 7H), 2.80-2.70 (m, 1H), 1.30-1.25 (m, 2H), 1.12-1.10 (m, 2H) 
                 5-Cyclopropyl-2-(2- methoxymethyl-1H- pyrrolo[2,3-b]pyridin- 4-yl)-4-piperazin- 1-yl-pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 2076 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 488 (M + H) 
                 1H-NMR: DMSO 13.13 (s, 1H), 9.18 (s, 1H), 8.70 (br m, 1H), 8.63 (d, 1H, J = 4.9 Hz), 8.51 (s, 1H), 8.37 (br m, 1H), 8.30 (m, 1H), 7.96 (s, 1H), 7.83 (m, 1H), 4.62 (m, 1H), 3.43 (m, 2H), 3.20 (m, 2H), 2.67 (m, 1H), 2.35 (m, 2H), 1.94 (m, 2H), 1.20 (m, 2H), 1.08 (m, 2H) 
                 4-{5-Cyclopropyl- 2-[2-(2,6- difluoro-phenylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-ylamino}- piperidin-2-one 
               
               
                   
               
               
                 2077 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 95%, RT: min, MI: 454 (MH)+ 
                 1H-NMR: DMSO 13.15 (s, 1H), 9.22 (s, 1H), 8.99 (br m, 2H), 8.64 (d, 1H, J = 4.9 Hz), 8.52 (s, 1H), 8.28 (m, 1H), 7.99 (s, 1H), 7.89 (m, 1H), 5.08 (m, 1H), 3.73 (m, 1H), 3.45 (m, 4H), 2.63 (m, 1H), 2.26 (m, 1H), 1.23 (m, 2H), 1.10 (m, 2H) 
                 [5-Cyclopropyl- 2-(1-methyl-2- trifluoromethyl-1H- pyrrolo[2,3-b]pyridin- 4-yl)-pyrido[3,4-d] pyrimidin-4-yl]- (R)-pyrrolidin-3-yl-amine 
               
               
                   
               
               
                 2078 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 94%, RT: min, MI: 475.23 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.13 (s, 1H), 8.95 (br s, 2H), 8.69-8.64 (m, 1H), 8.51- 8.45 (m, 1H), 8.23 (s, 1H), 8.21-8.07 (m, 2H), 7.99 (d, J = 8.3 Hz, 1H), 7.85 (t, J =  8.0 Hz, 1H), 7.60-7.53 (m, 2H), 3.99 (br s, 4H), 3.36 (br s, 4H), 2.75-2.67 (m, 1H), 1.30-1.25 (m, 2H), 1.14- 1.07 (m, 2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidin- 2-yl)-pyridin-2-yl]- [D4], [D3]uinolin-2-yl- amine 
               
               
                   
               
               
                 2079 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 95%, RT: min, MI: 466.28 (M + H) 
                 (dmso-d6) 11.76 (s, 1H), 9.19 (s, 1H), 8.93 (br s, 2H), 8.33 (d, J = 5.1 Hz, 1H), 8.22 (s, 1H), 8.11 (d, J = 5.1 Hz, 1H), 7.29 (br s, 1H), 5.08 (very br signal, exch. H&#39;s), 3.97 (br s, 4H), 3.40 (br s, 5H), 2.84-2.75 (m, 1H), 2.72 (br s, 1H), 2.40 (br s, 1H), 2.11-2.04 (m, 1H), 1.66-1.46 (m, 4H), 1.33-1.27 (m, 4H), 1.15- 1.11 (m, 3H) 
                 (±)-2-((endo)-2- Bicyclo[2.2.1]hept- 2-yl-1H-pyrrolo [2,3-b]pyridin-4-yl)- 5-cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidine 
               
               
                   
               
               
                 2080 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 92%, RT: min, MI: 430.24 (M + H) 
                 (dmso-d6) 11.92 (br s, 1H), 9.17 (s, 1H), 8.90 (br s, 1H), 8.78 (br s, 1H), 8.72 (s, 1H), 8.30 (d, J = 5.0 Hz, 1H), 8.05 (d, J = 5.0 Hz, 1H); 7.34 (br s, 1H), 4.57 (s, 2H), 4.25-4.14 (m, 1H), 3.90- 3.60 (m ,4H), 3.40-3.10 (m, 4H), 3.28 (s, 3H), 2.50-2.30 (m, 2H), 2.20-2.10 (m ,2H), 2.10-1.90 (m, 1H), 1.90- 1.80 (m, 1H) 
                 5-Cyclobutyl-2-(2- methoxymethyl-1H- pyrrolo[2,3-b]pyridin- 4-yl)-4- piperazin-1-yl-pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 2081 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 482 (M + H) 
                 1H-NMR: DMSO 13.14 (s, 1H), 9.38 (br m, 1H), 9.12 (s, 1H), 8.63 (d, 1H, J = 4.9 Hz), 8.25 (m, 1H), 8.19 (s, 1H), 7.99 (s, 1H), 4.83 (m, 1H), 3.58 (m ,2H), 3.26 (m, 2H), 3.12 (s, 3H), 2.84 (d, 3H, J = 4.6 Hz), 2.46 (m, 1H), 2.12 (br m, 4H), 1.23 (m, 2H), 1.00 (m, 2H) 
                 [5-Cyclopropyl-2-(2- trifluoromethyl-1H- pyrrolo[2,3-b] pyridin-4-yl)-pyrido [3,4-d]pyrimidin-4-yl]- methyl-(1-methyl- piperidin-4-yl)-amine 
               
               
                   
               
               
                 2082 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 3.10 min, MI: 386 [M + H] 
                 (500 MHz, d6-DMSO) 11.88 (brs, 1H), 9.22 (s, 1H), 8.99 (brs, 1H), 8.86 (brs, 1H), 8.78 (s, 1H), 8.38 (s, 1H), 8.12 (s, 1H), 7.65 (d, 1H), 7.46 (d, 1H), 4.32- 4.24 (m, 1H), 3.93-3.84 (m, 2H), 3.78-3.69 (m, 2H), 3.41-3.34 (m, 2H), 3.32- 3.24 (m, 2H), 2.27-2.18 (m, 2H), 2.15-2.06 (m, 1H), 1.96-1.87 (m, 1H). 
                 5-Cyclobutyl-4-piperazin- 1-yl-2-(1H-pyrrolo[2,3- b]pyridin-4-yl)-pyrido [3,4-d]pyrimidine 
               
               
                   
               
               
                 2083 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 454 (M + H) 
                 1H-NMR: DMSO 9.47 (br m, 1H), 8.98 (s, 1H), 8.87 (s, 1H), 8.18 (d, 2H, J = 4.8 Hz), 7.81 (s, 1H), 7.69 (m, 1H), 7.30 (m, 1H), 7.18 (m, 2H), 4.79 (m, 1H), 3.56 (m, 2H), 3.24 (m, 2H), 3.09 (s, 3H), 2.84 (d, 3H, J = 4.4 Hz), 2.44 (m, 1H), 2.10 (br m, 4H), 1.23 (m, 2H), 0.98 (m, 2H) 
                 {5-Cyclopropyl-2-[2-(2,6- difluoro-phenylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}- methyl-(1-methyl- piperidin-4-yl)-amine 
               
               
                   
               
               
                 2084 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 488 (M + H) 
                 1H-NMR: DMSO 9.45 (br m, 1H), 9.04 (s, 1H), 8.81 (s, 1H), 8.48 (s, 1H), 8.18 (d, 1H, J = 5.3 Hz), 7.78 (m, 2H), 7.71 (m, 1H), 7.30 (m, 1H), 7.18 (m, 2H), 4.49 (m, 1H), 3.59 (m, 2H), 3.21 (m, 2H), 2.85 (s, 3H), 2.32 (br m, 3H), 1.90 (m, 2H), 1.17 (m, 2H), 1.04 (m, 2H) 
                 {5-Cyclopropyl-2-[2-(2,6- difluoro-phenylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-(1- methyl- piperidin-4-yl)-amine 
               
               
                   
               
               
                 2085 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 516 (M + H) 
                 1H-NMR: DMSO 9.03 (br s, 2H), 8.46 (s, 1H), 8.19 (d, 1H, J = 5.4 Hz), 7.85 (m, 1H), 7.80 (s, 1H), 7.73 (m, 1H), 7.32 (m, 1H), 7.21 (m, 2H), 4.52 (m, 1H), 4.35 (m, 1H), 3.87 (m, 1H), 3.26 (m, 1H), 2.84 (m, 1H), 2.58 (m, 1H), 2.13 (m, 2H), 2.05 (s, 3H), 1.78 (br m, 2H), 1.18 (br m, 2H), 1.04 (m, 2H) 
                 1-(4-{5-Cyclopropyl-2- [2-(2,6-difluoro- phenylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-ylamino}- piperidin-1-yl)-ethanone 
               
               
                   
               
               
                 2086 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 4.06 min, MI: 490 [M + H] 
                 (500 MHz, d6-DMSO) 11.72 (s, 1H), 9.10 (s, 1H), 8.30 (d, 1H), 8.16 (s, 1H), 8.09 (d, 1H), 7.34-7.28 (m, 4H), 7.25-7.19 (m, 2H), 4.12-3.67 (m, 4H), 3.38- 3.28 (m, 4H), 2.78-2.70 (m, 1H), 1.81 (s, 6H), 1.28-1.20 (m, 2H), 1.10-1.05 (m, 2H). 
                 5-Cyclopropyl-2-[2-(1- methyl-1-phenyl- ethyl)-1H-pyrrolo [2,3-b]pyridin-4-yl]- 4-piperazin-1-yl-pyrido [3,4-d]pyrimidine 
               
               
                   
               
               
                 2087 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D3],  [D7] 
                   
                   
                 2-(3-Chloro-1H-pyrrolo [2,3-b]pyridin-4-yl)-5- cyclopropyl-4-piperazin- 1-yl-pyrido [3,4-d]pyrimidine 
               
               
                   
               
               
                 2088 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 454 (M + H) 
                 1H-NMR: DMSO 13.17 (s, 1H), 9.18 (s, 1H), 8.92 (br m, 2H), 8.64 (d, 1H, J = 4.9 Hz), 8.23 (m, 2H), 8.00 (s, 1H), 5.20 (m, 1H), 3.78 (m, 1H), 3.27-3.45 (br m, 3H), 3.14 (s, 3H), 2.42 (m, 1H), 2.26 (br m, 2H), 1.26 (m, 2H), 1.02 (m, 2H) 
                 [5-Cyclopropyl-2-(2- trifluoromethyl-1H- pyrrolo[2,3-b]pyridin-4- yl)-pyrido[3,4-d] pyrimidin-4-yl]-methyl- (R)-pyrrolidin-3-yl- amine 
               
               
                   
               
               
                 2089 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 96%, RT: min, MI: 475.21 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.13 (s, 1H), 9.05-8.85 (m, 4H), 8.71 (d, J = 4.9 Hz,  1H), 8.35-8.29 (m, 1H), 8.24 (s, 1H), 8.22-8.05 (m, 3H), 8.01-7.94 (m, 1H), 7.74- 7.68 (m, 1H), 3.95 (br s, 4H), 3.36 (br s, 4H), 2.72- 2.65 (m, 1H), 1.31-1.25 (m, 2H), 1.12-1.08 (m, 2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido [3,4-d]pyrimidin- 2-yl)-pyridin-2- yl]-iso[D4], [D3]uinolin- 1-yl-amine 
               
               
                   
               
               
                 2090 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D3] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 436 (M + H) 
                 1H-NMR (DMSO-d6, 400 MHz): 12.09 (s, 1H), 9.26 (s, 1H), 8.8-9.0 (m, 3H), 8.69 (d, 1H, J = 8.2 Hz), 8.59 (d, 1H, J = 5.1 Hz), 7.89 (d, 1H, J = 5.1 Hz), 7.55 (d, 1H, J = 7.9 Hz), 7.49 (m, 1H), 7.19 (m, 1H), 4.32 (m, 1H), 3.83 (m, 4H), 3.30 (m, 4H), 2.57 (m, 2H), 2.28 (m, 2H), 2.13 (m, 1H), 1.95 (m, 1H). 
                 4-(5-Cyclobutyl- 4-piperazin-1-yl- pyrido[3,4-d]pyrimidin- 2-yl)-9H-pyrido[2,3-b] indole 
               
               
                   
               
               
                 2091 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B01] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 382 (M + H) 
                 1H-NMR (DMSO-d6, 400 MHz): 12.07 (s, 1H), 9.43 (s, 1H), 8.89 (br s, 2H), 8.73 (d, 1H, J = 5.7 Hz), 8.58 (d, 1H, J = 5.1 Hz), 8.55 (d, 1H, J = 8.0 Hz), 8.11 (d, 1H, J = 5.2 Hz), 7.81 (d, 1H, J = 5.1 Hz), 7.55 (d, 1H, J = 8.0 Hz), 7.49 (m, 1H), 7.17 (m, 1H), 4.14 (m, 4H), 3.38 (m, 4H). 
                 4-(4-Piperazin-1-yl- pyrido[3,4-d]pyrimidin- 2-yl)-9H-pyrido[2,3-b] indole 
               
               
                   
               
               
                 2092 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 420 (M + H) 
                 1H-NMR (CD 3 CN, 400 MHz): 12.80 (s, 1H), 8.38 (d, 1H, J = 5.8) 8.25 (d, 1H, J = 5.8 Hz), 7.87 (s, 1H), 7.57 (s, 1H), 3.99 (m, 4H), 3.24 (m, 4H), 2.55 (m, 4H), 1.20 (m, 2H), 0.94 (m, 2H). 
                 8-Chloro-5-cyclopropyl- 2-(2-methyl- 1H-pyrrolo[2,3- b]pyridin-4-yl)-4- piperazin-1-yl- pyrido[3,4-d]pyrimidine 
               
               
                   
               
               
                 2093 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 444 (M + H) 
                 1H-NMR (DMSO-d6, 400 MHz): 9.07 (s, 1H), 9.00 (br s, 2H), 8.22 (s, 1H), 8.10 (d, 1H, J = 6.4 Hz), 8.02 (br s, 1H), 7.68 (d, 1H, J = 6.4 Hz), 4.67 (m, 1H), 4.48 (m, 1H), 3.8-4.0 (m, 5H), 3.32 (m, 4H), 2.66 (m, 1H), 2.10 (m, 1H), 1.5-1.7 (m, 4H), 1.47 (m, 1H), 1.25 (m, 2H), 1.08 (m, 2H); 
                 (±)-exo-[4-(5- Cyclopropyl-4- piperazin-1-yl-pyrido [3,4-d]pyrimidin-2-yl)- pyridin-2-yl]--7-oxa- bicyclo[2.2.1]hept-2-yl- amine 
               
               
                   
               
               
                 2094 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 446 (M + H) 
                 1H-NMR: DMSO 9.22 (s, 1H), 8.86 (br m, 3H), 8.81 (s, 1H), 8.20 (d, 1H, J = 5.2 Hz), 7.84 (s, 1H), 7.71 (m, 1H), 7.38 (m, 1H), 7.27 (m, 1H), 7.17 (m, 2H), 6.11 (br d, 1H, J = 17.8 Hz) 5.64 (d, 1H, 11.8 Hz), 3.74 (br s, 4H), 3.32 (br s, 4H) 
                 (2,6-Difluoro-phenyl)-[4- (4-piperazin-1-yl-5-vinyl- pyrido[3,4-d]pyrimidin- 2-yl)-pyridin-2-yl]-amine 
               
               
                   
               
               
                 2095 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 446 (M + H) 
                 1H-NMR: DMSO 10.35 (br s, 1H), 9.01 (s, 1H), 8.82 (br m, 1H), 8.64 (s, 1H) 8.41 (m, 2H), 8.30 (m, 1H), 8.20 (s, 1H), 8.08 (m, 1H), 8.02 (m, 1H), 4.85 (m, 1H), 3.44 (m, 2H), 3.15 (m, 2H), 3.12 (s, 3H), 2.44 (m, 1H), 2.07 (br m, 4H), 1.24 (m, 2H), 0.98 (m, 2H) 
                 {5-Cyclopropyl-2-[2- (3,5-difluoro- pyridin-2-ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-methyl- piperidin-4-yl-amine 
               
               
                   
               
               
                 2096 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 489 (M + H) 
                 1H-NMR: DMSO 8.99 (s, 1H), 8.96 (s, 1H), 8.19 (m, 2H), 7.75 (s, 1H), 7.69 (m, 1H), 7.31 (m ,1H), 7.20 (m, 2H), 4.77 (m, 1H), 4.56 (m, 1H), 3.94 (m, 1H), 3.16 (m, 1H), 3.11 (s, 3H), 2.67 (m, 1H), 2.40 (m, 1H), 2.04 (s, 3H), 1.88 (br m, 4H), 1.23 (m, 2H), 0.97 (m ,2H) 
                 1-[4-({5-Cyclopropyl- 2-[2-(2,6-difluoro- phenylamino)- pyridin-4-yl]-pyrido[3,4- d]primidin-4-yl}-methyl- amino)-piperidin-1-yl]- ethanone 
               
               
                   
               
               
                 2097 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 530 (M + H) 
                 (400 MHz, d6-DMSO, δ): 9.06 (s, 1H), 8.94 (br s, 2H), 8.21 (s, 1H), 8.13 (d, J = 6.3 Hz, 1H), 8.00-7.90 (m, 1H), 7.67 (d, J = 6.1 Hz, 1H), 7.33-7.28 (m, 2H), 7.23- 7.18 (m, 2H), 4.67-4.60 (m, 1H), 3.90 (br s, 4H), 3.42 (dd, J = 16.1, 7.2 Hz, 2H), 3.31 (br s, 4H), 2.96 (dd, J = 16.2, 4.7 Hz, 2H), 2.69- 2.62 (m, 1H), 1.28-1.22 (m, 2H), 1.11-1.05 (m, 2H). 
                 1-[4-({5-Cyclopropyl- 2-[2-(2,6- difluoro-phenylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-methyl- amino)-piperidin-1-yl]- ethanone 
               
               
                   
               
               
                 2098 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 98%, RT: min, MI: 464.30 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.07 (s, 1H), 8.90 (br s, 2H), 8.21 (s, 1H), 8.15 (d, J = 6.2 Hz, 1H), 8.00-7.90 (m, 1H), 7.70-7.64 (m, 1H), 7.39- 7.21 (m, 4H), 5.53-5.45 (m, 1H), 3.86 (br s, 4H), 3.31 (br s, 4H), 3.09-3.00 (m, 1H), 2.95-2.86 (m, 1H), 2.70-2.56 (m, 2H), 1.99- 1.90 (m, 1H), 1.29-1.23 (m, 2H), 1.11-1.06 (m, 2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)-pyridin- 2-yl]-(R)-indan-1-yl- amine 
               
               
                   
               
               
                 2099 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 98%, RT: min, MI: 464.29 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.07 (s, 1H), 8.96 (br s, 2H), 8.21 (s, 1H), 8.15 (d, J = 6.3 Hz, 1H), 8.03-7.95 (m, 1H), 7.71-7.66 (m, 1H), 7.40- 7.22 (m, 4H), 5.52-5.44 (m, 1H), 3.91 (br s, 4H), 3.31 (br s, 4H), 3.09-3.01 (m, 1H), 2.96-2.86 (m, 1H), 2.70-2.57 (m, 2H), 2.01- 1.90 (m, 1H), 1.29-1.23 (m, 2H), 1.11-1.06 (m, 2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)-pyridin- 2-yl]-(S)-indazn-1-yl- amine 
               
               
                   
               
               
                 2100 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 98%, RT: min, MI: 464.27 (MH)+ 
                 1H-NMR (DMSO-d6, 400 MHz): 9.00 (br s, 1H), 8.91 (s, 1H), 8.89 (br s, 1H), 8.21 (d, 1H, J = ), 7.95 (s, 1H), 7.85 (s, 1H), 7.71 (dd, 1H,  J = ), 7.29 (m, 1H), 7.14- 7.21 (m, 2H), 3.94 (br s,  4H), 3.30 (br s, 4H), 2.61  (m, 1H), 1.24 (m, 2H), 1.05  (m, 2H) 
                 [4-(8-Chloro-5- cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)-pyridin- 2-yl]-(2,6-difluoro- phenyl)-amine 
               
               
                   
               
               
                 2101 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 494 (M + H)+ 
                 1H-NMR (DMSO-d6, 400 MHz): 8.83 (s, 1H), 8.80 (br s, 2H), 8.20 (d, 1H, J = 5.7 Hz), 7.83 (s, 1H), 7.74 (s, 1H), 7.67 (dd, 1H, J = 1.4, 5.3 Hz), 7.27 (m, 1H), 7.11- 7.19 (m, 2H), 3.91 (m, 4H), 3.30 (m, 4H), 2.58 (m, 1H), 1.20 (m, 2H), 1.00 (m, 2H) 
                 [4-(5-Cyclopropyl- 8-fluoro-4-piperazin- 1-yl-pyrido[3,4-d] pyrimidin-2-yl)-pyridin-2- yl]-(2,6-difluoro-phenyl)- amine 
               
               
                   
               
               
                 2102 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 458 (M + H) 
                 1H-NMR (DMSO-d6, 400 MHz): 13.22 (s, 1H), 8.86 (br s, 2H), 8.66 (d, 1H, J = 5.0 Hz), 8.28 (d, 1H, J = 5.0 Hz), 7.94 (s, 1H), 7.78 (s, 1H), 3.96 (br s, 4H), 3.34 (br s, 4H), 2.61 (m, 1H), 1.21 (m, 2H), 1.03 (m, 2H) 
                 5-Cyclopropyl-8-fluoro- 4-piperazin-1-yl-2-(2- trifluoromethyl-1H- pyrrolo[2,3-b]pyridin- 4-yl)- pyrido[3,4-d]pyrimidine 
               
               
                   
               
               
                 2103 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 542 (M + H) 
                 1H-NMR: DMSO 9.23 (br m, 1H), 9.02 (s, 1H), 8.87 (s, 1H), 8.46 (s, 1H), 8.18 (d, 1H, J = 5.3 Hz), 8.12 (m, 1H), 7.84 (m, 1H), 7.71 (m, 1H), 7.30 (m, 1H), 7.18 (m, 2H), 3.73 (m, 2H), 3.58 (m, 1H), 3.36 (m, 2H), 2.74 (m, 2H), 2.17 (m, 5H), 1.98 (m, 2H), 1.73 (m, 3H), 1.48 (m, 2H), 1.25 (m, 2H), 1.00 (m, 2H) 
                 (1-Cyclobutyl-piperidin- 4-ylmethyl)- {5-cyclopropyl-2- [2-(2,6-difluoro- phenylamino)-pyridin- 4-yl]-pyrido [3,4-d]pyrimidin-4- yl}-amine 
               
               
                   
               
               
                 2104 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 98%, RT: min, MI:  466.19 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 10.18 (s, 1H), 9.08 (s, 1H), 8.87 (br s, 2H), 8.54-8.46 (m, 3H), 8.19 (s, 1H), 7.92 (dd, J = 5.2, 1.3 Hz,  1H), 7.59 (dd, J = 8.9, 7.5 Hz, 1H), 7.47 (d, J = 8.8 Hz, 1H), 3.94 (br s, 4H), 3.34 (br s, 4H), 2.73- 2.65 (m, 1H), 1.29-1.24 (m, 2H), 1.12-1.07 (m, 2H). 
                 Benzo[1,2,5]oxadiazol-4- yl-[4-(5-cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)-pyridin- 2-yl]-amine 
               
               
                   
               
               
                 2105 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 4.08 min, MI: 468.53 [M + H] 
                 (500 MHz, DMSO) 13.18 (1H, s), 9.27 (1H, s), 8.99 (1H, s, br), 8.88 (1H, s, br), 8.74 (1H, s), 8.63 (1H, d), 8.25 (1H, d), 7.96 (1H, s), 4.31 (4H, s, br), 3.96-3.93 (2H, m, br), 3.89-3.84 (1H, m), 3.77-3.74 (2H, m),  3.61-3.56 (1H, m),  2.13-2.12 (2H, m), 1.89-1.67 (6H, m). 
                 5-Cyclopentyl-4- piperazin-1-yl-2- (2-trifluoromethyl-1H- pyrrolo[2,3-b]pyridin-4- yl)-pyrido[3,4-d] pyrimidine 
               
               
                   
               
               
                 2106 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3], [D8] 
                 Method 5: RT: 3.19 min, MI: 422 [M + H] 
                 (400 MHz, d6-DMSO  90° C.) 12.58 (1H, s), 9.06 (1H, s), 8.53 (1H, d, J = 4.9 Hz), 8.18 (1H, d, J = 4.9 Hz), 8.11 (1H, s), 7.78 (1H, br m), 7.33 (1H, t, J = 54.2 Hz), 3.93-3.47 (4H, br m), 2.89 (4H, br s), 2.70-2.65 (1H, m), 1.29-1.25 (2H, m), 1.06-1.03 (2H, m). 
                 5-Cyclopropyl-2-(2- difluoromethyl-1H- pyrrolo[2,3-b] pyridin-4-yl)-4- piperazin-1-yl-pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 2107 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 488 (M + H) 
                 1H-NMR: DMSO 9.02 (s, 1H), 8.91 (s, 1H), 8.55 (m, 1H), 8.46 (s, 1H), 8.26 (m, 1H), 8.18 (d, 1H, J = 5.3 Hz), 8.09 (m, 1H), 7.81 (s, 1H), 7.71 (m, 1H), 7.31 (m, 1H), 7.19 (m, 2H), 3.72 (m, 2H), 3.32 (m, 2H), 2.88 (m, 2H), 2.54 (m, 1H), 2.14 (m, 1H), 1.90 (m, 2H), 1.47 (m, 2H), 1.25 (m, 2H), 1.01 (m, 2H) 
                 {5-Cyclopropyl-2-[2-(2,6- difluoro-phenylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}- piperidin-4-ylmethyl- amine 
               
               
                   
               
               
                 2108 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 93%, RT: min, MI: 458.27 (M + H) 
                 (dmso-d6) 11.74 (s, 1H), 9.14 (s, 1H), 8.93 (br s, 2H), 8.32 (d, J = 5.2 Hz, 1H), 8.18 (s, 1H), 8.09 (d, J = 5.2 Hz, 1H), 7.21 (d, J = 2.2 Hz, 1H), 3.93 (br s, 4H), 3.55 (s, 2H), 3.37 (br s, 4H), 3.26 (s, 3H), 2.80-2.71 (m, 1H), 1.40 (s, 6H), 1.30-1.20 (m, 2H), 1.12-1.05 (m, 2H) 
                 5-Cyclopropyl-2-[2-(2- methoxy-1,1- dimethyl-ethyl)-1H- pyrrolo[2,3-b]pyridin-4- yl]-4-piperazin-1-yl- pyrido[3,4-d]pyrimidine 
               
               
                   
               
               
                 2109 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 97%, RT: min, MI: 472.29 (M + H) 
                 (dmso-d6) 11.74 (br s, 1H), 9.21 (s, 1H), 8.99 (br s, 1H), 8.85 (br s, 1H), 8.79 (s, 1H), 8.31 (d, J = 5.2 Hz, 1H), 8.07 (d, J = 5.2 Hz, 1H), 7.19 (d, J = 2.2 Hz, 1H), 4.29 (quint, 1H), 3.90-3.70 (m, 4H), 3.54 (s, 2H), 3.40- 3.25 (m, 4H), 3.26 (s, 3H), 2.47 (m, 2H), 2.30-2.15 (m, 2H), 2.15-2.05 (m, 1H), 1.95-1.85 (m, 1H), 1.40 (s, 6H) 
                 5-Cyclobutyl-2-[2-(2- methoxy-1,1- dimethyl-ethyl)- 1H-pyrrolo[2,3-b]pyridin- 4-yl]-4-piperazin-1-yl- pyrido[3,4-d[pyrimidine 
               
               
                   
               
               
                 2110 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 461 (M + H)+ 
                 1H-NMR: DMSO 9.60 (br m, 1H), 8.98 (s, 1H), 8.90 (s, 1H), 8.18 (m, 2H), 7.81 (s, 1H), 7.69 (m, 1H), 7.28 (m, 1H), 7.19 (m, 2H), 4.84 (m, 1H), 3.64 (m, 1H), 3.48 (m, 2H), 3.09 (s, 3H), 3.05 (m, 2H), 2.45 (m, 1H), 2.07- 2.25 (br m, 8H), 1.77 (m, 2H), 1.24 (m, 2H), 0.99 (m, 2H) 
                 (1-Cyclobutyl-piperidin- 4-yl)-{5-cyclopropyl- 2-[2-(2,6- difluroo-phenylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}- methyl-amine 
               
               
                   
               
               
                 2111 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 3.20 min, MI: 456 [M + H] 
                 (500 MHz, d6-DMSO) 11.87 (brs, 1H), 9.16 (s, 1H), 8.31 (d, 1H), 8.16 (s, 1H), 8.08 (d, 1H), 7.21 (s, 1H), 4.11-3.73 (m ,4H), 4.00 (dd, 2H), 3.49 (t, 2H), 3.41-3.32 (m, 4H), 3.12- 3.04 (m, 1H), 2.78-2.70 (m, 1H), 2.02-1.97 (m, 2H), 1.87-1.76 (m, 2H), 1.29- 1.23 (m, 2H), 1.10-1.05 (m, 2H). 
                 5-Cyclopropyl- 4-piperazin-1-yl-2- [2-(tetrahydro-pyran-4- yl)-1H-pyrrolo[2,3-b] pyridin-4-yl]-pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 2112 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 3.25 min, MI: 400 [M + H] 
                 (500 MHz, d6-DMSO) 11.99 (1H, s), 9.25 (1H, s), 9.11 (1H, brs), 8.96 (1H, brs), 8.79 (1H, s), 8.31 (1H, d), 8.13-8.12 (1H, m), 7.22 (1H, s), 4.31-4.24 (1H, m), 3.93-3.85 (2H, m), 3.83- 3.72 (2H, m), 3.43-3.34 (2H, m), 3.32-3.21 (2H, m), 2.51 (3H, s), 2.47-2.42 (1H, m), 2.26-2.17 (2H, m), 2.15- 2.06 (1H, m), 1.94-1.87 (1H, m). 
                 5-Cyclobutyl-2-(2- methyl-1H- pyrrolo[2,3-b]pyridin- 4-yl)-4-piperazin-1-yl- pyrido[3,4-d[pyrimidine 
               
               
                   
               
               
                 2113 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4], [D3] 
                 Method 5: RT: 3.18 min, MI: 502 [M + H] 
                 (400 MHz, d6-DMSO,  90° C.) 11.25 (1H, s), 9.02 (1H, s), 8.63 (1H, s), 8.26 (1H, d, J = 5.0 Hz), 8.03 (1H, d, J = 5.0 Hz), 7.45-7.42 (2H, m), 7.37-7.34 (2H, m), 7.29- 7.25 (1H, m), 7.01 (1H, s), 4.34-4.30 (1H, m), 3.48 (4H, br s), 2.88-2.85 (4H, br. m), 2.55-2.50 (2H, m largely obscured by DMSO peak - visible but broad at lower T), 2.20-2.05 (3H, 
                 5-Cyclobutyl-2- [2-(1-phenyl- cyclopropyl)-1H- pyrrolo[2,3-b]pyridin- 4-yl]-4-piperazin-1-yl- pyrido[3,4-d]pyrimidine 
               
               
                   
                   
                   
                   
                 m), 1.97-1.92 (1H, m), 
                   
               
               
                   
                   
                   
                   
                 1.59-1.56 (2H, m), 1.39- 
                   
               
               
                   
                   
                   
                   
                 1.36 (2H, m). 
                   
               
               
                   
               
               
                 2114 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3], [D8] 
                 Method 5: RT: 2.55 min, MI: 436 [M + H] 
                 (400 MHz, d6-DMSO,  90° C.) 9.13 (1H, s), 8.68 (1H, s), 8.51 (1H, d, J = 5.0 Hz), 8.16 (1H, d, J = 5.0 Hz), 7.75 (1H, s), 7.23 (1H, t, J = 54.7 Hz), 4.36-4.32 (1H, m), 3.64-3.61 (4H, br m), 2.95-2.93 (4H, br. m), 2.56- 2.49 (2H, m overlapping with DMSO signal), 2.22- 2.07 (3H, m), 1.99-1.94 (1H, m). 
                 5-Cyclobutyl-2-(2- difluoromethyl-1H- pyrrolo[2,3-b] pyridin-4-yl)-4- piperazin-1-yl-pyrido [3,4-d]pyrimidine 
               
               
                   
               
               
                 2115 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 542 (M + H) 
                 1H-NMR: DMSO 9.20 (br m, 1H), 8.98 (s, 1H), 8.92 (s, 1H), 8.19 (d, 2H, J = 4.5 Hz), 7.83 (s, 1H), 7.73 (m, 1H), 7.32 (m, 1H), 7.18 (m, 2H), 4.87 (m, 1H), 3.54 (m, 3H), 3.25 (m, 2H), 3.10 (s, 3H), 2.45 (m, 1H), 2.15 (br m, 4H), 1.31 (d, 6H, J = 6.6 Hz), 1.26 (m, 2H), 0.99 (m, 2H) 
                 {5-Cyclopropyl- 2-[2-(2,6- difluoro-phenylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-(1- isopropyl-piperidin-4-yl)- methyl-amine 
               
               
                   
               
               
                 2116 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 530 (M + H) 
                 (400 MHz, d6-DMSO, δ): 10.19 (s, 1H), 9.08 (s, 1H), 8.85 (br s, 2H), 8.76 (s, 1H), 8.57 (d, J = 5.3 Hz,  1H), 8.20 (s, 1H), 8.13 (s, 1H), 7.99 (d, J = 9.6 Hz, 1H), 7.94 (dd, J = 5.4, 1.2 Hz,  1H), 7.56 (dd, J = 9.6, 1.8 Hz, 1H), 3.93 (br s, 4H), 3.34 (br s, 4H),  2.72-2.65 (m, 1H), 1.29-1.23 (m, 2H), 1.12-1.06 (m, 2H). 
                 Benzo[1,2,5]oxadiazol-5- yl-[4-(5-cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)-pyridin- 2-yl]-amine 
               
               
                   
               
               
                 2117 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B1] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 478 (M + H)+ 
                 1H-NMR (DMSO-d6, 400 MHz): 13.23 (s, 1H), 9.44 (s, 1H), 8.97 (br s, 1H),  8.85 (s, 1H), 8.77 (br s, 1H), 8.66 (d, 1H, J = 5.0 Hz), 8.28 (d, 1H, J = 5.0 Hz), 7.97 (s, 1H), 3.7-4.0 (m, 8H) 
                 5-Bromo-4-piperazin- 1-yl- 2-(2-trifluoromethyl-1H- pyrrolo[2,3-b]pyridin-4- yl)-pyrido[3,4-d] pyrimidine 
               
               
                   
               
               
                 2118 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 462 (M + H) 
                 1H-NMR (DMSO-d6, 400 MHz): 11.80 (s, 1H), 8.96 (br s, 1H), 8.77 (br s, 1H), 8.32 (d, 1H, J = 5.1 Hz), 8.11 (d, 1H, J = 5.1 Hz), 7.95 (s, 1H), 7.49 (d, 1H,  J = 2.3 Hz),  3.9-4.0 (m, 4H), 3.33 (m, 4H), 2.67 (m, 2H), 1.43 (s, 9H), 1.25 (m, 2H), 1.06 (m, 2H) 
                 2-(2-tert-Butyl-1H- pyrrolo[2,3-b]pyridin- 4-yl)-8-chloro- 5-cyclopropyl-4- piperazin-1-yl-pyrido [3,4-d]pyrimidine 
               
               
                   
               
               
                 2119 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4], [D3] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 446 (M + H) 
                 1H-NMR (DMSO-d6, 400 MHz): 11.80 (s, 1H), 8.88 (br s, 2H), 8.32 (d, 1H, J = 5.1 Hz), 8.08 (d, 1H, J = 5.1 Hz), 7.73 (s, 1H), 7.21 (d, 1H, J = 2.3 Hz), 3.9-4.0 (m, 4H), 3.34 (m ,4H), 2.67 (m, 1H), 1.43 (s, 9H), 1.21 (m, 2H), 1.01 (m, 2H) 
                 2-(2-tert-Butyl-1H- pyrrolo[2,3-b]pyridin- 4-yl)-5- cyclopropyl-8-fluoro-4- piperazin-1-yl-pyrido [3,4-d]pyrimidine 
               
               
                   
               
               
                 2120 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 466 (M + H) 
                 1H-NMR (DMSO-d6, 400 MHz): 11.82 (s, 1H), 9.35 (s, 1H), 9.01 (br s, 1H), 8.81 (s, 1H), 8.79 (br s, 1H), 8.32 (d, 1H, J = 5.2 Hz), 8.08 (d, 1H, J = 5.2 Hz), 7.16 (d, 1H, J = 2.2 Hz), 3.7-4.0 (m ,4H), 3.37 (m, 4H), 1.44 (s, 9H) 
                 5-Bromo-2-(2- tert-butyl-1H-pyrrolo [2,3-b]pyridin-4-yl)- 4-piperazin-1-yl-pyrido [3,4-d]pyrimidine 
               
               
                   
               
               
                 2121 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 95%, RT: min, MI: 468.26 
                 (dmso-d6) 11.70 (s, 1H), 9.15 (s, 1H), 8.94 (br s, 2H), 8.30 (d, J = 5.2 Hz, 1H), 8.17 (s, 1H), 8.09 (d, J = 5.2 Hz, 1H), 7.20 (s, 1H), 4.74- 4.70 (m, 1H), 4.63 (qpp d,  J = 3.7 Hz, 1H), 3.93 (br s, 4H), 3.36 (br s, 4H), 3.24 (dd, J = 8.8; 4.8 Hz, 1H), 2.80-2.70 (m, 1H), 2.10 1.95 (m, 2H), 1.67-1.50 (m, 4H), 1.30-1.20 (m, 2H), 1.15-1.05 (m, 2H) 
                 (±)-exo-5- Cyclopropyl-2-[2- (7-oxa-bicyclo[2.2.1] hept-2-yl)-1H- pyrrolo[2,3-b]pyridin- 4-yl]-4-piperazin-1-yl- pyrido[3,4-d]pyrimidine 
               
               
                   
               
               
                 2122 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 97%, RT: min, MI:  482.24 (M + H) 
                 (dmso-d6) 11.70 (br s, 1H), 9.22 (s, 1H), 8.98 (br s, 1H), 8.88 (br s, 1H), 8.78 (s, 1H), 8.30 (d, J = 5.2 Hz, 1H), 8.08 (d, J = 5.2 Hz, 1H), 7.18 (s, 1H), 4.73-4.70 (m, 1H), 4.63 (d, J = 3.6 Hz, 1H), 4.28 (app quint, 1H), 3.95-3.75 (m, 4H), 3.45- 3.30 (m, 4H), 3.23 (dd, J = 8.8; 4.8 Hz, 1H), 2.50-2.40 (m, 2H), 2.30-2.15 (m, 2H), 2.15-2.00 (m, 2H), 2.00- 1.85 (m, 2H), 1.75-1.55 (m, 
                 (±)-dxo-5- Cyclobutyl-2-[2-(7- oxa-bicyclo[2.2.1]hept-2- yl)-1H-pyrrolo[2,3-b] pyridin- 4-yl]-4-piperazin-1-yl- pyrido[3,4-d]pyrimidine 
               
               
                   
                   
                   
                   
                 4H) 
                   
               
               
                   
               
               
                 2123 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 552 (MH)+ 
                 1H-NMR: DMSO 8.98 (s, 1H), 8.91 (s, 1H), 8.19 (d, 2H, J = 4.2 Hz), 7.81 (s, 1H), 7.68 (m, 1H), 7.32 (m, 1H), 7.18 (m, 2H), 6.55 (br m, 1H), 4.80 (m, 1H), 3.63 (br m, 4H), 3.31 (m, 2H), 3.10 (s, 3H), 2.44 (m, 1H), 2.08 (br m, 4H), 1.24 (m, 2H), 0.99 (m, 2H) 
                 {5-Cyclopropyl-2- [2-(2,6- difluoro-phenylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}- [1-(2,2-difluoro-ethyl)- piperidin-4- yl]-methyl-amine 
               
               
                   
               
               
                 2124 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 96%, RT: min, MI: 464.28 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.35 (s, 1H), 9.06 (s, 1H), 8.86 (br s, 2H), 8.26 (d, J = 5.6 Hz, 1H), 8.18 (s,  1H), 7.94 (s, 1H), 7.68 (dd, J = 5.4, 1.3 Hz, 1H), 7.66 (s, 1H), 7.39 (dd, J = 8.0,  1.7 Hz, 1H), 7.16 (d, J = 8.0 Hz, 1H), 3.92 (br s, 4H), 3.33 (br s, 4H), 2.89-2.79 (m, 4H), 2.73-2.65 (m, 1H), 2.07- 1.98 (m, 2H), 1.28-1.23 (m, 2H), 1.11-1.06 (m, 2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d] pyrimidin-2-yl)-pyridin- 2-yl]-indan-5-yl-amine 
               
               
                   
               
               
                 2125 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 Method 5: RT: 2.88 min, MI: 529 [M + H] 
                 (500 MH, d6-DMSO) 9.69 (1H, s), 9.06 (1H, s), 8.82 (1H, s), 8.43 (1H, d), 8.21 (1H, s), 7.98 (1H, dd), 7.56 (1H, m), 3.93 (4H, s), 3.36 (2H, s,), 1.95 (1H, m), 1.39 (3H, m), 1.28 (3H, m), 1.06 (2H, m), 0.98 (2H, m), 0.79 (2H, m). 
                 (5-Cyclopropyl- 3,6-difluoro- pyridin-2-yl)-{4-[5- cyclopropyl-4-(3,3- dimethyl-piperazin- 1-yl)-pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-amine 
               
               
                   
               
               
                 2126 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 98%, RT: min, MI: 502.1 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 11.53 (s, 1H), 9.09 (s, 1H), 9.00 (s, 1H), 8.89 (br s, 2H), 8.61 (dd, J = 5.2, 0.5 Hz,  1H), 8.21-8.18 (m, 2H),  7.79-7.75 (m, 2H), 7.64-7.55 (m, 3H), 3.92 (br s, 4H), 3.37- 3.28 (m, 4H), 2.72-2.64 (m, 1H), 1.28-1.22 (m, 2H), 1.11-1.05 (m, 2H). 
                 N-[4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d] pyrimidin-2-yl)-pyridin- 2-yl]-2,2-difluoro-2- phenyl-acetamide 
               
               
                   
               
               
                 2127 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 3.40 min, MI: 430 [M + H] 
                 (600 MHz, d6-DMSO) 12.06 (1H, s), 9.08 (1H, s), 8.37 (1H, d, J = 5.0 Hz), 9.11-8.10 (2H, m), 7.45 (1H, br d, J = 1.6 Hz), 3.96- 3.51 (4H, bery broad m), 2.94 (4H, br s), 2.70-2.66 (1H, m), 1.58-1.542H, m), 1.36-1.34 (2H, m), 1.27- 1.24 (2H, m), 1.05-1.04 (2H, m). 
                 5-Cyclopropyl-2-[2-(1- fluoro-cyclopropyl)-1H- pyrrolo[2,3-b]pyridin- 4-yl]-4-piperazin- 1-yl-pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 2128 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 505 (MH)+ 
                 1H-NMR: DMSO 9.65 (br s, 1H), 9.27 (s, 1H), 8.86 (s, 1H), 8.57 (s, 1H), 8.25 (d, 1H, J = 5.3 Hz), 7.85 (s, 1H), 7.72 (m, 1H), 7.30 (m, 1H), 7.19 (m, 2H), 4.3 5 (m, 1H), 3.61 (m, 2H), 3.30 (m, 2H), 2.88 (s, 3H), 2.46 (m, 1H), 2.27 (m, 2H), 1.93 (m, 2H), 1.22 (m, 2H), 1.07 (m, 2H) 
                 {4-[5-Cyclopropyl-4-(1- methyl-piperidin-4- yslulfanyl)-pyrido[3,4- d]pyrimidin-2-yl]- pyridin-2-yl}-(2,6- difluoro-phenyl)-amine 
               
               
                   
               
               
                 2129 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 503 (MH)+ 
                 1H-NMR: DMSO 10.33 (br s, 1H), 9.62 (br s, 1H), 9.01 (s, 1H), 8.61 (s, 1H), 8.41 (d, 1H, J = 5.7 Hz), 8.31 (m, 1H), 8.20 (s, 1H), 8.07 (m, 1H), 7.99 (m, 1H), 4.80 (m, 1H), 3.57 (m, 2H), 3.20 (m, 2H), 3.12 (s, 3H), 2.82 (m, 3H), 2.44 (m, 1H), 2.07 (br m, 4H), 1.25 (m, 2H), 0.99 (m, 2H) 
                 {5-Cyclopropyl-2- [2-(3,5-difluoro- pyridin-2-ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}- methyl-(1-methyl- piperidin-4-yl)-amine 
               
               
                   
               
               
                 2130 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 90.012%, RT: min, MI: 522 
                   
                 [4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d] pyrimidin-2-yl)-pyridin- 2-yl]-[2-fluoro-4-(1- methyl-1H-pyrazol-4-yl)- phenyl]-amine 
               
               
                   
               
               
                 2131 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 98%, RT: min, MI: 450.0 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.52 (s, 1H), 8.96 (s, 1H), 8.83 (br s, 2H), 8.31 (d, J = 5.5 Hz, 1H),  8.18 (s, 1H), 7.95 (s, 1H), 7.75-7.70 (m, 3H), 7.34-7.29 (m, 2H), 6.96 (t, J = 8.0 Hz, 1H), 4.12- 4.06 (m, 2H), 3.88-3.82 (m, 2H), 3.45-3.35 (m, 2H), 3.15-2.95 (m, 4H), 2.45- 2.37 (m, 1H), 1.31-1.25 (m, 2H), 1.04-0.98 (m, 2H). 
                 {4-[5-Cyclopropyl-4- (hexahydro-pyrrolo[3,4- c]pyrrol-2-yl)- pyrido[3,4-d] pyrimidin-2-yl]-pyridin- 2-yl}-phenyl-amine 
               
               
                   
               
               
                 2132 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 97%, RT: min, MI: 487.0 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 10.27 (s, 1H), 8.99 (s, 1H), 8.86 (br s, 2H), 8.72 (s, 1H), 8.41 (d, J = 5.5 Hz, 1H),  8.29 (d, J = 2.6 Hz, 1H), 8.20 (s, 1H), 8.10-8.04 (m, 1H), 7.99 (dd, J = 5.7, 1.4 Hz, 1H), 4.14-4.08 (m, 2H), 3.89- 3.83 (m, 2H), 3.45-3.35 (m, 2H), 3.15-2.95 (m, 4H), 2.44-2.36 (m, 1H), 1.31- 1.26 (m, 2H), 1.04-0.99 (m, 2H). 
                 {4-[5-Cyclopropyl-4- (hexahydro-pyrrolo[3,4- c]pyrrol-2-yl)- pyrido[3,4-d] pyrimidin-2-yl]-pyridin- 2-yl)-(3,5-difluoro- pyridin-2-yl)-amine 
               
               
                   
               
               
                 2133 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 96%, RT: min, MI: 533.18 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.76 (s, 1H), 9.07 (s, 1H), 8.87 (br s, 2H), 8.67 (d, J = 2.1 Hz, 1H), 8.42 (d, J = 5.3 Hz, 1H),  8.19 (s, 1H), 8.00 (s, 1H), 7.88 (d, J = 9.1 Hz, 1H), 7.80-7.76 (m, 2H), 3.92 (br s, 4H), 3.34 (br s, 4H), 2.74-2.65 (m, 1H), 1.29-1.23 (m, 2H), 1.11- 1.06 (m, 2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d] pyrimidin-2-yl)-pyridin- 2-yl]-(2-trifluoromethyl- benzooxazol-5-yl)-amine 
               
               
                   
               
               
                 2134 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 95%, RT: min, MI: 471 (MH)+ 
                 1H-NMR: DMSO 13.25 (s, 1H), 9.46 (s, 1H), 8.70 (m, 2H), 8.59 (s, 1H), 8.49 (m, 1H), 8.32 (m, 1H), 8.05 (s, 1H), 4.58 (m, 1H), 3.40 (m, 2H), 3.28 (m, 2H), 2.56 (m, 1H), 2.40 (m, 2H), 1.97 (m, 2H), 1.24 (m, 2H), 1.08 (m, 2H) 
                 5-Cyclopropyl- 4-(piperidin- 4-ylsulfanyl)-2-(2- trifluoromethyl-1H- pyrrolo[2,3-b] pyridin-4-yl)- pyrido[3,4-d]pyrimidine 
               
               
                   
               
               
                 2135 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 97%, RT: min, MI: 480.1 (M + H) 
                 1H-NMR (dmso-d6): 11.76 (s, 1H), 9.24 (s, 1H), 9.03 (br s, 1H), 8.92 (br s, 1H), 8.79 (s, 1H), 8.29 (d, J = 5.2 Hz, 1H), 8.07 (d, J = 5.2 Hz, 1H), 7.25 (s, 1H), 4.29 (quint, J = 8.8 Hz, 1H), 3.88 (br s, 2H), 3.79 (br s, 2H), 3.40-3.20 (m, 5H), 2.69 (br s, 1H), 2.50-2.40 (m, 2H), 2.36 (br s, 1H), 2.30-1.80 (m, 5H), 1.70-1.40 (m, 4H), 1.30-1.20 (m, 2H), 1.15- 1.05 (m, 1H) 
                 (±) endo-2-(2- Bicyclo[2.2.1]hept- 2-yl-1H-pyrrolo [2,3-b]pyridin-4-yl)-5- cyclobutyl-4-piperazin-1- yl-pyrido[3,4-d] pyrimidine 
               
               
                   
               
               
                 2136 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 95%, RT: min, MI: 502 (M + H) 
                 1H-NMR: DMSO 13.16 (s, 1H), 8.75 (m, 1H), 8.65 (d, 1H, J = 4.9 Hz), 8.37 (m, 1H), 8.32 (m, 1H), 8.21 (s, 1H), 7.98 (s, 1H), 4.95 (m, 1H), 3.47 (m, 2H), 3.21 (m, 2H), 3.11 (s, 3H), 2.40 (m, 1H), 1.91-2.18 (br m, 4H), 1.14-1.33 (br m, 2H), 0.96 (m, 2H) 
                 [8-Chloro-5- cyclopropyl-2-(2- trifluoromethyl-1H- pyrrolo[2,3-b]pyridin- 4-yl)-pyrido[3,4-d] pyrimidin-4-yl]-methyl- piperidin-4-yl-amine 
               
               
                   
               
               
                 2137 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 478.27 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.07 (s, 1H), 8.94 (br s, 2H), 8.22 (s, 1H), 8.10 (d, J = 6.2 Hz, 1H), 8.02 (br s, 1H), 7.69-7.64 (m, 1H), 7.17- 7.11 (m, 4H), 4.21-4.13 (m, 1H), 3.93 (br s, 4H), 3.32 (br s, 4H), 3.20 (dd, J = 16.5, 5.2 Hz, 1H), 2.94 (t, J = 6.3 Hz, 2H), 2.80 (dd, J = 16.4, 8.4 Hz, 1H), 2.70-2.63 (m, 1H), 2.20-2.13 (m, 1H), 1.89-1.77 (m, 1H), 1.29- 1.23 (m ,2H), 1.11-1.06 (m, 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidin- 2-yl)-pyridin-2- yl]-(1,2,3,4-tetrahydro- naphthalen-2-yl)-amine 
               
               
                   
                   
                   
                   
                 2H). 
                   
               
               
                   
               
               
                 2138 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 503 (M + H) 
                 1H-NMR: DMSO 12.20 (br s, 1H), 9.03 (s, 1H), 8.84 (m, 1H), 8.69 (d, 2H, J = 5.7 Hz), 8.57 (m, 1H), 8.45 (m, 1H), 8.22 (m, 3H), 8.04 (m, 1H), 7.88 (m, 1H), 7.61 (m, 1H), 7.56 (m, 1H), 4.89 (m, 1H), 3.45 (m, 2H), 3.19 (m, 2H), 3.15 (s, 3H), 2.45 (m, 1H), 2.07 (br m, 4H), 1.26 (m, 2H), 1.00 (m, 2H) 
                 {5-Cylcopropyl-2-[2- ([D4], [D3]uinolin-2- ylamino)-pyridin-4-yl]- pyrido[3,4-d] pyrimidin-4- yl}-methyl-piperidin- 4-yl-amine 
               
               
                   
               
               
                 2139 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 95%, RT: min, MI: 482 (M + H) 
                 1H-NMR: DMSO 13.15 (s, 1H), 9.09 (s, 1H), 8.63 (d, 1H, J = 4.9 Hz), 8.48 (m, 1H), 8.25 (d, 1H, J = 4.9 Hz), 8.16 (s, 1H), 8.04 (m, 1H), 7.96 (s, 1H), 3.31 (s, 3H), 3.17 (m, 2H), 2.78 (m, 2H), 2.43 (m, 1H), 2.23 (m, 1H), 1.50-1.75 (br m, 2H), 1.30 (br m, 2H), 1.03 (br m, 6H) 
                 [5-Cyclopropyl-2-(2- trifluoromethyl-1H- pyrrolo[2,3-b] pyridin-4-yl)-pyrido [3,4-d]pyrimidin-4-yl]- methyl-piperidin-4- ylmethyl-amine 
               
               
                   
               
               
                 2140 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 97%, RT: min, MI: 480.1 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.08 (s, 1H), 8.94 (br s, 2H), 8.29-8.17 (m, 2H), 8.12 (d, J = 5.9 Hz, 1H), 7.70 (d, J = 6.9 Hz, 1H), 7.36-7.23 (m, 4H), 5.41-5.35 (m, 1H), 4.71-4.66 (m, 1H), 3.92 (br s, 4H), 3.31 (br s, 4H), 3.15 (dd, J = 16.3, 5.7 Hz, 1H), 2.93 (dd, J = 16.3, 2.5 Hz, 1H), 2.70-2.62 (m, 1H), 1.29-1.23 (m, 2H), 1.11- 1.06 (m, 2H). 
                 (1S,2R)-1- [4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidin- 2-yl)-pyridin-2- ylamino]-indan-2-ol 
               
               
                   
               
               
                 2141 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 98%: RT: min, MI: 480.1 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.08 (s, 1H), 8.98 (br s, 2H), 8.22 (s, 1H), 8.15 (d, J = 6.4 Hz, 1H), 8.09 (br s, 1H), 7.72 (d, J = 6.2 Hz, 1H), 7.32-7.22 (m, 4H), 5.30- 5.24 (m, 1H), 4.39 (dd, J = 13.9, 7.1 Hz, 1H), 3.92 (br s, 4H), 3.32 (br s, 4H), 3.25 (dd, J = 1.5.7, 7.2 Hz, 1H), 2.83 (dd, J = 15.4, 7.5 Hz, 1H), 2.70-2.62 (m, 1H), 1.29-1.23 (m, 2H), 1.11- 1.06 (m, 2H). 
                 (1S,2S)-1- [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido [3,4-d]pyrimidin- 2-yl)-pyridin-2- ylamino]-indan-2-ol 
               
               
                   
               
               
                 2142 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4]   
                 LCMS: Purity: 98%, RT: min, MI: 480.1 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.08 (s, 1H), 8.94 (br s, 2H), 8.29-8.17 (m, 2H), 8.13 (d, J = 6.1 Hz, 1H), 7.71 (d, J = 5.6 Hz, 1H), 7.36-7.23 (m, 4H), 5.41-5.35 (m, 1H), 4.70-4.65 (m, 1H), 3.92 (br s, 4H), 3.31 (br s, 4H), 3.15 (dd, J = 16.1, 5.4 Hz, 1H), 2.93 (dd, J = 16.1, 2.6 Hz, 1H), 2.70-2.62 (m, 1H), 1.29-1.23 (m, 2H), 1.11- 1.06 (m, 2H). 
                 (1R,2S)-1- [4-(5-Cyclopropyl- 4-piperazin-1-yl-pyrido [3,4-d]pyrimidin- 2-yl)-pyridin-2- ylamino]-indan-2-ol 
               
               
                   
               
               
                 2143 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 99%, RT: min, MI: 480.1 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.09 (s, 1H), 9.04 (br s, 2H), 8.23 (s, 1H), 8.16 (d, J = 6.5 Hz, 1H), 8.13 (br s, 1H), 7.74 (d, J = 6.2 Hz, 1H), 7.34-7.23 (m, 4H), 5.27 (t, J = 6.8 Hz, 1H), 4.39 (dd, J = 13.9, 7.1 Hz, 1H), 3.91 (br s, 4H), 3.32 (br s, 4H), 3.25 (dd, J = 15.6, 7.1 Hz, 1H), 2.83 (dd, J = 15.5, 7.6 Hz, 1H), 2.70-2.62 (m, 1H), 1.30-1.23 (m, 2H), 1.11- 1.06 (m, 2H). 
                 (1R,2R)-1-[4-(5- Cyclopropyl-4- piperazin-1-yl-pyrido [3,4-d]pyrimidin-2- yl)-pyridin-2-ylamino]- indan-2-ol 
               
               
                   
               
               
                 2144 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 83%, RT: min, MI: 498.0 (M + H) 
                 (dmso-d6) 9.16 (br s, 1H), 8.83 (br s, 1H), 8.74 (br s, 2H), 8.41 (d, J = 4.8 Hz, 1H), 8.12 (d, J = 4.8 Hz, 1H), 7.70 (br s, 1H), 7.55- 7.46 (m, 1H), 7.30-7.22 (m, 2H), 4.30-4.15 (m, 1H), 3.90-3.60 (m, 4H), 3.40- 3.15 (m, 4H), 2.45-2.35 (m, 2H), 2.20-2.10 (m, 2H), 2.10-1.98 (m, 1H), 1.90- 1.80 (m, 1H) 
                 5-Cyclobutyl-2-[2-(2,6- difluoro-phenyl)-1H- pyrrolo[2,3-b] pyridin-4-yl]-4- piperazin-1-yl-pyrido [3,4-d]pyrimidine 
               
               
                   
               
               
                 2145 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 95%, RT: min, MI: 484.2 (M + H) 
                 (dmso-d6) 12.23 (d, J = 1.3 Hz, 1H), 9.14 (s, 1H), 8.91 (br s, 2H), 8.49 (d, J = 5.0 Hz, 1H), 8.19 (d, J = 5.0 Hz, 1H), 8.18 (s, 1H), 7.78 (br s, 1H), 7.56 (m, 1H), 7.33 (m, 2H), 3.93 (br s, 4H), 3.36 (br s, 4H), 2.75 (m, 1H), 1.30-1.23 (m, 2H), 1.12- 1.06 (m, 2H) 
                 5-Cyclopropyl-2-[2-(2,6- difluoro-phenyl)-1H- pyrrolo[2,3-b]pyridin- 4-yl]-4-piperazin- 1-yl-pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 2146 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 96%, RT: min, MI: 426.1 (M + H) 
                 (dmso-d6) 11.82 (br s, 1H), 9.16 (s, 1H), 8.93 (br s, 2H), 8.30 (d, J = 5.2 Hz, 1H), 8.17 (s, 1H), 8.09 (d, J = 5.2 Hz, 1H), 7.24 (d, J = 1.7 Hz, 1H), 3.91 (br s, 4H), 3.74 (quint, J = 8.4 Hz, 1H), 3.37 (br s, 4H), 2.75 (m, 1H), 2.45-2.75 (m, 4H), 2.35- 1.98 (m, 1H), 1.96-1.85 (m, 1H), 1.30-1.22 (m, 2H), 1.12-1.08 (m, 2H) 
                 2-(2-Cyclobutyl-1H- pyrrolo[2,3-b] pyridin-4-yl)-5- cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidine 
               
               
                   
               
               
                 2147 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 92%, RT: min, MI: 440.28 (M + H) 
                 (dmso-d6) 11.89 (br s, 1H), 9.25 (s, 1H), 9.10 (br s, 1H), 8.94 (br s, 1H), 8.79 (s, 1H), 8.30 (d, J = 5.2 Hz, 1H), 8.09 (d, J = 5.2 Hz, 1H), 7.23 (d, J = 1.6 Hz, 1H), 4.29 (quint, 1H), 3.88 (br s, 2H), 3.79 (br s, 2H), 3.75 (quint, J = 8.8 Hz, 1H), 3.50-3.20 (m, 4H), 2.50- 2.43 (m, 2H), 2.43-2.31 (m, 4H), 2.31-2.16 (m, 2H), 2.16-1.97 (m, 2H), 1.97- 1.07 (m, 2H) 
                 5-Cyclobutyl-2-(2- cyclobutyl- 1H-pyrrolo[2,3-b] pyridin-4-yl)-4-piperazin- 1-yl-pyrido[3,4-d] pyrimidine 
               
               
                   
               
               
                 2148 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 98%, RT: min,, MI: 495 (M + H) 
                 1H NMR (400 MHz, DMSO-d6) 9.80-10.03 (1 H, m), 8.83-9.14 (2 H, m), 8.81 (1 H, s), 8.43 (1 H, d, J = 5.5 Hz), 8.26 (1 H, d, J = 2.5 Hz), 7.90-8.08 (3 H, m), 3.97 (4 H, br. s.), 3.32 (4 H, br. s.), 2.57-2.64 (1 H, m), 1.18-1.30 (2 H, m), 1.01-1.11 (2 H, m) 
                 [4-(8-Chloro- 5-cyclopropyl-4- piperazin-1-yl-pyrido [3,4-d]pyrimidin- 2-yl)-pyridin-2- yl]-(3,5-difluoro-pyridin- 2-yl)-amine 
               
               
                   
               
               
                 2149 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 98%, RT: min, MI: 478.24 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.91 (s, 1H), 9.34 (s, 1H), 9.07 (s, 1H), 8.97 (br s, 2H), 8.68 (d, J = 1.4 Hz,  1H), 8.45 (d, J = 5.3 Hz, 1H), 8.20 (s, 1H), 8.04 (s, 1H), 7.82 (dd, J = 5.4, 1.4 Hz, 1H), 7.78 (d, J = 8.9 Hz, 1H), 7.65 (dd, J = 9.0, 1.8 Hz, 1H), 4.03 (s, 3H), 3.93 (br s, 4H), 3.35 (br s, 4H), 2.74-2.65 (m, 1H), 1.29-1.23 (m, 2H), 1.11-1.06 (m, 2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d] pyrimidin-2-yl)-pyridin- 2-yl]-(3-methyl-3H- benzimidazol-5-yl)-amine 
               
               
                   
               
               
                 2150 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 Method 5: RT: 2.34 min, MI: 522 [M + H] 
                 (500 MH, DMSO) 9.43 (1H, s), 9.06 (1H, s), 8.29 (1H, d), 8.18 (1H, s), 7.91 (1H, s), 7.68 (3H, m), 7.05 (2H, d), 4.72 (2H, m), 3.91 (4H, s, broad), 3.33 (4H, s,), 2.69 (1H, m), 1.26 (2H, m), 1.08 (2H, m). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidin- 2-yl)-pyridin-2- yl]-[4-(2,2,2-trifluoro- ethoxy)-phenyl]-amine 
               
               
                   
               
               
                 2151 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 506 (MH)+ 
                 1H-NMR: DMSO 10.29 (br s, 1H), 9.01 (s, 1H), 8.80 (br m, 1H), 8.73 (s, 1H), 8.45 (d, 1H, J = 5.5 Hz), 8.38 (br m, 1H), 8.27 (m, 1H), 8.20 (s, 1H), 8.10 (m, 1H), 8.03 (m, 1H), 4.84 (m, 1H), 3.44 (m, 2H), 3.15 (m, 2H), 3.12 (s, 3H), 2.44 (m, 1H), 2.07 (br m, 4H), 1.25 (m, 2H), 0.98 (m, 2H) 
                 {2-[2-(5-Chloro- 3-fluoro-pyridin-2- ylamino)-pyridin- 4-yl]-5-cyclopropyl- pyrido[3,4-d] pyrimidin-4-yl}- methyl-piperidin-4-yl- amine 
               
               
                   
               
               
                 2152 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 95%, RT: min, MI: 454.23 (M + H) 
                 (dmso-d6) 11.71 (d, J = 1.3 Hz, 1H), 9.09 (s, 1H), 8.89 (br s, 2H), 8.23 (d, J = 5.2 Hz, 1H), 8.10 (s, 1H), 8.02 (d, J = 5.2 Hz, 1H), 7.11 (d, J = 1.7 Hz, 1H), 3.84 (br s, 4H), 3.30 (br s, 4H), 2.76 (m, 1H), 2.68 (m, 1H), 2.15 (m, 2H), 1.77 (m, 2H), 1.67 (m, 1H), 1.51 (m, 2H), 1.36 (m, 2H), 1.28-1.13 (m, 3H), 1.06-0.80 (m, 2H) 
                 5-Cyclopropyl-2-(2- cyclohexyl-1H- pyrrolo[2,3-b]pyridin- 4-yl)-4-piperazin- 1-yl-pyrido[3,4-d] pyrimidine 
               
               
                   
               
               
                 2153 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 94%, RT: min, MI: 468.28 
                 (dmso-d6) 11.72 (s, 1H), 9.17 (s, 1H), 8.99 (br s, 1H), 8.84 (br s, 1H), 8.72 (s, 1H), 8.22 (d, J = 5.3 Hz, 1H), 8.01 (d, J = 5.3 Hz, 1H), 7.1 (d, J = 1.8 Hz, 1H), 6.28 (br s, esch. protons), 4.11 (m, 1H), 3.76 (m, 4H), 3.17 (m, 4H), 2.75 (m, 1H), 2.42 (m, 2H), 2.15 (m, 2H), 2.58- 1.95 (m, 3H), 1.77 (m, 4H), 1.50 (m, 2H), 1.35 (m, 2H), 1.24 (m, 1H) 
                 5-Cyclobutyl-2-(2- cyclohexyl- 1H-pyrrolo[2,3-b] pyridin-4-yl)-4-piperazin- 1-yl-pyrido[3,4-d] pyrimidine 
               
               
                   
               
               
                 2154 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 94%, RT: min, MI: 593.17 (M + H) 
                 (dmso-d6) 9.10 (s, 1H), 9.05 (br s, 1H), 9.02 (br s, 1H), 8.92 (br s, 2H), 8.53 (s, 1H), 8.49 (dd, J = 8.3, 2.3 Hz, 1H), 8.36 (d, J = 5.2 Hz, 1H), 8.22 (s, 1H), 8.10 (d,  J = 8.3 Hz, 1H), 8.06 (s, 1H), 7.77 (dd, J = 5.3, 1.3 Hz, 1H), 3.88 (br s, 4H), 3.37 (br s,4H), 2.71 (m, 1H), 1.28 (m, 2H), 1.12 (m, 2H) 
                 [3-Chloro-1-(5- trifluoromethyl- pyridin-2-yl)-1H- pyrazol-4-yl]-[4-(5- cyclopropyl-4- piperazin-1-yl-pyrido [3,4-d]pyrimidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
               
               
                 2155 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 490 (M + H) 
                 1H-NMR: DMSO 13.14 (s, 1H), 9.73 (br m, 1H), 9.35 (br m, 1H), 9.26 (s, 1H), 8.64 (d, 1H, J = 4.9 Hz), 8.56 (s, 1H), 8.34 (d, 1H,  J = 4.9 Hz), 7.97 (m, 2H), 5.50 (m, 1H), 4.02 (m, 1H), 3.82-3.90 (br m,1H), 3.45 (m, 2H), 2.61 (m, 1H), 2.54 (m, 1H), 2.08 (m, 1H), 1.21 (m, 3H), 1.05 (m, 1H) 
                 [5-Cyclopropyl-2-(2- trilfuoromethyl-1H- pyrrolo[2,3-b] pyridin-4-yl)-pyrido [3,4-d]pyrimidin-4-yl]- (3,3-difluoro-piperidin- 4-yl)-amine 
               
               
                   
               
               
                 2156 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 511 (M + H) 
                 1H-NMR: DMSO 10.06 (br s, 1H), 9.84 (br m, 1H), 9.37 (br m, 1H), 9.14 (s, 1H), 8.65 (s, 1H), 8.56 (s, 1H), 8.41 (d, 1H, J = 5.5 Hz), 8.28 (m, 1H), 8.06 (m, 3H), 5.50 (m, 1H), 4.01 (m, 1H), 3.76-3.87 (br m, 1H), 3.45 (m, 1H), 3.35 (m, 1H), 2.60 (m, 1H), 2.46 (m, 1H), 2.07 (m, 1H), 1.20 (m, 3H), 1.03 (m, 1H) 
                 {5-Cyclopropyl- 2-[2-(3,5-difluoro- pyridin-2-ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-(3,3- difluoro-piperidin-4-yl)- amine 
               
               
                   
               
               
                 2157 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 503 (M + H) 
                 1H-NMR: DMSO 10.17 (br s, 1H), 9.06 (s, 1H), 8.81(br m, 1H), 8.66 (s, 1H), 8.61 (s, 1H), 8.40 (d, 1H, J = 5.6 Hz), 8.35 (m, 1H), 8.29 (d, 1H, J = 2.5 Hz), 8.05 (m, 1H), 7.99 (m, 1H), 4.82 (m, 1H), 4.16 (m, 1H), 3.51 (m, 1H), 3.39 (m, 1H), 3.15 (m, 2H), 2.98 (s, 3H), 2.64 (m, 1H), 2.22-2.37 (br m, 4H), 1.84-2.11 (br m, 5H) 
                 {5-Cyclobutyl-2-[2-(3,5- difluoro-pyridin- 2-ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}- methyl-piperidin-4-yl- amine 
               
               
                   
               
               
                 2158 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 97%, RT: min, MI: 480.26 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.08 (s, 1H), 8.97 (br s, 2H), 8.22 (s, 1H), 8.15 (d, J = 6.5 Hz, 1H), 8.09 (s, 1H), 7.71 (d, J = 6.4 Hz, 1H),  7.40-7.27 (m, 4H), 5.10 (d, J = 6.6 Hz, 1H), 4.40-4.30 (m, 1H), 3.93 (br s, 4H), 3.44 (dd, J = 15.6, 7.7 Hz, 1H), 3.32 (br s, 4H), 2.82 (dd, J = 15.1, 8.1 Hz, 1H), 2.70-2.63 (m, 1H), 1.29-1.23 (m, 2H), 1.11-1.06 (m, 2H). 
                 trans-2-[4-(5- Cyclopropyl-4-piperazin- 1-yl-pyrido[3,4- d]pyrimidin-2-yl)-pyridin- 2-ylamino]-indan-1-ol 
               
               
                   
               
               
                 2159 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 98%, RT: min, MI: 468.1 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.10-8.90 (m, 3H), 8.21 (d, J = 2.7 Hz, 1H), 8.15-7.95 (m, 2H), 7.67 (d, J = 5.2 Hz, 1H), 7.47-7.27 (m, 5H), 5.04 (s, 1H), 4.10-3.65 (m, 6H), 3.32 (br s, 4H), 2.70- 2.60 (m, 1H), 1.29-1.22 (m, 2H), 1.10-1.05 (m, 2H). 
                 (R)-2-[4-(5- Cyclopropyl-4-piperazin- 1-yl-pyrido[3,4-d] pyrimidin-2-yl)-pyridin- 2-ylamino]-2-phenyl- ethanol 
               
               
                   
               
               
                 2160 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS Purity: 96%, RT: min, MI: 502.1 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.04 (s, 1H), 8.82 (br s, 2H), 8.19 (s, 1H), 8.07 (d, J = 5.7 Hz, 1H), 7.95-7.87 (m, 4H), 7.62 (dd, J =  8.6, 1.7 Hz, 1H), 7.58 (br s, 1H), 7.52-7.46 (m, 2H), 5.27-5.22 (m, 1H), 3.83 (br s, 4H), 3.30 (br s, 4H), 2.69-2.61 (m, 1H), 1.63 (d, J = 6.7 Hz, 3H), 1.28-1.22 (m, 2H), 1.10- 1.05 (m, 2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d] pyrimidin-2-yl)-pyridin- 2-yl]-((R)-1-naphthalen- 2-yl-ethyl)-amine 
               
               
                   
               
               
                 2161 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;90%, RT: min, MI: 484.1 (M + H) 
                 (dmso-d6) 9.13 (s, 1H),  9.03 (br signal, 2H), 8.81 (s, 1H), 8.08 (d, J = 6.0 Hz, 1H), 7.89 (br s, 1H), 7.62 (d, J = 6.0 Hz, 1H), 7.47 (m, 1H), 7.32 (m, 1H), 7.28-7.13 (m, 2H), 5.33 (m, 1H), 4.23 (m, 1H), 3.80 (m, 4H), 3.30 (m, 4H), 2.45 (m, 2H), 2.24- 2.00 (m, 3H), 1.92 (m, 1H), 1.55 (d, J = 6.8 Hz, 3H) 
                 [4-(5-Cyclobutyl-4- piperazin-1-yl- pyrido[3,4-d] pyrimidin-2-yl)- pyridin-2-yl]-[(R)- 1-(2-fluoro-phenyl)- ethyl]-amine 
               
               
                   
               
               
                 2162 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 Method 5: RT: 3.11 min, MI: 508 [M + H] 
                 (500 MH, d6-DMSO) 9.68 (1H, s), 9.07 (1H, s), 8.35 (1H, d), 8.18 (1H, s), 7.97 (1H, s), 7.85 (2H, d), 7.76 (1H, d), 7.30 (2H, d), 3.92 (4H, s, broad), 3.33 (4H, s), 2.69 (1H, m), 1.25 (2H, m), 1.08 (2H, m). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d] pyrimidin-2-yl)- pyridin-2-yl]-(4- trifluoromethoxy- phenyl)-amine 
               
               
                   
               
               
                 2163 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 521 (M + H) 
                 1H-NMR: 9.80 (s, 1H), 9.05 (s, 1H), 8.73 (m, 1H), 8.65 (s, 1H), 8.56 (s, 1H), 8.41 (d, 1H, J = 5.2 Hz), 8.30 (m, 2H), 7.95 (m, 1H), 4.79 (m, 1H), 4.16 (m, 1H), 3.50 (m, 1H), 3.37 (m, 1H), 3.15 (m, 2H), 2.98 (s, 3H), 2.62 (m, 1H), 2.23-2.37 (br m, 4H), 1.84-2.10 (br m, 5H) 
                 {5-Cyclobutyl- 2-[2-(3,5,6-trifluoro- pyridin-2-ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}- methyl-piperidin-4-yl- amine 
               
               
                   
               
               
                 2164 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 90%, RT: min, MI: 468.24 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.06 (s, 1H), 8.99 (br s, 2H), 8.21 (s, 1H), 8.12-7.95 (m, 2H), 7.67 (d, J = 6.3 Hz, 1H), 7.49-7.27 (m, 5H), 5.08- 5.00 (m, 1H), 4.10-3.65 (m, 6H), 3.33 (br s, 4H), 2.70- 2.61 (m, 1H), 1.29-1.23 (m, 2H), 1.11-1.05 (m, 2H). 
                 (S)-2-[5-(5- Cyclopropyl-4- piperazin-1-yl-pyrido [3,4-d]pyrimidin- 2-yl)-pyridin- 2-ylamino]-2-phenyl- ethanol 
               
               
                   
               
               
                 2165 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 502.24 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.00 (s, 1H), 8.86 (br s, 2H), 8.27-8.22 (m, 1H), 8.18 (s, 1H), 8.07 (d, J = 6.0 Hz,  1H), 7.85 (d, J =  8.0 Hz, 1H), 7.66-7.47 (m, 4H), 5.91- 5.85 (m, 1H), 3.80 (br s, 4H), 3.24 (br s, 4H), 2.66- 2.59 (m, 1H), 1.67 (d, J =  6.4 Hz, 3H), 1.27-1.21  (m, 2H), 1.09-1.04 (m, 2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]- ((R)-1-naphthalen-1-yl- ethyl)-amine 
               
               
                   
               
               
                 2166 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 96%, RT: min, MI: 488.23 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.05 (d, J = 2.2 Hz,  1H), 8.89 (br s, 2H), 8.19 (s, 1H), 8.12 (d, J = 5.8 Hz, 1H), 7.85 (br s, 1H), 7.64-7.49 (m, 6H), 4.30-4.19 (m, 2H),  3.92 (br s, 4H), 3.31 (br s, 4H), 2.74- 2.64 (m, 1H), 1.28-1.22 (m, 2H), 1.10-1.05 (m ,2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl-pyrido [3,4-d]pyrimidin- 2-yl)-pyridin-2- yl]-(2,2-difluoro-2- phenyl-ethyl)-amine 
               
               
                   
               
               
                 2167 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 503 (M + H) 
                 1H-NMR: DMSO  10.33 (br s, 1H), 9.00 (s, 1H), 8.71 (s, 1H), 8.50 (m, 1H), 8.41 (d, 1H, J = 5.7 Hz), 8.28 (d, 1H, J = 2.5 Hz), 8.17 (s, 1H), 8.08 (m, 2H), 7.99 (m, 1H), 3.30 (s, 3h), 3.16 (m, 2H), 2.80 (m, 2H), 2.38 (m, 1H), 2.19 (m, 1H), 1.57 (br m, 2H), 1.29 (m, 2H), 1.03 (m, 6H) 
                 {5-Cyclopropyl-2- [2-(3,5-difluoro- pyridin-2-ylamino)- pyridin-4-yl]- pyrido[3,4-d] pyrimidin-4-yl}-methyl- piperidin-4-ylmethyl- amine 
               
               
                   
               
               
                 2168 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: &gt;95%, RT: min, MI: 477 (M + H) 
                 1H-NMR: DMSO 10.17 (br s, 1H), 9.05 (s, 1H), 8.64 (s, 1H), 8.48 (s, 1H), 8.40 (d, 1H, J = 5.6 Hz), 8.28 (d, 1H, J = 2.5 Hz), 8.06 (m, 1H), 7.98 (m, 1lH), 7.87 (m, 1H), 4.53 (m, 1H), 3.95 (m, 2H), 3.53 (m, 2H), 2.61 (m, 1H), 2.13 (m, 2H), 1.79 (m, 2H), 1.22 (m, 2H), 1.06 (m, 2H) 
                 {5-Cyclopropyl-2- [2-(3,5-difluoro- pyridin-2-ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}- (tetrahydro-pyran-4-yl)- amine 
               
               
                   
               
               
                 2169 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 541 (M + H) 
                 1H-NMR: DMSO 9.76 (s, 1H), 8.73 (s, 1H), 8.71 (m, 1H), 8.43 (d, 1H, J = 5.2 Hz), 8.29 (m, 2H), 7.95 (m, 2H), 4.87 (m, 1H), 3.45 (m, 2H), 3.10 (s, 3H), 2.98 (m, 2H), 2.38 (m, 1H), 1.90- 2.28 (br m, 4H), 1.14-1.29 (br m, 2H), 0.95 (m, 2H) 
                 {8-Chloro-5- cyclopropyl-2-[2-(3,5,6- trifluoro-pyridin-2- ylamino)-pyridin-4-yl]- pyrido[3,4-d]  pyrimidin-4-yl}- methyl-piperidin-4-yl- amine 
               
               
                   
               
               
                 2170 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 523 (M + H) 
                 1H-NMR: DMSO 10.02 (br s, 1H), 8.79 (m, 1H), 8.66 (s, 1H), 8.39 (m, 2H), 8.26 (d, 1H, J = 2.5 Hz), 8.03 (m, 1H), 7.96 (2H), 4.89 (m, 1H), 3.45 (m, 2H), 3.12 (m, 2H), 3.10 (s, 3H), 2.37 (m, 1H), 1.90-2.15 (br m, 4H), 1.14-1.29 (br m, 2H), 0.95 (m, 2H) 
                 {8-Chloro-5- cyclopropyl-2-[2- (3,5-difluoro-pyridin-2- ylamino)-pyridin-4-yl]- pyrido[3,4-d]pyrimidin- 4-yl}-methyl-piperidin- 4-yl-amine 
               
               
                   
               
               
                 2171 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 477 (M + H) 
                 1H-NMR: DMSO 10.16 (s, 1H), 9.05-9.10 (m, 3H), 8.88 (s, 1H), 8.45 (m, 1H), 8.26 (d, 1H, J = 2.1 Hz), 8.20 (s, 1H), 8.10 (m, 1H), 8.02 (m, 1H), 3.94 (m, 4H), 3.34 (m, 4H), 2.69 (m, 1H), 1.27 (m, 2H), 1.09 (m, 2H) 
                 (5-Chloro-3- fluoro-pyridin-2- yl)-[4-(5-cyclopropyl-4- piperazin-1-yl-pyrido[3,4- d]pyrimidin-2-yl)- pyridin-2-yl]-amine 
               
               
                   
               
               
                 2172 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 490 (M + H) 
                 1H-NMR: DMSO 10.48 (br s, 1H), 8.99 (s, 1H), 8.65 (s, 1H), 8.41 (d, 1H, J = 5.8 Hz), 8.30 (d, 1H, J = 2.4 Hz), 8.18 (s, 1H), 8.09 (m, 1H), 7.98 (m, 1H), 4.81 (m, 1H), 3.97 (m, 2H), 3.48 (m, 2H), 3.15 (s, 3H), 2.40 (m, 1H), 1.75-2.07 (br m, 4H), 1.23 (m, 2H), 0.98 (m, 2H) 
                 {5-Cyclopropyl- 2-[2-(3,5-difluoro- pyridin-2-ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}- methyl-(tetrahydro- pyran-4-yl)-amine 
               
               
                   
               
               
                 2173 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 530 (M + H) 
                 1H-NMR: DMSO 10.73 (br s, 1H), 8.94 (s, 1H), 8.71 (s, 1H), 8.42 (d, 1H, J = 5.9 Hz), 8.29 (d, 1H, J = 2.5 Hz), 8.19 (s, 1H), 8.13 (m, 1H), 8.04 (m, 1H), 4.03 (m, 1H), 3.84 (m, 4H), 3.67 (m, 1H), 3.29 (m, 2H), 2.28 (m, 1H), 2.11 (m, 1H), 1.98 (m, 1H), 1.53 (m ,4H), 1.16- 1.37 (br m, 4H), 1.03 (m, 1H), 0.94 (m, 1H) 
                 (4-{5-Cyclopropyl-4-[3- (tetrahydro-pyran-4-yl)- pyrrolidin-1-yl]- pyrido[3,4-d]pyrimidin- 2-yl}-pyridin-2- yl)-(3,5-difluoro-pyridin- 2-yl)-amine 
               
               
                   
               
               
                 2174 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 489 (M + H) 
                 1H-NMR: DMSO 10.09 (s, 1H), 9.08 (s, 1H), 8.73 (s, 1H), 8.59 (m, 1H), 8.53 (s, 1H), 8.50 (m, 1H), 8.41 (d, 1H, J = 5.5 Hz), 8.24 (d, 1H, J = 2.5 Hz), 8.05 (m, 1H), 7.95 (m, 1H), 7.69 (s, 1H), 3.24 (m, 2H), 3.17 (m, 2H), 2.74 (m, 2H), 2.64 (m, 1H), 2.06 (m, 2H), 1.75 (s, 3H), 1.22 (m, 2H), 1.16 (m, 2H) 
                 {5-Cylcopropyl- 2-[2-(3,5-difluoro- pyridin-2-ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-(4- methyl-piperidin-4-yl)- amine 
               
               
                   
               
               
                 2175 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 503 (M + H) 
                 1H-NMR: DMSO 10.15 (br s, 1H), 9.09 (s, 1H), 9.07 (m, 1H), 8.63 (s, 1H), 8.52 (s, 1H), 8.41 (d, 1H, J = 5.6 Hz), 8.35 (m, 1H), 8.27 (d, 1H, J = 2.5 Hz), 8.05 (m, 2H), 7.67 (d, 1H, J = 8.7 Hz), 4.82 (m, 1H), 3.37 (m, 1H), 3.20 (m, 2H), 3.06 (m, 1H), 2.60 (m, 1H), 2.12 (m, 1H), 1.96 (m, 1H), 1.26 (m, 1H), 1.19 (s, 3H), 1.16 (m, 3H), 1.11 (s, 3H) 
                 {5-Cyclopropyl- 2-[2-(3,5-difluoro- pyridin-2-ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-(3,3- dimethyl-piperidin-4-yl)- amine 
               
               
                   
               
               
                 2176 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 521 (M + H) 
                 1H-NMR: DMSO 9.72 (s, 1H), 9.06 (s, 1H), 8.99 (m, 1H), 8.58 (s, 1H), 8.51 (s, 1H), 8.40 (m, 1H), 8.27 (m, 2H), 8.00 (m, 1H), 7.64 (d, 1H, J = 8.8 Hz), 4.81 (m, 1H), 3.32 (m, 1H), 3.22 (m, 1H), 3.19 (m, 1H), 3.01 (m, 1H), 2.59 (m, 1H), 2.14 (m, 1H), 1.95 (m, 1H), 1.25 (m, 1H), 1.19 (s, 3H), 1.14 (m, 3H), 1.09 (s, 3H) 
                 {5-Cylcopropyl- 2-[2-(3,5,6-trifluoro- pyridin-2-ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-(3,3- dimethyl-piperidin-4-yl)- amine 
               
               
                   
               
               
                 2177 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 92%, RT: min, MI: 492.26 (MH)+ 
                 (400 MHz, d6-DMSO, δ): 9.06 (s, 1H), 8.85 (br s, 2H), 8.20 (s, 1H), 8.16 (d, J = 6.0 Hz, 1H), 7.61 (br s, 1H), 7.34-7.20 (m, 4H), 5.62- 5.55 (m, 1H), 3.88 (br s, 4H), 3.31 (br s, 4H), 2.70- 2.63 (m, 1H), 1.85-1.79 (m, 1H), 1.40 (s, 3H), 1.28-1.23 (m, 6H), 1.11-1.06 (m, 2H). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidin- 2-yl)-pyridin-2- yl]-(3,3-dimethyl-indan- 1-yl)-amine 
               
               
                   
               
               
                 2178 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 99%, RT: min, MI: 513 (M + H) 
                 1H NMR (400 MHz, DMSO-d6) 9.79 (1 H, s), 8.65-9.06 (3 H, m), 8.41- 8.51 (1 H, m), 8.20-8.36 (1 H, m), 7.90-8.04 (2 H, m), 3.98 (4 H, br. s.), 3.30 (4 H, br. s.), 2.56-2.65 (1 H, m), 1.19-1.28 (2 H, m), 1.00- 1.10 (2 H, m) 
                 [4-(8-Chloro- 5-cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidin- 2-yl)-pyridin-2-yl]- (3,5,6,-trifluoro- pyridin-2-yl)-amine 
               
               
                   
               
               
                 2179 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 96%, RT: min, MI: 467.21 
                 (dmso-d6) 12.45 (d, J = 1.4 Hz, 1H), 9.13 (s, 1H), 8.96 (br s, 2H), 8.62 (m, 1H), 8.51 (d, J = 5.0 Hz, 1H), 8.20 (m, 3H), 7.93 (m, 1H), 7.53 (m, 1H), 3.98 (br s, 4H), 3.38 (br s, 4H), 2.76 (m, 1H), 1.28 (m, 2H), 1.11 (m, 2H) 
                 5-Cyclopropyl-2- [2-(3-fluoro- pyridin-2-yl)-1H- pyrrolo[2,3-b]pyridin- 4-yl]-4-piperazin- 1-yl-pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 2180 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 96%, RT: min, MI: 481.22 (M + H) 
                 (dmso-d6) 12.45 (d, J = 1.5 Hz, 1H), 9.20 (s, 1H), 8.99 (br s, 1H), 8.89 (br s, 1H), 8.81 (s, 1H), 8.61 (m, 1H), 8.51 (d, J = 5.0 Hz, 1H), 8.19 (d, J = 5.0 Hz, 1H), 8.17 (m, 1H), 7.93 (m, 1H), 7.53 (m, 1H), 4.30 (m, 1H), 3.87 (m, 4H), 3.35 (m, 4H), 2.47 (m, 2H), 2.24 (m, 2H), 2.12 (m, 1H), 1.93 (m, 1H) 
                 5-Cyclobutyl- 2-[2-(3-fluoro-pyridin- 2-yl)-1H-pyrrolo[2,3- b]pyridin-4-yl]- 4-piperazin-1-yl- pyrido[3,4-d]pyrimidine 
               
               
                   
               
               
                 2181 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 3.27 min, MI: 516 [M + H] 
                 (500 MHz, d6-DMSO) 11.86 (brs, 1H), 9.19 (s, 1H), 8.97 (brs, 1H), 8.82 (brs, 1H), 8.77 (s, 1H), 8.28 (d, 1H), 8.06 (d, 1H), 7.53- 7.40 (m, 2H), 7.38-7.30 (m, 2H), 7.25-7.15 (m, 2H), 4.27 (q, 1H), 3.90-3.56 (m, 5H), 3.40-3.20 (m, 4H), 3.08 (m, 1H), 2.97-2.85 (m, 2H), 2.78-2.67 (m, 2H), 2.27-2.16 (m, 2H), 2.15- 2.03 (m, 2H), 1.95-1.87 (m, 2H). 
                 5-Cyclobutyl-2-[2- (1-phenyl-cyclobutyl)- 1H-pyrrolo[2,3- b]pyridin-4-yl]-4- piperazin-1-yl- pyrido[3,4-d]pyrimidine 
               
               
                   
               
               
                 2182 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 2.98 min, MI: 496 [M + H] 
                 (500 MHz, d6-DMSO) 12.11 (brs, 1H), 9.25 (s, 1H), 9.07 (brs, 1H), 8.92 (brs, 1H), 8.79 (s, 1H), 8.43 (d, 1H), 8.12 (d, 1H), 7.46 (d, 1H), 4.28 (q, 1H), 3.99- 3.70 (m, 4H), 3.45-3.20 (m, 4H), 2.52-2.42 (m, 2H), 2.28-2.16 (m, 2H), 2.10 (m, 1H), 1.92 (m, 1H), 1.69 (s, 6H). 
                 5-Cyclobutyl- 4-piperazin-1-yl-2-[2- (2,2,2-trifluoro-1,1- dimethyl-ethyl)-1H- pyrrolo[2,3- b]pyridin- 4-yl]-pyrido [3,4-d]pyrimidine 
               
               
                   
               
               
                 2183 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 3.06 min, MI: 508 [M + H] 
                 (d6-DMSO, 600 MHz) 12.20 (brs, 1H), 9.25 (s, 1H), 8.98 (brs, 1H), 8.84 (brs, 1h), 8.80 (s, 1H), 8.43 (d, 1H), 8.14 (d, 1H), 7.49 (d, 1H), 4.29 (q, 1H), 3.98-3.71 (m, 4H), 3.46-3.21 (m, 4H), 2.84-2.59 (m, 4H), 2.50- 2.41 (m, 2H), 2.30-2.18 (m, 2H), 2.18-2.00 (m, 3H), 1.93 (m, 1H). 
                 5-Cyclobutyl-4- piperazin-1-yl-2-[2- (1-trifluoromethyl- cyclobutyl)-1H-pyrrolo [2,3-b]pyridin-4- yl]-pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 2184 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 5.02 min, MI: 456 [M + H] 
                 (500 MHz, d6-DMSO) 11.80 (1H, s), 9.05 (1H, s), 8.29 (1H, d, J = 5.0 Hz), 8.08 (1H, s), 8.06 (1H, d, J = 5.0 Hz), 7.28 (1H, d, J = 1.3 Hz), 4.13 (1H, t, J = 7.6 Hz), 3.98-3.93 (1H, m), 8.89-8.84 (1H, m), 3.80- 3.77 (1H, t, J = 7.7 Hz), 3.68-3.61 (1H, m), 3.92- 3.50 (4H, very broad s), 2.89 (4H, s), 2.71-2.65 (1H, m), 2.42-2.35 (1H, m), 2.21- 2.14 (1H, m), 1.28-1.24 
                 5-Cyclobutyl- 4-piperazin-1-yl-2-[2- (tetrahydro-furan-3- yl)-1H-pyrrolo[2,3-b] pyridin-4-yl]-pyrido[3,4- d]pyrimidine 
               
               
                   
                   
                   
                   
                 (2H, m), 1.05-1.02 (2H, 
                   
               
               
                   
                   
                   
                   
                 m). 
                   
               
               
                   
               
               
                 2185 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 2.51 min, MI: 456 [M + H] 
                 (500 MHz, d6-DMSO) 11.82 (1H, s), 9.13 (1H, s), 8.70 (1H, s), 8.32 (1H, d, J = 4.9 Hz), 8.06 (1H, d, J = 4.9 Hz), 7.33 (1H, d, J = 1.7 Hz), 5.09 (1H, t, J = 6.8 Hz), 4.32-4.25 (1H, m), 4.03-3.98 (1H, m) 3.87- 3.82 (1H, m), 3.68 (2H, br s), 3.51 (2H, br s), 2.94 (2H, br s), 2.87 (2H, br s), 2.38- 2.28 (1H, m), 2.23-2.15 (2H, m), 2.12-1.96 (5H, m), 1.93-1.89 (1H, m). 
                 5-Cyclobutyl-4- piperazin-1-yl-2-[2- (tetrahydro-furan-2- yl)-1H-pyrrolo[2,3-b] pyridin-4-yl]-pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 2186 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95% RT: min, MI: 493 (M + H) 
                 1H-NMR: DMSO 9.97 (br s, 1H), 9.21 (m, 1H), 9.12 (s, 1H), 8.79 (m, 1H), 8.62 (s, 1H), 8.54 (s, 1H), 8.39 (d, 1H, J = 5.5 Hz), 8.28 (d, 1H, J = 2.5 Hz), 8.02 (m, 3H), 5.37-5.44 (br m, 1H), 4.85-4.96 (br m, 1H), 3.77 (m, 1H), 3.40-3.63 (br m, 2H), 3.27 (m, 1H), 2.59 (m, 1H), 2.33 (m, 1H), 2.07 (m, 1H), 1.21 (m, 2H), 1.13 (m, 2H) 
                 {5-Cyclopropyl- 2-[2-(3,5-difluoro- pyridin-2-ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-(3- fluoro-piperidin-4-yl)- amine 
               
               
                   
               
               
                 2187 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 519 (M + H) 
                 1H NMR (400 MHz, DMSO-d6) 9.76 (1H, s), 9.05 (1H, s), 8.86 (2H, br. s), 8.46 (1H, d, J = 5.0 Hz), 8.20-8.35 (1H, m), 7.95- 8.05 (2H, m), 3.74-4.06 (4H, m), 3.49-3.63 (1H, m), 3.31 (4H, br. s.), 2.57- 2.70 (1H, m), 1.05-1.25 (6H, m), 0.90-1.03 (2H, m) 
                 [4-(5,8- Dicyclopropyl-4- piperazin-1-yl-pyrido [3,4-d]pyrimidin- 2-yl)-pyridin-2- yl]-(3,5,6-trifluoro- pyridin-2-yl)-amine 
               
               
                   
               
               
                 2188 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 90%, RT: min, MI: 501 (M + H) 
                 1H NMR (400 Mhz, DMSO-d6) 9.84 (1H, br. s), 8.63-9.04 (3H, m), 8.41 (1H, d, J = 5.0 Hz), 8.25 (1H, d, J = 2.5 Hz), 7.92-8.09 (3H, m), 3.90 (4H, br. s), 3.47-3.58 (1H, m), 3.32 (4H, br. s), 2.57-2.65 (1H, m), 1.05-1.26 (6H, m), 0.90-1.00 (2H, m) 
                 [4-(5,8- Dicyclopropyl-4- piperazin-1-yl-pyrido [3,4-d]pyrimidin- 2-yl)-pyridin-2- yl]-(3,5-difluoro- pyridin-2-yl)-amine 
               
               
                   
               
               
                 2189 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 90%, RT: min, MI: 500 (M + H) 
                 1H NMR (400 MHz, DMSO-d6) 8.83 (2H, s), 8.19 (1H, d, J = 5.3 Hz),  8.00 (1H, s), 7.88 (1H, s), 7.73 (1H, dd, J = 5.4, 1.4 Hz), 7.23- 7.34 (1H, m), 7.11-7.21 (2H, m), 3.85-3.96 (4H, m), 3.46-3.49 (1H, m), 3.30 (4H, br. s), 2.57-2.65 (1H, m), 1.05-1.23 (6H, m), 0.96 (2H, m) 
                 [4-(5,8- Dicyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidin- 2-yl)-pyridin-2-yl]- (2,6-difluoro-phenyl)- amine 
               
               
                   
               
               
                 2190 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 95%, RT: min, MI: 468 (M + H) 
                 1H NMR (400 MHz, DMSO-d6) 11.80 (1H, d, J = 1.8 Hz), 8.48-9.20 (2H, m), 8.32 (1H, d, J = 5.0 Hz), 8.12 (1H, d, J =  5.0 Hz), 8.00 (1H, s), 7.24 (1H, d, J = 2.3 Hz), 3.71-4.20 (4H, m), 3.47-3.59 (1H, m), 3.34 (4H, br. s), 2.63-2.76 (1H,  m), 1.41 (9H, s), 1.10-1.28 (6H, m), 0.89-1.00 (2H, m) 
                 2-(2-tert-Butyl-1H- pyrrolo[2,3- b]pyridin- 4-yl)-5,8-dicyclopropyl- 4-piperazin-1-yl-pyrido [3,4-d]pyrimidine 
               
               
                   
               
               
                 2191 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4]   
                 Method 5: RT: 1.86 min, MI: 444 [M + H] 
                 (500 MHz, DMSO) 9.08 (1H, s), 9.07 (1H, s), 8.76 (1H, s), 8.46 (1H, d), 8.35 (1H, m), 8.19 (1H, s), 7.93 (1H, dd), 7.63 (1H, dd), 7.43 (2H, dd),  7.17 (2H, m), 3.95 (4H, br s), 3.33 (4H, s), 2.69 (1H, m), 1.25 (2H,  m), 1.09 (2H, m). 
                 [4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d] pyrimidin-2-yl)- pyridin-2-yl]-(6- fluoro-pyridazin-3-yl)- amine 
               
               
                   
               
               
                 2192 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 3.08 min, MI: 442 [M + H] 
                 (500 MHz, d6-DMSO) 11.80 (1H, s), 9.05 (1H, s), 8.29 (1H, d, J = 5.0 Hz), 8.08 (1H, s),  8.06 (1H, d, J = 5.0 Hz), 7.28 (1H, d, J = 1.3 Hz), 4.13 (1H, t, J = 7.6 Hz), 3.98-3.93 (1H, m), 8.89-8.84 (1H, m), 3.80- 3.77 (1H, t, J = 7.7 Hz), 3.68-3.61 (1H, m), 3.92- 3.50 (4H very broad s),  2.89 (4H, s), 2.71-2.65 (1H, m), 
                 5-Cyclopropyl-4- piperazin-1-yl-2-[2- (tetrahydro-furan-3- yl)-1H-pyrrolo[2,3-b] pyridin-4-yl]-pyrido [3,4-d]pyrimidine 
               
               
                   
                   
                   
                   
                 2.42-2.35 (1H, m), 2.21- 
                   
               
               
                   
                   
                   
                   
                 2.14 (1H, m), 1.28-1.24 
                   
               
               
                   
                   
                   
                   
                 (2H, m), 1.05-1.02 (2H, m). 
                   
               
               
                   
               
               
                 2193 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B1] 
                 LCMS: Purity: 90%, RT: min, MI: 488 (M + H)+ 
                 1H NMR (400 MHz, DMSO-d6) δ ppm 9.55 (br. s, 1H) 9.05 (br. s, 1H) 8.79- 8.87 (m, 2H) 8.21 (d, J = 5.3 Hz, 1H) 7.82 (s, 1H) 7.69 (dd, J = 5.3, 1.3 Hz, 1H)  7.23-7.35 (m, 1H)  7.10-7.22 (m, 2H) 3.51-4.03 (m, 9H) 
                 (2,6-Difluoro-phenyl)- [4-(4-piperazin-1-yl-5- trifluoromethyl- pyrido[3,4-d] pyrimidin-2-yl)-pyridin- 2-yl]-amine 
               
               
                   
               
               
                 2194 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B1] 
                 LCMS: Purity: 90%, RT: min, MI: 489 (M + H)+ 
                 1H NMR (400 MHz, DMSO-d6) δ ppm 9.65- 9.72 (m, 1H) 9.58 (s, 1H) 9.06 (s, 1H) 8.80-8.98 (m, 2H) 8.76 (br. s, 1H) 8.38- 8.47 (m, 1H) 8.27 (br. s, 1H) 7.99 (t, J = 8.4 Hz, 1H) 7.87-7.94 (m, 1H) 3.70- 4.04 (m, 8H) 
                 (3,5-Difluoro-pyridin-2- yl)-[4-(4-piperazin- 1-yl-5-trifluoromethyl- pyrido[3,4-d] pyrimidin-2-yl)-pyridin- 2-yl]-amine 
               
               
                   
               
               
                 2195 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B1] 
                 LCMS: Purity: 90%, RT: min, MI: 507 (M + H)+ 
                 1H NMR (400 MHz, DMSO-d6) δ ppm 9.79- 9.83 (m, 1H) 9.56 (s, 1H) 9.04-9.07 (m, 1H) 8.82- 8.93 (m, 2H) 8.78-8.81 (m, 1H) 8.47 (d, J = 5.0 Hz, 1 H) 8.23-8.33 (m, 1H) 7.96 (dd, J = 5.3, 1.5 Hz, 1H)  3.70-4.12 (m, 9H) 
                 [4-(4-Piperazin-1-yl-5- trifluoromethyl-pyrido [3,4-d]pyrimidin-2-yl)- pyridin-2-yl]-(3,5,6- trifluoro-pyridin-2- yl)-amine 
               
               
                   
               
               
                 2196 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 517 (M + H) 
                 1H-NMR: DMSO 10.42 (br s, 1H), 9.14 (br m, 1H), 9.01 (s, 1H), 8.61 (br m, 1H), 8.41 (d, 1H, J = 5.7 Hz), 8.30 (br m, 1H), 8.28 (d, 1H, J = 2.4 Hz), 8.16 (s, 1H), 8.07 (m, 2H), 5.56 (m, 1H), 3.45 (m, 1H), 3.30 (m, 2H), 3.16 (s, 3H), 2.78 (m, 1H), 2.41 (m, 1H), 2.22 (m, 1H), 1.91 (m, 1H), 0.98- 1.47 (br m, 10H) 
                 {5-Cyclopropyl- 2-[2-(3,5-difluoro- pyridin-2-ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-(3,3- dimethyl-piperidin-4-yl)- methyl-amine 
               
               
                   
               
               
                 2197 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D3] 
                 LCMS: Purity: 90%, RT: min, MI: 402 (M + H)+ 
                 NH protons coalesced with water. 1H NMR (400 MHz, CDCl 3 ) δ ppm 9.10 (s, 1H) 8.04 (s, 1H) 7.95 (d, J = 4.5 Hz, 1H) 7.53 (d, J = 5.5 Hz, 1H) 7.27 (s, 1H) 4.83 (br. s, 1H) 3.54-3.92 (m, 4H), 3.48 (s, 2H) 3.04 (t, J = 4.8 Hz, 4H) 2.73 (tt, J = 8.5, 5.2 Hz, 1H) 1.40 (s, 6H) 0.98- 1.05 (m, 2H) 0.85-0.91 (m, 2H) 
                 5-Cyclopropyl-2-(2,2- dimethyl-2,3-dihydro- 1H-pyrrolo[2,3-b] pyridin-4-yl)-4- piperazin-1-yl-pyrido [3,4-d]pyrimidine 
               
               
                   
               
               
                 2198 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: LPurity: 95%, RT: min, MI: 475 (M + H) 
                 1H-NMR: DMSO 10.23 (br s, 1H), 9.05 (s, 1H), 8.73 (s, 1H), 8.42 (d, 1H, J = 5.6 Hz), 8.29 (d, 1H, J = 2.4 Hz), 8.19 (s, 1H) , 8.08 (br m, 4H), 4.44 (m, 1H), 4.07- 4.23 (br m, 2H), 3.22-3.47 (br m, 3H), 2.67 (m ,1H), 2.07 (m, 1H), 1.84 (m, 1H), 1.61 (m, 1H), 1.26 (m, 2H), 1.05 (m, 2H) 
                 {4-[4-(3-Amino- piperidin-1-yl)-5- cyclopropyl-pyrido[3,4- d]pyrimidin-2-yl]- pyridin- 2-yl}-(3,5-difluoro- pyridin-2-yl)-amine 
               
               
                   
               
               
                 2199 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D3],  [D9] 
                 Method 5: RT: 3.31 min, MI: 440 [M + H] 
                 (500 MHz, d6-DMSO) 11.59 (brs, 1H), 9.15 (s, 1H), 9.04 (brs, 1H), 8.91 (brs, 1H), 8.79 (s, 1H), 8.11 (d, 1H), 7.58 (d, 1H), 4.32- 4.21 (m, 1H), 3.89-3.63 (m, 4H), 3.39-3.19 (m, 4H), 2.78-2.70 (m, 2H), 2.64- 2.52 (m, 2H), 2.28-2.16  (m, 2H), 2.15-2.02 (m, 1H), 1.97-1.87 (m, 1H), 1.85- 1.72 (m, 2H), 1.70-1.54 (m, 2H). 
                 4-(5-Cyclobutyl- 4-piperazin-1-yl- pyrido[3,4-d]pyrimidin- 2-yl)-6,7,8,9-tetrahydro- 5H-pyrido[2,3-b]indole 
               
               
                   
               
               
                 2200 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D3] 
                 LCMS: Purity: 98%, RT: min, MI: 470 (M + H) 
                 1H-NMR (DMSO-d6, 400 MHz): 12.30 (s, 1H), 9.22 (s, 1H), 9.06 (d, 1H, J = 2.1 Hz), 8.90 (br s, 2H), 8.86 (s, 1H), 8.65 (d, 1H, J = 5.1 Hz), 8.03 (5.1 Hz), 7.58 (d, 1H, J = 8.6 Hz), 7.54 (dd, 1H, J = 2.1, 8.6 Hz), 4.30 (pent, 1H, J = 8.6 Hz), 3.86 (m, 4H), 3.2-3.4 (m, 4H), 2.28 (m, 2H), 2.14 (m, 1H), 1.94 (m, 1H) 
                 6-Chloro-4-(5- cyclobutyl-4-piperazin- 1-yl-pyrido[3,4-d] pyrimidin-2-yl)-9H- pyrido[2,3-b]indole 
               
               
                   
               
               
                 2201 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 95%, RT: min, MI: 410.0 (MH)+ 
                 (dmso-d6) 12.40 (d, J = 1.7 Hz, 1H), 9.14 (s, 1H), 8.95 (br s, 2H), 8.46 (d, J = 5.0 Hz, 1H), 8.18 (m, 2H), 8.10 (m, 1H), 7.98 (m,  1H), 7.52- 7.35 (m, 3H), 3.98 (br s, 4H), 3.38 (br s, 4H), 2.76 (m, 1H), 1.27 (m, 2H), 1.10 (m, 2H) 
                 5-Cyclopropyl-2-[2- (2-fluoro-phenyl)-1H- pyrrolo[2,3-b]pyridin- 4-yl]-4-piperazin- 1-yl-pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 2202 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 95%, RT: min, MI: 466.22 (M + H) 
                 (dmso-d6) 12.32 (d, J = 1.7 Hz, 1H), 9.14 (s, 1H), 8.94 (br s, 2H), 8.47 (d, J = 5.0 Hz, 1H), 8.19 (d, J = 5.0  Hz, 1H), 8.19 (s, 1H),  7.94 (d, J = 2.2 Hz, 1H), 7.85 (dd, J = 7.7, 1.7 Hz, 1H), 7.67 (dd, J = 7.8, 1.4 Hz, 1H), 7.55- 7.45 (m, 2H), 3.96 (br s, 4H), 3.37 (br s, 4H), 2.76 (m, 1H), 1.27 (m, 2H), 1.10 (m, 2H) 
                 2-[2-(2-Chloro- phenyl)-1H-pyrrolo [2,3-b]pyridin-4-yl]- 5-cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidine 
               
               
                   
               
               
                 2203 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 97%, RT: min, MI: 482.18 (M + H) 
                 (dmso-d6) 12.40 (s, 1H), 9.22 (s, 1H),  9.00 (br s, 1H), 8.89 (br s, 1H), 8.80 (s, 1H), 8.46 (d, J = 5.0 Hz, 1H), 8.17 (d, J = 5.0 Hz, 1H), 8.10 (m, 1H), 7.96 (m, 1H), 7.52-7.36 (m, 3H), 4.30 (m, 1H), 3.87 (m, 4H), 3.35 (m, 4H), 2.48 (m, 2H), 2.24 (m, 2H), 2.11 (m, 1H), 1.93 (m, 1H) 
                 5-Cyclobutyl- 2-[2-(2-fluoro-phenyl)- 1H-pyrrolo[2,3-b] pyridin-4-yl]-4- piperazin- 1-yl-pyrido[3,4-d] pyrimidine 
               
               
                   
               
               
                 2204 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 LCMS: Purity: 97%, RT: min, MI: 480.22 (M + H) 
                 (dmso-d6) 12.32 (d, J = 1.7 Hz, 1H), 9.22 (s, 1H), 8.98 (br s, 1H), 8.85 (br s, 1H), 8.80 (s, 1H), 8.46 (d, J = 5.0 Hz, 1H), 8.18 (d, J = 5.0 Hz, 1H), 7.92 (d, J = 2.2 Hz, 1H), 7.84 (dd, J = 7.6, 1.8 Hz, 1H), 7.67 (dd, J= 7.9, 1.6 Hz, 1H), 7.56-7.44 (m, 2H), 4.30 (m, 1H), 3.84 (m, 4H), 3.34 (m, 4H), 2.47 (m, 2H), 2.24 (m, 2H), 2.11 (m, 1H), 1.93 (m, 1H) 
                 2-[2-(2-Chloro- phenyl)-1H-pyrrolo [2,3-b]pyridin-4-yl]- 5-cyclobutyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidine 
               
               
                   
               
               
                 2205 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 489 (M + H) 
                 1H-NMR: DMSO 10.08 (br s, 1H), 9.05 (s, 1H), 8.70 (br m, 3H), 8.40 (d, 1H, J = 5.5 Hz), 8.29 (d, 1H, J = 2.2 Hz), 8.18 (s, 1H), 8.00 (m, 2H), 4.56 (br m, 1H), 4.18 (br m, 1H), 3.50 (m, 2H), 3.16 (m, 1H), 2.63 (s, 3H), 2.54 (m, 1H), 2.12 (m, 1H), 1.82 (m, 1H), 1.64 (m, 2H), 1.25 (m, 2H), 1.05 (m, 2H) 
                 {4-[5-Cyclopropyl- 4-(3-methylamino- piperidin-1-yl)-pyrido [3,4-d]pyrimidin-2-yl]- pyridin-2-yl}-(3,5- difluoro- pyridin-2-yl)-amine 
               
               
                   
               
               
                 2206 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 LCMS: Purity: 95%, RT: min, MI: 497 (M + H) 
                 1H-NMR: DMSO 10.38 (br s, 1H), 9.66 (s, 1H), 9.09 (s, 1H), 8.67 (s, 1H), 8.55 (s, 1H), 8.43 (d, 1H, J = 5.7 Hz), 8.22 (d, 1H, J = 2.5 Hz), 8.10 (m, 1H), 7.94 (m, 1H), 7.76 (m, 2H), 6.77 (m, 2H), 2.79 (m, 1H), 2.76 (s, 3H), 1.30 (m, 2H), 1.14 (m, 2H) 
                 N-{5-Cyclopropyl- 2-[2-(3,5-difluoro- pyridin-2-ylamino)- pyridin-4-yl]-pyrido[3,4- d]pyrimidin-4-yl}-N′- methyl-benzene-1,4- diamine 
               
               
                   
               
               
                 2207 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3] 
                 Method 5: RT: 2.87 min, MI: 494 [M + H] 
                 (500 MHz, d6-DMSO) 12.17 (brs, 1H), 9.17 (s, 1H), 8.89 (brs, 2H), 8.42 (t, 1H), 8.17 (d, 1H), 8.14 (t, 1H), 7.49 (s, 1H), 4.21-3.56 (m, 6H), 2.82-2.64 (m, 6H), 2.17-1.98 (m, 3H), 1.34- 1.20 (m, 2H), 1.14-1.03 (m, 2H). 
                 5-Cyclopropyl- 4-piperazin-1-yl-2-[2- (1-trifluoromethyl- cyclobutyl)-1H- pyrrolo[2,3-b]pyridin- 4-yl]-pyrido[3,4- d]pyrimidine 
               
               
                   
               
               
                 2208 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D3],  [D9] 
                 Method 5: RT: 2.88 min, MI: 426 [M + H] 
                 (500 MHz, d6-DMSO) 11.53 (s, 1H), 9.06 (s, 1H), 8.21 (d, 1H), 8.17 (s, 1H), 7.56 (d, 1H), 4.09-3.61 (m, 4H), 3.35-3.28 (m, 4H), 2.78-2.68 (m, 3H), 2.64- 2.58 (m, 2H), 1.85-1.77 (m, 2H), 1.69-1.61 (m, 2H), 1.30-1.23 (m, 2H), 1.12- 1.07 (m, 2H). 
                 4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidin- 2-yl)-6,7,8,9- tetrahydro-5H-pyrido [2,3-b]indole 
               
               
                   
               
               
                 2209 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D4],  [D3], [D7] 
                 Method 5: RT: 3.45 min, MI: 474 [M + H] 
                 (500 MHz, d6-DMSO) 8.96 (1H, s), 8.59 (1H, d), 8.13 (1H, s), 7.57 (1H, d), 3.89- 3.46 (4H, m), 2.84 (4H, s), 2.71-2.59 (1H, m), 1.29- 1.24 (2H, m), 1.06-1.01 (2H, m). 
                 2-(3-Chloro- 2-methyl-1H-pyrrolo [2,3-b]pyridin-4-yl)- 5-cyclopropyl-4- piperazin-1-yl- pyrido[3,4-d]pyrimidine 
               
               
                   
               
               
                 2210 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [B4] 
                 Method 5: RT: 1.44 min, MI: 446 [M + H] 
                 (500 MHz, DMSO) 9.07 (1H, s), 8.74 (1H, s), 8.12 (1H, d), 7.54 (1H, s), 7.42 (1H, dd), 6.79 (1H, d), 4.24 (1H, m), 3.98 (1H, m), 3.89 (2H, m), 3.78-3.67 (4H, m), 3.42 (2H, m), 3.19 (2H, m), 3.09 (2H, m), 2.46 (2H, m), 2.19 (2H, m), 2.09 (1H, m), 1.90 (3H, m), 1.46 (2H, m). 
                 [4-(5-Cyclobutyl-4- piperazin-1-yl- pyrido[3,4-d] pyrimidin-2-yl)- pyridin-2-yl]- (tetrahydro-pyran-4-yl)- amine 
               
               
                   
               
               
                 2211  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [D3], [D10] 
                 Method 5: RT: 2.71 min, MI: 416 [M + H] 
                 (300 MHz, DMSO-d6) d 11.20 (s, 1H), 9.08 (s, 1H), 8.94 (bs, 2H), 8.25 (d, J = 5.5 Hz, 1H), 8.21 (s, 1H), 7.80 (d, J = 5.5 Hz, 1H), 3.86 (bs, 4H), 3.32 (bs, 4H), 2.73-2.64 (m, 1H), 1.55 (s, 6H), 1.31-1.19 (m, 2H), 1.14-1.04 (m, 2H) 
                 4-(5-Cyclopropyl-4- piperazin-1-yl- pyrido[3,4- d]pyrimidin-2-yl)-3,3- dimethyl-1,3-dihydro- pyrrolo[2,3- b] pyridin-2-one 
               
               
                   
               
            
           
         
       
     
     VI. Biology 
     PKC ι  IC 50 , Assay 
     Assays are based on the ability of PKCι to phosphorylate a commercially available peptide substrate in vitro. The peptide substrate is FAM-PKCε pseudopeptide derived peptide, and comprises the amino acid sequence 5FAM-ERMRPRKRQGSVRRRV-NH 2 . Recombinant, full-length human PKCι expressed in Sf21 insect cells is also commercially available. Recombinant, kinase-domain human PKCι is expressed and purified in-house. 
     The procedure below explains how dose response curves for inhibitors of PKCι are obtained. The screen described is for a 384 well format but the assay can be adapted to 1536 or other formats as required. 
     Compounds to be tested are dissolved in 100% DMSO. Compounds are diluted as required to give a final concentration of 4% DMSO (v/v) in the assay. 1 μl is plated into 384 well black low-binding flat bottomed assay plates which are used immediately. Dilutions and additions of compound to assay plates are carried out using Matrix WellMate® and Matrix PlateMate® Plus liquid handling systems. 
     On the day of the screen PKCι/substrate working solution, and ATP working solution, are prepared in buffer containing 20 mM tris-HCl pH7.5, 10 mM MgCl 2 , 0.01% Triton X100, 250 μM EGTA and 1 mM DTT. The final concentration of PKCι used varies depending on the batch of protein but is typically 15 pM. The final concentration of peptide substrate in the assay is 100 nM. ATP is used at a final concentration of 150 μM or 25 μM in the assays containing full-length or kinase-domain PKCι respectively, which corresponds to five times or equal to the K M   APP  for ATP for each enzyme, respectively. The final buffer concentration in the assay is 18 mM tris-HCl pH7.5, 9 mM MgCl 2 , 0.009% Triton X100, 225 μM EGTA and 0.9 mM DTT. Relevant controls are included, namely no compound and no enzyme. 5 μl PKCι/substrate working solution at 30 pM and 200 nM, respectively, is added to the wells, followed by 4 μl ATP working solution at 375 μM or 62.5 μM for full-length or kinase-domain PKCι respectively, using a 16 channel Matrix pipette. The reaction is allowed to incubate for 60 minutes at room temperature, before the reaction is stopped and developed by the addition of 20 μl IMAP™ development reagent (Molecular Devices). IMAP development reagent consists of 0.25% (v/v) IMAP progressive binding reagent, 17% (v/v) IMAP progressive binding buffer A and 3% (v/v) IMAP progressive binding buffer B. The plates are then incubated for 2 hours at room temperature before being read using an appropriate plate reader, for example a Molecular Devices HT Analyst or a BMG Pherastar. Plates are read using a fluorescence polarisation protocol with excitation at 485 nm and emission at 530 nm, and dichroic mirror at 505 nm. 
     Percentage inhibition values are calculated from fluorescence polarisation values, using the no compound and no enzyme control values as 0% and 100% inhibition, respectively. IC50 determination is performed with ExcelFit software (IDBS) using curve fit 205. Z′ factors are determined for each plate tested and are all above 0.5. 
     RESULTS 
     Biological data for the Example compounds is presented in the following table. Activities are set forth as follows: 
     IC50 in IMAP assay against full length PKCi at 150 μM ATP:
         ++++=&lt;100 nM   +++=100 nM to 1,000 nM   ++=1,000 nM to 10,000 nM   +=10,000 nM to 40,000 nM       

     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                 Example 
                 Activity 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                   
                 1 
                 +++ 
               
               
                   
                 2 
                 +++ 
               
               
                   
                 3 
                 + 
               
               
                   
                 4 
                 ++ 
               
               
                   
                 5 
                 + 
               
               
                   
                 6 
                 ++++ 
               
               
                   
                 7 
                 ++++ 
               
               
                   
                 8 
                 +++ 
               
               
                   
                 9 
                 ++++ 
               
               
                   
                 10 
                 +++ 
               
               
                   
                 11 
                 ++++ 
               
               
                   
                 12 
                 ++++ 
               
               
                   
                 13 
                 ++ 
               
               
                   
                 14 
                 +++ 
               
               
                   
                 15 
                 ++ 
               
               
                   
                 16 
                 +++ 
               
               
                   
                 17 
                 ++ 
               
               
                   
                 18 
                 + 
               
               
                   
                 19 
                 + 
               
               
                   
                 20 
                 + 
               
               
                   
                 21 
                 + 
               
               
                   
                 22 
                 + 
               
               
                   
                 23 
                 + 
               
               
                   
                 24 
                 + 
               
               
                   
                 25 
                 +++ 
               
               
                   
                 26 
                 + 
               
               
                   
                 27 
                 + 
               
               
                   
                 28 
                 +++ 
               
               
                   
                 29 
                 ++ 
               
               
                   
                 30 
                 ++ 
               
               
                   
                 31 
                 +++ 
               
               
                   
                 32 
                 +++ 
               
               
                   
                 33 
                 ++ 
               
               
                   
                 34 
                 + 
               
               
                   
                 35 
                 + 
               
               
                   
                 36 
                 + 
               
               
                   
                 37 
                 ++++ 
               
               
                   
                 38 
                 +++ 
               
               
                   
                 39 
                 + 
               
               
                   
                 40 
                 ++ 
               
               
                   
                 41 
                 ++++ 
               
               
                   
                 42 
                 + 
               
               
                   
                 43 
                 ++ 
               
               
                   
                 44 
                 +++ 
               
               
                   
                 45 
                 ++ 
               
               
                   
                 46 
                 ++++ 
               
               
                   
                 47 
                 ++++ 
               
               
                   
                 48 
                 ++ 
               
               
                   
                 49 
                 ++ 
               
               
                   
                 50 
                 + 
               
               
                   
                 51 
                 ++ 
               
               
                   
                 52 
                 ++ 
               
               
                   
                 53 
                 +++ 
               
               
                   
                 54 
                 ++ 
               
               
                   
                 55 
                 ++ 
               
               
                   
                 56 
                 + 
               
               
                   
                 57 
                 + 
               
               
                   
                 58 
                 +++ 
               
               
                   
                 59 
                 + 
               
               
                   
                 60 
                 ++ 
               
               
                   
                 61 
                 ++ 
               
               
                   
                 62 
                 ++ 
               
               
                   
                 63 
                 +++ 
               
               
                   
                 64 
                 + 
               
               
                   
                 65 
                 + 
               
               
                   
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                 + 
               
               
                   
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                 + 
               
               
                   
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                 +++ 
               
               
                   
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                 + 
               
               
                   
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                 ++ 
               
               
                   
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                 ++ 
               
               
                   
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                 ++ 
               
               
                   
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                 + 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++ 
               
               
                   
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                 + 
               
               
                   
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                 +++ 
               
               
                   
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                 +++ 
               
               
                   
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                 ++ 
               
               
                   
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                 + 
               
               
                   
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                 + 
               
               
                   
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                 + 
               
               
                   
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                 ++ 
               
               
                   
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                 + 
               
               
                   
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                 +++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 +++ 
               
               
                   
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                 +++ 
               
               
                   
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                 ++ 
               
               
                   
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                 +++ 
               
               
                   
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                 +++ 
               
               
                   
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                 +++ 
               
               
                   
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                 +++ 
               
               
                   
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                 +++ 
               
               
                   
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                 ++ 
               
               
                   
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                 +++ 
               
               
                   
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                 +++ 
               
               
                   
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                 ++ 
               
               
                   
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                 +++ 
               
               
                   
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                 +++ 
               
               
                   
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                 ++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++ 
               
               
                   
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                 ++ 
               
               
                   
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                 +++ 
               
               
                   
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                 +++ 
               
               
                   
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                 +++ 
               
               
                   
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                 +++ 
               
               
                   
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                 + 
               
               
                   
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                 +++ 
               
               
                   
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                 +++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++ 
               
               
                   
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                 ++ 
               
               
                   
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                 ++ 
               
               
                   
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                 ++ 
               
               
                   
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                 ++ 
               
               
                   
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                 +++ 
               
               
                   
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                 +++ 
               
               
                   
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                 ++ 
               
               
                   
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                 ++ 
               
               
                   
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                 ++ 
               
               
                   
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                 +++ 
               
               
                   
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                 + 
               
               
                   
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                 ++ 
               
               
                   
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                 +++ 
               
               
                   
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                 ++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
                 140 
                 +++ 
               
               
                   
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                 +++ 
               
               
                   
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                 ++ 
               
               
                   
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                 ++++ 
               
               
                   
                 151 
                 +++ 
               
               
                   
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                 ++ 
               
               
                   
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                 ++ 
               
               
                   
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                 +++ 
               
               
                   
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                 ++ 
               
               
                   
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                 ++ 
               
               
                   
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                 ++ 
               
               
                   
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                 ++ 
               
               
                   
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                 + 
               
               
                   
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                 + 
               
               
                   
                 200 
                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 +++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 +++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 +++ 
               
               
                   
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                 +++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 +++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 +++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 +++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 +++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++ 
               
               
                   
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                 ++++ 
               
               
                   
                 225 
                 +++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
                 230 
                 ++++ 
               
               
                   
                 231 
                 + 
               
               
                   
                 232 
                 +++ 
               
               
                   
                 233 
                 +++ 
               
               
                   
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                 +++ 
               
               
                   
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                 +++ 
               
               
                   
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                 +++ 
               
               
                   
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                 ++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
                 242 
                 ++++ 
               
               
                   
                 243 
                 ++ 
               
               
                   
                 244 
                 ++ 
               
               
                   
                 245 
                 ++ 
               
               
                   
                 246 
                 +++ 
               
               
                   
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                 +++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
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                 +++ 
               
               
                   
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                 +++ 
               
               
                   
                 252 
                 +++ 
               
               
                   
                 253 
                 ++++ 
               
               
                   
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                 ++++ 
               
               
                   
                 255 
                 +++ 
               
               
                   
                 256 
                 ++++ 
               
               
                   
                 257 
                 +++ 
               
               
                   
                 258 
                 ++++ 
               
               
                   
                 259 
                 ++++ 
               
               
                   
                 260 
                 + 
               
               
                   
                 261 
                 +++ 
               
               
                   
                 262 
                 +++ 
               
               
                   
                 263 
                 ++++ 
               
               
                   
                 264 
                 ++++ 
               
               
                   
                 265 
                 ++++ 
               
               
                   
                 266 
                 ++++ 
               
               
                   
                 267 
                 ++++ 
               
               
                   
                 268 
                 +++ 
               
               
                   
                 269 
                 ++++ 
               
               
                   
                 270 
                 +++ 
               
               
                   
                 271 
                 ++++ 
               
               
                   
                 272 
                 ++++ 
               
               
                   
                 273 
                 ++++ 
               
               
                   
                 274 
                 +++ 
               
               
                   
                 275 
                 ++++ 
               
               
                   
                 276 
                 ++++ 
               
               
                   
                 277 
                 ++++ 
               
               
                   
                 278 
                 + 
               
               
                   
                 279 
                 ++++ 
               
               
                   
                 280 
                 ++++ 
               
               
                   
                 281 
                 ++++ 
               
               
                   
                 282 
                 ++++ 
               
               
                   
                 283 
                 ++++ 
               
               
                   
                 284 
                 +++ 
               
               
                   
                 285 
                 ++++ 
               
               
                   
                 303 
                 +++ 
               
               
                   
                 304 
                 +++ 
               
               
                   
                 305 
                 +++ 
               
               
                   
                 306 
                 ++ 
               
               
                   
                 307 
                 +++ 
               
               
                   
                 308 
                 +++ 
               
               
                   
                 309 
                 +++ 
               
               
                   
                 310 
                 +++ 
               
               
                   
                 311 
                 ++++ 
               
               
                   
                 313 
                 ++++ 
               
               
                   
                 314 
                 ++++ 
               
               
                   
                 316 
                 +++ 
               
               
                   
                 317 
                 +++ 
               
               
                   
                 318 
                 ++++ 
               
               
                   
                 319 
                 ++++ 
               
               
                   
                 320 
                 ++++ 
               
               
                   
                 321 
                 ++++ 
               
               
                   
                 322 
                 +++ 
               
               
                   
                 323 
                 ++++ 
               
               
                   
                 324 
                 ++++ 
               
               
                   
                 325 
                 + 
               
               
                   
                 326 
                 +++ 
               
               
                   
                 327 
                 ++++ 
               
               
                   
                 328 
                 ++ 
               
               
                   
                 329 
                 ++++ 
               
               
                   
                 330 
                 ++++ 
               
               
                   
                 331 
                 ++++ 
               
               
                   
                 332 
                 ++++ 
               
               
                   
                 333 
                 ++ 
               
               
                   
                 334 
                 ++ 
               
               
                   
                 335 
                 +++ 
               
               
                   
                 336 
                 +++ 
               
               
                   
                 337 
                 ++++ 
               
               
                   
                 338 
                 ++ 
               
               
                   
                 339 
                 ++++ 
               
               
                   
                 341 
                 ++++ 
               
               
                   
                 342 
                 +++ 
               
               
                   
                 343 
                 +++ 
               
               
                   
                 344 
                 ++++ 
               
               
                   
                 345 
                 ++++ 
               
               
                   
                 346 
                 ++++ 
               
               
                   
                 347 
                 ++++ 
               
               
                   
                 348 
                 ++++ 
               
               
                   
                 349 
                 ++++ 
               
               
                   
                 350 
                 ++++ 
               
               
                   
                 351 
                 ++++ 
               
               
                   
                 352 
                 ++++ 
               
               
                   
                 353 
                 ++++ 
               
               
                   
                 354 
                 ++ 
               
               
                   
                 355 
                 ++++ 
               
               
                   
                 356 
                 ++++ 
               
               
                   
                 357 
                 ++++ 
               
               
                   
                 358 
                 +++ 
               
               
                   
                 359 
                 +++ 
               
               
                   
                 360 
                 +++ 
               
               
                   
                 361 
                 ++++ 
               
               
                   
                 362 
                 ++++ 
               
               
                   
                 363 
                 ++++ 
               
               
                   
                 364 
                 ++++ 
               
               
                   
                 365 
                 ++++ 
               
               
                   
                 366 
                 ++++ 
               
               
                   
                 367 
                 ++++ 
               
               
                   
                 368 
                 ++++ 
               
               
                   
                 369 
                 ++++ 
               
               
                   
                 370 
                 ++++ 
               
               
                   
                 371 
                 ++++ 
               
               
                   
                 372 
                 ++++ 
               
               
                   
                 373 
                 ++++ 
               
               
                   
                 374 
                 ++++ 
               
               
                   
                 375 
                 ++++ 
               
               
                   
                 376 
                 +++ 
               
               
                   
                 377 
                 +++ 
               
               
                   
                 378 
                 ++++ 
               
               
                   
                 379 
                 ++++ 
               
               
                   
                 380 
                 ++++ 
               
               
                   
                 382 
                 ++++ 
               
               
                   
                 383 
                 ++++ 
               
               
                   
                 384 
                 +++ 
               
               
                   
                 385 
                 +++ 
               
               
                   
                 386 
                 +++ 
               
               
                   
                 387 
                 ++++ 
               
               
                   
                 388 
                 + 
               
               
                   
                 389 
                 +++ 
               
               
                   
                 390 
                 +++ 
               
               
                   
                 391 
                 ++++ 
               
               
                   
                 392 
                 ++++ 
               
               
                   
                 393 
                 ++++ 
               
               
                   
                 394 
                 ++++ 
               
               
                   
                 395 
                 +++ 
               
               
                   
                 396 
                 ++++ 
               
               
                   
                 397 
                 +++ 
               
               
                   
                 398 
                 +++ 
               
               
                   
                 399 
                 ++++ 
               
               
                   
                 400 
                 ++++ 
               
               
                   
                 401 
                 ++++ 
               
               
                   
                 402 
                 +++ 
               
               
                   
                 403 
                 +++ 
               
               
                   
                 404 
                 +++ 
               
               
                   
                 405 
                 ++++ 
               
               
                   
                 406 
                 +++ 
               
               
                   
                 407 
                 +++ 
               
               
                   
                 408 
                 +++ 
               
               
                   
                 409 
                 +++ 
               
               
                   
                 410 
                 +++ 
               
               
                   
                 411 
                 ++++ 
               
               
                   
                 412 
                 ++++ 
               
               
                   
                 413 
                 ++++ 
               
               
                   
                 414 
                 ++++ 
               
               
                   
                 415 
                 ++++ 
               
               
                   
                 416 
                 ++++ 
               
               
                   
                 417 
                 +++ 
               
               
                   
                 418 
                 ++++ 
               
               
                   
                 419 
                 +++ 
               
               
                   
                 420 
                 +++ 
               
               
                   
                 421 
                 ++++ 
               
               
                   
                 422 
                 ++++ 
               
               
                   
                 423 
                 +++ 
               
               
                   
                 424 
                 ++++ 
               
               
                   
                 425 
                 ++ 
               
               
                   
                 426 
                 ++ 
               
               
                   
                 427 
                 ++ 
               
               
                   
                 428 
                 ++ 
               
               
                   
                 429 
                 ++ 
               
               
                   
                 430 
                 +++ 
               
               
                   
                 431 
                 +++ 
               
               
                   
                 432 
                 +++ 
               
               
                   
                 433 
                 ++ 
               
               
                   
                 434 
                 ++++ 
               
               
                   
                 435 
                 +++ 
               
               
                   
                 436 
                 +++ 
               
               
                   
                 437 
                 +++ 
               
               
                   
                 438 
                 ++ 
               
               
                   
                 439 
                 ++++ 
               
               
                   
                 440 
                 ++++ 
               
               
                   
                 441 
                 ++++ 
               
               
                   
                 442 
                 ++++ 
               
               
                   
                 443 
                 ++ 
               
               
                   
                 444 
                 ++++ 
               
               
                   
                 445 
                 +++ 
               
               
                   
                 446 
                 +++ 
               
               
                   
                 447 
                 ++++ 
               
               
                   
                 448 
                 ++++ 
               
               
                   
                 449 
                 ++++ 
               
               
                   
                 450 
                 ++++ 
               
               
                   
                 451 
                 ++++ 
               
               
                   
                 452 
                 +++ 
               
               
                   
                 453 
                 ++++ 
               
               
                   
                 454 
                 +++ 
               
               
                   
                 455 
                 +++ 
               
               
                   
                 456 
                 +++ 
               
               
                   
                 457 
                 +++ 
               
               
                   
                 458 
                 ++ 
               
               
                   
                 459 
                 + 
               
               
                   
                 460 
                 + 
               
               
                   
                 461 
                 ++ 
               
               
                   
                 462 
                 + 
               
               
                   
                 463 
                 ++ 
               
               
                   
                 464 
                 +++ 
               
               
                   
                 465 
                 ++ 
               
               
                   
                 466 
                 ++ 
               
               
                   
                 467 
                 ++ 
               
               
                   
                 468 
                 +++ 
               
               
                   
                 469 
                 ++ 
               
               
                   
                 470 
                 ++ 
               
               
                   
                 471 
                 ++ 
               
               
                   
                 473 
                 ++++ 
               
               
                   
                 474 
                 ++++ 
               
               
                   
                 475 
                 ++++ 
               
               
                   
                 476 
                 ++++ 
               
               
                   
                 477 
                 ++++ 
               
               
                   
                 478 
                 ++++ 
               
               
                   
                 481 
                 ++++ 
               
               
                   
                 482 
                 +++ 
               
               
                   
                 483 
                 ++++ 
               
               
                   
                 484 
                 ++++ 
               
               
                   
                 485 
                 ++++ 
               
               
                   
                 486 
                 ++++ 
               
               
                   
                 487 
                 ++++ 
               
               
                   
                 488 
                 +++ 
               
               
                   
                 489 
                 ++++ 
               
               
                   
                 490 
                 ++++ 
               
               
                   
                 491 
                 ++++ 
               
               
                   
                 492 
                 ++++ 
               
               
                   
                 493 
                 ++++ 
               
               
                   
                 494 
                 +++ 
               
               
                   
                 495 
                 ++++ 
               
               
                   
                 496 
                 + 
               
               
                   
                 497 
                 + 
               
               
                   
                 498 
                 + 
               
               
                   
                 499 
                 + 
               
               
                   
                 500 
                 +++ 
               
               
                   
                 501 
                 + 
               
               
                   
                 502 
                 ++ 
               
               
                   
                 503 
                 ++ 
               
               
                   
                 504 
                 ++++ 
               
               
                   
                 505 
                 ++++ 
               
               
                   
                 506 
                 +++ 
               
               
                   
                 507 
                 ++++ 
               
               
                   
                 508 
                 ++++ 
               
               
                   
                 509 
                 ++++ 
               
               
                   
                 510 
                 ++++ 
               
               
                   
                 511 
                 +++ 
               
               
                   
                 512 
                 ++++ 
               
               
                   
                 513 
                 ++++ 
               
               
                   
                 514 
                 ++++ 
               
               
                   
                 515 
                 ++++ 
               
               
                   
                 516 
                 ++++ 
               
               
                   
                 517 
                 +++ 
               
               
                   
                 518 
                 ++++ 
               
               
                   
                 519 
                 +++ 
               
               
                   
                 520 
                 ++++ 
               
               
                   
                 521 
                 ++++ 
               
               
                   
                 522 
                 +++ 
               
               
                   
                 523 
                 ++++ 
               
               
                   
                 524 
                 ++++ 
               
               
                   
                 525 
                 +++ 
               
               
                   
                 526 
                 ++++ 
               
               
                   
                 527 
                 ++++ 
               
               
                   
                 528 
                 +++ 
               
               
                   
                 529 
                 ++++ 
               
               
                   
                 530 
                 ++++ 
               
               
                   
                 531 
                 ++++ 
               
               
                   
                 532 
                 ++++ 
               
               
                   
                 533 
                 +++ 
               
               
                   
                 534 
                 ++++ 
               
               
                   
                 535 
                 +++ 
               
               
                   
                 536 
                 ++ 
               
               
                   
                 537 
                 ++++ 
               
               
                   
                 538 
                 ++++ 
               
               
                   
                 539 
                 ++++ 
               
               
                   
                 540 
                 ++++ 
               
               
                   
                 541 
                 ++++ 
               
               
                   
                 542 
                 +++ 
               
               
                   
                 543 
                 ++++ 
               
               
                   
                 544 
                 ++++ 
               
               
                   
                 545 
                 ++++ 
               
               
                   
                 546 
                 ++++ 
               
               
                   
                 547 
                 ++++ 
               
               
                   
                 548 
                 ++++ 
               
               
                   
                 549 
                 ++++ 
               
               
                   
                 550 
                 ++++ 
               
               
                   
                 551 
                 ++++ 
               
               
                   
                 552 
                 ++++ 
               
               
                   
                 553 
                 ++++ 
               
               
                   
                 554 
                 +++ 
               
               
                   
                 555 
                 +++ 
               
               
                   
                 556 
                 ++++ 
               
               
                   
                 557 
                 ++++ 
               
               
                   
                 558 
                 +++ 
               
               
                   
                 559 
                 ++++ 
               
               
                   
                 560 
                 +++ 
               
               
                   
                 561 
                 ++++ 
               
               
                   
                 562 
                 +++ 
               
               
                   
                 563 
                 ++++ 
               
               
                   
                 564 
                 ++++ 
               
               
                   
                 565 
                 ++++ 
               
               
                   
                 566 
                 ++++ 
               
               
                   
                 567 
                 ++++ 
               
               
                   
                 568 
                 ++++ 
               
               
                   
                 569 
                 ++++ 
               
               
                   
                 570 
                 ++++ 
               
               
                   
                 571 
                 ++++ 
               
               
                   
                 572 
                 ++++ 
               
               
                   
                 573 
                 ++++ 
               
               
                   
                 574 
                 ++++ 
               
               
                   
                 575 
                 ++++ 
               
               
                   
                 576 
                 ++++ 
               
               
                   
                 577 
                 ++++ 
               
               
                   
                 578 
                 ++++ 
               
               
                   
                 579 
                 + 
               
               
                   
                 580 
                 ++++ 
               
               
                   
                 581 
                 ++++ 
               
               
                   
                 582 
                 ++++ 
               
               
                   
                 583 
                 ++++ 
               
               
                   
                 584 
                 ++++ 
               
               
                   
                 585 
                 ++++ 
               
               
                   
                 586 
                 ++++ 
               
               
                   
                 587 
                 ++++ 
               
               
                   
                 588 
                 ++++ 
               
               
                   
                 589 
                 ++++ 
               
               
                   
                 590 
                 ++++ 
               
               
                   
                 591 
                 ++++ 
               
               
                   
                 592 
                 ++++ 
               
               
                   
                 593 
                 + 
               
               
                   
                 594 
                 ++++ 
               
               
                   
                 595 
                 ++++ 
               
               
                   
                 596 
                 + 
               
               
                   
                 597 
                 + 
               
               
                   
                 598 
                 ++++ 
               
               
                   
                 599 
                 ++++ 
               
               
                   
                 600 
                 ++ 
               
               
                   
                 601 
                 ++++ 
               
               
                   
                 602 
                 ++++ 
               
               
                   
                 603 
                 ++++ 
               
               
                   
                 604 
                 ++++ 
               
               
                   
                 605 
                 ++++ 
               
               
                   
                 606 
                 +++ 
               
               
                   
                 607 
                 +++ 
               
               
                   
                 608 
                 +++ 
               
               
                   
                 609 
                 ++++ 
               
               
                   
                 610 
                 ++++ 
               
               
                   
                 611 
                 +++ 
               
               
                   
                 612 
                 ++++ 
               
               
                   
                 613 
                 ++++ 
               
               
                   
                 614 
                 ++++ 
               
               
                   
                 615 
                 +++ 
               
               
                   
                 616 
                 ++++ 
               
               
                   
                 617 
                 ++++ 
               
               
                   
                 618 
                 ++++ 
               
               
                   
                 619 
                 ++++ 
               
               
                   
                 620 
                 ++++ 
               
               
                   
                 621 
                 ++++ 
               
               
                   
                 622 
                 ++++ 
               
               
                   
                 623 
                 ++++ 
               
               
                   
                 624 
                 +++ 
               
               
                   
                 625 
                 +++ 
               
               
                   
                 626 
                 ++++ 
               
               
                   
                 627 
                 ++++ 
               
               
                   
                 628 
                 ++++ 
               
               
                   
                 629 
                 ++++ 
               
               
                   
                 630 
                 ++++ 
               
               
                   
                 631 
                 +++ 
               
               
                   
                 632 
                 ++++ 
               
               
                   
                 633 
                 ++++ 
               
               
                   
                 634 
                 ++++ 
               
               
                   
                 635 
                 ++++ 
               
               
                   
                 636 
                 ++++ 
               
               
                   
                 637 
                 ++++ 
               
               
                   
                 638 
                 +++ 
               
               
                   
                 639 
                 ++++ 
               
               
                   
                 640 
                 ++++ 
               
               
                   
                 641 
                 ++++ 
               
               
                   
                 642 
                 +++ 
               
               
                   
                 643 
                 ++ 
               
               
                   
                 644 
                 ++++ 
               
               
                   
                 645 
                 ++++ 
               
               
                   
                 646 
                 ++++ 
               
               
                   
                 649 
                 ++++ 
               
               
                   
                 650 
                 ++++ 
               
               
                   
                 651 
                 ++++ 
               
               
                   
                 652 
                 ++++ 
               
               
                   
                 653 
                 ++++ 
               
               
                   
                 654 
                 ++++ 
               
               
                   
                 655 
                 ++ 
               
               
                   
                 656 
                 +++ 
               
               
                   
                 657 
                 +++ 
               
               
                   
                 658 
                 ++ 
               
               
                   
                 659 
                 +++ 
               
               
                   
                 660 
                 + 
               
               
                   
                 661 
                 ++ 
               
               
                   
                 662 
                 ++ 
               
               
                   
                 663 
                 +++ 
               
               
                   
                 664 
                 ++ 
               
               
                   
                 665 
                 ++ 
               
               
                   
                 666 
                 ++ 
               
               
                   
                 667 
                 ++++ 
               
               
                   
                 668 
                 ++++ 
               
               
                   
                 669 
                 ++ 
               
               
                   
                 670 
                 ++++ 
               
               
                   
                 671 
                 ++++ 
               
               
                   
                 672 
                 ++++ 
               
               
                   
                 673 
                 ++++ 
               
               
                   
                 674 
                 ++ 
               
               
                   
                 675 
                 +++ 
               
               
                   
                 676 
                 +++ 
               
               
                   
                 677 
                 +++ 
               
               
                   
                 678 
                 ++++ 
               
               
                   
                 679 
                 ++ 
               
               
                   
                 680 
                 ++++ 
               
               
                   
                 681 
                 ++++ 
               
               
                   
                 682 
                 +++ 
               
               
                   
                 683 
                 ++ 
               
               
                   
                 684 
                 +++ 
               
               
                   
                 685 
                 +++ 
               
               
                   
                 686 
                 +++ 
               
               
                   
                 687 
                 +++ 
               
               
                   
                 688 
                 ++++ 
               
               
                   
                 689 
                 ++++ 
               
               
                   
                 690 
                 ++++ 
               
               
                   
                 691 
                 ++++ 
               
               
                   
                 692 
                 ++++ 
               
               
                   
                 693 
                 ++++ 
               
               
                   
                 694 
                 ++++ 
               
               
                   
                 695 
                 ++++ 
               
               
                   
                 696 
                 ++++ 
               
               
                   
                 697 
                 +++ 
               
               
                   
                 698 
                 +++ 
               
               
                   
                 699 
                 ++++ 
               
               
                   
                 700 
                 ++++ 
               
               
                   
                 701 
                 + 
               
               
                   
                 702 
                 +++ 
               
               
                   
                 703 
                 ++++ 
               
               
                   
                 704 
                 ++++ 
               
               
                   
                 705 
                 ++++ 
               
               
                   
                 706 
                 +++ 
               
               
                   
                 707 
                 + 
               
               
                   
                 708 
                 +++ 
               
               
                   
                 709 
                 +++ 
               
               
                   
                 710 
                 +++ 
               
               
                   
                 711 
                 +++ 
               
               
                   
                 712 
                 ++++ 
               
               
                   
                 713 
                 +++ 
               
               
                   
                 714 
                 ++++ 
               
               
                   
                 715 
                 ++++ 
               
               
                   
                 716 
                 ++++ 
               
               
                   
                 717 
                 ++++ 
               
               
                   
                 718 
                 ++++ 
               
               
                   
                 719 
                 ++++ 
               
               
                   
                 720 
                 ++++ 
               
               
                   
                 721 
                 ++++ 
               
               
                   
                 722 
                 ++++ 
               
               
                   
                 723 
                 ++ 
               
               
                   
                 724 
                 ++++ 
               
               
                   
                 725 
                 ++++ 
               
               
                   
                 726 
                 +++ 
               
               
                   
                 727 
                 ++++ 
               
               
                   
                 728 
                 +++ 
               
               
                   
                 729 
                 ++++ 
               
               
                   
                 730 
                 ++++ 
               
               
                   
                 731 
                 ++++ 
               
               
                   
                 732 
                 ++++ 
               
               
                   
                 733 
                 ++ 
               
               
                   
                 734 
                 ++++ 
               
               
                   
                 735 
                 +++ 
               
               
                   
                 736 
                 ++++ 
               
               
                   
                 737 
                 ++++ 
               
               
                   
                 738 
                 ++++ 
               
               
                   
                 739 
                 +++ 
               
               
                   
                 740 
                 +++ 
               
               
                   
                 741 
                 +++ 
               
               
                   
                 742 
                 ++++ 
               
               
                   
                 743 
                 ++++ 
               
               
                   
                 744 
                 ++++ 
               
               
                   
                 745 
                 +++ 
               
               
                   
                 746 
                 ++++ 
               
               
                   
                 747 
                 ++++ 
               
               
                   
                 748 
                 ++++ 
               
               
                   
                 749 
                 ++++ 
               
               
                   
                 750 
                 ++++ 
               
               
                   
                 751 
                 ++++ 
               
               
                   
                 752 
                 ++++ 
               
               
                   
                 753 
                 ++++ 
               
               
                   
                 754 
                 ++++ 
               
               
                   
                 756 
                 ++++ 
               
               
                   
                 757 
                 +++ 
               
               
                   
                 758 
                 ++++ 
               
               
                   
                 760 
                 +++ 
               
               
                   
                 761 
                 +++ 
               
               
                   
                 762 
                 ++++ 
               
               
                   
                 763 
                 ++++ 
               
               
                   
                 764 
                 ++++ 
               
               
                   
                 765 
                 ++++ 
               
               
                   
                 766 
                 +++ 
               
               
                   
                 767 
                 +++ 
               
               
                   
                 768 
                 ++++ 
               
               
                   
                 769 
                 ++++ 
               
               
                   
                 770 
                 +++ 
               
               
                   
                 771 
                 ++ 
               
               
                   
                 772 
                 +++ 
               
               
                   
                 773 
                 +++ 
               
               
                   
                 774 
                 ++++ 
               
               
                   
                 775 
                 ++++ 
               
               
                   
                 776 
                 +++ 
               
               
                   
                 777 
                 +++ 
               
               
                   
                 778 
                 ++++ 
               
               
                   
                 779 
                 ++++ 
               
               
                   
                 780 
                 ++++ 
               
               
                   
                 781 
                 +++ 
               
               
                   
                 782 
                 +++ 
               
               
                   
                 783 
                 ++++ 
               
               
                   
                 784 
                 ++++ 
               
               
                   
                 785 
                 ++++ 
               
               
                   
                 786 
                 ++++ 
               
               
                   
                 787 
                 ++++ 
               
               
                   
                 788 
                 +++ 
               
               
                   
                 789 
                 +++ 
               
               
                   
                 790 
                 ++++ 
               
               
                   
                 791 
                 ++++ 
               
               
                   
                 793 
                 +++ 
               
               
                   
                 794 
                 ++++ 
               
               
                   
                 795 
                 ++++ 
               
               
                   
                 796 
                 ++++ 
               
               
                   
                 797 
                 +++ 
               
               
                   
                 798 
                 ++++ 
               
               
                   
                 799 
                 ++++ 
               
               
                   
                 800 
                 ++++ 
               
               
                   
                 801 
                 ++++ 
               
               
                   
                 802 
                 ++++ 
               
               
                   
                 803 
                 +++ 
               
               
                   
                 804 
                 +++ 
               
               
                   
                 805 
                 +++ 
               
               
                   
                 806 
                 ++ 
               
               
                   
                 807 
                 ++++ 
               
               
                   
                 808 
                 ++++ 
               
               
                   
                 809 
                 ++++ 
               
               
                   
                 810 
                 ++++ 
               
               
                   
                 811 
                 ++++ 
               
               
                   
                 812 
                 ++++ 
               
               
                   
                 813 
                 ++++ 
               
               
                   
                 814 
                 ++++ 
               
               
                   
                 815 
                 ++++ 
               
               
                   
                 816 
                 ++++ 
               
               
                   
                 817 
                 ++++ 
               
               
                   
                 818 
                 ++++ 
               
               
                   
                 819 
                 + 
               
               
                   
                 820 
                 ++++ 
               
               
                   
                 821 
                 ++++ 
               
               
                   
                 822 
                 ++ 
               
               
                   
                 823 
                 ++++ 
               
               
                   
                 824 
                 ++++ 
               
               
                   
                 825 
                 ++++ 
               
               
                   
                 826 
                 +++ 
               
               
                   
                 827 
                 ++++ 
               
               
                   
                 828 
                 ++++ 
               
               
                   
                 829 
                 ++++ 
               
               
                   
                 830 
                 ++ 
               
               
                   
                 831 
                 ++++ 
               
               
                   
                 832 
                 ++++ 
               
               
                   
                 833 
                 ++++ 
               
               
                   
                 834 
                 ++++ 
               
               
                   
                 835 
                 ++++ 
               
               
                   
                 836 
                 ++++ 
               
               
                   
                 837 
                 ++++ 
               
               
                   
                 838 
                 ++++ 
               
               
                   
                 839 
                 ++++ 
               
               
                   
                 840 
                 ++++ 
               
               
                   
                 841 
                 ++++ 
               
               
                   
                 842 
                 ++++ 
               
               
                   
                 843 
                 ++++ 
               
               
                   
                 844 
                 ++++ 
               
               
                   
                 845 
                 ++++ 
               
               
                   
                 846 
                 ++++ 
               
               
                   
                 1000 
                 ++ 
               
               
                   
                 1001 
                 ++ 
               
               
                   
                 1002 
                 ++++ 
               
               
                   
                 1003 
                 +++ 
               
               
                   
                 1004 
                 ++ 
               
               
                   
                 1005 
                 +++ 
               
               
                   
                 1006 
                 +++ 
               
               
                   
                 1007 
                 ++ 
               
               
                   
                 1008 
                 +++ 
               
               
                   
                 1009 
                 ++ 
               
               
                   
                 1010 
                 +++ 
               
               
                   
                 1011 
                 ++ 
               
               
                   
                 1012 
                 ++ 
               
               
                   
                 1013 
                 +++ 
               
               
                   
                 1014 
                 +++ 
               
               
                   
                 1015 
                 +++ 
               
               
                   
                 1016 
                 ++++ 
               
               
                   
                 1017 
                 ++++ 
               
               
                   
                 1018 
                 ++++ 
               
               
                   
                 1200 
                 ++++ 
               
               
                   
                 1201 
                 ++++ 
               
               
                   
                 1202 
                 ++++ 
               
               
                   
                 1203 
                 ++++ 
               
               
                   
                 1204 
                 +++ 
               
               
                   
                 1205 
                 +++ 
               
               
                   
                 1206 
                 ++++ 
               
               
                   
                 1207 
                 +++ 
               
               
                   
                 1208 
                 +++ 
               
               
                   
                 1209 
                 ++++ 
               
               
                   
                 1210 
                 ++++ 
               
               
                   
                 1211 
                 ++++ 
               
               
                   
                 1212 
                 ++++ 
               
               
                   
                 1213 
                 ++++ 
               
               
                   
                 1214 
                 ++++ 
               
               
                   
                 1215 
                 ++++ 
               
               
                   
                 1216 
                 ++++ 
               
               
                   
                 1217 
                 ++++ 
               
               
                   
                 1218 
                 ++++ 
               
               
                   
                 1219 
                 ++++ 
               
               
                   
                 1220 
                 ++++ 
               
               
                   
                 1221 
                 ++++ 
               
               
                   
                 1222 
                 ++++ 
               
               
                   
                 1223 
                 ++++ 
               
               
                   
                 1224 
                 + 
               
               
                   
                 1226 
                 ++++ 
               
               
                   
                 1227 
                 + 
               
               
                   
                 1228 
                 ++++ 
               
               
                   
                 1229 
                 ++++ 
               
               
                   
                 1230 
                 ++++ 
               
               
                   
                 1231 
                 ++++ 
               
               
                   
                 1232 
                 ++++ 
               
               
                   
                 1233 
                 ++++ 
               
               
                   
                 1234 
                 +++ 
               
               
                   
                 1235 
                 +++ 
               
               
                   
                 1236 
                 ++ 
               
               
                   
                 1237 
                 +++ 
               
               
                   
                 1238 
                 ++++ 
               
               
                   
                 1239 
                 ++++ 
               
               
                   
                 1240 
                 ++++ 
               
               
                   
                 1241 
                 +++ 
               
               
                   
                 1242 
                 ++ 
               
               
                   
                 1243 
                 ++ 
               
               
                   
                 1244 
                 ++++ 
               
               
                   
                 1245 
                 + 
               
               
                   
                 1246 
                 + 
               
               
                   
                 1247 
                 ++++ 
               
               
                   
                 1248 
                 + 
               
               
                   
                 1249 
                 ++++ 
               
               
                   
                 1250 
                 ++++ 
               
               
                   
                 1251 
                 ++++ 
               
               
                   
                 1252 
                 ++++ 
               
               
                   
                 1253 
                 ++++ 
               
               
                   
                 1254 
                 +++ 
               
               
                   
                 1255 
                 ++++ 
               
               
                   
                 2001 
                 ++++ 
               
               
                   
                 2002 
                 ++++ 
               
               
                   
                 2003 
                 ++++ 
               
               
                   
                 2004 
                 ++++ 
               
               
                   
                 2005 
                 ++++ 
               
               
                   
                 2006 
                 ++++ 
               
               
                   
                 2007 
                 ++++ 
               
               
                   
                 2008 
                 ++++ 
               
               
                   
                 2009 
                 ++++ 
               
               
                   
                 2010 
                 ++++ 
               
               
                   
                 2011 
                 ++++ 
               
               
                   
                 2012 
                 ++++ 
               
               
                   
                 2013 
                 ++++ 
               
               
                   
                 2014 
                 ++++ 
               
               
                   
                 2015 
                 ++++ 
               
               
                   
                 2016 
                 ++++ 
               
               
                   
                 2017 
                 ++++ 
               
               
                   
                 2018 
                 ++++ 
               
               
                   
                 2019 
                 ++++ 
               
               
                   
                 2020 
                 ++++ 
               
               
                   
                 2021 
                 ++++ 
               
               
                   
                 2022 
                 ++++ 
               
               
                   
                 2023 
                 ++++ 
               
               
                   
                 2024 
                 ++++ 
               
               
                   
                 2025 
                 ++++ 
               
               
                   
                 2026 
                 ++++ 
               
               
                   
                 2027 
                 ++++ 
               
               
                   
                 2028 
                 ++++ 
               
               
                   
                 2029 
                 ++++ 
               
               
                   
                 2030 
                 ++++ 
               
               
                   
                 2031 
                 ++++ 
               
               
                   
                 2032 
                 ++++ 
               
               
                   
                 2033 
                 ++++ 
               
               
                   
                 2034 
                 ++++ 
               
               
                   
                 2035 
                 ++++ 
               
               
                   
                 2036 
                 ++++ 
               
               
                   
                 2037 
                 ++++ 
               
               
                   
                 2038 
                 ++++ 
               
               
                   
                 2039 
                 ++++ 
               
               
                   
                 2040 
                 ++++ 
               
               
                   
                 2041 
                 ++++ 
               
               
                   
                 2042 
                 ++++ 
               
               
                   
                 2043 
                 ++++ 
               
               
                   
                 2044 
                 ++++ 
               
               
                   
                 2045 
                 ++++ 
               
               
                   
                 2046 
                 ++++ 
               
               
                   
                 2047 
                 ++++ 
               
               
                   
                 2048 
                 ++++ 
               
               
                   
                 2049 
                 ++++ 
               
               
                   
                 2050 
                 ++++ 
               
               
                   
                 2051 
                 ++++ 
               
               
                   
                 2052 
                 ++++ 
               
               
                   
                 2053 
                 ++++ 
               
               
                   
                 2054 
                 ++++ 
               
               
                   
                 2055 
                 ++++ 
               
               
                   
                 2056 
                 ++++ 
               
               
                   
                 2057 
                 ++++ 
               
               
                   
                 2058 
                 ++++ 
               
               
                   
                 2059 
                 ++++ 
               
               
                   
                 2060 
                 ++++ 
               
               
                   
                 2061 
                 ++++ 
               
               
                   
                 2062 
                 ++++ 
               
               
                   
                 2063 
                 ++++ 
               
               
                   
                 2064 
                 ++++ 
               
               
                   
                 2065 
                 ++++ 
               
               
                   
                 2066 
                 ++++ 
               
               
                   
                 2067 
                 ++++ 
               
               
                   
                 2068 
                 ++++ 
               
               
                   
                 2069 
                 ++++ 
               
               
                   
                 2070 
                 ++++ 
               
               
                   
                 2071 
                 ++++ 
               
               
                   
                 2072 
                 ++++ 
               
               
                   
                 2073 
                 ++++ 
               
               
                   
                 2074 
                 ++++ 
               
               
                   
                 2075 
                 ++++ 
               
               
                   
                 2076 
                 +++ 
               
               
                   
                 2077 
                 + 
               
               
                   
                 2078 
                 ++++ 
               
               
                   
                 2079 
                 ++++ 
               
               
                   
                 2080 
                 ++++ 
               
               
                   
                 2081 
                 ++++ 
               
               
                   
                 2082 
                 ++++ 
               
               
                   
                 2083 
                 ++++ 
               
               
                   
                 2084 
                 ++++ 
               
               
                   
                 2085 
                 +++ 
               
               
                   
                 2086 
                 ++++ 
               
               
                   
                 2087 
                 ++++ 
               
               
                   
                 2088 
                 ++++ 
               
               
                   
                 2089 
                 ++++ 
               
               
                   
                 2090 
                 +++ 
               
               
                   
                 2091 
                 ++++ 
               
               
                   
                 2092 
                 ++++ 
               
               
                   
                 2093 
                 ++++ 
               
               
                   
                 2094 
                 ++++ 
               
               
                   
                 2095 
                 ++++ 
               
               
                   
                 2096 
                 +++ 
               
               
                   
                 2097 
                 ++++ 
               
               
                   
                 2098 
                 ++++ 
               
               
                   
                 2099 
                 ++++ 
               
               
                   
                 2100 
                 ++++ 
               
               
                   
                 2101 
                 ++++ 
               
               
                   
                 2102 
                 ++++ 
               
               
                   
                 2103 
                 +++ 
               
               
                   
                 2104 
                 ++++ 
               
               
                   
                 2105 
                 ++++ 
               
               
                   
                 2106 
                 ++++ 
               
               
                   
                 2107 
                 ++++ 
               
               
                   
                 2108 
                 ++++ 
               
               
                   
                 2109 
                 ++++ 
               
               
                   
                 2110 
                 +++ 
               
               
                   
                 2111 
                 ++++ 
               
               
                   
                 2112 
                 ++++ 
               
               
                   
                 2113 
                 ++++ 
               
               
                   
                 2114 
                 ++++ 
               
               
                   
                 2115 
                 ++++ 
               
               
                   
                 2116 
                 ++++ 
               
               
                   
                 2117 
                 ++++ 
               
               
                   
                 2118 
                 ++++ 
               
               
                   
                 2119 
                 ++++ 
               
               
                   
                 2120 
                 ++++ 
               
               
                   
                 2121 
                 ++++ 
               
               
                   
                 2122 
                 ++++ 
               
               
                   
                 2123 
                 +++ 
               
               
                   
                 2124 
                 ++++ 
               
               
                   
                 2125 
                 ++++ 
               
               
                   
                 2126 
                 ++++ 
               
               
                   
                 2127 
                 ++++ 
               
               
                   
                 2128 
                 +++ 
               
               
                   
                 2129 
                 ++++ 
               
               
                   
                 2130 
                 ++++ 
               
               
                   
                 2131 
                 ++++ 
               
               
                   
                 2132 
                 ++++ 
               
               
                   
                 2133 
                 ++++ 
               
               
                   
                 2134 
                 ++++ 
               
               
                   
                 2135 
                 ++++ 
               
               
                   
                 2136 
                 ++++ 
               
               
                   
                 2137 
                 ++++ 
               
               
                   
                 2138 
                 ++++ 
               
               
                   
                 2139 
                 ++++ 
               
               
                   
                 2140 
                 ++++ 
               
               
                   
                 2141 
                 ++++ 
               
               
                   
                 2142 
                 +++ 
               
               
                   
                 2143 
                 ++++ 
               
               
                   
                 2144 
                 ++++ 
               
               
                   
                 2145 
                 ++++ 
               
               
                   
                 2146 
                 ++++ 
               
               
                   
                 2147 
                 ++++ 
               
               
                   
                 2148 
                 ++++ 
               
               
                   
                 2149 
                 ++++ 
               
               
                   
                 2150 
                 ++++ 
               
               
                   
                 2151 
                 ++++ 
               
               
                   
                 2152 
                 ++++ 
               
               
                   
                 2153 
                 ++++ 
               
               
                   
                 2154 
                 ++++ 
               
               
                   
                 2155 
                 +++ 
               
               
                   
                 2156 
                 +++ 
               
               
                   
                 2157 
                 ++++ 
               
               
                   
                 2158 
                 ++++ 
               
               
                   
                 2159 
                 +++ 
               
               
                   
                 2160 
                 ++++ 
               
               
                   
                 2161 
                 ++++ 
               
               
                   
                 2162 
                 ++++ 
               
               
                   
                 2163 
                 ++++ 
               
               
                   
                 2164 
                 ++++ 
               
               
                   
                 2165 
                 ++++ 
               
               
                   
                 2166 
                 ++++ 
               
               
                   
                 2167 
                 ++++ 
               
               
                   
                 2168 
                 + 
               
               
                   
                 2169 
                 ++++ 
               
               
                   
                 2170 
                 ++++ 
               
               
                   
                 2171 
                 ++++ 
               
               
                   
                 2172 
                 ++ 
               
               
                   
                 2173 
                 ++ 
               
               
                   
                 2174 
                 ++++ 
               
               
                   
                 2175 
                 ++++ 
               
               
                   
                 2176 
                 ++++ 
               
               
                   
                 2177 
                 ++++ 
               
               
                   
                 2178 
                 ++++ 
               
               
                   
                 2179 
                 ++++ 
               
               
                   
                 2180 
                 ++++ 
               
               
                   
                 2181 
                 ++++ 
               
               
                   
                 2182 
                 ++++ 
               
               
                   
                 2183 
                 ++++ 
               
               
                   
                 2184 
                 ++++ 
               
               
                   
                 2185 
                 ++++ 
               
               
                   
                 2186 
                 +++ 
               
               
                   
                 2187 
                 +++ 
               
               
                   
                 2188 
                 +++ 
               
               
                   
                 2189 
                 +++ 
               
               
                   
                 2190 
                 ++++ 
               
               
                   
                 2191 
                 ++++ 
               
               
                   
                 2192 
                 ++++ 
               
               
                   
                 2193 
                 ++++ 
               
               
                   
                 2194 
                 ++++ 
               
               
                   
                 2195 
                 ++++ 
               
               
                   
                 2196 
                 ++++ 
               
               
                   
                 2198 
                 ++++ 
               
               
                   
                 2199 
                 +++ 
               
               
                   
                 2200 
                 ++++ 
               
               
                   
                 2201 
                 ++++ 
               
               
                   
                 2202 
                 ++++ 
               
               
                   
                 2203 
                 ++++ 
               
               
                   
                 2204 
                 ++++ 
               
               
                   
                 2205 
                 ++++ 
               
               
                   
                 2206 
                 + 
               
               
                   
                 2207 
                 ++++ 
               
               
                   
                 2208 
                 +++ 
               
               
                   
                 2209 
                 ++++ 
               
               
                   
                 2210 
                 ++++ 
               
               
                   
                 2211 
                 ++ 
               
               
                   
                   
               
            
           
         
       
     
     Preferably, a compound of the present application (i.e., a compound of formula (I) or a salt thereof) has an IC 50  in an IMAP assay against full length PKCι at 150 μM ATP of &lt;40 μM. In one embodiment, a compound of the present application has an IC 50  in an IMAP assay against full length PKCι at 150 μM ATP of 40 μM-10 μM. More preferably, a compound of the present application has an IC 50  in an IMAP assay against full length PKCι at 150 μM ATP of 10 μM-1 μM. In one embodiment, a compound of the present application has an IC 50  in an IMAP assay against full length PKCι at 150 μM ATP of 1 μM-0.1 μM. More preferably, a compound of the present application has an IC 50  in an IMAP assay against full length PKCι at 150 μM ATP of &lt;0.1 μM. 
     Preferably, a compound of the present application (i.e., a compound of formula (I) or a salt thereof) has an IC 50  in an IMAP assay against kinase domain PKCι at 25 μM ATP of &lt;40 μM. In one embodiment, a compound of the present application has an IC 50  in an IMAP assay against kinase domain PKCι at 25 μM ATP of 40 μM-10 μM. More preferably, a compound of the present application has an IC 50  in an IMAP assay against kinase domain PKCι at 25 μM ATP of 10 μM-1 μM. In one embodiment, a compound of the present application has an IC 50  in an IMAP assay against kinase domain PKCι at 25 μM ATP of 1 μM-0.1 μM. More preferably, a compound of the present application has an IC 50  in an IMAP assay against kinase domain PKCι at 25 μM ATP of &lt;0.1 μM. 
     As those skilled in the art will appreciate, numerous modifications and variations of the present application are possible in light of the above teachings. It is therefore understood that within the scope of the appended claims, the application may be practiced otherwise than as specifically described herein, and the scope of the application is intended to encompass all such variations. 
     Each publication referenced herein is incorporated by reference in its entirety for all purposes. 
     Additional preferred Embodiments of the present application include: 
     1. A compound of formula (I) 
                         
or a salt form thereof, wherein
         G is a group of formula       

     
       
         
         
             
             
         
       
         
         
           
             X is chosen from H, C 1-10 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —C(═O)C(═O)R 28 , —NR 24 R 28 , —NR 24 NR 24 R 28 , —N═NR 28 , —NR 24 OR 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)C(═O)R 28 , —NR 24 C(═O)OR 28 , —NR 24 C(═O)C(═O)OR 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 C(═O)NR 24 C(═O)R 28 , —NR 24 C(═O)NR 24 C(═O)OR 28 , —NR 24 C(═O)C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —NR 24 S(═O) 2 NR 24 R 28 , —OR, —OC(═O)R 28 , —OC(═O)NR 24 R 28 , —OC(═O)OR 28 , —OS(═O)R 28 , —OS(═O) 2 R 28 , —OS(═O) 2 OR 28 , —OS(═O) 2 NR 24 R 28 , —S(═O) n R 28 , —S(═O) 2 NR 24 R 28 , and —S(═O)NR 24 R 28 ; 
             R 7 , R 8 , R 9 , R 12 , R 13 , R 14 , R 15 , R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —(═O)C(═O)R 20 , —C(═NR 25 )R 20 , —C(═NR 25 )NR 22 R 23 , —C(═NOH)NR 22 R 23 , —C(═NOR 26 )R 20 , —C(═NNR 22 R 23 )R 20 , —C(═NNR 24 C(═O)R 21 )R 20 , —C(═NNR 24 C(═O)OR 21 )R 20 , —C(═S)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═NR 25 )NR 22 R 23 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 C(═S)R 20 , —NR 24 C(═S)OR 20 , —NR 24 C(═S)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)(NR 22 R 23 )(NR 22 R 23 ), —NR 24 P(═)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OC(═NR 25 )NR 22 R 23 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 78 R 78 , —OP(═O)(NR 22 R 23 )(NR 22 R 23 ), —OP(═O)(OR 20 )(OR 20 ), —OP(═O)(SR 20 )(SR 20 ), —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —SP(═O)R 78 R 78 , —SP(═O)(NR 22 R 23 )(NR 22 R 23 ), —SP(═O)(OR 20 )(OR 20 ), —SP(═O)(SR 20 )(SR 20 ), —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), —P(═O)(OR 20 )(OR 20 ), and —P(═O)(SR 20 )(SR 20 ); 
             or any of R 7  and R 8 , R 12  and R 13 , R 14  and R 15 , R a  and R b , R a  and R c , R a  and R e , R a  and R g , R b  and R d , R b  and R f , R b  and R h , R c  and R d , R c  and R e , R c  and R g , R d  and R f , R d  and R h , R e  and R f , R e  and R g , R f  and R h , and R g  and R h  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 19 ; 
             R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 39 , C 2-6 alkenyl optionally substituted by 1-11 R 39 , C 2-6 alkynyl optionally substituted by 1-9 R 39 , C 6-11 aryl optionally substituted by 1-11 R 39 , C 7-16 arylalkyl optionally substituted by 1-19 R 39 , C 3-11 cycloalkyl optionally substituted by 1-21 R 39 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 39 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 39 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 39 , 5-15 membered heteroaryl optionally substituted by 1-15 R 39 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 39 , halogen, —CN, —C(═O)R 30 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —C(═O)C(═O)R 30 , —C(═NR 35 )R 30 , —C(═NR 35 )NR 32 R 33 , —C(═NOH)NR 32 R 33 , —C(═NOR 36 )R 30 , —C(═NNR 32 R 33 )R 30 , —C(═NNR 34 C(═O)R 31 )R 30 , —C(═NNR 34 C(═O)OR 31 )R 30 , —C(═S)NR 32 R 33 , —NC, —NO 2 , —NR 32 R 33 , —NR 34 NR 32 R 33 , —N═NR 34 , ═NR 30 , ═NOR 30 , —NR 34 OR 36 , —NR 34 C(═O)R 30 , —NR 34 C(═O)C(═O)R 30 , —NR 34 C(═O)OR 31 , —NR 34 C(═O)C(═O)OR 31 , —NR 34 C(═O)NR 32 R 33 , —NR 34 C(═O)NR 34 C(═O)R 30 , —NR 34 C(═O)NR 34 C(═O)OR 30 , —NR 34 C(═NR 35 )NR 32 R 33 , —NR 34 C(═O)C(═O)NR 32 R 33 , —NR 34 C(═S)R 30 , —NR 34 C(═S)OR 30 , —NR 34 C(═S)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —NR 34 P(═O)R 78 R 78 , —NR 34 P(═O)(NR 32 R 33 )(NR 32 R 33 ), —NR 34 P(═)(OR 30 )(OR 30 ), —NR 34 P(═O)(SR 30 )(SR 30 ), —OR 30 , ═O, —OCN, —OC(═O)R 30 , —OC(═O)NR 32 R 33 , —OC(═O)OR 30 , —OC(═NR 35 )NR 32 R 33 , —OS(═O)R 30 , —OS(═O) 2 R 30 , —OS(═O) 2 OR 30 , —OS(═O) 2 NR 32 R 33 , —OP(═O)R 78 R 78 , —OP(═O)(NR 32 R 33 )(NR 32 R 33 ), —OP(═O)(OR 30 )(OR 30 ), —OP(═O)(SR 30 )(SR 30 ), —Si(R 34 ) 3 , —SCN, ═S, —S(═O) n R 30 , —S(═O) 2 OR 30 , —SO 3 R 37 , —S(═O) 2 NR 32 R 33 , —S(═O)NR 32 R 33 , —SP(═O)R 78 R 78 , —SP(═O)(NR 32 R 33 )(NR 32 R 33 ), —SP(═O)(OR 30 )(OR 30 ), —SP(═O)(SR 30 )(SR 30 ), —P(═O)R 78 R 78 , —P(═O)(NR 32 R 33 )(NR 32 R 33 ), —P(═O)(OR 30 )(OR 30 ), and —P(═O)(SR 30 )(SR 30 ); 
             R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 49 , C 2-6 alkenyl optionally substituted by 1-11 R 49 , C 2-6 alkynyl optionally substituted by 1-9 R 49 , C 6-11 aryl optionally substituted by 1-11 R 49 , C 7-16 arylalkyl optionally substituted by 1-19 R 49 , C 3-11 cycloalkyl optionally substituted by 1-21 R 49 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 49 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 49 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 49 , 5-15 membered heteroaryl optionally substituted by 1-15 R 49 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 49 ; 
             R 28  at each occurrence is independently chosen from C 1-10 alkyl optionally substituted by 1-13 R 49 , C 2-10 alkenyl optionally substituted by 1-11 R 49 , C 2-6 alkynyl optionally substituted by 1-9 R 49 , C 6-11 aryl optionally substituted by 1-11 R 49 , C 7-16 arylalkyl optionally substituted by 1-19 R 49 , C 3-11 cycloalkyl optionally substituted by 1-21 R 49 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 49 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 49 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 49 , 5-15 membered heteroaryl optionally substituted by 1-15 R 49 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 49 ; 
             R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 59 , C 2-6 alkenyl optionally substituted by 1-11 R 59 , C 2-6 alkynyl optionally substituted by 1-9 R 59 , C 6-11 aryl optionally substituted by 1-11 R 59 , C 7-16 arylalkyl optionally substituted by 1-19 R 59 , C 3-11 cycloalkyl optionally substituted by 1-21 R 59 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 59 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 59 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 59 , 5-15 membered heteroaryl optionally substituted by 1-15 R 59 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 59 ;
           or any R 22  and R 23  and/or R 32  and R 33  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 69  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 69 ;   
         
             R 39 , R 49 , R 59  and R 69  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 79 , C 2-6 alkenyl optionally substituted by 1-11 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-19 R 79 , C 3-11 cycloalkyl optionally substituted by 1-21 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 79 , 5-15 membered heteroaryl optionally substituted by 1-15 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —C(═O)C(═O)R 70 , —C(═NR 75 )R 70 , —C(═NR 75 )NR 72 R 73 , —C(═NOH)NR 72 R 73 , —C(═NOR 76 )R 70 , —C(═NNR 72 R 73 )R 70 , —C(═NNR 74 C(═O)R 71 )R 70 , —C(═NNR 74 C(═O)OR 71 )R 70 , —C(═S)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 NR 72 R 73 , —N═NR 74 , ═NR 70 , ═NOR 70 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 C(═O)NR 74 C(═O)OR 70 , —NR 74 C(═NR 75 )NR 72 R 73 , —NR 74 C(═O)C(═O)NR 72 R 73 , —NR 74 C(═S)R 70 , —NR 74 C(═S)OR 70 , —NR 74 C(═S)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —NR 74 P(═O)R 78 R 78 , —NR 74 P(═O)(NR 72 NR 73 )(NR 72 R 73 ), —NR 74 P(═O)(OR 70 )(OR 70 ), —NR 74 P(═O)(SR 70 )(SR 70 ), —OR 70 , ═O, —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —OC(═NR 75 )NR 72 R 73 , —OS(═O)R 70 , —OS(═O) 2 R 70 , —OS(═O) 2 OR 70 , —OS(═O) 2 NR 72 R 73 , —OP(═O)R 78 R 78 , —OP(═O)(NR 72 R 73 )(NR 72 R 73 ), —OP(═O)(OR 70 )(OR 70 ), —OP(═O)(SR 70 )(SR 70 ), —Si(R 74 ) 3 , —SCN, ═S, —S(═O) n R 70 , —S(═O) 2 OR 70 , —SO 3 R 77 , —S(═O) 2 NR 72 R 73 , —S(═O)NR 72 R 73 , —SP(═O)R 78 R 78 , —SP(═O)(NR 72 R 73 )(NR 72 R 73 ), —SP(═O)(OR 70 )(OR 70 ), —SP(═O)(SR 70 )(SR 70 ), —P(═O)R 78 R 78 , —P(═O)(NR 72 R 73 )(NR 72 R 73 ), —P(═O)(OR 70 )(OR 70 ), and —P(═O)(SR 70 )(SR 70 ); 
             R 70 , R 71 , R 74 , R 75 , R 76  and R 77  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 89 , C 2-6 alkenyl optionally substituted by 1-11 R 89 , C 2-6 alkynyl optionally substituted by 1-9 R 89 , C 6-11 aryl optionally substituted by 1-11 R 89 , C 7-16 arylalkyl optionally substituted by 1-19 R 89 , C 3-11 cycloalkyl optionally substituted by 1-21 R 89 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 89 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 89 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 89 , 5-15 membered heteroaryl optionally substituted by 1-15 R 89 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 89 ; 
             R 72  and R 73  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 99 , C 2-6 alkenyl optionally substituted by 1-11 R 99 , C 2-6 alkynyl optionally substituted by 1-9 R 99 , C 6-11 aryl optionally substituted by 1-11 R 99 , C 7-16 arylalkyl optionally substituted by 1-19 R 99 , C 3-11 cycloalkyl optionally substituted by 1-21 R 99 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 99 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 99 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 99 , 5-15 membered heteroaryl optionally substituted by 1-15 R 99 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 99 ;
           or any R 72  and R 73  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 109  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 109 ;   
         
             R 78  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 89 , C 2-6 alkenyl optionally substituted by 1-11 R 89 , C 2-6 alkynyl optionally substituted by 1-9 R 89 , C 6-11 aryl optionally substituted by 1-11 R 89 , C 7-16 arylalkyl optionally substituted by 1-19 R 89 , C 3-11 cycloalkyl optionally substituted by 1-21 R 89 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 89 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 89 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 89 , 5-15 membered heteroaryl optionally substituted by 1-15 R 89 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 89 ;
           or any two R 78  attached to the same phosphorus atom can, together with the phosphorus atom linking them, form a 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 89 ;   
         
             R 79 , R 89 , R 99  and R 109  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 119 , C 2-6 alkenyl optionally substituted by 1-11 R 119 , C 2-6 alkynyl optionally substituted by 1-9 R 119 , C 6-11 aryl optionally substituted by 1-11 R 119 , C 7-16 arylalkyl optionally substituted by 1-19 R 119 , C 3-11 cycloalkyl optionally substituted by 1-21 R 119 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 119 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 119 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 119 , 5-15 membered heteroaryl optionally substituted by 1-15 R 119 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 119 , halogen, —CN, —C(═)R 110 , —C(═O)OR 110 , —C(═O)NR 112 R 113 , —C(═O)C(═O)R 110 , —C(═NR 115 )R 110 , —C(═NR 115 )NR 112 R 113 , —C(═NOH)NR 112 R 113 , —C(═NOR 116 )R 110 , —C(═NNR 112 R 113 )R 110 , —C(═NNR 114 C(═O)R 111 )R 110 , —C(═NNR 114 C(═O)OR 111 )R 110 , —C(═S)NR 112 R 113 , —NC, —NO 2 , —NR 112 R 113 , —NR 114 NR 112 R 113 , —N═NR 114 , ═NR 110 , ═NOR 110 , —NR 114 OR 116 , —NR 114 C(═O)R 110 , —NR 114 C(═O)C(═O)R 110 , —NR 114 C(═O)OR 111 , —NR 114 C(═O)C(═O)OR 111 , —NR 114 C(═O)NR 112 R 113 , —NR 114 C(═O)NR 114 C(═O)R 110 , —NR 114 C(═O)NR 114 C(═O)OR 110 , —NR 114 C(═NR 115 )NR 112 R 113 , —NR 114 C(═O)C(═O)NR 112 R 113 , —NR 114 C(═S)R 110 , —NR 114 C(═S)OR 110 , —NR 114 C(═S)NR 112 R 113 , —NR 114 S(═O) 2 R 111 , —NR 114 S(═O) 2 NR 112 R 113 , —NR 114 P(═O)R 118 R 18 , —NR 114 P(═O)(NR 112 R 113 )(NR 112 R 113 ), —NR 114 P(═O)(OR 110 )(OR 110 ), —NR 114 P(═O)(SR 110 )(SR 110 ), —OR 110 , ═O, —OCN, —OC(═O)R 110 , —OC(═O)NR 112 R 113 , —OC(═O)OR 110 , —OC(═NR 115 )NR 112 R 113 , —OS(═O)R 110 , —OS(═O) 2 R 110 , —OS(═O) 2 OR 110 , —OS(═O) 2 NR 112 R 113 , —OP(═O)R 118 R 118 , —OP(═O)(NR 112 R 113 )(NR 112 R 113 ), —OP(═O)(OR 110 )(OR 110 ), —OP(═O)(SR 110 )(SR 110 ), —Si(R 114 ) 3 , —SCN, ═S, —S(═O) n R 110 , —S(═O) 2 OR 110 , —SO 3 R 111 , —S(═O) 2 NR 112 R 113 , —S(═O)NR 112 R 113 , —SP(═O)R 118 R 118 , —SP(═O)(NR 112 R 113 )(NR 112 R 113 ), —SP(═O)(OR 110 )(OR 110 ), —SP(═O)(SR 110 )(SR 110 ), —P(═O)R 11 R 118 , —P(═O)(NR 112 R 113 )(NR 112 R 113 ), —P(═O)(OR 110 )(OR 110 ), and —P(═O)(SR 110 )(SR 110 ); 
             R 110 , R 111 , R 114 , R 115 , R 116  and R 117  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 129 , C 2-6 alkenyl optionally substituted by 1-11 R 129 , C 2-6 alkynyl optionally substituted by 1-9 R 129 , C 6-11 aryl optionally substituted by 1-11 R 129 , C 7-16 arylalkyl optionally substituted by 1-19 R 129 , C 3-11 cycloalkyl optionally substituted by 1-21 R 129 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 129 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 129 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 129 , 5-15 membered heteroaryl optionally substituted by 1-15 R 129 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 129 ; 
             R 112  and R 113  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 139 , C 2-6 alkenyl optionally substituted by 1-11 R 139 , C 2-6 alkynyl optionally substituted by 1-9 R 139 , C 6-11 aryl optionally substituted by 1-11 R 139 , C 7-16 arylalkyl optionally substituted by 1-19 R 139 , C 3-11 cycloalkyl optionally substituted by 1-21 R 139 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 139 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 139 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 139 , 5-15 membered heteroaryl optionally substituted by 1-15 R 139 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 39 ;
           or any R 112  and R 113  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 149  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 49 ;   
         
             R 118  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 129 , C 2-6 alkenyl optionally substituted by 1-11 R 129 , C 2-6 alkynyl optionally substituted by 1-9 R 129 , C 6-11 aryl optionally substituted by 1-11 R 129 , C 7-16 arylalkyl optionally substituted by 1-19 R 129 , C 3-11 cycloalkyl optionally substituted by 1-21 R 129 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 129 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 129 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 129 , 5-15 membered heteroaryl optionally substituted by 1-15 R 129 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 129 ; 
             R 119 , R 129 , R 139  and R 149  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 159 , C 2-6 alkenyl optionally substituted by 1-11 R 159 , C 2-6 alkynyl optionally substituted by 1-9 R 159 , C 6-11 aryl optionally substituted by 1-11 R 159 , C 7-16 arylalkyl optionally substituted by 1-19 R 159 , C 3-11 cycloalkyl optionally substituted by 1-21 R 159 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 159 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 159 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 159 , 5-15 membered heteroaryl optionally substituted by 1-15 R 159 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 159 , halogen, —CN, —C(═O)R 150 , —C(═O)OR 150 , —C(═O)NR 152 R 153 , —C(═O)C(═O)R 150 , —C(═NR 155 )R 150 , —C(═NR 155 )NR 152 R 153 , —C(═NOH)NR 152 R 153 , —C(═NOR 156 )R 150 , —C(═NNR 152 R 153 )R 150 , —C(═NNR 154 C(═O)R 151 )R 150 , —C(═NNR 154 C(═O)OR 151 )R 150 , —C(═S)NR 152 R 153 , —NC, —NO 2 , —NR 152 R 153 , —NR 154 NR 152 R 153 , —N═NR 154 , ═NR 150 , ═NOR 15 , —NR 154 OR 156 , —NR 154 C(═O)R 150 , —NR 154 C(═O)C(═O)R 150 , —NR 154 C(═)OR 151 , —NR 154 C(═O)C(═O)OR 151 , —NR 54 C(═O)NR 152 R 153 , —NR 154 C(═O)NR 154 C(═O)R 150 , —NR 154 C(═O)NR 154 C(═O)OR 150 , —NR 154 C(═NR 155 )NR 152 R 153 , —NR 154 C(═O)C(═O)NR 152 R 153 , —NR 154 C(═S)R 150 , —NR 154 C(═S)OR 150 , —NR 154 C(═S)NR 152 R 153 , —NR 154 S(═O) 2 R 151 , —NR 154 S(═O) 2 NR 152 R 153 , —NR 154 P(═O)R 158 R 158 , —NR 154 P(═O)(NR 152 R 153 )(NR 152 R 153 ), —NR 154 P(═O)(OR 150 )(OR 150 ), —NR 154 P(═O)(SR 150 )(SR 150 ), —OR 150 , ═O, —OCN, —OC(═O)R 150 , —OC(═O)NR 152 R 153 , —OC(═O)OR 150 , —OC(═NR 155 )NR 152 R 153 , —OS(═O)R 150 , —OS(═O) 2 R 150 , —OS(═O) 2 OR 150 , —OS(═O) 2 NR 152 R 153 , —OP(═O)R 158 R 158 , —OP(═O)(NR 152 R 153 )(NR 152 R 153 ), —OP(═O)(OR 150 )(OR 150 ), —OP(═O)(SR(SR 150 )(SR 150 ), —Si(R 154 ) 3 , —SCN, ═S, —S(═O) n R 150 , —S(═O) 2 OR 150 , —SO 3 R 1515 , —S(═O) 2 NR 152 R 153 , —S(═O)NR 152 R 153 , —SP(═O)R 158 R 158 , —SP(═O)(NR 152 R 153 )(NR 152 R 153 ), —SP(═O)(OR 150 )(OR 150 ), —SP(═O)(SR 150 )(SR 150 ), —P(═O)R 158 R 158 , —P(═O)(NR 152 R 153 )(NR 152 R 153 ), —P(═O)(OR 150 )(OR 150 ), and —P(═O)(SR 150 )(SR 150 ); 
             R 150 , R 151 , R 154 , R 155 , R 156  and R 157  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 169 , C 2-6 alkenyl optionally substituted by 1-11 R 169 , C 2-6 alkynyl optionally substituted by 1-9 R 169 , C 6-11 aryl optionally substituted by 1-11 R 169 , C 7-16 arylalkyl optionally substituted by 1-19 R 169 , C 3-11 cycloalkyl optionally substituted by 1-21 R 169 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 169 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 169 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 169 , 5-15 membered heteroaryl optionally substituted by 1-15 R 169 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 69 ; 
             R 152  and R 153  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 179 , C 2-6 alkenyl optionally substituted by 1-11 R 179 , C 2-6 alkynyl optionally substituted by 1-9 R 179 , C 6-11 aryl optionally substituted by 1-11 R 179 , C 7-16 arylalkyl optionally substituted by 1-19 R 179 , C 3-11 cycloalkyl optionally substituted by 1-21 R 179 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 179 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 179 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 179 , 5-15 membered heteroaryl optionally substituted by 1-15 R 179 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 179 ;
           or any R 152  and R 153  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 189  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 189 ;   
         
             R 158  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 169 , C 2-6 alkenyl optionally substituted by 1-11 R 169 , C 2-6 alkynyl optionally substituted by 1-9 R 169 , C 6-11 aryl optionally substituted by 1-11 R 169 , C 7-16 arylalkyl optionally substituted by 1-19 R 169 , C 3-11 cycloalkyl optionally substituted by 1-21 R 169 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 169 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 169 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 169 , 5-15 membered heteroaryl optionally substituted by 1-15 R 169 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 69 ; 
             R 159 , R 169 , R 179  and R 189  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 199 , C 2-6 alkenyl optionally substituted by 1-11 R 199 , C 2-6 alkynyl optionally substituted by 1-9 R 199 , C 6-11 aryl optionally substituted by 1-11 R 199 , C 7-16 arylalkyl optionally substituted by 1-19 R 199 , C 3-11 cycloalkyl optionally substituted by 1-21 R 199 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 199 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 199 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 199 , 5-15 membered heteroaryl optionally substituted by 1-15 R 199 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 199 , halogen, —CN, —C(═O)R 190 , —C(═O)OR 190 , —C(═O)NR 192 R 193 , —C(═O)C(═O)R 190 , —C(═NR 195 )R 190 , —C(═NR 195 )NR 192 R 193 , —C(═NOH)NR 192 R 193 , —C(═NOR 196 )R 190 , —C(═NNR 192 R 193 )R 190 , —C(═NNR 194 C(═O)R 191 )R 190 , —C(═NNR 194 C(═O)OR 191 )R 190 , —C(═S)NR 192 R 193 , —NC, —NO 2 , —NR 192 R 193 , —NR 194 NR 192 R 193 , —N═NR 194 , ═NR 190 , ═NOR 190 , —NR 194 OR 196 , —NR 194 C(═O)R 190 , —NR 194 C(═O)C(═O)R 190 , —NR 194 C(═O)OR 191 , —NR 194 C(═O)C(═)OR 191 , —NR 194 C(═O)NR 192 R 193 , —NR 194 C(═O)NR 194 C(═O)R 190 , —NR 194 C(═O)NR 194 C(═O)OR 190 , —NR 194 C(═NR 195 )NR 192 R 193 , —NR 194 C(═O)C(═O)NR 192 R 193 , —NR 194 C(═S)R 190 , —NR 194 C(═S)OR 190 , —NR 194 C(═S)NR 192 R 193 , —NR 194 S(═O) 2 R 191 , —NR 194 S(═O) 2 NR 192 R 193 , —NR 194 C(═O)R 198 R 198 , —NR 194 P(═O)(NR 192 R 193 )(NR 192 R 193 ), —NR 194 P(═O)(OR 190 )(OR 190 ), —NR 194 P(═O)(SR 190 )(SR 190 ), —OR 190 , ═O, —OCN, —OC(═O)R 190 , —OC(═O)NR 192 R 193 , —OC(═O)OR 190 , —OC(═NR 195 )NR 192 R 193 , —OS(═O)R 190 , —OS(═O) 2 R 190 , —OS(═O) 2 OR 190 , —OS(═O) 2 NR 192 R 193 , —OP(═O)R 198 R 198 , —OP(═O)(NR 192 R 193 )(NR 192 R 193 ), —OP(═O)(OR 190 )(OR 190 ), —OP(═O)(SR 190 )(SR 190 ), —Si(R 194 ) 3 , —SCN, ═S, —S(═O) n R 190 , —S(═O) 2 R 190 , —SO 3 R 1919 , —S(═O) 2 NR 192 R 193 , —S(═O)NR 192 R 193 , —SP(═O)R 198 R 198 , —SP(═O)(NR 192 R 193 )(NR 192 R 193 ), —SP(═O)(OR 190 )(OR 190 ), —SP(═O)(SR 190 )(SR 190 ), —P(═O)R 198 R 198 , —P(═O)(NR 192 R 193 )(NR 192 R 193 ), —P(═O)(OR 190 )(OR 190 ), and —P(═O)(SR 190 )(SR 190 ); 
             R 190 , R 191 , R 194 , R 195 , R 196  and R 197  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 209 , C 2-6 alkenyl optionally substituted by 1-11 R 209 , C 2-6 alkynyl optionally substituted by 1-9 R 209 , C 6-11 aryl optionally substituted by 1-11 R 209 , C 7-16 arylalkyl optionally substituted by 1-19 R 209 , C 3-11 cycloalkyl optionally substituted by 1-21 R 209 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 209 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 209 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 209 , 5-15 membered heteroaryl optionally substituted by 1-15 R 209 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 209 ; 
             R 192  and R 193  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 219 , C 2-6 alkenyl optionally substituted by 1-11 R 219 , C 2-6 alkynyl optionally substituted by 1-9 R 219 , C 6-11 aryl optionally substituted by 1-11 R 219 , C 7-16 arylalkyl optionally substituted by 1-19 R 219 , C 3-11 cycloalkyl optionally substituted by 1-21 R 219 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 219 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 219 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 219 , 5-15 membered heteroaryl optionally substituted by 1-15 R 219 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 219 ;
           or any R 192  and R 193  may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 229  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 229 ;   
         
             R 198  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 209 , C 2-6 alkenyl optionally substituted by 1-11 R 209 , C 2-6 alkynyl optionally substituted by 1-9 R 209 , C 6-11 aryl optionally substituted by 1-11 R 209 , C 7-16 arylalkyl optionally substituted by 1-19 R 209 , C 3-11 cycloalkyl optionally substituted by 1-21 R 209 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 209 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 209 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 209 , 5-15 membered heteroaryl optionally substituted by 1-15 R 209 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 209 ; 
             R 199 , R 209 , R 219  and R 229  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 halogen, C 2-6 alkenyl, C 2-6 alkynyl, C 6-11 aryl, C 7-16 arylalkyl, C 3-11 cycloalkyl, C 4-17 cycloalkylalkyl, 3-15 membered heterocycloalkyl, 4-21 membered heterocycloalkylalkyl, 5-15 membered heteroaryl, 6-21 membered heteroarylalkyl, halogen, —CN, —C(═O)R 230 , —C(═)OR 230 , —C(═O)NR 230 R 230 , —C(═O)C(═O)R 230 , —C(═NR 230 )R 230 , —C(═NR 230 )NR 230 R 230 , —C(═NOH)NR 230 R 230 , —C(═NOR 230 )R 230 , —C(═NNR 23 R 230 )R 230 , —C(═NNR 230 C(═O)R 230 )R 230 , —C(═NNR 230 C(═O)OR 230 )R 230 , —C(═S)NR 230 R 230 , —NC, —NO 2 , —NR 230 R 230 , —NR 230 NR 230 R 230 , —N═NR 230 , ═NR 230 , ═NOR 230 , —NR 230 OR 230 , —NR 230 C(═O)R 230 , —NR 230 C(═O)C(═O)R 230 , —NR 230 C(═O)OR 230 , —NR 230 C(═O)C(═O)OR 230 , —NR 230 C(═O)NR 230 R 230 , —NR 230 C(═O)NR 230 C(═O)R 230 C(═O)R 230 , —NR 230 C(═O)NR 230 C(═O)OR 230 , —NR 230 C(═NR 230 )NR 230 R 230 , —NR 230 C(═O)C(═O)NR 230 R 230 , —NR 230 C(═S)R 230 , —NR 230 C(═S)OR 230 , —NR 230 C(═S)NR 230 R 230 , —NR 230 S(═O) 2 R 230 , —NR 230 S(═O) 2 NR 230 R 230 , —NR 230 P(═O)R 231 R 231 , —NR 230 P(═O)(NR 230 R 230 )(NR 230 R 230 ), —NR 230 P(═O)(OR 230 )(OR 230 ), —NR 230 P(═O)(SR 230 )(SR 230 ), —OR 230 , ═O, —OCN, —OC(═O)R 230 , —OC(═O)NR 230 R 230 , —OC(═O)OR 230 , —OC(═NR 230 )NR 230 R 230 , —OS(═O)R 230 , —OS(═O) 2 R 230 , —OS(═O) 2 OR 230 , —OS(═O) 2 NR 230 R 230 , —OP(═O)R 231 R 231 , —OP(═O)(NR 230 R 230 )(NR 230 R 230 ), —OP(═O)(OR 230 )(OR 230 ), —OP(═O)(SR 230 )(SR 230 ), —Si(R 230 ) 3 , —SCN, ═S, —S(═O) n R 230 , —S(═O) 2 OR 230 , —SO 3 R 230 , —S(═O) 2 NR 230 R 230 , —S(═O)NR 230 R 230 , —SP(═O)R 231 R 231 , —SP(═O)(NR 230 R 230 )(NR 230 R 230 ), —SP(═O)(OR 230 )(OR 230 ), —SP(═O)(SR 230 )(SR 230 ), —P(═O)R 231 R 231 , —P(═O)(NR 230 R 230 )(NR 230 R 230 ), —P(═O)(OR 230 )(OR 230 ), and —P(═O)(SR 230 )(SR 230 ); 
             R 230  at each occurrence is independently chosen from H, C 1-6 alkyl and C 1-6 -haloalkyl; 
             R 231  at each occurrence is independently chosen from C 1-6 alkyl and C 1-6 -haloalkyl; and 
             n at each occurrence is independently chosen from 0, 1, and 2;
 
with the proviso that the compound is not
 
           
         
       
    
     
       
         
         
             
             
         
       
         
         
           
             in which D is H or 
           
         
       
    
     
       
         
         
             
             
         
       
         
         
           
             or a salt form thereof; 
           
         
       
    
                         
in which D is
 
                         
or a salt form thereof; or
 
                         
in which D is H or —CH 3 , or a salt form thereof.
 
2. A compound as defined in preferred Embodiment 1, wherein X is chosen from 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 S(═O) 2 R 28 , and —OR 28 .
 
3. A compound as defined in preferred Embodiment 1, wherein X is chosen from 5-6 membered heterocycloalkyl optionally substituted by 1-6 R 19 , and —NR 24 R 28 .
 
4. A compound as defined in preferred Embodiment 1, wherein X is chosen from morpholinyl optionally substituted by 1-6 R 19 , piperidinyl optionally substituted by 1-6 R 19 , piperazinyl optionally substituted by 1-6 R 19 , and —NR 24 R 28 .
 
5. A compound as defined in preferred Embodiment 1, wherein X is
 
                         
and
         A is —NR 1 R 2 , —CR i R j R k , —OR 18a , or —SR 18 b;   Q is —NR 11 —, —CR m R n —, —O—, or —S—;   R k  is H, halogen, —CN, —NO 2 , —NR 16 R 17 , —OR 18c , —SR 18d , or —CR o R p R q ;   R q  is H, halogen, —CN, —NO 2 , —NR 16a R 17a  or —OR 18e ;   R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 79 , C 2-6 alkenyl optionally substituted by 1-11 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-19 R 79 , C 3-11 cycloalkyl optionally substituted by 1-21 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 79 , 5-15 membered heteroaryl optionally substituted by 1-15 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 79 , and —OR 70 ;   R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 79 , C 2-6 alkenyl optionally substituted by 1-11 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-19 R 79 , C 3-11 cycloalkyl optionally substituted by 1-21 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 79 , 5-15 membered heteroaryl optionally substituted by 1-15 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 79 , halogen, —CN, —C(═O)R 70 , —C(═)OR 70 , —C(═O)NR 72 R 73 , —C(═O)C(═O)R 70 , —C(═NR 75 )R 70 , —C(═NR 75 )NR 72 R 73 , —C(═NOH)NR 72 R 73 , —C(═NOR 76 )R 70 , —C(═NNR 72 R 73 )R 70 , —C(═NNR 74 C(═O)R 7 )R 71 )R 70 , —C(═NNR 74 C(═O)OR 71 )R 70 , —C(═S)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 NR 72 R 73 , —N═NR 74 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)C(═)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 C(═O)NR 74 C(═O)OR 70 , —NR 74 C(═NR 75 )NR 72 R 73 , —NR 74 C(═O)C(═O)NR 72 R 73 , —NR 74 C(═S)R 70 , —NR 74 C(═S)OR 70 , —NR 74 C(═S)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —NR 74 P(═O)R 78 R 78 , —NR 74 P(═O)(NR 72 R 73 )(NR 72 R 73 ), —NR 74 P(═O)(OR 70 )(OR 70 ), —NR 74 P(═O)(SR 70 )(SR 70 ), —OR 70 , —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —OC(═NR 75 )NR 72 R 73 , —OS(═O)R 70 , —OS(═O) 2 R 70 , —OS(═O) 2 OR 70 , —OS(═O) 2 NR 72 R 73 , —OP(═O)R 78 R 78 , —OP(═O)(NR 72 R 73 )(NR 72 R 73 ), —OP(═O)(OR 70 )(OR 70 ), —OP(═O)(SR 70 )(SR 70 ), —Si(R 74 ) 3 , —SCN, —S(═O) n R 70 , —S(═O) 2 OR 70 , —SO 3 R 77 , —S(═O) 2 NR 72 R 73 , —S(═O)NR 72 R 73 , —SP(═O)R 78 R 78 , —SP(═O)(NR 72 R 73 )(NR 72 R 73 ), —SP(═O)(OR 70 )(OR 70 ), —SP(═O)(SR 70 )(SR 70 ), —P(═O)R 78 R 78 , —P(═O)R 73 R 73 )(NR 72 R 73 ), —P(═O)(OR 70 )(OR 70 ), and —P(═O)(SR 70 )(SR 70 );   or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R, R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n  can, together with the atoms linking them, form a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 79 ;   or any of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 79 , C 3-11 cycloalkyl optionally substituted by 1-21 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 79 ;   or R 4  and R 5  or R n  and R 5  can together form a double bond;   or any of R 3  and R 4 , R 5  and R 6 , R i  and R j , and R m  and R n  can together form ═O, ═NR 70 , ═NOR 70 , or ═S.
 
6. A compound as defined in preferred Embodiment 5, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a  R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , —CN, —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , and —OR 70 ; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 1 , R 16  and R 5 , R j  and R 11 , and R 18a  and R 11  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or R 3  and R 4  can together form ═O.
 
7. A compound as defined in preferred Embodiment 5, wherein R 1 , R 11 , R 16 , R 17 , R 16a , R 17a  R 18a , R 18b , R 18c , R 18d , and R 18e  are independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 2  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 3  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NO 2 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R, R 1  and R 11 , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18c  and R i , R 18c  and R 3 , R 18c  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3  and R 4 , R 3  and R 6 , R 5  and R 6 , R i  and R j , R i  and R 4 , R i  and R 5 , R i  and R n , R m  and R n , R 4  and R m , and R 6  and R m  can, together with the atoms linking them, form a C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , or a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3  and R 4 , R 5  and R 6 , R i  and R j , and R m  and R n  can together form ═O.
 
8. A compound as defined in preferred Embodiments 6 or 7, wherein 1-2 of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , R 18a  and R 3 , R 18a  and R 5 , R 18a  and R 11 , R 18a  and R n , R 18b  and R 3 , R 18b  and R 5 , R 18b  and R 11 , R 18b  and R n , R 18e  and R i , R 18e  and R 3 , R 18e  and R 5 , R 18c  and R 11 , R 18c  and R n , R 18d  and R i , R 18d  and R 3 , R 18d  and R 5 , R 18d  and R 11 , and R 18d  and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl.
 
9. A compound as defined in preferred Embodiment 5, wherein R 1 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e  are H; R 2  is chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p  are H; R 3  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1  and R 2 , R 1  and R 3 , R 1  and R 5 , R 1  and R 11 , R 1  and R n , R 4  and R 11 , R 6  and R 11 , R 16  and R 17 , R 16  and R i , R 16  and R 3 , R 16  and R 5 , R 16  and R 11 , R 16  and R n , R j  and R 11 , and R 18a  and R 11  can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3  and R 4 , R 5  and R 6 , R i  and R j , and R m  and R n  can together form ═O.
 
10. A compound as defined in any of preferred Embodiments 5-9, wherein R q  is —NR 16a R 17a  or —OR 18e .
 
11. A compound as defined in any of preferred Embodiments 5-10, wherein R k  is —NR 16 R 17  or —OR 18c .
 
12. A compound as defined in any of preferred Embodiments 5-11, wherein A is —NR 1 R 2 , —CR i R j R k , or —OR 18a .
 
13. A compound as defined in any of preferred Embodiments 5-11, wherein A is —NR 1 R 2 .
 
14. A compound as defined in any of preferred Embodiments 5-13, wherein Q is —NR 11 —, —CR m R n —, or —O—.
 
15. A compound as defined in any of preferred Embodiments 5-13, wherein Q is —NR 11 —.
 
16. A compound as defined in any of preferred Embodiments 1-15, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 7-11 arylalkyl, C 3-7 cycloalkyl, C 4-8 cycloalkylalkyl, 3-7 membered heterocycloalkyl, 4-8 membered heterocycloalkylalkyl, 5-6 membered heteroaryl, 6-21 membered heteroarylalkyl, halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7  and R 8  can, together with the atoms linking them, form a C 6-10 aryl, C 3-7 cycloalkyl, 3-7 membered heterocycloalkyl or a 5-6 membered heteroaryl.
 
17. A compound as defined in any of preferred Embodiments 1-15, wherein R 7 , R 8 , and R 9  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —S(═O) n R 20 .
 
18. A compound as defined in any of preferred Embodiments 1-15, wherein R 7  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; R 8  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; and R 9  is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —(═O) 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 .
 
19. A compound as defined in any of preferred Embodiments 1-15, wherein R 7  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 3-6 cycloalkyl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; R 8  is chosen from H and halogen; and R 9  is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —S(═O) n R 20 .
 
20. A compound as defined in any of preferred Embodiments 1-19, wherein R 8  is H.
 
21. A compound as defined in any of preferred Embodiments 1-20, wherein G is a group of formula
       

                         
and R 12 , R 13 , R 14 , and R 15  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or either or both of R 12  and R 13 , and/or R 14  and R 15 , can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19  or a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 .
 
22. A compound as defined in any of preferred Embodiments 1-21, wherein G is a group of formula
 
                         
and R 12 , R 14 , and R 15  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and halogen; R 13  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .
 
23. A compound as defined in any of preferred Embodiments 1-21, wherein G is a group of formula
 
                         
and R 12  and R 14  are H; R 15  is chosen from H and halogen; R 13  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19  or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .
 
24. A compound as defined in any of preferred Embodiments 1-21, wherein G is a group of formula
 
                         
and R 14  is H; R 12  and R 15  are independently chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , and —NR 24 S(═O) 2 NR 22 R 23 ; or R 12  and R 13  can, together with the atoms linking them, form a 5-6 membered heteroaryl optionally substituted by 1-6 R 19 .
 
25. A compound as defined in any of preferred Embodiments 1-21, wherein G is a group of formula
 
                         
and R 14  and R 15  are H; R 12  is chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1-2 R 19 .
 
26. A compound as defined in any of preferred Embodiments 1-21, wherein G is a group of formula
 
                         
and R 14  is H; R 12  and R 15  are independently chosen from H and halogen; R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a pyrrolyl ring optionally substituted by 1 R 19 .
 
27. A compound as defined in any of preferred Embodiments 1-21, wherein G is a group of formula
 
                         
and R 12 , R 13 , R 14 , and R 15  are H; or R 12  and R 13 , together with the atoms linking them, form a pyrrolyl ring.
 
28. A compound as defined in any of preferred Embodiments 1-21, wherein G is a group of formula
 
                         
and R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , 5-10 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 .
 
29. A compound as defined in any of preferred Embodiments 1-21, wherein G is a group of formula
 
                         
and R a , R b , R c , R d , R e , R f , R g , and R h  are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and benzyl optionally substituted by 1-3 R 19 .
 
30. A compound as defined in any of preferred Embodiments 1-21, wherein G is a group of formula
 
                         
and R a , R b , R c , R e , R f , R g , and R h  are H; and R d  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , 5-10 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 .
 
31. A compound as defined in any of preferred Embodiments 1-21, wherein G is a group of formula
 
                         
and R a , R b , R c , R e , R f , R g , and R h  are H; and R d  is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and benzyl optionally substituted by 1-3 R 19 .
 
32. A compound as defined in any of preferred Embodiments 1-21, wherein G is a group of formula
 
                         
and R a , R b , R c , R d  R e , R f , R g , and R h  are H.
 
33. A compound as defined in any of preferred Embodiments 1-32, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkenyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 6-10 aryl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 30 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NO 2 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —NR 34 C(═O)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —OR 30 , ═O, —OC(═O)R 30 , —OC(═O)NR 32 R 33 , —Si(R 34 ) 3 , ═S, —S(═O) n R 30 , and —S(═O) 2 NR 32 R 33 .
 
34. A compound as defined in any of preferred Embodiments 1-32, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl, C 6-10 aryl, C 7-11 arylalkyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —C(═O)R 30 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , and —OR 30 .
 
35. A compound as defined in any of preferred Embodiments 1-32, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl, phenyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl, halogen, —C(═O)OR 30 , —NR 32 R 33 , and —OR 30 .
 
36. A compound as defined in any of preferred Embodiments 1-32, wherein R 19  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —OR 3  and ═O.
 
37. A compound as defined in any of preferred Embodiments 1-36, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , and C 3-6 cycloalkyl optionally substituted by 1-3 R 49 .
 
38. A compound as defined in any of preferred Embodiments 1-36, wherein R 20  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is H.
 
39. A compound as defined in any of preferred Embodiments 1-36, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36  and R 37  at each occurrence is independently chosen from H and C 1-6 alkyl.
 
40. A compound as defined in any of preferred Embodiments 1-39, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 59 .
 
41. A compound as defined in any of preferred Embodiments 1-39, wherein R 22  at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl optionally substituted by 1-3 R 59 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32  and R 33  at each occurrence is independently chosen from H and C 1-6 alkyl.
 
42. A compound as defined in any of preferred Embodiments 1-39, wherein R 22 , R 23 , R 32  and R 33  at each occurrence is independently chosen from H and C 1-6 alkyl.
 
43. A compound as defined in any of preferred Embodiments 1-42, wherein R 39 , R 49 , R 59  and R 69  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , phenyl optionally substituted by 1-3 R 79 , benzyl optionally substituted by 1-3 R 79 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)NR 72 R 73 , —NR 72 R 73 , —OR 70 , and —S(═O) n R 70 .
 
44. A compound as defined in any of preferred Embodiments 1-42, wherein R 39 , R 49 , R 59  and R 69  at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 .
 
45. A compound as defined in any of preferred Embodiments 1-44, wherein R 70 , R 71 , R 74 , R 75 , R 76  and R 77  at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 89 .
 
46. A compound as defined in any of preferred Embodiments 1-44, wherein R 72  and R 73  at each occurrence is independently chosen from H and C 1-6 alkyl.
 
47. A compound as defined in any of preferred Embodiments 1-46, wherein R 79  and R 89 , R 99  and R 109  at each occurrence is independently chosen from C 1-6 alkyl and phenyl.
 
48. A compound as defined in any of preferred Embodiments 1-46, wherein R 79 , R 89 , R 99  and R 109  at each occurrence is independently C 1-6 alkyl.
 
49. A compound as defined in any of preferred Embodiments 1 or 33-48, wherein X is chosen from —NHR 28  and 3-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 ; R 7  is chosen from H, C 3-6 cycloalkyl, and —OR 20 ; R 8  is chosen from H and halogen; R 9  is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5, 6, or 9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —SR 20 ; R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, C 7-16 arylalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 ; and R a , R b , R c , R d , R e , R f , R g , and R h  are H.
 
50. A compound as defined in preferred Embodiment 49, wherein X is chosen from —NHR 28  and 5-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 .
 
51. A compound as defined in preferred Embodiment 49, wherein X is chosen from —NHR 28  and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 .
 
52. A compound as defined in preferred Embodiment 49, wherein X is chosen from —NHR 28  and 5-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 6-11 aryl optionally substituted by 1-3 R 39 , C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 .
 
53. A compound as defined in preferred Embodiment 49, wherein X is chosen from —NHR 28  and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 .
 
54. A compound as defined in preferred Embodiment 49, wherein X is chosen from —NHR 28  and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, and —OH.
 
55. A compound as defined in preferred Embodiment 49, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-6 R 4 ), —NH(3-10 membered heterocycloalkyl optionally substituted by 1-6 R 49 ), —NH(4-11 membered heterocycloalkylalkyl optionally substituted by 1-6 R 49 ), and 3-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 .
 
56. A compound as defined in preferred Embodiment 49, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-3 R 49 ), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 .
 
57. A compound as defined in preferred Embodiment 49, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-3 R 49 ), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 .
 
58. A compound as defined in preferred Embodiment 49, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-3 R 49 ), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 6-11 aryl optionally substituted by 1-3 R 39 , C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 .
 
59. A compound as defined in preferred Embodiment 49, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-3 R 49 ), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, C 6-11 aryl, C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heterocycloalkyl, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 3 , and —OR 30 .
 
60. A compound as defined in preferred Embodiment 49, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 3 , and —OR 3 .
 
61. A compound as defined in preferred Embodiment 49, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl), —NH(5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms), —NH(6-10 membered heterocycloalkylalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, C 6-11 aryl, C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heterocycloalkyl, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 .
 
62. A compound as defined in preferred Embodiment 49, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms), —NH(6-10 membered heterocycloalkylalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 .
 
63. A compound as defined in preferred Embodiment 49, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ) and —NH(5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms).
 
64. A compound as defined in any of preferred Embodiments 1 or 33-63, wherein R 7  is chosen from H, C 3-6 cycloalkyl, and —O(C 1-6 alkyl); R 8  is chosen from H and halogen; and R 9  is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5, 6, or 9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —SR 20 .
 
65. A compound as defined in any of preferred Embodiments 1 or 33-63, wherein R 7  is chosen from H, C 3-6 cycloalkyl, and —OR 20 ; R 8  is H; and R 9  is H.
 
66. A compound as defined in any of preferred Embodiments 1 or 33-63, wherein R 7  is chosen from H, C 3-6 cycloalkyl, and —O(C 1-6 alkyl); R 8  is H; and R 9  is H.
 
67. A compound as defined in any of preferred Embodiments 1 or 33-63, wherein R 7  is chosen from H, cyclopropyl, and —O(C 1-6 alkyl); R 8  is chosen from H and halogen; and R 9  is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5, 6, or 9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —SR 20 .
 
68. A compound as defined in any of preferred Embodiments 1 or 33-63, wherein R 7  is chosen from H, cyclopropyl, and —O(C 1-6 alkyl); R 8  is H; and R 9  is H.
 
69. A compound as defined in any of preferred Embodiments 1 or 33-63, wherein R 7  is chosen from H, cyclopropyl, and —O(CH 3 ); R 8  is H; and R 9  is H.
 
70. A compound as defined in any of preferred Embodiments 1 or 33-63, wherein R 7  is chosen from H, cyclopropyl, and —O(C 1-6 alkyl); R 8  is chosen from H and halogen; and R 9  is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5, 6, or 9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —SR 20 .
 
71. A compound as defined in any of preferred Embodiments 1 or 33-63, wherein R 7  is chosen from H, C 3-6 cycloalkyl, and —O(CH 3 ); R 8  is chosen from H and halogen; and R 9  is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5, 6, or 9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —SR 20 .
 
72. A compound as defined in any of preferred Embodiments 1 or 33-71, wherein R 12 , R 14  and R 15  are H, and R 13  is chosen from H, C 7-16 arylalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .
 
73. A compound as defined in any of preferred Embodiments 1 or 33-71, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, C 7-16 arylalkyl optionally substituted by 1-3 R 19 , 5-10 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 .
 
74. A compound as defined in any of preferred Embodiments 1 or 33-71, wherein R 12 , R 14  and R 15  are H, and R 13  is chosen from H, halogen, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 .
 
75. A compound as defined in any of preferred Embodiments 1 or 33-71, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, halogen, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19  in which the heterocycloalkyl contains carbon atoms and 1 or 2 nitrogen atoms, or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19  in which the heteroaryl contains carbon atoms and 1 or 2 nitrogen atoms.
 
76. A compound as defined in any of preferred Embodiments 1 or 33-71, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, halogen, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13 , can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19  in which the heterocycloalkyl contains carbon atoms and 1 nitrogen atom, or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19  in which the heteroaryl contains carbon atoms and 1 nitrogen atom.
 
77. A compound as defined in any of preferred Embodiments 1 or 33-71, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19  in which the heterocycloalkyl contains carbon atoms and 1 or 2 nitrogen atoms, or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19  in which the heteroaryl contains carbon atoms and 1 or 2 nitrogen atoms.
 
78. A compound as defined in any of preferred Embodiments 1 or 33-71, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19  in which the heterocycloalkyl contains carbon atoms and 1 nitrogen atom, or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19  in which the heteroaryl contains carbon atoms and 1 nitrogen atom.
 
79. A compound as defined in any of preferred Embodiments 1 or 33-71, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, —NHR 23 , and —NHC(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 .
 
80. A compound as defined in any of preferred Embodiments 1 or 33-71, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, —NHR 23 , and —NHC(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19  in which the heterocycloalkyl contains carbon atoms and 1 or 2 nitrogen atoms, or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19  in which the heteroaryl contains carbon atoms and 1 or 2 nitrogen atoms.
 
81. A compound as defined in any of preferred Embodiments 1 or 33-71, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, —NHR 23 , and —NHC(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 .
 
82. A compound as defined in any of preferred Embodiments 1 or 33-71, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, —NHR 23 , and —NHC(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5-10 membered heteroaryl optionally substituted by 1-3 R 19  in which the heteroaryl contains carbon atoms and 1 or 2 nitrogen atoms.
 
83. A compound as defined in any of preferred Embodiments 1 or 33-71, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H, —NHR 23 , and —NHC(═O)R 20 ; or R 12  and R 13  can, together with the atoms linking them, form a 5-10 membered heteroaryl optionally substituted by 1-3 R 19  in which the heteroaryl contains carbon atoms and 1 nitrogen atom.
 
84. A compound as defined in any of preferred Embodiments 1 or 33-71, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H and —NHR 23 ; or R 12  and R 13  can, together with the atoms linking them, form a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 .
 
85. A compound as defined in any of preferred Embodiments 1 or 33-71, wherein R 12 , R 14 , and R 15  are H, and R 13  is chosen from H and —NHR 23 ; or R 12  and R 13  can, together with the atoms linking them, form a 5-10 membered heteroaryl optionally substituted by 1-3 R 19  in which the heteroaryl contains carbon atoms and 1 or 2 nitrogen atoms.
 
86. A compound chosen from:
     1-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   (5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-(R)-pyrrolidin-3-yl-amine;   N-(2-aminoethyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2R)-2-aminopropyl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-aminopropyl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   (3R)—N-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]pyrrolidin-3-amine;   (3R)—N-[2-(3-fluoropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]pyrrolidin-3-amine;   N-[(2S)-2-amino-3-phenylpropyl]-5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-2-(3-fluoropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-chloro-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-6-chloro-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   1-[6-chloro-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   (3S)-3-benzyl-1-[6-chloro-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   (2S)-1-phenyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-2-ol;   (3 S)-3-benzyl-1-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   (3R)-3-benzyl-1-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   1-methyl-4-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   1-methyl-4-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]-1,4-diazepane;   (2S)-2,4-dibenzyl-1-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   4-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]morpholine;   tert-butyl 4-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine-1-carboxylate;   tert-butyl 4-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]-1,4-diazepane-1-carboxylate;   4-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]thiomorpholine;   N,N-Dimethyl[(2S)-1-phenyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-2-yl]amine;   N-[(2S)-2-amino-3-phenylpropyl]-N-methyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   4-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazin-2-one;   N-[(2S)-1-amino-3-phenylpropan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   (2R)-2-benzyl-1-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   (3 S)-3-benzyl-1-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   1-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   1-[8-chloro-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   1-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]-1,4-diazepane;   2-{4-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazin-1-yl}ethan-1-ol;   (3 S)-1-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]pyrrolidin-3-ol;   (3R)-1-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]pyrrolidin-3-ol;   (3R)-3-benzyl-1-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   (2 S)-2-benzyl-1-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   methyl (2S,4S)-4-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pyrrolidine-2-carboxylate;   methyl (2S,4S)-4-[(2S,4S)-4-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pyrrolidine-2-amido]pyrrolidine-2-carboxylate;   [(2S)-1-{[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}-3-phenylpropan-2-yl](methyl)amine;   N-[(3R)-oxolan-3-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   1-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]-3-(trifluoromethyl)piperazine;   (3 S)-1-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]-3-methylpiperazine;   (3R)-1-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]pyrrolidin-3-amine;   [(2R)-4-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazin-2-yl]methanol;   N-[(2R,3R)-2-amino-3-fluoro-3-phenylpropyl]-5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   2-[(2S)-2-benzyl-4-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazin-1-yl]acetamide;   [(2S)-1-{[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}-3-phenylpropan-2-yl]dimethylamine;   (3 S)-1-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]pyrrolidin-3-ol;   1-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]-3,5-cis-dimethylpiperazine;   (3R)-1-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]-3-methylpiperazine;   (3 S)-1-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]pyrrolidin-3-amine;   3-(fluoromethyl)-1-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   N-(propan-2-yl)-1-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperidine-4-carboxamide;   4-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine-1-carboxamide;   N-cyclohexyl-4-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine-1-carboxamide;   2-{4-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazin-2-yl}acetonitrile;   1-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]-3-(trifluoromethyl)piperazine;   1-[8-chloro-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]-3-(trifluoromethyl)piperazine;   (3S)-3-ethyl-1-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   (3 S)-3-(propan-2-yl)-1-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   1-[2-(3-fluoropyridin-4-yl)-5-methoxypyrido[3,4-d]pyrimidin-4-yl]piperazine;   4-{4-[(8aR)-octahydropyrrolo[1,2-a]piperazin-2-yl]pyrido[3,4-d]pyrimidin-2-yl}pyridine;   1-[2-(3-fluoropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   1-[2-(3-fluoropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]-3-(trifluoromethyl)piperazine;   4-{4-[(3aS)-octahydro-1H-pyrrolo[3,2-c]pyridin-5-yl]pyrido[3,4-d]pyrimidin-2-yl}pyridine;   (3S)-3-benzyl-1-[8-chloro-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   3-phenyl-1-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   4-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]morpholine;   3-ethynyl-1-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   2-benzyl-4-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]morpholine;   {1-[8-chloro-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]azetidin-3-yl}methanol;   (3R)-3-[fluoro(phenyl)methyl]-1-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   1-[8-chloro-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperidin-4-ol;   (3R)-3-[fluoro(phenyl)methyl]-1-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   (4-fluorophenyl)[(2R)-4-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazin-2-yl]methanol;   N—[(S)-1-Benzyl-2-(2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ylamino)-ethyl]-formamide;   N—[(S)-1-Benzyl-2-(2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-ylamino)-ethyl]-acetamide;   methyl[(2S)-1-phenyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-2-yl]amine;   (2S)-2-benzyl-4-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]-1-methylpiperazine;   2-{[(2S)-1-phenyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-2-yl]amino}acetamide;   N-(1-phenyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-2-yl)methanesulfonamide;   (1-phenyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-2-yl)urea;   3-ethyl-1-(1-phenyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-2-yl)urea;   (3aR)-5-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]-hexahydro-1H-[1,3]oxazolo[3,4-a]piperazin-1-one;   2-{4-[5-methoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazin-1-yl}acetonitrile;   N-{3-[4-((S)-2-Amino-3-phenyl-propylamino)-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-8-yl]-phenyl}-methanesulfonamide;   N-[(2S)-2-amino-3-phenylpropyl]-8-(1H-pyrazol-5-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-phenyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   4-(4-{[(2S)-2-amino-3-phenylpropyl]amino}-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-8-yl)phenol;   3-(4-{[(2S)-2-amino-3-phenylpropyl]amino}-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-8-yl)phenol;   N-[(2S)-2-amino-3-phenylpropyl]-8-(2-methoxyphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(3-methoxyphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(4-methoxyphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(2-chlorophenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(1-benzofuran-5-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(1-methyl-1H-pyrazol-4-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(pyridin-3-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-2,8-bis(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(3-chlorophenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(4-chlorophenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(1-methyl-1H-pyrazol-5-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   2-(4-{[(2S)-2-amino-3-phenylpropyl]amino}-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-8-yl)phenol;   N-[(2S)-2-amino-3-phenylpropyl]-8-[3-(3-chlorophenyl)phenyl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-[4-(4-chlorophenyl)phenyl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-2-(pyridin-4-yl)-8-(pyrimidin-5-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(3-aminophenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(1-benzofuran-7-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(5-methylthiophen-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(dimethyl-1,2-oxazol-4-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(furan-3-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-2-(pyridin-4-yl)-8-(thiophen-3-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(furan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(1H-1,3-benzodiazol-5-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(3-ethoxyphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(2-methylphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(3-methylphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-[3-(1H-pyrazol-5-yl)phenyl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-[5-(aminomethyl)furan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   (R)-3-Phenyl-N-(2-pyridin-4-yl-8-pyridin-2-yl-pyrido[3,4-d]pyrimidin-4-yl)-propane-1,2-diamine;   N 4 —((R)-2-Amino-3-phenyl-propyl)-N 8 -phenyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine-4,8-diamine;   4-N-[(2S)-2-amino-3-phenylpropyl]-2-(pyridin-4-yl)-8-N-(pyrimidin-2-yl)pyrido[3,4-d]pyrimidine-4,8-diamine;   4-N-[(2S)-2-amino-3-phenylpropyl]-8-N-(3-chlorophenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidine-4,8-diamine;   4-N-[(2S)-2-amino-3-phenylpropyl]-2-(pyridin-4-yl)-8-N-(1H-1,2,4-triazol-3-yl)pyrido[3,4-d]pyrimidine-4,8-diamine;   (R)—N 1 -[8-(4-Methyl-piperazin-1-yl)-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl]-3-phenyl-propane-1,2-diamine;   (R)-3-Phenyl-N 1 -(8-phenylsulfanyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-propane-1,2-diamine;   N-[(2S)-2-amino-3-phenylpropyl]-8-phenoxy-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   N-[(2S)-2-amino-3-phenylpropyl]-8-(methylsulfanyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   4-(4-{[(2S)-2-amino-3-phenylpropyl]amino}-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-8-yl)-2-methylbut-3-yn-2-ol;   5-Chloro-4-piperazin-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine;   1-[5-bromo-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   1-[5,8-dichloro-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   5-Butyl-4-piperazin-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine;   1-[5-ethyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   N-[(2S)-2-amino-3-phenylpropyl]-5-ethyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;   1-[5-methyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   1-[5-cyclopropyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]piperazine;   1-{5-[(benzyloxy)methyl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl}piperazine;   5-Chloro-4-piperazin-1-yl-8-(1H-pyrazol-3-yl)-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine;   5-chloro-N,N-dimethyl-4-(piperazin-1-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-8-amine;   5-Isopropenyl-4-piperazin-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine;   5-Methoxy-4-piperidin-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine;   3-Amino-1-(5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-pyrrolidine-3-carboxylic acid amide;   3-Amino-1-(5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-pyrrolidine-3-carboxylic acid phenylamide;   4-Amino-1-(5-methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperidine-4-carboxylic acid;   [(S)-1-(4-chloro-phenyl)-3-hydroxy-propyl]-amide;   4-(5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-2-carboxylic acid methyl ester;   4-(5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-2-carboxylic acid phenylamide;   4-(5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-2-carboxylic acid benzylamide;   4-(5-Methoxy-2-pyridin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-2-carboxylic acid phenethyl-amide;   4-Piperazin-1-yl-8-propyl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine;   8-Methyl-4-piperazin-1-yl-2-pyridin-4-yl-pyrido[3,4-d]pyrimidine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-phenyl-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyrazin-2-yl-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-trifluoromethyl-oxazol-2-yl)-amine;   (4,5-Dimethyl-oxazol-2-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (4-Cyclopropyl-thiazol-2-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   3-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-benzonitrile;   (2-Fluoro-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-trifluoromethyl-phenyl)-amine;   4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamine;   N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-morpholin-4-yl-acetamide;   N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-piperidin-1-yl-acetamide;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyrimidin-4-yl-amine;   N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-benzamide;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-methyl-amine;   N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide;   N-{4-[4-(4-Hydroxy-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide;   Cyclopropanecarboxylic acid [4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amide;   N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2,2-dimethyl-propionamide;   Tetrahydro-pyran-4-carboxylic acid[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amide;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-thiazol-2-yl-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-oxazol-2-yl-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-methyl-oxazol-2-yl)-amine;   {(S)-4-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-2-yl}-methanol;   1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-4-methyl-piperidin-4-ol;   {4-[4-((S)-3-Isopropyl-piperazin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine;   2-{(S)-4-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-2-yl}-ethanol;   N-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-N′,N′-dimethyl-benzene-1,4-diamine;   {5-Methoxy-2-[2-(3-morpholin-4-yl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   {2-[2-(2-Fluoro-phenylamino)-pyridin-4-yl]-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   {5-Methoxy-2-[2-(4-morpholin-4-yl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   {2-[2-(4-Fluoro-phenylamino)-pyridin-4-yl]-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   {4-[5-Methoxy-4-(3-trifluoromethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine;   {(S)-4-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-2-yl}-acetonitrile;   {4-[4-((R)-3-Fluoromethyl-piperazin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]pyridin-2-yl}-phenyl-amine;   Cyclopropanecarboxylic acid {4-[4-(4-hydroxy-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-amide;   {4-[4-((S)-3-Fluoromethyl-piperazin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine;   {4-[4-((S)-3-Cyclopropyl-piperazin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine;   {4-[4-((R)-3-Fluoromethyl-piperazin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2,3,6-trifluoro-phenyl)-amine;   [5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-(R)-pyrrolidin-3-yl-amine;   {5-Methoxy-2-[2-(pyrazin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   Thiophene-2-carboxylic acid {4-[5-methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-amide;   Cyclopentyl-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   Cyclohexyl-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   {2-[2-(Pyrazin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   {1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol;   2-{3-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-R-pyrrolidin-1-yl}-acetamide;   [4-(5-Chloro-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-phenyl-amine;   [4-(5-Chloro-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-phenyl)-amine;   (2-Fluoro-phenyl)-{2-[2-(2-fluoro-phenylamino)-pyridin-4-yl]-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-5-yl}-amine;   4-{5-(4-Cyano-pyridin-2-ylamino)-2-[2-(4-cyano-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperazine;   {4-[5-Chloro-4-((S)-3-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine;   N-[4-(5-Chloro-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide;   [4-(5-Chloro-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,3-difluoro-phenyl)-amine;   [4-(5-Chloro-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-fluoro-pyridin-2-yl)-amine;   [4-(5-Chloro-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,6-difluoro-phenyl)-amine;   [4-(5-Chloro-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,4-difluoro-phenyl)-amine;   [4-(5-Chloro-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-methyl-pyridin-2-yl)-amine;   [4-(5-Chloro-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,3,6-trifluoro-phenyl)-amine;   [4-(5-Chloro-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-fluoro-pyridin-2-yl)-amine;   [4-(5-Chloro-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-trifluoromethyl-pyridin-2-yl)-amine;   5-[4-(5-Chloro-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-pyridine-2-carbonitrile;   {4-Piperazin-1-yl-2-[2-(2,3,6-trifluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-5-yl}-(2,3,6-trifluoro-phenyl)-amine;   (2,6-Difluoro-phenyl)-{2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-5-yl}-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,6-difluoro-phenyl)-amine;   2-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-isonicotinonitrile;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,3,6-trifluoro-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-methyl-pyridin-2-yl)-amine;   {4-[5-Cyclopropyl-4-(3-trifluoromethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(6-fluoro-pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-trifluoromethyl-pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-trifluoromethyl-pyridin-3-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-fluoro-pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4,5-dimethyl-oxazol-2-yl)-amine;   {4-[5-Cyclopropyl-4-((S)-3-cyclopropyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine;   1-{5-Cyclopropyl-2-[2-(2-fluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-ol;   {4-[5-Cyclopropyl-4-((S)-3-isopropyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine;   {4-[5-Cyclopropyl-4-((S)-3-cyclopropyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2-fluoro-phenyl)-amine;   {4-[5-Cyclopropyl-4-((S)-3-cyclopropyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(6-fluoro-pyridin-2-yl)-amine;   (4-{5-Cyclopropyl-4-[3-(1,1-difluoro-ethyl)-piperazin-1-yl]-pyrido[3,4-d]pyrimidin-2-yl}-pyridin-2-yl)-phenyl-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-phenyl-amine;   {(S)-4-[5-Cyclopropyl-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-2-yl}-acetonitrile;   Cyclopentyl-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   Cyclohexyl-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(tetrahydro-pyran-4-yl)-amine;   Cyclopentyl-{4-[5-cyclopropyl-4-(3-trifluoromethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-amine;   Adamantan-1-yl-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   2-Amino-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-benzamide;   4-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-benzamide;   4-Amino-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-benzamide;   {4-[(1S,4S)-4-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine;   Pyrazine-2-carboxylic acid {4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-amide;   3-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-benzamide;   3-Amino-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-benzamide;   2-(4-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenoxy)-acetamide;   2-(3-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenoxy)-acetamide;   2-(4-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenyl)-acetamide;   2-(4-Amino-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide;   2-(3-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenyl)-acetamide;   2-(3-Amino-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide;   {2-[2-(5-Phenyl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   {2-[2-(6-Morpholin-4-yl-pyridin-3-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   (2-{2-[6-(4-Methyl-piperazin-1-yl)-pyridin-3-ylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-(R)-pyrrolidin-3-yl-amine;   2-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile;   {2-[2-(4-Imidazol-1-ylmethyl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   2-(3-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenoxy)-acetamide;   2-(3-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenyl)-acetamide;   2-(3-Amino-phenyl)-N-{4-[5-methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide;   2-(4-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenyl)-acetamide;   2-(4-Amino-phenyl)-N-{4-[5-methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide;   1-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile;   {5-Methoxy-2-[2-(5-phenyl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   {5-Methoxy-2-[2-(6-morpholin-4-yl-pyridin-3-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   (5-Methoxy-2-{2-[6-(4-methyl-piperazin-1-yl)-pyridin-3-ylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-(R)-pyrrolidin-3-yl-amine;   2-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile;   {2-[2-(4-Imidazol-1-ylmethyl-phenylamino)-pyridin-4-yl]-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   2-Phenyl-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide;   2-(4-Methoxy-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide;   2-(2-Methoxy-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide;   2-(3-Methoxy-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide;   {2-[2-(4-Methyl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   {2-[2-(4-Chloro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   6-{4-[4-((R)-Pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-nicotinonitrile;   2-[4-(4-Piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-isonicotinonitrile;   {2-[2-(4-Morpholin-4-yl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   6-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-nicotinonitrile;   {2-[2-(5-Methyl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   {2-[2-(5-Chloro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   2-[2-(Pyrimidin-4-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   2-(3-Cyano-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide;   2-(4-Cyano-phenyl)-N-{4-[4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide;   (R)-Pyrrolidin-3-yl-{2-[2-(4-trifluoromethyl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-amine;   (R)-Pyrrolidin-3-yl-{2-[2-(5-trifluoromethyl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-amine;   2-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-isonicotinonitrile;   6-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-nicotinonitrile;   {4-[5-Methoxy-4-(4-morpholin-4-yl-piperidin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine;   2-(4-Cyano-phenyl)-N-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide;   2-(3-Cyano-phenyl)-N-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide;   {2-[2-(5-Morpholin-4-yl-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   {2-[2-(2-Methoxy-4-morpholin-4-yl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   (2-Methoxy-4-morpholin-4-yl-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   {5-Methoxy-2-[2-(2-methoxy-4-morpholin-4-yl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   (5-Methoxy-2-{2-[4-(tetrahydro-pyran-4-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-(R)-pyrrolidin-3-yl-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[4-(tetrahydro-pyran-4-yl)-phenyl]-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-methyl-pyridin-2-yl)-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-methyl-pyridin-2-yl)-amine;   (4-Chloro-pyridin-2-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (5-Chloro-pyridin-2-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-trifluoromethyl-pyridin-2-yl)-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-trifluoromethyl-pyridin-2-yl)-amine;   2-(4-Chloro-phenyl)-N-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide;   2-(3-Chloro-phenyl)-N-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide;   N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-phenyl-acetamide;   2-(3-Methoxy-phenyl)-N-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide;   N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-(3-trifluoromethyl-phenyl)-acetamide;   2-(4-Methoxy-phenyl)-N-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-morpholin-4-yl-pyridin-3-yl)-amine;   {2-[2-(Pyridin-3-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   {5-Methoxy-2-[2-(pyridin-3-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyridin-3-yl-amine;   2-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-isonicotinamide;   6-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-nicotinamide;   (3-Methoxy-4-morpholin-4-yl-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-methyl-4-morpholin-4-yl-phenyl)-amine;   5-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-pyridine-2-carbonitrile;   {5-Methoxy-2-[2-(pyrimidin-5-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyrimidin-5-yl-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyrimidin-5-yl-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyridin-2-yl-amine;   2-[4-(5-Methoxy-4-morpholin-4-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-isonicotinonitrile;   2-(3-Cyano-phenyl)-N-[4-(5-methoxy-4-morpholin-4-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,4,5-trimethoxy-phenyl)-amine;   N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-(4-trifluoromethyl-phenyl)-acetamide;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-phenyl-pyridin-3-yl)-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-methyl-pyridin-3-yl)-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-methoxy-pyridin-3-yl)-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-trifluoromethyl-pyridin-3-yl)-amine;   N-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-2-pyridin-3-yl-acetamide;   2-{4-[5-Methoxy-4-(4-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile;   2-(3-Chloro-phenyl)-N-{4-[5-methoxy-4-(4-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide;   N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-pyridin-3-yl-acetamide;   N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-pyridin-4-yl-acetamide;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-methoxy-pyridin-2-yl)-amine;   2-{4-[4-(4-Hydroxy-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile;   2-(3-Cyano-phenyl)-N-{4-[4-(4-hydroxy-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide;   2-(3-Cyano-phenyl)-N-{4-[5-methoxy-4-(4-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide;   (6-Chloro-pyridin-3-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (R)—N-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-2-phenyl-propionamide;   (S)—N-{4-[5-Methoxy-4-((R)-pyrrolidin-3-ylamino)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-2-phenyl-propionamide;   (R)—N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-phenyl-propionamide;   (S)—N-[4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-phenyl-propionamide;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-methyl-pyridin-2-yl)-amine;   (3-Fluoro-pyridin-2-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-piperazin-1-ylpyridin-3-yl)-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[2-methyl-4-(4-methyl-piperazin-1-yl)-phenyl]-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(1-piperidin-4-yl-1H-pyrazol-4-yl)-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-methyl-pyridin-2-yl)-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-methyl-pyridin-3-yl)-amine;   (5-Chloro-pyridin-3-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (2-Fluoro-4-morpholin-4-yl-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   3-Fluoro-4-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-benzonitrile;   4-Fluoro-3-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-benzonitrile;   (2,6-Difluoro-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (2-Fluoro-6-methyl-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyrimidin-2-yl-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-methoxy-pyridin-3-yl)-amine;   (S)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-3-ol;   2-{4-[4-((S)-3-Hydroxy-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile;   1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-ol;   (R)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-3-ol;   2-{4-[4-((R)-3-Hydroxy-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile;   [5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-(S)-1-pyrrolidin-2-ylmethyl-amine;   [5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-(R)-1-pyrrolidin-2-ylmethyl-amine;   2-{4-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-1-yl}-ethanol;   {1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-azetidin-3-yl}-methanol;   {(R)-4-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-2-yl}-methanol;   (R)-7-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-hexahydro-oxazolo[3,4-a]pyrazin-3-one;   (±)-cis-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol;   (±)-trans-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol;   4-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-2-one;   (2,3-Difluoro-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (2,5-Difluoro-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,4,6-trifluoro-phenyl)-amine;   ((R)-4-{2-[2-(2,6-Difluoro-phenylamino)-pyridin-4-yl]-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl}-piperazin-2-yl)-methanol;   3-Hydroxymethyl-1-[5-methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-ol;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,3,6-trifluoro-phenyl)-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-trifluoromethyl-phenyl)-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-trifluoromethyl-phenyl)-amine;   (6-Fluoro-pyridin-2-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-methoxy-pyridin-2-yl)-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-trifluoromethyl-pyridin-2-yl)-amine;   (2-Fluoro-pyridin-3-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (2-Fluoro-3-methyl-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (2-Fluoro-3-trifluoromethyl-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (2,4-Difluoro-phenyl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,3,4-trifluoro-phenyl)-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,4,5-trifluoro-phenyl)-amine;   (3S,4S)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol;   (3R,4R)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol;   3-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ylamino]-propionamide;   [4-(5-Methoxy-4-piperidin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-phenyl-amine;   {4-[4-(4,4-Difluoro-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine;   1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-4-carbonitrile;   {4-[4-(4-Fluoro-piperidin-1-yl)-5-methoxy-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine;   (3R,4S)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol;   (3S,4R)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol;   {(R)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-pyrrolidin-3-yl}-methanol;   {(S)-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-pyrrolidin-3-yl}-methanol;   (meso)-cis-1-[5-Methoxy-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-azepane-4,5-diol;   1-{2-[2-(6-Fluoro-pyridin-2-ylamino)-pyridin-4-yl]-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-ol;   1-{5-Methoxy-2-[2-(6-methoxy-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-ol;   ((S)-1-{2-[2-(6-Fluoro-pyridin-2-ylamino)-pyridin-4-yl]-5-methoxy-pyrido[3,4-d]pyrimidin-4-yl}-pyrrolidin-3-yl)-methanol;   ((S)-1-{5-Methoxy-2-[2-(6-methoxy-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-pyrrolidin-3-yl)-methanol;   2-(4-Cyano-phenyl)-N-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-methyl-4-morpholin-4-yl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-morpholin-4-yl-pyridin-3-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyridin-3-yl-amine;   (2-Chloro-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-methyl-pyridin-3-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-phenyl-amine;   2-{4-[5-Cyclopropyl-4-(4-hydroxy-piperidin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-fluoro-pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-phenyl)-amine;   (±)-2-{4-[5-Cyclopropyl-4-cis-3,4-dihydroxy-piperidin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-o-tolyl-amine;   2-{4-[5-Cyclopropyl-4-((3R,4S)-3,4-dihydroxy-piperidin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile;   2-{4-[5-Cyclopropyl-4-((3S,4R)-3,4-dihydroxy-piperidin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile;   4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-N-(1-phenylpyrazol-4-yl)pyridin-2-amine;   (2,3-Dimethyl-2H-indazol-6-yl)-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3, 4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [1-(2-Fluoro-phenyl)-1H-pyrazol-4-yl]-[4-(5-methoxy-4-piperazin-1-yl-pyrido[3, 4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(1-phenyl-1H-pyrazol-4-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,3-dimethyl-2H-indazol-6-yl)-amine;   Phenyl-[4-(4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-pyridin-3-yl)-amine;   [4-(5-Methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-methyl-isoxazol-3-yl)-amine;   2-[2-(3-Piperazin-1-yl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-ol;   2-[2-(3-Piperazin-1-ylmethyl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-ol;   2-[2-(1-Piperidin-4-ylmethyl-1H-pyrazol-4-ylamino)-pyridin-4-yl]-pyrido[3, 4-d]pyrimidin-4-ol;   {5-Methoxy-2-[2-(3-piperazin-1-yl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-amine;   (5-Methoxy-2-{2-[4-(2-pyrrolidin-1-yl-ethoxy)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-methyl-amine;   {5-Methoxy-2-[2-(3-piperidin-4-yl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-amine;   [4-(5-Methoxy-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-piperazin-1-yl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-5-methyl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,5-dimethyl-phenyl)-amine;   5-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-pyridine-2-carbonitrile;   4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyrazin-2-yl-amine;   Cyclopropyl-{4-[5-cyclopropyl-4-(3-trifluoromethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(R)-tetrahydro-furan-3-yl-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4,4-difluoro-cyclohexyl)-amine;   {4-[5-Cyclopropyl-4-((R)-3-fluoromethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(4-trifluoromethyl-pyridin-2-yl)-amine;   {4-[5-Cyclopropyl-4-((R)-3-fluoromethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(6-fluoro-pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-methoxy-pyridin-3-yl)-amine;   (6-Chloro-pyridin-2-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-methoxy-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-trifluoromethyl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-methoxymethyl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(S)-tetrahydro-furan-3-yl-amine;   2-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-benzonitrile;   tert-Butyl-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,5-difluoro-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-5-trifluoromethyl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-fluoro-2-methyl-phenyl)-amine;   3-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-4-methyl-benzonitrile;   7-[5-Cyclopropyl-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-hexahydro-oxazolo[3,4-a]pyrazin-3-one;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-fluoro-pyridin-2-yl)-amine;   (2-Chloro-6-methyl-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   3-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-4-fluoro-benzonitrile;   (4-tert-Butyl-2-chloro-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   2-{4-[5-Cyclopropyl-4-((R)-3-fluoromethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile;   {4-[5-Cyclopropyl-4-((R)-3-fluoromethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2-fluoro-pyridin-3-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,2,2-trifluoro-ethyl)-amine;   2-{4-[5-Cyclopropyl-4-(3-oxo-tetrahydro-oxazolo[3,4-a]pyrazin-7-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-trifluoromethyl-pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-fluoro-pyridin-3-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-trifluoromethyl-pyridin-3-yl)-amine;   {4-[5-Cyclopropyl-4-(2,5-diaza-bicyclo[4.1.0]hept-2-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine;   {4-[5-Cyclopropyl-4-(2,5-diaza-bicyclo[4.1.0.]hept-2-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2,6-difluoro-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,6-dichloro-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,3-dimethyl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,6-dimethyl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,3-dichloro-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,3-dichloro-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-methyl-pyridin-3-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyridazin-3-yl-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-methyl-pyridin-3-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-methoxy-pyridin-3-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,6-difluoro-pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[4-(dimethyl-phosphinoyl)-phenyl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[4-(diethyl-phosphinoyl)-phenyl]-amine;   N 5 -[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-N 2 ,N 2 -dimethyl-pyridine-2, 5-diamine;   {4-[5-Cyclopropyl-4-((R)-3-fluoromethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-methoxy-2-methyl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-methyl-5-trifluoromethyl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-5-trifluoromethoxy-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-5-methanesulfonyl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,6-difluoro-3-methyl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-isopropyl-2-methyl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pent-deuterio-phenyl-amine;   1-{2-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-phenyl}-ethanol;   (1R,2S)-2-Amino-cyclopentanecarboxylic acid [4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amide;   1-{4-[2-(2-Chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-2-yl}-cyclopropanol;   [4-(5-Cyclopropyl-4-piperazin-1-yl-yl-pyridin-2-yl]-pyrazolo[1,5-a]pyridin-6-yl-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-yl-pyridin-2-yl]-pyrazolo[1,5-a]pyridin-5-yl-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-trifluoromethyl-pyridazin-3-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,6-difluoro-3-methoxy-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-ethoxy-2,6-difluoro-phenyl)-amine;   (2-Chloro-3-methyl-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   {4-[5-Cyclopropyl-4-((S)-3-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine;   (2-Chloro-4-fluoro-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-methoxy-phenyl)-amine;   (2-Chloro-4-methyl-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,4-dimethyl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-3-methyl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-4-methyl-phenyl)-amine;   (2-Chloro-5-fluoro-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (2-Chloro-5-methyl-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (2-Chloro-3-fluoro-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   5-Cyclopropyl-2-(6,7-dimethoxy-quinolin-4-yl)-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-5-methoxy-phenyl)-amine;   N-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-acetamide;   4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamine;   N-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-isobutyramide;   Cyclopropanecarboxylic acid [4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amide;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,3-difluoro-cyclobutyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-((R)-1-phenyl-ethyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-((S)-1-phenyl-ethyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-methoxy-pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-3-methoxy-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,6-difluoro-4-methoxy-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-methoxy-2-methyl-phenyl)-amine;   (2-Chloro-5-methoxy-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-fluoro-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-trifluoromethyl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-trifluoromethyl-phenyl)-amine;   (2-Chloro-5-trifluoromethyl-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,4-difluoro-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(1-methyl-1H-pyrazol-3-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-fluoro-cyclohexyl)-amine;   (+/−)-(cis)-1-(5-Cyclopropyl-2-{2-[3-(4-methyl-piperazin-1-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-piperidine-3,4-diol;   (4-Cyclopropyl-2,6-difluoro-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,6-difluoro-4-methyl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(1-methyl-1H-imidazol-4-yl)-amine;   2-{4-[5-Cyclopropyl-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-1-yl}-ethanol;   (S)-3-{4-[5-Cyclopropyl-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-1-yl}-propane-1,2-diol;   (R)-3-{4-[5-Cyclopropyl-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-1-yl}-propane-1,2-diol;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyridin-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-methoxy-4-methyl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,4-dimethoxy-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,4,5-trimethoxy-phenyl)-amine;   N-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-phenyl-acetamide;   N-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-3,3,3-trifluoro-propionamide;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[4-(1-methyl-4-oxo-4λ 5 -[1,4]azaphosphinan-4-yl)-phenyl]-amine;   2-(2-Chloro-pyridin-4-yl)-5-cyclopropyl-4-[3-(2,2,2-trifluoro-ethyl)-piperazin-1-yl]-pyrido[3,4-d]pyrimidine;   (2-Chloro-6-fluoro-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (6-Chloro-2-fluoro-3-methyl-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (3-Chloro-2,6-difluoro-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Cyclobutyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-phenyl-amine;   [4-(5-Cyclobutyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,6-difluoro-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,3-difluoro-cyclopentyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-isopropyl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-ethyl-phenyl)-amine;   2-(2-Chloro-pyridin-4-yl)-5-cyclopropyl-4-(3-trifluoromethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[4-(1-ethyl-4-oxo-4λ 5 -[1,4]azaphosphinan-4-yl)-2-methoxy-phenyl]-amine;   N-(4-{5-Cyclopropyl-4-[3-(2,2,2-trifluoro-ethyl)-piperazin-1-yl]-pyrido[3,4-d]pyrimidin-2-yl}-pyridin-2-yl)-acetamide;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-fluoro-3-methoxy-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,4-difluoro-5-methoxy-phenyl)-amine;   Cyclopropylmethyl-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-methyl-amine;   4-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-2-fluoro-benzonitrile;   [4-(5-Cyclopropyl-4-[1,4]diazepan-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-phenyl-amine;   4-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-cyclohexanol;   (2-Chloro-6-fluoro-3-methoxy-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (2-Chloro-3,6-difluoro-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   {4-[5-Cyclopropyl-4-(2,2,3,3,5,5,6,6-octadeuterio-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine;   (4-Cyclopropyl-3-methoxy-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   4-[5-Cyclopropyl-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acidamide;   N-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2-(2,6-difluoro-phenyl)-acetamide;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-5-propyl-phenyl)-amine;   (4-Cyclopropyl-2-fluoro-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (4-{5-Cyclopropyl-4-[3-(2,2,2-trifluoro-ethyl)-piperazin-1-yl]-pyrido[3,4-d]pyrimidin-2-yl}-pyridin-2-yl)-(2,6-difluoro-phenyl)-amine;   (4-{5-Cyclopropyl-4-[3-(2,2,2-trifluoro-ethyl)-piperazin-1-yl]-pyrido[3,4-d]pyrimidin-2-yl}-pyridin-2-yl)-phenyl-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[(R)-1-(3-fluoro-phenyl)-ethyl]-amine;   4-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-benzonitrile;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-trifluoromethyl-phenyl)-amine;   (3-Chloro-2,6-difluoro-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,4,6-trifluoro-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,4-difluoro-phenyl)-amine;   4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[(R)-1-(4-fluoro-phenyl)-ethyl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[(R)-1-(2,6-difluoro-phenyl)-ethyl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-5-fluoro-pyridin-2-yl]-phenyl-amine;   1-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidine-4-carboxylic acid isopropylamide;   1-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidine-4-carboxylic acid amide;   N-(1-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-yl)-acetamide;   1-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidine-4-carboxylic acid (2-fluoro-ethyl)-amide;   N-{4-[5-Cyclopropyl-4-((S)-3-trifluoromethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide;   2-(2-Chloro-pyridin-4-yl)-5-cyclopropyl-4-((R)-3-trifluoromethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidine;   (4-{5-Cyclopropyl-4-[4-(2-methoxy-ethyl)-piperazin-1-yl]-pyrido[3,4-d]pyrimidin-2-yl}-pyridin-2-yl)-phenyl-amine;   (4-{5-Cyclopropyl-4-[4-(2-methoxy-ethyl)-piperazin-1-yl]-pyrido[3,4-d]pyrimidin-2-yl}-pyridin-2-yl)-(4-fluoro-phenyl)-amine;   (4-{(5-Cyclopropyl-4-[4-(2-methanesulfonyl-ethyl)-piperazin-1-yl]-pyrido[3,4-d]pyrimidin-2-yl}-pyridin-2-yl)-phenyl-amine;   (4-{(5-Cyclopropyl-4-[4-(2-methanesulfonyl-ethyl)-piperazin-1-yl]-pyrido[3,4-d]pyrimidin-2-yl}-pyridin-2-yl)-(4-fluoro-phenyl)-amine;   Cyclopropanecarboxylic acid (4-{5-cyclopropyl-4-[4-(2-methanesulfonyl-ethyl)-piperazin-1-yl]-pyrido[3,4-d]pyrimidin-2-yl}-pyridin-2-yl)-amide;   Cyclopropanecarboxylic acid (4-{5-cyclopropyl-4-[4-(2-methoxy-ethyl)-piperazin-1-yl]-pyrido[3,4-d]pyrimidin-2-yl}-pyridin-2-yl)-amide;   (5-Cyclopropyl-2-fluoro-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   1-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidine-4-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide;   1-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidine-4-carboxylic acid methylamide;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,4-difluoro-pyridin-3-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,6-difluoro-pyridin-3-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-fluoro-pyridin-3-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,3-difluoro-cyclohexyl)-amine;   1-[2-(2-Cyclohexylamino-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-4-carboxylicacid isopropylamide;   (+/−)-(cis)-1-[5-Cyclopropyl-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol;   (+/−)-(trans)-1-[5-Cyclopropyl-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol;   (+/−)-2-{4-[5-Cyclopropyl-4-((trans)-3,4-dihydroxy-piperidin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-isonicotinonitrile;   (+/−)-(trans)-1-(5-Cyclopropyl-2-{2-[3-(4-methyl-piperazin-1-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4d]pyrimidin-4-yl)-piperidine-3,4-diol;   1-[2-(2-Cyclopentylamino-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-4-carboxylicacid isopropylamide;   4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,5,6-trifluoro-pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[3-(4-methyl-piperazin-1-yl)-phenyl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,3,6-trifluoro-pyridin-4-yl)-amine;   Biphenyl-4-yl-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   4-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-benzoic acid;   1-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidine-4-carboxylic acid (2-hydroxy-ethyl)-amide;   1-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidine-4-carboxylic acid dimethylamide;   4-(5-Cyclopropyl-2-{2-[3-(4-methyl-piperazin-1-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid amide;   1-(5-Cyclopropyl-2-{2-[3-(4-methyl-piperazin-1-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-piperidin-4-ol;   5-Cyclopropyl-2-(2-fluoro-pyridin-4-yl)-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   {4-[4-(4-Amino-piperidin-1-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2,6-difluoro-phenyl)-amine;   {4-[5-Cyclopropyl-4-((S)-3-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2-fluoro-phenyl)-amine;   {4-[5-Cyclopropyl-4-((S)-3-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2,6-difluoro-phenyl)-amine;   {4-[5-Cyclopropyl-4-((S)-3-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(4-fluoro-phenyl)-amine;   {4-[5-Cyclopropyl-4-((S)-3-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(3,6-difluoro-pyridin-2-yl)-amine;   (+/−)-(1RS,2RS,4SR)-Bicyclo[2.2.1]hept-2-yl-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   {4-[4-(4-Aminomethyl-piperidin-1-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2,6-difluoro-phenyl)-amine;   [5-Cyclopropyl-2-(2-phenylamino-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-(S)-1-pyrrolidin-2-ylmethyl-amine;   {5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(S)-1-pyrrolidin-2-ylmethyl-amine;   [4-(5-Cyclopropyl-4-[1,4]diazepan-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-fluoro-phenyl)-amine;   Bicyclo[1.1.1]pent-1-yl-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-3-fluoro-pyridin-2-yl]-phenyl-amine;   [4-(5-Cyclopropyl-4-[1,4]diazepan-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,6-difluoro-phenyl)-amine;   (+/−)-cis-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-fluoro-cyclobutyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,5-difluoro-pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,5-difluoro-pyridin-4-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,2,2-trifluoro-1-phenyl-ethyl)-amine;   1-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidine-3-carboxylic acid methylamide;   {4-[4-(3-Amino-pyrrolidin-1-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2,6-difluoro-phenyl)-amine;   {4-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-phenyl}-acetic acid;   [4-(5-Cyclopropyl-4-piperidin-1-yl-pyrido[3,4d]pyrimidin-2-yl)-pyridin-2-yl]-[3-(4-methyl-piperazin-1-yl)-phenyl]-amine;   3-{4-[5-Cyclopropyl-4-((3R,4S)-3,4-dihydroxy-piperidin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-benzonitrile;   Chroman-4-yl-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   N-(1-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-pyrrolidin-3-yl)-acetamide;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-4-isopropyl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-ethyl-2-fluoro-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-5-isopropyl-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-ethyl-2-fluoro-phenyl)-amine;   {4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2,6-difluoro-phenyl)-amine;   {4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(4-fluoro-phenyl)-amine;   (R)-1-(5-Cyclopropyl-2-{2-[3-(4-methyl-piperazin-1-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-piperidin-3-ol;   [(R)-1-(5-Cyclopropyl-2-{2-[3-(4-methyl-piperazin-1-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-pyrrolidin-3-yl]-methanol;   [(S)-1-(5-Cyclopropyl-2-{2-[3-(4-methyl-piperazin-1-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-pyrrolidin-3-yl]-methanol;   1-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidine-4-carboxylic acid ethylamide;   (6-Cyclopropyl-2,4-difluoro-pyridin-3-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (6-Cyclopropyl-2-fluoro-pyridin-3-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   1-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-pyrrolidine-3-carboxylic acid methylamide;   (S)-1-(5-Cyclopropyl-2-{2-[3-(4-methyl-piperazin-1-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-pyrrolidin-3-ol;   1-(3-{4-[5-Cyclopropyl-4-(4-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-phenyl)-piperidin-4-ol;   1-{5-Cyclopropyl-2-[2-(3-piperazin-1-yl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-ol;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[1-(1-methyl-1H-pyrazol-4-yl)-ethyl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-fluoro-6-morpholin-4-yl-pyridin-3-yl)-amine;   1-{5-Cyclopropyl-2-[2-(1-piperidin-4-ylmethyl-1H-pyrazol-4-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-ol;   4-((R)-3-Benzyloxymethyl-piperazin-1-yl)-2-(2-chloro-pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidine;   (3-Cyclopropyl-phenyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (1-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-yl)-(4-methyl-piperazin-1-yl)-methanone;   1-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidine-4-carboxylic acid (2-dimethylamino-ethyl)-amide;   (S)-1-(5-Cyclopropyl-2-{2-[3-(4-methyl-piperazin-1-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-piperidin-3-ol;   (R)-1-(5-Cyclopropyl-2-{2-[3-(4-methyl-piperazin-1-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-pyrrolidin-3-ol;   1-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidine-4-carboxylic acid (2-methoxy-ethyl)-amide;   4-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-3,5-difluoro-benzonitrile;   (1-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-yl)-piperazin-1-yl-methanone;   4-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-benzamide;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[1,2,4]triazolo[1,5-a]pyridin-2-yl-amine;   1-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidine-4-carboxylic acid (2-methylamino-ethyl)-amide;   6-{4-[5-Cyclopropyl-4-((cis)-3,4-dihydroxy-piperidin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-ylamino}-pyridine-2-carbonitrile;   6-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-pyridine-2-carbonitrile;   1-(5-Cyclopropyl-2-{2-[3-(4-methyl-piperazin-1-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-3,3-difluoro-piperidine-4,4-diol;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4,6-difluoro-pyridin-3-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,5-difluoro-pyridin-3-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyridin-2-yl-amine;   (3R,4S)-1-(5-Cyclopropyl-2-{2-[3-(4-methyl-piperazin-1-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-piperidine-3,4-diol;   (3R,4S)-1-(5-Cyclopropyl-2-{2-[3-(4-methyl-piperazin-1-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-piperidine-3,4-diol;   (3S,4S)-1-(5-Cyclopropyl-2-{2-[3-(4-methyl-piperazin-1-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-piperidine-3,4-diol;   (3S,4S)-1-(5-Cyclopropyl-2-{2-[3-(4-methyl-piperazin-1-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-piperidine-3,4-diol;   {4-[5-Cyclopropyl-4-(2-methylamino-ethoxy)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2,6-difluoro-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-fluoro-pyridin-2-yl)-amine;   {4-[5-Cyclopropyl-4-(piperidin-4-yloxy)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2,6-difluoro-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(1-methyl-1H-pyrazol-4-ylmethyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-phenethyl-amine;   [4-(5-Cyclopropyl-4-pyrrolidin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[3-(4-methyl-piperazin-1-yl)-phenyl]-amine;   [4-(4-Azetidin-1-yl-5-cyclopropyl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[3-(4-methyl-piperazin-1-yl)-phenyl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-fluoro-6-methoxy-pyridin-2-yl)-amine;   {4-[5-Cyclopropyl-4-(3,5-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(3,6-difluoro-pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-5-fluoro-pyridin-2-yl]-(2,6-difluoro-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-5-fluoro-pyridin-2-yl]-(4-fluoro-phenyl)-amine;   [4-(5-Cyclopropyl-4-pyrrolidin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-piperazin-1-yl-phenyl)-amine;   [4-(4-Azetidin-1-yl-5-cyclopropyl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-piperazin-1-yl-phenyl)-amine;   N-{4-[4-((R)-3-Benzyloxymethyl-piperazin-1-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide;   {4-[5-Cyclopropyl-4-((R)-3-methanesulfonylmethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine;   N-{4-[5-Cyclopropyl-4-((R)-3-methanesulfonylmethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-acetamide;   {4-[5-Cyclopropyl-4-((R)-3-methanesulfonylmethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(4-fluoro-phenyl)-amine;   {4-[5-Cyclopropyl-4-((R)-3-methanesulfonylmethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2,6-difluoro-phenyl)-amine;   Cyclopropanecarboxylic acid {4-[5-cyclopropyl-4-((R)-3-methanesulfonylmethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-amide;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,4,6-trifluoro-pyridin-2-yl)-amine;   N-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-N′-methyl-ethane-1,2-diamine;   N-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-N′,N′-dimethyl-ethane-1,2-diamine;   1-(5-Cyclopropyl-2-{2-[3-(4-methyl-piperazin-1-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-azetidin-3-ol;   1-{5-Cyclopropyl-2-[2-(3-piperazin-1-yl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-azetidin-3-ol;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(1-isopropyl-1H-pyrazol-3-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(1-ethyl-5-methyl-1H-pyrazol-3-yl)-amine;   [4-(5-Cyclopropyl-4-piperidin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[6-(4-methyl-piperazin-1-yl)-pyridin-2-yl]-amine;   [4-(5-Cyclopropyl-4-piperidin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[6-(4-methyl-piperazin-1-yl)-pyridin-2-yl]-amine;   [4-(5-Cyclobutyl-4-piperazin-1-yl-pyrido[3, 4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,5-difluoro-pyridin-2-yl)-amine;   [4-(5-Cyclobutyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-fluoro-pyridin-2-yl)-amine;   [4-(5-Cyclobutyl-4-piperazin-1-yl-pyrido[3, 4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-fluoro-pyridin-2-yl)-amine;   [4-(5-Cyclobutyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,4,6-trifluoro-pyridin-2-yl)-amine;   {4-[5-Cyclopropyl-4-(3,5-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2,6-difluoro-phenyl)-amine;   (R)-4-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperazine-2-carbonitrile;   {4-[5-Cyclopropyl-4-(1,2,3,6-tetrahydro-pyridin-4-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2,6-difluoro-phenyl)-amine;   {5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-yl-amine;   {4-[5-Cyclopropyl-4-(piperidin-4-ylsulfanyl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2,6-difluoro-phenyl)-amine;   (3S,4S)-1-(5-Cyclopropyl-2-{2-[3-(4-methyl-piperazin-1-yl)-phenylamino]-pyridin-4-yl}-pyrido[3,4-d]pyrimidin-4-yl)-pyrrolidine-3,4-diol;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(1-cyclopropyl-1H-pyrazol-4-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[1-(tetrahydro-pyran-4-yl)-1H-pyrazol-4-yl]-amine;   (1-Cyclopentyl-1H-pyrazol-4-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   N-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-N,N′,N′-trimethyl-ethane-1,2-diamine;   {4-[5-Cyclobutyl-4-((S)-3-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(3, 6-difluoro-pyridin-2-yl)-amine;   [4-(5-Cyclobutyl-4-piperazin-1-yl-pyrido[3, 4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,6-difluoro-pyridin-2-yl)-amine;   {4-[5-Cyclopropyl-4-((S)-3-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(3-fluoro-pyridin-2-yl)-amine;   (6-Chloro-3-fluoro-pyridin-2-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[(R)-1-(3,6-difluoro-pyridin-2-yl)-ethyl]-amine;   N-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-N′,N′-dimethyl-butane-1,4-diamine;   [4-(4-Azepan-1-yl-5-cyclopropyl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[3-(4-methyl-piperazin-1-yl)-phenyl]-amine;   1-{5-Cyclopropyl-2-[2-(6-fluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-ol;   (R)-1-{5-Cyclopropyl-2-[2-(6-fluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-3-ol;   [4-(5-Cyclobutyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,5,6-trifluoro-pyridin-2-yl)-amine;   {4-[5-Cyclobutyl-4-((S)-3-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(3,5,6-trifluoro-pyridin-2-yl)-amine;   [4-(5-Cyclobutyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-trifluoromethyl-pyridin-2-yl)-amine;   ((R)-1-Cyclopropyl-ethyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   ((R)-1-Cyclohexyl-ethyl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (5-Cyclopropyl-3-fluoro-pyridin-2-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   1-{4-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-piperidin-1-yl}-2,2-dimethyl-propan-1-one;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[1-(2,2,2-trifluoro-ethyl)-piperidin-4-yl]-amine;   {4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(3,5,6-trifluoro-pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl]-(1-methanesulfonyl-piperidin-4-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[1-(2-fluoro-phenyl)-1H-pyrazol-4-yl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[1-(2,6-difluoro-phenyl)-1H-pyrazol-4-yl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[1-(2,4,6-trifluoro-phenyl)-1H-pyrazol-4-yl]-amine;   1-{5-Cyclopropyl-2-[2-(2-methyl-2,3-dihydro-1H-isoindol-5-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-ol;   4-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-3,5-difluoro-benzamide;   (1 S,2 S,4R)-Bicyclo[2.2.1]hept-2-yl-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (1 R,2R,4S)-Bicyclo[2.2.1]hept-2-yl-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-amine;   {4-[5-Cyclopropyl-4-(2-dimethylamino-ethoxy)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2,6-difluoro-phenyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-trifluoromethyl-pyridin-2-yl)-amine;   {4-[5-Cyclopropyl-4-((3R,5S)-3,5-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(3,5,6-trifluoro-pyridin-2-yl)-amine;   {4-[5-Cyclopropyl-4-(4,7-diaza-spiro[2.5]oct-7-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2,6-difluoro-phenyl)-amine;   {4-[5-Cyclopropyl-4-((S)-3-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(3,5,6-trifluoro-pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(7-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-amine;   {4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(1-methyl-1H-pyrazol-3-yl)-amine;   {5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-piperidin-4-yl-amine;   1-{5-Cyclopropyl-2-[2-(3-morpholin-4-yl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-ol;   ((R)-1-Cyclohexyl-ethyl)-{4-[5-cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4,6-difluoro-pyridin-2-yl)-amine;   {5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-pyrrolidin-3-yl-amine;   {4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(3,6-difluoro-pyridin-2-yl)-amine;   {4-[5-Cyclopropyl-4-((S)-3-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(5-trifluoromethyl-pyridin-2-yl)-amine;   {4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(3-fluoro-pyridin-2-yl)-amine;   -[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-N-methyl-benzamide;   {5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-3-yl-amine;   {4-[5-Cyclopropyl-4-((3R,5S)-3,5-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2,6-difluoro-phenyl)-amine;   6-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-nicotinamide;   {4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(3,4,6-trifluoro-pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(8-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-amine;   4-((S)-3-Benzyl-piperazin-1-yl)-2-morpholin-4-yl-pyrido[3,4-d]pyrimidine;   [2-(2-Benzyl-morpholin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-(R)-pyrrolidin-3-yl-amine;   (S)—N 1 -(5-Methoxy-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-3-phenyl-propane-1,2-diamine;   5-Methoxy-2-morpholin-4-yl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Methoxy-2-(2-phenoxymethyl-morpholin-4-yl)-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   [(R)-4-(5-Methoxy-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazin-2-yl]-methanol;   5-Methoxy-2-morpholin-4-yl-4-((R)-3-phenoxymethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidine;   [(S)-1-(5-Methoxy-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperidin-3-yl]-phenyl-amine;   4-[(R)-3-(2-Fluoro-phenoxymethyl)-piperazin-1-yl]-5-methoxy-2-morpholin-4-yl-pyrido[3,4-d]pyrimidine;   5-Methoxy-4-((R)-3-methoxymethyl-piperazin-1-yl)-2-morpholin-4-yl-pyrido[3,4-d]pyrimidine;   4-[(R)-3-(4-Fluoro-phenoxymethyl)-piperazin-1-yl]-5-methoxy-2-morpholin-4-yl-pyrido[3,4-d]pyrimidine;   (2-Morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-(R)-pyrrolidin-3-yl-amine;   [2-Morpholin-4-yl-8-(2H-pyrazol-3-yl)-pyrido[3,4-d]pyrimidin-4-yl]-(R)-pyrrolidin-3-yl-amine;   N 4 —((S)-2-Amino-3-phenyl-propyl)-2-morpholin-4-yl-pyrido[3,4-d]pyrimidine-4,8-diamine;   (S)—N 1 -(2-Morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-3-phenyl-propane-1,2-diamine;   5-Bromo-2-morpholin-4-yl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   Synthesis of 5-Cyclopropyl-2-morpholin-4-yl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   4-((S)-3-Benzyl-piperazin-1-yl)-5-cyclopropyl-2-morpholin-4-yl-pyrido[3,4-d]pyrimidine;   [(S)-4-(5-Cyclopropyl-2-morpholin-4-yl-pyrido[3,4-d]pyrimidin-4-yl)-piperazin-2-yl]-acetonitrile;   5-Methoxy-4-piperazin-1-yl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   5-Methoxy-2-(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   2-(2-Benzyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   2-[2-(2-Fluoro-benzyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-5-methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   2-(2-Ethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-5methoxy-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Methoxy-4-((R)-3-methoxymethyl-piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   {(R)-4-[5-Methoxy-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-2-yl}-methanol;   4-Piperazin-1-yl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   (R)-Pyrrolidin-3-yl-[2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-amine;   5-Cyclopropyl-4-piperazin-1-yl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   8-Chloro-5-cyclopropyl-4-piperazin-1-yl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   5-Isopropyl-4-piperazin-1-yl-2-(l H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   [5-Cyclopropyl-4-piperazin-1-yl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-4-((R)-3-trifluoromethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-4-((S)-3-trifluoromethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-2-(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-(3-trifluoromethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-4-((S)-3-cyclopropyl-piperazin-1-yl)-2-(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-2-(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-4-(3-trifluoromethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidine;   4-((S)-3-Benzyl-piperazin-1-yl)-5-cyclopropyl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-4-((S)-3-cyclopropyl-piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   {(S)-4-[5-Cyclopropyl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazin-2-yl}-acetonitrile;   5-Cyclopropyl-4-piperazin-1-yl-2-(2-thiophen-2-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-2-(2-cyclopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   4-[5-Cyclopropyl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid ethyl ester;   5-Cyclopropyl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-ol;   5-Cyclopropyl-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-4-morpholin-4-yl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-4-piperazin-1-yl-2-(2-triduteriomethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   2-(2-tert-Butyl-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)-5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-2-[2-(4-fluoro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   2-(2-tert-Butyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-2-(5-fluoro-2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-4-((S)-3-methyl-piperazin-1-yl)-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   (+/−)-(cis)-1-[5-Cyclopropyl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol;   (+/−)-(trans)-1-[5-Cyclopropyl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-3,4-diol;   5-Cyclopropyl-4-(3-trifluoromethyl-piperazin-1-yl)-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-4-piperidin-1-yl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-4-piperazin-1-yl-2-[2-(1-trifluoromethyl-cyclopropyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-pyrido[3,4-d]pyrimidine;   1-[5-Cyclopropyl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-ol;   5-Cyclopropyl-2-[2-(1-phenyl-cyclopropyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   1-[5-Cyclopropyl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidine-4-carbonitrile;   {1-[5-Cyclopropyl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol;   {1-[5-Cyclopropyl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-azetidin-3-yl}-methanol;   1-{5-Cyclopropyl-2-[2-(1-phenyl-cyclopropyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-ol;   5-Cyclopropyl-4-(1,1-dioxo-1λ 6 -thiomorpholin-4-yl)-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-4-thiomorpholin-4-yl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   1-[2-(2-tert-Butyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-ol;   4-Azetidin-1-yl-5-cyclopropyl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   1-[2-(2-tert-Butyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-[1,4]diazepan-5-one;   (R)-1-[2-(2-tert-Butyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl]-pyrrolidin-3-ol;   5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)spiro[1,3-dihydropyrrolo[2,3-b]pyridine-2,1′-cyclohexane];   4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-9H-pyrido[2,3-b]indole;   1-[5-Cyclopropyl-2-(9H-pyrido[2,3-b]indol-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-ol;   4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-9H-pyrido[2,3-b]indole; or a salt form thereof.
 
87. A compound of formula (I) or a salt form thereof according to embodiment 1 wherein G is
   

                         
88. A compound of formula (I) or a salt form thereof according to embodiment 1 wherein G is
 
                         
89. A compound of formula (I) or a salt form thereof according to embodiment 1 or 88 wherein G is
 
                         
X is chosen from 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , —NR 24 R 28 , and —S(═O) n R 28 ;
 
R 7 , R 8 , R 9  are each independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , and halogen.
 
90. A compound of formula (I) or a salt form thereof according to any of embodiments 1, 88 or 89 wherein R 24  at each occurrence is independently chosen from H, and C 1-6 alkyl optionally substituted by 1-13 R 49 ; and
 
R 28  is selected from 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 49 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 49  and C 6-11 aryl optionally substituted by 1-11 R 49 .
 
91. A compound of formula (I) or a salt form thereof according to any of embodiments 1 or 88-90 wherein R 12  and R 13  are taken together to form C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19  or a 5-15 membered heteroaryl optionally substituted by 1-15 R 19  
 
92. A compound of formula (I) or a salt form thereof according to any of embodiments 1 or 88-90 wherein R 12 , R 14  and R 15  are each H and R 13  is —NR 22 R 23  or —NR 34 C(═O)R 30 .
 
93. A compound of formula (I) or a salt form thereof according to embodiment 92 wherein R 22  and R 23  are each independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 49 , C 6-11 aryl optionally substituted by 1-11 R 49 , C 7-16 arylalkyl optionally substituted by 1-19 R 49 , C 3-11 cycloalkyl optionally substituted by 1-21 R 49 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 49 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 49 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 49 , 5-15 membered heteroaryl optionally substituted by 1-15 R 49 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 49 .
 
94. A compound that is selected from:
     2-(2-tert-Butyl-H-pyrrolo[2,3-b]pyridin-4-yl)-5-cyclopropyl-4-((S)-3-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidine;   2-(2-tert-Butyl-H-pyrrolo[2,3-b]pyridin-4-yl)-5-cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidine;   4-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-N,N-dimethyl-benzamide;   {4-[5-Cyclopropyl-4-((S)-3-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(3,4,6-trifluoro-pyridin-2-yl)-amine;   (+/−)-cis-1-{5-Cyclopropyl-2-[2-(3-morpholin-4-yl-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidine-3,4-diol;   {4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-((R)-1-cyclopropyl-ethyl)-amine;   {4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-((R)-1-phenyl-ethyl)-amine;   2-(2-tert-Butyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-5-cyclobutyl-4-((S)-3-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-2-{2-[1-(2-fluoro-phenyl)-cyclopropyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   2-(2-tert-Butyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-5-cyclobutyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   [4-(5-Cyclobutyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4,6-difluoro-pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-amine;   (5-Cyclobutyl-3-fluoro-pyridin-2-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   {5-Cyclopropyl-2-[2-(3,5,6-trifluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-piperidin-4-yl-amine;   (4-Chloro-1-ethyl-1H-pyrazol-3-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-amine;   {4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-[1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-amine;   {4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(1-isopropyl-1H-pyrazol-3-yl)-amine;   {5-Cyclopropyl-2-[2-(3,4,6-trifluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-piperidin-4-yl-amine;   {5-Cyclopropyl-2-[2-(3,5,6-trifluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-pyrrolidin-3-yl-amine;   {5-Cyclopropyl-2-[2-(3,4,6-trifluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-pyrrolidin-3-yl-amine;   [4-(5-Cyclobutyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[1,2,4]triazolo[1,5-a]pyridin-2-yl-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-morpholin-4-yl-phenyl)-amine;   5-Cyclobutyl-4-piperazin-1-yl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   {5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-pyrrolidin-3-yl-amine;   Azetidin-3-yl-{5-cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-amine;   4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-5,8-difluoro-9H-pyrido[2,3-b]indole;   2-(2-tert-Butyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-5-cyclobutyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidine;   Azetidin-3-yl-{5-cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-amine;   [4-Chloro-1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-8-fluoro-9H-pyrido[2,3-b]indole;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(8-fluoro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(7-fluoro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-amine;   {5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(S)-pyrrolidin-3-yl-amine;   {5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-7,8-difluoro-9H-pyrido[2,3-b]indole;   {4-[5-Cyclopropyl-4-((cis)-3,5-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(3,4,6-trifluoro-pyridin-2-yl)-amine;   {5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(2,2-dimethyl-piperidin-4-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-fluoro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6,8-difluoro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(5-fluoro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-amine;   [4-(5-Cyclobutyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-((R)-1-phenyl-ethyl)-amine;   (4-Chloro-1-ethyl-1H-pyrazol-3-yl)-{4-[5-cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-amine;   Benzooxazol-2-yl-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   Benzothiazol-2-yl-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(1-methyl-1H-benzoimidazol-2-yl)-amine;   (5-Cyclopropyl-3,6-difluoro-pyridin-2-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   5-Cyclopropyl-2-{2-[1-(4-fluoro-phenyl)-cyclopropyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   {4-[5-Cyclopropyl-4-((S)-3-methyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-[1-(2,2,2-trifluoro-ethyl)-piperidin-4-yl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-naphthalen-2-yl-amine;   Biphenyl-3-yl-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   {4-[5-Cyclopropyl-4-((R)-3-trifluoromethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-[3-(4-methyl-piperazin-1-yl)-phenyl]-amine;   {4-[5-Cyclopropyl-4-((R)-3-trifluoromethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(1-methyl-1H-pyrazol-3-yl)-amine;   {5-Cyclopropyl-2-[2-(3,4,6-trifluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[2-fluoro-4-(2-methyl-2H-pyrazol-3-yl)-phenyl]-amine;   {5-Cyclopropyl-2-[2-(3,5,6-trifluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(R)-pyrrolidin-3-yl-amine;   {5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-(R)-pyrrolidin-3-yl-amine;   Azepan-4-yl-{5-cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-naphthalen-1-yl-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-iso[D3-4]uinolin-3-yl-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(1-methyl-1H-indazol-3-yl)-amine;   {5-Cyclopropyl-2-[2-(3,4,6-trifluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-yl-amine;   5-Cyclopropyl-4-piperazin-1-yl-2-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-2-[2-(1-phenyl-cyclobutyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   {5-Cyclopropyl-2-[2-(3,5,6-trifluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-yl-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[1-(tetrahydro-furan-2-yl)-ethyl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[(R)-1-(2-fluoro-phenyl)-ethyl]-amine;   [5-Cyclopropyl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-piperidin-4-yl-amine;   [5-Cyclopropyl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-(R)-pyrrolidin-3-yl-amine;   [5-Cyclopropyl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-methyl-piperidin-4-yl-amine;   8-Chloro-5-cyclopropyl-4-piperazin-1-yl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-pyrazolo[1,5-a]pyridin-2-yl-amine;   {4-[5-Cyclopropyl-4-((cis)-3,5-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-[1-(2,2,2-trifluoro-ethyl)-piperidin-4-yl]-amine;   2-(2-Chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)-5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-2-(2-methoxymethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   4-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-ylamino}-piperidin-2-one;   [5-Cyclopropyl-2-(1-methyl-2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-(R)-pyrrolidin-3-yl-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[D3-4]uinolin-2-yl-amine;   (±)-2-((endo)-2-Bicyclo[2.2.1]hept-2-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Cyclobutyl-2-(2-methoxymethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   [5-Cyclopropyl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-methyl-(1-methyl-piperidin-4-yl)-amine;   5-Cyclobutyl-4-piperazin-1-yl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   {5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-(1-methyl-piperidin-4-yl)-amine;   {5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(1-methyl-piperidin-4-yl)-amine;   1-(4-{5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-ylamino}-piperidin-1-yl)-ethanone;   5-Cyclopropyl-2-[2-(1-methyl-1-phenyl-ethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   2-(3-Chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)-5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   [5-Cyclopropyl-2-(2-trifluoromethyl-H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-methyl-(R)-pyrrolidin-3-yl-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-iso[D3-4]uinolin-1-yl-amine;   4-(5-Cyclobutyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-9H-pyrido[2,3-b]indole   4-(4-Piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-9H-pyrido[2,3-b]indole;   8-Chloro-5-cyclopropyl-2-(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   (±)-exo-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-7-oxa-bicyclo[2.2.1]hept-2-yl-amine;   (2,6-Difluoro-phenyl)-[4-(4-piperazin-1-yl-5-vinyl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   {5-Cyclopropyl-2-[2-(3,5-difluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-piperidin-4-yl-amine;   1-[4-({5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-amino)-piperidin-1-yl]-ethanone;   1-[4-({5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-amino)-piperidin-1-yl]-ethanone;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(R)-indan-1-yl-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(S)-indan-1-yl-amine;   [4-(8-Chloro-5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,6-difluoro-phenyl)-amine;   [4-(5-Cyclopropyl-8-fluoro-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,6-difluoro-phenyl)-amine;   5-Cyclopropyl-8-fluoro-4-piperazin-1-yl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   (1-Cyclobutyl-piperidin-4-ylmethyl)-{5-cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-amine;   Benzo[1,2,5]oxadiazol-4-yl-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   5-Cyclopentyl-4-piperazin-1-yl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-2-(2-difluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   {5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-piperidin-4-ylmethyl-amine;   5-Cyclopropyl-2-[2-(2-methoxy-1,1-dimethyl-ethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Cyclobutyl-2-[2-(2-methoxy-1,1-dimethyl-ethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   (1-Cyclobutyl-piperidin-4-yl)-{5-cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-amine;   5-Cyclopropyl-4-piperazin-1-yl-2-[2-(tetrahydro-pyran-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-pyrido[3,4-d]pyrimidine;   5-Cyclobutyl-2-(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Cyclobutyl-2-[2-(1-phenyl-cyclopropyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Cyclobutyl-2-(2-difluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   {5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(1-isopropyl-piperidin-4-yl)-methyl-amine;   Benzo[1,2,5]oxadiazol-5-yl-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   5-Bromo-4-piperazin-1-yl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   2-(2-tert-Butyl-H-pyrrolo[2,3-b]pyridin-4-yl)-8-chloro-5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   2-(2-tert-Butyl-H-pyrrolo[2,3-b]pyridin-4-yl)-5-cyclopropyl-8-fluoro-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Bromo-2-(2-tert-butyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   (±)-exo-5-Cyclopropyl-2-[2-(7-oxa-bicyclo[2.2.1]hept-2-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   (±)-exo-5-Cyclobutyl-2-[2-(7-oxa-bicyclo[2.2.1]hept-2-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   {5-Cyclopropyl-2-[2-(2,6-difluoro-phenylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-[1-(2,2-difluoro-ethyl)-piperidin-4-yl]-methyl-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-indan-5-yl-amine;   (5-Cyclopropyl-3,6-difluoro-pyridin-2-yl)-{4-[5-cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-amine;   N-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-2,2-difluoro-2-phenyl-acetamide;   5-Cyclopropyl-2-[2-(1-fluoro-cyclopropyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   {4-[5-Cyclopropyl-4-(1-methyl-piperidin-4-ylsulfanyl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(2,6-difluoro-phenyl)-amine;   {5-Cyclopropyl-2-[2-(3,5-difluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-(1-methyl-piperidin-4-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-phenyl]-amine;   {4-[5-Cyclopropyl-4-(hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-phenyl-amine;   {4-[5-Cyclopropyl-4-(hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(3, 5-difluoro-pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2-trifluoromethyl-benzooxazol-5-yl)-amine;   5-Cyclopropyl-4-(piperidin-4-ylsulfanyl)-2-(2-trifluoromethyl-1H-pyrrolo[2, 3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidine;   (±)-endo-2-(2-Bicyclo[2.2.1]hept-2-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-5-cyclobutyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   [8-Chloro-5-cyclopropyl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-methyl-piperidin-4-yl-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amine;   {5-Cyclopropyl-2-[2-([D3-4]uinolin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-piperidin-4-yl-amine;   [5-Cyclopropyl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-methyl-piperidin-4-ylmethyl-amine;   (1S,2R)-1-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-indan-2-ol;   (1S,2S)-1-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-indan-2-ol;   (1R,2S)-1-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-indan-2-ol;   (1R,2R)-1-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-indan-2-ol;   5-Cyclobutyl-2-[2-(2,6-difluoro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Cyclopropyl-2-[2-(2,6-difluoro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   2-(2-Cyclobutyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Cyclobutyl-2-(2-cyclobutyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   [4-(8-Chloro-5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,5-difluoro-pyridin-2-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3-methyl-3H-benzoimidazol-5-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[4-(2,2,2-trifluoro-ethoxy)-phenyl]-amine;   {2-[2-(5-Chloro-3-fluoro-pyridin-2-ylamino)-pyridin-4-yl]-5-cyclopropyl-pyrido[3,4-d]pyrimidin-4-yl}-methyl-piperidin-4-yl-amine;   5-Cyclopropyl-2-(2-cyclohexyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Cyclobutyl-2-(2-cyclohexyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   [3-Chloro-1-(5-trifluoromethyl-pyridin-2-yl)-1H-pyrazol-4-yl]-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [5-Cyclopropyl-2-(2-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrido[3,4-d]pyrimidin-4-yl]-(3,3-difluoro-piperidin-4-yl)-amine;   {5-Cyclopropyl-2-[2-(3,5-difluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(3,3-difluoro-piperidin-4-yl)-amine;   {5-Cyclobutyl-2-[2-(3,5-difluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-piperidin-4-yl-amine;   trans-2-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-indan-1-ol;   (R)-2-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-2-phenyl-ethanol;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-((R)-1-naphthalen-2-yl-ethyl)-amine;   [4-(5-Cyclobutyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[(R)-1-(2-fluoro-phenyl)-ethyl]-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(4-trifluoromethoxy-phenyl)-amine;   {5-Cyclobutyl-2-[2-(3,5,6-trifluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-piperidin-4-yl-amine;   (S)-2-[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-ylamino]-2-phenyl-ethanol;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-((R)-1-naphthalen-1-yl-ethyl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,2-difluoro-2-phenyl-ethyl)-amine;   {5-Cyclopropyl-2-[2-(3,5-difluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-piperidin-4-ylmethyl-amine;   {5-Cyclopropyl-2-[2-(3,5-difluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(tetrahydro-pyran-4-yl)-amine;   {8-Chloro-5-cyclopropyl-2-[2-(3,5,6-trifluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-piperidin-4-yl-amine;   {8-Chloro-5-cyclopropyl-2-[2-(3,5-difluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-piperidin-4-yl-amine;   (5-Chloro-3-fluoro-pyridin-2-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   {5-Cyclopropyl-2-[2-(3,5-difluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-(tetrahydro-pyran-4-yl)-amine;   (4-{5-Cyclopropyl-4-[3-(tetrahydro-pyran-4-yl)-pyrrolidin-1-yl]-pyrido[3,4-d]pyrimidin-2-yl}-pyridin-2-yl)-(3,5-difluoro-pyridin-2-yl)-amine;   {5-Cyclopropyl-2-[2-(3,5-difluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(4-methyl-piperidin-4-yl)-amine;   {5-Cyclopropyl-2-[2-(3,5-difluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(3,3-dimethyl-piperidin-4-yl)-amine;   {5-Cyclopropyl-2-[2-(3,5,6-trifluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(3,3-dimethyl-piperidin-4-yl)-amine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,3-dimethyl-indan-1-yl)-amine;   [4-(8-Chloro-5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,5,6-trifluoro-pyridin-2-yl)-amine;   5-Cyclopropyl-2-[2-(3-fluoro-pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Cyclobutyl-2-[2-(3-fluoro-pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Cyclobutyl-2-[2-(1-phenyl-cyclobutyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Cyclobutyl-4-piperazin-1-yl-2-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-pyrido[3,4-d]pyrimidine;   5-Cyclobutyl-4-piperazin-1-yl-2-[2-(1-trifluoromethyl-cyclobutyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-pyrido[3,4-d]pyrimidine;   5-Cyclobutyl-4-piperazin-1-yl-2-[2-(tetrahydro-furan-3-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-pyrido[3,4-d]pyrimidine;   5-Cyclobutyl-4-piperazin-1-yl-2-[2-(tetrahydro-furan-2-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-pyrido[3,4-d]pyrimidine;   {5-Cyclopropyl-2-[2-(3,5-difluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(3-fluoro-piperidin-4-yl)-amine;   [4-(5,8-Dicyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,5,6-trifluoro-pyridin-2-yl)-amine;   [4-(5,8-Dicyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,5-difluoro-pyridin-2-yl)-amine;   [4-(5,8-Dicyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(2,6-difluoro-phenyl)-amine;   2-(2-tert-Butyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-5,8-dicyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(6-fluoro-pyridazin-3-yl)-amine;   5-Cyclopropyl-4-piperazin-1-yl-2-[2-(tetrahydro-furan-3-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-pyrido[3,4-d]pyrimidine;   (2,6-Difluoro-phenyl)-[4-(4-piperazin-1-yl-5-trifluoromethyl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   (3,5-Difluoro-pyridin-2-yl)-[4-(4-piperazin-1-yl-5-trifluoromethyl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;   [4-(4-Piperazin-1-yl-5-trifluoromethyl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(3,5,6-trifluoro-pyridin-2-yl)-amine;   {5-Cyclopropyl-2-[2-(3,5-difluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-(3,3-dimethyl-piperidin-4-yl)-methyl-amine;   5-Cyclopropyl-2-(2,2-dimethyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   {4-[4-(3-Amino-piperidin-1-yl)-5-cyclopropyl-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(3,5-difluoro-pyridin-2-yl)-amine;   4-(5-Cyclobutyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-b]indole;   6-Chloro-4-(5-cyclobutyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-9H-pyrido[2,3-b]indole;   5-Cyclopropyl-2-[2-(2-fluoro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   2-[2-(2-Chloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   5-Cyclobutyl-2-[2-(2-fluoro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   2-[2-(2-Chloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-5-cyclobutyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   {4-[5-Cyclopropyl-4-(3-methylamino-piperidin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(3,5-difluoro-pyridin-2-yl)-amine;   N-{5-Cyclopropyl-2-[2-(3,5-difluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-N′-methyl-benzene-1,4-diamine;   5-Cyclopropyl-4-piperazin-1-yl-2-[2-(1-trifluoromethyl-cyclobutyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-pyrido[3,4-d]pyrimidine;   4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-b]indole;   2-(3-Chloro-2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidine;   [4-(5-Cyclobutyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-(tetrahydro-pyran-4-yl)-amine;   4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-3,3-dimethyl-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one;
 
or a salt thereof.