# Patent

## Title
Combination therapies comprising quinoxaline inhibitors of P13K-alpha for use in the treatment of cancer

## Abstract

The present invention provides methods of treating cancer by administering a compound of Formula I, optionally as a pharmaceutically acceptable salt, solvate and/or hydrate thereof, in combination with other cancer treatments.

## Background
This application is a US national phase of international application PCT/US2008/004570 filed on Apr. 8, 2008, which claims priority to U.S. Provisional Patent Application Ser. No. 60/923,164 filed on Apr. 11, 2007, the disclosures of which are incorporated herein by reference.
CROSS-REFERENCE TO RELATED APPLICATIONS
The Applicants claim priority under 35 U.S.C. 119(e) to copending Provisional Application No. 60/923,164 filed on Apr. 11, 2007, the disclosure of which is incorporated herein by reference in its entirety.


FIELD OF THE INVENTION
This invention relates to methods of treating cancer with a compound that inhibits lipid kinase enzymatic activity and the resultant modulation of cellular activities (such as proliferation, differentiation, programmed cell death, migration, chemoinvasion and metabolism) in combination with anticancer agents.
BACKGROUND OF THE INVENTION
Improvements in the specificity of agents used to treat various disease states such as cancer, metabolic, and inflammatory diseases is of considerable interest because of the therapeutic benefits which would be realized if the side effects associated with the administration of these agents could be reduced. Traditionally, dramatic improvements in the treatment of cancer are associated with identification of therapeutic agents acting through novel mechanisms.
Phosphatidylinositol 3-kinase (PI3K or PIK3CA) is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. PTEN, a tumor suppressor which inhibits cell growth through multiple mechanisms, can dephosphorylate PIP3, the major product of PIK3CA. PIP3, in turn, is required for translocation of protein kinase B (AKT1, PKB) to the cell membrane, where it is phosphorylated and activated by upstream kinases. The effect of PTEN on cell death is mediated through the PIK3CA/AKT1 pathway.
PI3Kα has been implicated in the control of cytoskeletal reorganization, apoptosis, vesicular trafficking, proliferation and differentiation processes. Increased copy number and expression of PIK3CA or activating mutations in the p110a catalytic subunit of PIK3CA are associated with a number of malignancies such as ovarian cancer (Campbell et al., Cancer Res 2004, 64, 7678-7681; Levine et al., Clin Cancer Res 2005, 11, 2875-2878; Wang et al., Hum Mutat 2005, 25, 322; Lee et al., Gynecol Oncol 2005, 97, 26-34), cervical cancer, breast cancer (Bachman, et al. Cancer Biol Ther 2004, 3, 772-775; Levine, et al., supra; Li et al., Breast Cancer Res Treat 2006, 96, 91-95; Saal et al., Cancer Res 2005, 65, 2554-2559; Samuels and Velculescu, Cell Cycle 2004, 3, 1221-1224), colorectal cancer (Samuels, et al. Science 2004, 304, 554; Velho et al. Eur J Cancer 2005, 41, 1649-1654), endometrial cancer (Oda et al. Cancer Res. 2005, 65, 10669-10673), gastric carcinomas (Byun et al., Int J Cancer 2003, 104, 318-327; Li et al., supra; Velho et al., supra; Lee et al., Oncogene 2005, 24, 1477-1480), hepatocellular carcinoma (Lee et al., id.), small and non-small cell lung cancer (Tang et al., Lung Cancer 2006, 51, 181-191; Massion et al., Am J Respir Crit. Care Med 2004, 170, 1088-1094), thyroid carcinoma (Wu et al., J Clin Endocrinol Metab 2005, 90, 4688-4693), acute myelogenous leukemia (AML) (Sujobert et al., Blood 1997, 106, 1063-1066), chronic myelogenous leukemia (CML) (Hickey and Cotter J Biol Chem 2006, 281, 2441-2450), and glioblastomas (Hartmann et al. Acta Neuropathol (Berl) 2005, 109, 639-642; Samuels et al., supra).
In view of the important role of PI3K-α in biological processes and disease states, inhibitors and/or modulators of this lipid kinase are desirable. In addition, it is well established that combining treatments with different mechanisms of action often leads to enhanced anti-tumor activity as compared to single treatments administered alone. This is true for combinations of chemotherapies (e.g. Kyrgiou M. et. al. J Natl Cancer Inst 2006, 98, 1655) and combinations of antibodies and chemotherapy (e.g. Pasetto L M et. al. Anticancer Res 2006, 26, 3973.
For example, activation of the PI3K pathway contributes to the resistance of human tumor cells to a wide variety of chemotherapeutic agents, including microtubule stabilizing agents such as taxol (Brognard, J., et. al. Cancer Res 2001, 61, 3986-3997; Clark, A. S., et. al. Mol Cancer Ther 2002, 1, 707-717; Kraus, A. C., et. al. Oncogene 2002, 21, 8683-8695; Krystal, G. W., et. al. Mol Cancer Ther 2002, 1, 913-922; and Yuan, Z. Q., et. al. J Biol Chem 2003, 278, 23432-23440). Taxol is widely used to treat advanced cancers including prostate carcinomas, which frequently harbor deletions in the PTEN gene, resulting in elevated signaling downstream of PI3K. A number of preclinical studies suggest that inhibiting signaling downstream of PI3K restores or enhances the ability of chemotherapeutic agents such as taxol to kill tumor cells (Brognard, J., et. al. Cancer Res 2001, 61, 3986-3997; Clark, A. S., et. al. Mol Cancer Ther 2002, 1, 707-717; Kraus, A. C., et. al. Oncogene 2002, 21, 8683-8695; Krystal, G. W., et. al. Mol Cancer Ther 2002, 1, 913-922; and Saga, Y., et. al. Clin Cancer Res 2002, 8, 1248-1252).
Rapamycin, another chemotherapeutic agent, is a potent inhibitor of the mTOR/Raptor complex. Inhibition of mTOR/Raptor prevents p70S6K and S6 phosphorylation, but also leads to relief of a negative feedback loop emanating from p70S6K that serves to downregulate PI3K (Sarbassov, D. D., et. al. Science 2005, 307, 1098-1101). As a result, rapamycin treatment can lead to upregulation of PI3K and increased phosphorylation of AKT (O'Donnell, A., et. al. paper presented at Proc Am Soc Clin Oncol. 2003; and O'Reilly, K. E., et. al. Cancer Res 2006, 66, 1500-1508). Thus, combining rapamycin with inhibitors of PI3K can enhance the efficacy of rapamycin (Powis, G. et. al. Clinical Cancer Research 2006, 12, 2964-2966; Sun, S.-Y., et. al. Cancer Research 2005, 65, 7052-7058).
A growing body of clinical and preclinical data indicates that activation of the PI3K pathway confers resistance to EGFR inhibitors such as erlotinib (Bianco, R., et. al. Oncogene 2003, 22, 2812-2822; Chakravarti, A., et. al. Cancer Res 2002, 62, 200-207; and Janmaat, M. L., et. al. Clin Cancer Res 2003, 9, 2316-2326). Both NSCLC patients with K-Ras mutations and glioblastoma patients with PTEN deletions fail to respond to erlotinib, potentially because of genetic activation of the PI3K pathway (Mellinghoff, I. K., et. al. N. Eng. J Med. 2006, 353, 2012-2024). Preclinical studies have shown that downregulation of PI3K signaling in EGFR-expressing tumor cells confers increased sensitivity to EGFR inhibitors (Ihle, N. T., et. al. Mol Cancer Ther 2005, 4, 1349-1357). Thus, treating cancer with a PI3K inhibitor in combination with an EGFR inhibitor, such as erlotinib, is desirable.
Activation of the PI3K pathway also contributes to the resistance of human tumor cells to DNA damaging agents, such as platins. A number of preclinical studies suggest that inhibiting signaling downstream of PI3K restores or enhances the ability of chemotherapeutic agents such as platins to kill tumor cells (Brognard, J., et. al. Cancer Res 2001, 61, 3986-3997; and Yuan, Z. Q., et. al. J Biol Chem 2003, 278, 23432-23440). Carboplatin is widely used to treat advanced cancers including non-small cell lung carcinomas (NSCLC), which frequently harbor activating mutations in the K-Ras gene, resulting in activation of PI3K (Aviel-Ronen S., et. al. Clin Lung Cancer 2006, 8, 30-38). NSCLC patients with K-Ras mutations do not respond to EGFR inhibitors such as Tarceva, and thus represent a significant unmet medical need (Janne P A, et. al. J Clin Oncology 2005, 23, 3227-3234). Thus, treating NSCLC with a DNA-damaging agent such as a platin in combination with an inhibitor of PI3K is desirable in light of the lack of efficacious treatments.
Treatments that combine an inhibitor of PI3K-α with other anti-cancer agents are desirable and needed.
SUMMARY OF THE INVENTION
The following only summarizes certain aspects of the invention and is not intended to be limiting in nature. These aspects and other aspects and embodiments are described more fully below. All references cited in this specification are hereby incorporated by reference in their entirety. In the event of a discrepancy between the express disclosure of this specification and the references incorporated by reference, the express disclosure of this specification shall control.
The compositions of the invention are used to treat diseases associated with abnormal and or unregulated cellular activities. Disease states which can be treated by the methods and compositions provided herein include cancer. The invention is directed to methods of treating these diseases by administering a Compound of Formula I or II in combination with one or more treatments.
One aspect of the Invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a compound of Formula I:




or a single isomer thereof where the compound is optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof; or administering a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I and a pharmaceutically acceptable carrier, excipient, or diluent in combination with one or more treatments independently selected from surgery, one or more chemotherapeutic agents, one or more hormone therapies, one or more antibodies, one or more immunotherapies, radioactive iodine therapy, and radiation, where the Compound of Formula I is that wherein:

    W1, W2, W3, and W4 are —C(R1)═; or one or two of W1, W2, W3, and W4 are independently —N═ and the remaining are —C(R1)═; and where each R1 is independently hydrogen, alkyl, haloalkyl, nitro, alkoxy, haloalkoxy, halo, hydroxy, cyano, amino, alkylamino, or dialkylamino;
    R51 is hydrogen or alkyl;
    R52 is hydrogen or halo;
    R50, R53, and R54 are independently hydrogen, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, hydroxy, alkoxy, alkenyloxy, haloalkoxy, nitro, amino, alkylamino, dialkylamino, —N(R55)C(O)—C1-C6-alkylene-N(R55a)R55b, alkylcarbonyl, alkenylcarbonyl, carboxy, alkoxycarbonyl, cyano, alkylthio, —S(O)2NR55R55a, or alkylcarbonylamino and where R55 and R55b are independently hydrogen, alkyl, or alkenyl and R55a is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy; or R53 and R54 together with the carbons to which they are attached form a 5- or 6-membered heteroaryl or 5- or 6-membered heterocycloalkyl;
    B is phenyl substituted with R3a and optionally further substituted with one, two, or three R3; or
    B is heteroaryl optionally substituted with one, two, or three R3;
    R3a is cyano; hydroxyamino; carboxy; alkoxycarbonyl; alkylamino; dialkylamino; alkylcarbonyl; haloalkoxy; alkylsulfonyl; aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; or
    
        a) —N(R7)C(O)—C1-C6-alkylene-N(R7a)(R7b) where R7 is hydrogen, alkyl, or alkenyl and R7a and R7b are independently hydrogen, alkyl, alkenyl, hydroxyalkyl, haloalkyl, alkoxy, alkoxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, arylalkyl, or arylalkyloxy and where the aryl, cycloalkyl, heterocycloalkyl and heteroaryl rings in R7a and R7b (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, amino, alkylamino, dialkylamino, hydroxy, halo, alkoxy, alkylthio, and oxo);
        b) —C(O)NR8R8a where R8 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or haloalkoxy and R8a is hydrogen, alkyl, alkenyl, hydroxyalkyl, cyanoalkyl, alkoxyalkyl, alkylthioalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, or arylalkyl and where the aryl, cycloalkyl, heteroaryl, and heterocycloalkyl rings in R8a (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, alkenyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, oxo, amino, alkylamino, dialkylamino, alkylcarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxycarbonyl, and —C(O)H;
        c) —NR9C(O)R9a where R9 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or haloalkoxy and R9a is hydrogen, C2-C6-alkyl, alkenyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, or arylalkyl; where the aryl, cycloalkyl, heteroaryl, and heterocycloalkyl rings in R9a (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, alkenyl, alkoxy, hydroxy, hydroxyalkyl, halo, haloalkyl, haloalkoxy, oxo, amino, alkylamino, dialkylamino, alkylcarbonyl, alkoxycarbonyl, —C(O)H, aryl (optionally substituted with one or two halo), arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, cyloalkyl, cyloalkylalkyl, and cycloalkylcarbonyl;
        d) —C(O)N(R10)—C1-C6-alkylene-N(R10a)R10b where R10a is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, or hydroxyalkyl and R10 and R10b are independently hydrogen, alkyl, alkenyl, haloalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, or hydroxyalkyl;
        e) —NR11C(O)NR11aR11b where R11a is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy and R11 and R11b are independently hydrogen, alkyl, alkenyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl;
        f) —C(O)R12 where R12 is heterocycloalkyl optionally substituted with 1, 2, or 3 groups selected from alkyl, oxo, amino, alkylamino, and heterocycloalkylalkyl;
        g) —NR13C(O)OR13a where R13 is hydrogen, alkyl, or alkenyl and R13a is aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aryl, or arylalkyl;
        h) —C(O)N(R14)N(R14a)(R14b) where R14, R14a, and R14b are independently hydrogen, alkyl, or alkenyl;
        i) —S(O)2N(R15)—C1-C6-alkylene-N(R15a)R15b where R15, R15a, and R15b are independently hydrogen, alkyl, or alkenyl;
        j) —C(O)N(R16)—C1-C6-alkylene-C(O)OR16a where R16 is hydrogen, alkyl, or alkenyl and R16a is alkyl or alkenyl;
        k) heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl;
        l) —N(R17)—C(═N(R17b)(R17a))(NR17cR17d) where R17, R17a, R17b, R17c, and R17d are independently hydrogen, alkyl, or alkenyl;
        m) —N(R18)C(O)—C1-C6-alkylene-N(R18b)C(O)R18a where R18a is hydrogen, alkyl, alkenyl, or alkoxy and R18 and R18b are independently hydrogen, alkyl, or alkenyl;
        n) —C(O)N(R19)—C1-C6-alkylene-C(O)R19a where R19 is hydrogen, alkyl, or alkenyl and R19a is amino, alkylamino, dialkylamino, or heterocycloalkyl;
        o) —N(R20)C(O)—C1-C6-alkylene-C(O)R20a where R20 is hydrogen, alkyl, or alkenyl and R20a is cycloalkyl or heterocycloalkyl;
        p) —NR21S(O)2—C1-C6-alkylene-N(R21b)R21a where R21 is hydrogen, alkyl, or alkenyl and R21a and R21b are independently hydrogen, alkyl, or alkenyl;
        q) —N(R22)C(O)—C1-C6-alkylene-N(R22b)—N(R22c)(R22a) where R22, R22a and R22b are independently hydrogen, alkyl, or alkenyl;
        r) —C0-C6-alkylene-N(R23)—C1-C6-alkylene-N(R23b)R23a where R23, R23a and R23b are independently hydrogen, alkyl, or alkenyl; or
        s) —NR24C(O)—C1-C6-alkylene-OR24a where R24 is hydrogen, alkyl, or alkenyl and R24a is alkoxyalkyl or aryl optionally substituted with one or two halo or alkyl; and
    
    
    where each of the alkylene in R3a is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, amino, alkylamino, and dialkylamino; and
    each R3 (when R3 is present) is independently alkyl; alkenyl; alkynyl; halo; hydroxy; oxo; alkoxy; cyano; hydroxyamino; carboxy; alkoxycarbonyl; amino; alkylamino; dialkylamino; alkylcarbonyl; haloalkoxy; alkylsulfonyl; aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; or
    
        a) —N(R7)C(O)—C1-C6-alkylene-N(R7a)(R7b) where R7 is hydrogen, alkyl, or alkenyl and R7a and R7b are independently hydrogen, alkyl, alkenyl, hydroxyalkyl, haloalkyl, alkoxy, alkoxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, arylalkyl, or arylalkyloxy and where the aryl, cycloalkyl, heterocycloalkyl and heteroaryl rings in R7a and R7b (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, amino, alkylamino, dialkylamino, hydroxy, halo, alkoxy, alkylthio, and oxo);
        b) —C(O)NR8R8a where R8 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or haloalkoxy and R8a is hydrogen, alkyl, alkenyl, hydroxyalkyl, cyanoalkyl, alkoxyalkyl, alkylthioalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, or arylalkyl and where the aryl, cycloalkyl, heteroaryl, and heterocycloalkyl rings in R8a (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, alkenyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, oxo, amino, alkylamino, dialkylamino, alkylcarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxycarbonyl, and —C(O)H;
        c) —NR9C(O)R9a where R9 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or haloalkoxy and R9a is hydrogen, C2-C6-alkyl, alkenyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, or arylalkyl; where the aryl, cycloalkyl, heteroaryl, and heterocycloalkyl rings in R9a (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, alkenyl, alkoxy, hydroxy, hydroxyalkyl, halo, haloalkyl, haloalkoxy, oxo, amino, alkylamino, dialkylamino, alkylcarbonyl, alkoxycarbonyl, —C(O)H, aryl (optionally substituted with one or two halo), arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, cyloalkyl, cyloalkylalkyl, and cycloalkylcarbonyl;
        d) —C(O)N(R10)—C1-C6-alkylene-N(R10a)R10b where R10a is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or hydroxyalkyl and R10 and R10b are independently hydrogen, alkyl, alkenyl, haloalkyl, or hydroxyalkyl;
        e) —NR11C(O)NR11aR11b where R11a is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy and R11 and R11b are independently hydrogen, alkyl, alkenyl, aminoalkyl, alkylaminooalkyl, dialkylaminoalkyl;
        f) —C(O)R12 where R12 is heterocycloalkyl optionally substituted with 1, 2, or 3 groups selected from alkyl, oxo, amino, alkylamino, and heterocycloalkylalkyl;
        g) —NR13C(O)OR13a where R13 is hydrogen, alkyl, or alkenyl and R13a is aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aryl, or arylalkyl);
        h) —C(O)N(R14)N(R14a)(R14b) where R14, R14a, and R14b are independently hydrogen, alkyl, or alkenyl;
        i) —S(O)2N(R15)—C1-C6-alkylene-N(R15a)R15b where R15, R15a, and R15b are independently hydrogen, alkyl, or alkenyl;
        j) —C(O)N(R16)—C1-C6-alkylene-C(O)OR16a where R16 is hydrogen, alkyl, or alkenyl and R16a is alkyl or alkenyl;
        k) heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl;
        l) —N(R17)—C(═N(R17b)(R17a))(NR17cR17d) where R17, R17a, R17b, R17c, and R17d are independently hydrogen, alkyl, or alkenyl;
        m) —N(R18)C(O)—C1-C6-alkylene-N(R18b)C(O)R18a where R18a is hydrogen, alkyl, alkenyl, or alkoxy and R18 and R18b are independently hydrogen, alkyl, or alkenyl;
        n) —C(O)N(R19)—C1-C6-alkylene-C(O)R19a where R19 is hydrogen, alkyl, or alkenyl and R19a is amino, alkylamino, dialkylamino, or heterocycloalkyl;
        o) —N(R20)C(O)—C1-C6-alkylene-C(O)R20a where R20 is hydrogen, alkyl, or alkenyl and R20a is cycloalkyl or heterocycloalkyl;
        p) —NR21S(O)2—C1-C6-alkylene-N(R21b)R21a where R21 is hydrogen, alkyl, or alkenyl and R21a and R21b are independently hydrogen, alkyl, or alkenyl;
        q) —N(R22)C(O)—C1-C6-alkylene-N(R22b)—N(R22c)(R22a), where R22, R22a and R22b are independently hydrogen, alkyl, or alkenyl;
        r) —C0-C6-alkylene-N(R23)—C1-C6-alkylene-N(R23b)R23a where R23, R23a and R23b are independently hydrogen, alkyl, or alkenyl; or
        s) —NR24C(O)—C1-C6-alkylene-OR24a where R24 is hydrogen, alkyl, or alkenyl and R24a is alkoxyalkyl or aryl optionally substituted with one or two halo or alkyl;
    
    
    wherein each of the alkylene in R3 is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, amino, alkylamino, and dialkylamino; and
    provided that when R50 and R52 are hydrogen, R51 is hydrogen or methyl, R53 is hydrogen or methoxy, and R54 is hydrogen or methoxy, then B is not 2,3-dihydro-1,4-benzodioxinyl, thien-2-yl, or thien-2-yl substituted with one R3 where R3 is halo.


A second aspect of the Invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a compound of Formula II:




or a pharmaceutically acceptable salt or solvate, thereof; or administering a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula II and a pharmaceutically acceptable carrier, excipient, or diluent in combination with one or more treatments independently selected from surgery, one or more chemotherapeutic agents, one or more of the hormone therapies, one or more of the antibodies, one or more immunotherapies, radioactive iodine therapy, and radiation wherein the Compound of Formula I is that wherein:

    W1, W2, W3, and W4 are —C(R1a)═; or one or two of W1, W2, W3, and W4 are independently —N═ and the remaining are —C(R1a)═;
    X1 is —N(R5a)—;
    A is aryl, —S(O)2-aryl, heteroaryl, cycloalkyl, heterocycloalkyl, halo, haloalkyl, haloalkoxy, alkyl, alkoxy, or -alkyl-N(R7)R7a, where each of the aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkyl and alkoxy groups, each either alone or as part of another group within A, are independently optionally substituted with one, two, three, or four R2a; or
    B1 is aryl, arylalkyl, alkyl, heteroaryl, or heteroaryalkyl, wherein each of the aryl, heteroaryl and alkyl groups are independently optionally substituted with one, two, three, or four R3d;
    each R1a is independently selected from hydrogen, alkoxy, alkyl, nitro, halo, cyano, and —C0-C6-alkyl-N(R7)R7a, wherein each of the alkyl and alkoxy groups is optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, alkoxy, halo, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, —N(R8)R8a, and —C(O)OR6;
    each R2a (when R2a is present) is independently selected from alkyl, alkenyl, -alkenyl-C(O)OR6, —OR6, —N(R7)C(O)R6, —N(R7)C(O)—C0-C6 alkyl-N(R7b)R7a, —OC(O)—C0-C6 alkyl-N(R7)R7a, —N(R7)C(O)—C1-C6 alkylC(O)OR6, C0-C6-alkyl-C(O)R6, oxo, dioxo, —S(O)2—N(R7)R7a, —C(O)OR6, —CH(R6)2—C(O)OR6, —S(O)2R6, cycloalkyl, heterocycloalkyl, heteroaryl, —C(O)N(R7)-alkyl-OR6, —C0-C6 alkyl-C(O)N(R7)—C0-C6-alkyl-C(O)OR6, —C0-C6-alkyl-C(O)N(R7)R7a, aryl, arylalkyl, —S—(C1-C6 alkyl), halo, oxo, nitro, —SCN, cyano, and —C0-C6 alkyl-N(R7)R7a, wherein each of the alkyl (including, for example the alkyl within alkoxy), aryl, cycloalkyl, heterocycloalkyl, and heteroaryl groups, either alone or as part of another group within R2, is independently optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, halo, haloalkyl, haloalkoxy, oxo, nitro, cyano, hydroxy, —N(R8)R8a, alkoxy, and —C(O)OR9;
    each R3d (when R3d is present) is independently oxo, nitro, halo, cyano, alkyl, alkenyl, alkynyl, alkoxy, C3-C6-cycloalkyl, —C0-C6-alkyl-heterocycloalkyl, —C0-C6 alkyl-N(R7)C(O)—C0-C6-alkyl-N(R7b)R7a, —C0-C6 alkyl-N(R7)C(O)—C0-C6-alkyl-N(R7b)C(O)R7a, —C0-C6 alkyl-C(O)—C0-C6-alkyl-N(R7)R7a, —C0-C6-alkyl-C(O)N(R7)—C0-C6-alkyl-N(R7b)R7a, —C0-C6-alkyl-C(O)N(R7)—C1-C6alkylC(O)OR7a, —C0-C6 alkyl-N(R7)C(O)—C0-C6-alkyl-(R7a), —C0-C6 alkyl-N(R7)—C0-C6-alkyl-N(R7b)R7a, —C0-C6 alkyl-N(R7)C(O)—C0-C6-alkyl-N(R7b)—N(R7c)R7a, —C0-C6 alkyl-N(R7)C(O)O—C0-C6-alkyl-aryl, —C0-C6 alkyl-C(O)N(R7)—C0-C6-alkyl-N(R7b)R7a, —C0-C6 alkyl-N(R7)—C0-C6 alkyl-C(═N(R7b)(R7a))(NR7cR7d), —C0-C6-alkyl-aryl, —C0-C6-alkyl-heteroaryl, —C0-C6 alkyl-heterocycloalkyl, —O—C0-C6 alkyl-N(R7)R7a, —C0-C6 alkyl-OR6, —C0-C6 alkyl-C(O)OR6, C0-C6-alkyl-N(R7)R7a, —C0-C6 alkyl-C(O)NR7R7a, —C0-C6 alkyl-C(O)R7, —SRS, —S(O)2R7, —S(O)3R7, —S(O)R7, —SO2N(R7)R7a, —SO2N(R7)—C0-C6-alkyl-N(R7b)R7a, —C0-C6-alkyl-N(R7)-aryl, —C0-C6-alkyl-N(R7)-heteroaryl, —C0-C6-alkyl-N(R7)— heterocycloalkyl, —C0-C6-alkyl-C(O)N(R7)—C0-C6-alkyl-cycloalkyl, C0-C6-alkyl-C(O)N(R7)—C0-C6-alkyl-aryl, C0-C6 alkyl-C(O)N(R7)—C0-C6 alkyl-heteroaryl, C0-C6-alkyl-C(O)N(R7)—C0-C6-alkyl-heterocycloalkyl, —C0-C6-alkyl-N(R7)C(O)—C0-C6-alkyl-cycloalkyl, —C0-C6-alkyl-N(R7)C(O)—C0-C6-alkyl-aryl, C0-C6-alkyl-N(R7)C(O)—C0-C6-alkyl-heteroaryl, —C0-C6-alkyl-N(R7)C(O)—C0-C6-alkyl-heterocycloalkyl, C0-C6-alkyl-N(R7)C(O)—C0-C6-alkyl-heterocycloalkyl-aryl, —N(R7)C(O)OR6, or —NHC(O)H, wherein each of the alkyl, alkenyl, cycloalkyl, aryl, (including, for example the alkyl within alkoxy), heterocycloalkyl, and heteroaryl groups, either alone or as part of another group within R3d, is independently optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, alkenyl, cycloalkyl, halo, haloalkyl, haloalkoxy, —C(O)R9, nitro, cyano, oxo, —C0-C6-alkyl-N(R8)R8a, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —C(O)OR9, alkylthio, and hydroxyalkyl;
    R4 is hydrogen, aryl, —C0-C6-alkyl-N(R7)R7a, alkoxy, or C1-C6 alkyl, wherein each of the alkyl and aryl groups, either alone or as part of another group in R4, is independently optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, halo, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, —N(R8)R8a, alkoxy, and —C(O)OR6; or
    R4 and X1 together with the atoms to which they are attached form a heterocycloalkyl or heteroaryl group, wherein R5a is absent when X is —N(R5a)—, wherein each of the heterocycloalkyl or heteroaryl is optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, halo, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, —N(R7)R7a, alkoxy, and —C(O)OR6;
    R5a is hydrogen, —C1-C6 alkyl-N(R7)R7a, alkoxy, alkyl, or aryl, wherein each of the alkyl and aryl is optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, halo, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, —N(R8)R8a, C1-C6 alkoxy, or —C(O)OR6; or
    R5a and R4 together with the atoms to which they are attached form a heterocycloalkyl or heteroaryl group, wherein the heterocycloalkyl and heteroaryl is optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, halo, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, —N(R7)R7a, C1-C6 alkoxy, and —C(O)OR6;
    R6 and R9 are independently hydrogen, hydroxy, alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, or aryl, each alkyl, aryl, cycloalkyl, heterocycloalkyl, and heteroaryl, either alone or as part of another group within R6 and R9, is independently optionally substituted with 1, 2, 3, 4, or 5 groups independently selected from amino, hydroxy, alkoxy, alkyl, and halo; and
    R7, R7a R7b, R7c, R7d, R8, and R8a are independently hydrogen, alkyl, alkenyl, hydroxy, alkyloxy, alkenyloxy, —O—C0-C6 alkyl-aryl, —C0-C6 alkyl-C(O)OR6, —C0-C6 alkyl-C(O)R6, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, or heterocycloalkylalkyl, wherein each of the alkyl, aryl, heteroaryl, and heterocycloalkyl, either alone or part of another group within R7, R7a R7b, R7c, R7d, R8, and R8a is independently optionally substituted with 1, 2, 3, 4, or 5 groups selected from amino, alkylamino, dialkylamino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, —S—C1-C6 alkyl, cyano, nitro, hydroxy, C1-C6 alkoxy, C1-C6 alkyl, halo, aryl, heterocycloalkylalkyl, and heteroaryl optionally substituted with one or two C1-C6 alkyl.





FIG. 1 illustrates tumor growth inhibition after treatment with Compound A, a PI3K inhibitor, as a single agent and regression after treatment with Compound A in combination with taxol in a PC-3 prostate carcinoma tumor model.
FIG. 2 illustrates tumor growth inhibition after treatment with Compound A, a PI3K inhibitor, as a single agent and regression after treatment with Compound A in combination with rapamycin in a PC-3 prostate carcinoma tumor model.
FIG. 3 illustrates tumor growth inhibition after treatment with Compound A, a PI3K inhibitor, as a single agent as well as in combination with carboplatin in a Calu-6 non-small cell lung cancer tumor model.
FIG. 4a illustrates tumor growth inhibition after treatment with Compound A, a PI3K inhibitor, as a single agent and regression after treatment with Compound A in combination with Compound B, an EGFR inhibitor, in an A549 non-small cell lung cancer tumor model.
FIG. 4b-1 illustrates tumor growth inhibition after treatment with Compound A, a PI3K inhibitor, as a single agent and regression after treatment with Compound A in combination with Compound B, an EGFR inhibitor, in an MCF7 breast cancer tumor model (Study 1).
FIG. 4b-2 illustrates tumor growth inhibition after treatment with Compound A, a PI3K inhibitor, as a single agent and regression after treatment with Compound A in combination with Compound B, an EGFR inhibitor, in an MCF7 breast cancer tumor model (Study 2).
FIG. 5 illustrates tumor growth inhibition after treatment with Compound A, a PI3K inhibitor, as a single agent and regression after treatment with Compound A in combination with Erlotinib, an EGFR inhibitor, in an MDA-MB-468 breast carcinoma tumor model.



DETAILED DESCRIPTION OF THE INVENTION
Abbreviations and Definitions
The following abbreviations and terms have the indicated meanings throughout:














Abbreviation
Meaning









br
broad



° C.
degrees Celsius



CBZ
CarboBenZoxy = benzyloxycarbonyl



d
doublet



dd
doublet of doublet



dt
doublet of triplet



EI
Electron Impact ionization



Et
Ethyl



g
gram(s)



GC
gas chromatography



h or hr
hour(s)



HPLC
high pressure liquid chromatography



L
liter(s)



M
molar or molarity



m
Multiplet



mg
milligram(s)



MHz
megahertz (frequency)



Min
minute(s)



mL
milliliter(s)



mM
Millimolar



mmol
millimole(s)



mol
mole(s)



MS
mass spectral analysis



N
normal or normality



nM
Nanomolar



NMR
nuclear magnetic resonance spectroscopy



q
Quartet



RT
Room temperature



s
Singlet



s-
Secondary



t-
Tertiary



t or tr
Triplet



TFA
trifluoroacetic acid



THF
Tetrahydrofuran



μL
microliter(s)



μM
Micromole(s) or micromolar










Definitions for a Compound of Formula I, Ia, and II
The symbol “—” means a single bond, “═” means a double bond, “≡” means a triple bond, and  means a single bond and optionally a double bond. When chemical structures are depicted or described, unless explicitly stated otherwise, all carbons are assumed to have hydrogen substitution to conform to a valence of four.
“Administration” and variants thereof (e.g., “administering” a compound) in reference to a compound of the invention means introducing the compound or a prodrug of the compound into the system of the animal in need of treatment. When a compound of the invention or prodrug thereof is provided in combination with one or more other active agents (e.g., surgery, radiation, and chemotherapy, etc.), “administration” and its variants are each understood to include concurrent and sequential introduction of the compound or prodrug thereof and other agents.
“Alkenyl” or “lower alkenyl” means a straight or branched hydrocarbon radical having from 2 to 6 carbon atoms and at least one double bond and includes ethenyl, propenyl, 1-but-3-enyl, 1-pent-3-enyl, 1-hex-5-enyl and the like.
“Alkenylcarbonyl” means a C(O)R group where R is alkenyl, as defined herein.
“Alkenyloxy” or “lower alkenyloxy” means an —OR group where R is alkenyl, as defined herein. Representative examples include methoxy, ethoxy, 1-methoxyprop-1-en-3-yl, propoxy, isopropoxy, cyclopropyloxy, cyclohexyloxy and the like.
“Alkoxy” or “lower alkoxy” means an —OR group where R is alkyl, as defined herein. Representative examples include methoxy, ethoxy, 1-methoxyprop-1-en-3-yl, propoxy, isopropoxy, cyclopropyloxy, cyclohexyloxy and the like.
“Alkoxyalkyl” means an alkyl group, as defined herein, substituted with one, two, or three alkoxy groups, as defined herein.
“Akoxycarbonyl” means a —C(O)OR group where R is alkyl as defined herein.
“Alkoxyycarbonylalkyl” means an alkyl group, as defined herein, substituted with one, two, or three alkoxycarbonyl groups, as defined herein.
“Alkyl” or “lower alkyl” means a linear or branched hydrocarbon group having one to six carbon atoms. Examples of lower alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, s-butyl, t-butyl, isobutyl, pentyl, hexyl and the like. A “C0” alkyl (as in “C0-C6-alkyl”) is a covalent bond. “C6 alkyl” refers to, for example, n-hexyl, iso-hexyl, and the like.
“Alkylamino” means a —NHR radical where R is alkyl as defined herein, or an N-oxide derivative thereof, e.g., methylamino, ethylamino, n-, iso-propylamino, n-, iso-, tert-butylamino, or methylamino-N-oxide, and the like.
“Alkylaminoalkyl” means an alkyl group substituted with one or two alkylamino groups, as defined herein.
“Alkylaminoalkyloxy” means an —OR group where R is alkylaminoalkyl, as defined herein.
“Alkylcarbonyl” means a C(O)R group where R is alkyl, as defined herein.
“Alkylcarbonylamino” means a —NRC(O)R′ group where R is hydrogen or alkyl, as defined herein, and R′ is alkyl, as defined herein.
“Alkylene” refers to straight or branched divalent hydrocarbon, containing no unsaturation and having from two to eight carbon atoms. Examples of alkylene include eth-diyl (—CH2CH2—), prop-1,3-diyl (—CH2CH2CH2—), 2,2-dimethylprop-1,3-diyl (—CH2C(CH3)2CH2—), and the like.
“Alkylsulfonyl” means a —S(O)2R group where R is alkyl, as defined herein.
“Alkylthio” means a —SR group where R is alkyl, as defined herein. Examples of alkylthio include methylthio and ethylthio, and the like.
“Alkylthioalkyl” means an alkyl group substituted with one or two alkylthio groups, as defined herein, e.g. 2-(methylthio)-ethyl and 2-(ethylthio)-ethyl.
“Alkynyl” or “lower alkynyl” means a straight or branched hydrocarbon radical having from 2 to 6 carbon atoms and at least one triple bond and includes ethynyl, propynyl, butynyl, pentyn-2-yl and the like.
“Amino” means a —NH2.
“Aminoalkyl” means an alkyl group substituted with at least one, for example one, two, or three, amino groups.
“Aminoalkyloxy” means an —OR group where R is aminoalkyl, as defined herein.
“Aryl” means a monovalent six- to fourteen-membered, mono- or bi-carbocyclic ring, wherein the monocyclic ring is aromatic and at least one of the rings in the bicyclic ring is aromatic. Representative examples include phenyl, naphthyl, and indanyl, and the like.
“Arylalkyl” means an alkyl group, as defined herein, substituted with one or two aryl groups, as defined herein. Examples include benzyl, phenethyl, phenylvinyl, phenylallyl and the like.
“Aryloxy” means a —OR group where R is aryl as defined herein.
“Arylalkyloxy” means a —OR group where R is arylalkyl as defined herein.
“Arylsulfonyl” means a —SO2R group where R is aryl as defined herein.
“Carboxyalkyl” means an alkyl group, as defined herein, substituted with one, two, or three —C(O)OH groups.
“Carboxy ester” means a —C(O)OR group where R is lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, aryl or arylalkyl, each of which is defined herein. Representative examples include methoxycarbonyl, ethoxycarbonyl, and benzyloxycarbonyl, and the like.
“Cyanoalkyl” means an alkyl, alkenyl, or alkynyl radical, as defined herein, substituted with at least one, for example one, two, or three, cyano groups.
“Cycloalkyl” means a monocyclic or polycyclic hydrocarbon radical having three to thirteen carbon atoms. The cycloalkyl can be saturated or partially unsaturated, but cannot contain an aromatic ring. Cycloalkyl includes fused, bridged, and spiro ring systems. Examples of such radicals include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
“Cycloalkylalkyl” means alkyl group substituted with one or two cycloalkyl groups, as defined herein. Representative examples include cyclopropylmethyl and 2-cyclobutyl-ethyl, and the like.
“Cycloalkylcarbonyl” means a —C(O)R group where R is cycloalkyl as defined herein.
“Dialkylamino” means a —NRR′ radical where R and R′ are independently alkyl as defined herein, or an N-oxide derivative, or a protected derivative thereof, e.g., dimethylamino, diethylamino, N,N-methylpropylamino or N,N-methylethylamino, and the like.
“Dialkylaminoalkyl” means an alkyl group substituted with one or dialkylamino groups, as defined herein.
“Dialkylaminoalkyloxy” means an —OR group where R is dialkylaminoalkyl, as defined herein.
“Fused ring system” and “fused ring” refer to a polycyclic ring system that contains bridged or fused rings; that is, where two rings have more than one shared atom in their ring structures. In this application, fused-polycyclics and fused ring systems are not necessarily all aromatic ring systems. Typically, but not necessarily, fused-polycyclics share a vicinal set of atoms, for example naphthalene or 1,2,3,4-tetrahydro-naphthalene. A spiro ring system is not a fused-polycyclic by this definition, but fused polycyclic ring systems of the invention may themselves have spiro rings attached thereto via a single ring atom of the fused-polycyclic. In some examples, as appreciated by one of ordinary skill in the art, two adjacent groups on an aromatic system may be fused together to form a ring structure. The fused ring structure may contain heteroatoms and may be optionally substituted with one or more groups. It should additionally be noted that saturated carbons of such fused groups (i.e. saturated ring structures) can contain two substitution groups.
“Haloalkoxy” means an —OR′ group where R′ is haloalkyl as defined herein, e.g., trifluoromethoxy or 2,2,2-trifluoroethoxy, and the like.
“Haloalkoxyalkyl” means an alkyl group, as defined herein, substituted with one, two, or three haloalkoxy, as defined herein.
“Halogen” or “halo” means fluoro, chloro, bromo and iodo.
“Haloalkenyl means an alkenyl group, as defined herein, substituted with one or more halogens, for example one to five halo atoms.
“Haloalkyl” means an alkyl group, as defined herein, substituted with one or more halogens, for example one to five halo atoms. Representative examples includes 2,2-difluoroethyl, trifluoromethyl, and 2-chloro-1-fluoroethyl, and the like.
“Heteroaryl” means a monocyclic, fused bicyclic, or fused tricyclic, monovalent radical of 5 to 14 ring atoms containing one or more, for example one, two, three, or four ring heteroatoms independently selected from —O—, —S(O)n—(n is 0, 1, or 2), —N—, —N(Rx)—, and the remaining ring atoms being carbon, wherein the ring comprising a monocyclic radical is aromatic and wherein at least one of the fused rings comprising a bicyclic or tricyclic radical is aromatic. One or two ring carbon atoms of any nonaromatic rings comprising a bicyclic or tricyclic radical may be replaced by a —C(O)—, —C(S)—, or —C(═NH)— group. Rx is hydrogen, alkyl, hydroxy, alkoxy, acyl, or alkylsulfonyl. Fused bicyclic radical includes bridged ring systems. Unless stated otherwise, the valency may be located on any atom of any ring of the heteroaryl group, valency rules permitting. In particular, when the point of valency is located on the nitrogen, Rx is absent. In another embodiment, the term heteroaryl includes, but is not limited to, 1,2,4-triazolyl, 1,3,5-triazolyl, phthalimidyl, pyridinyl, pyrrolyl, imidazolyl, thienyl, furanyl, indolyl, 2,3-dihydro-1H-indolyl (including, for example, 2,3-dihydro-1H-indol-2-yl or 2,3-dihydro-1H-indol-5-yl, and the like), isoindolyl, indolinyl, isoindolinyl, benzimidazolyl, benzodioxol-4-yl, benzofuranyl, cinnolinyl, indolizinyl, naphthyridin-3-yl, phthalazin-3-yl, phthalazin-4-yl, pteridinyl, purinyl, quinazolinyl, quinoxalinyl, tetrazoyl, pyrazolyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, isooxazolyl, oxadiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl, tetrahydroisoquinolinyl (including, for example, tetrahydroisoquinolin-4-yl or tetrahydroisoquinolin-6-yl, and the like), pyrrolo[3,2-c]pyridinyl (including, for example, pyrrolo[3,2-c]pyridin-2-yl or pyrrolo[3,2-c]pyridin-7-yl, and the like), benzopyranyl, thiazolyl, isothiazolyl, thiadiazolyl, benzothiazolyl, benzothienyl, and the derivatives thereof, or N-oxide or a protected derivative thereof.
“Hetereoarylalkyl” means an alkyl group substituted with one or two heteroaryl groups as defined herein.
“Heterocycloalkyl” means a saturated or partially unsaturated monovalent monocyclic group of 3 to 8 ring atoms or a saturated or partially unsaturated monovalent fused bicyclic group of 5 to 12 ring atoms in which one or more, for example one, two, three, or four ring heteroatoms independently selected from —O—, —S(O)n— (n is 0, 1, or 2), —N═, —N(Ry)— (where Ry is hydrogen, alkyl, hydroxy, alkoxy, acyl, or alkylsulfonyl), the remaining ring atoms being carbon. One or two ring carbon atoms may be replaced by a —C(O)—, —C(S)—, or —C(═NH)— group. Fused bicyclic radical includes bridged ring systems. Unless otherwise stated, the valency of the group may be located on any atom of any ring within the radical, valency rules permitting. In particular, when the point of valency is located on a nitrogen atom, Ry is absent. In another embodiment the term heterocycloalkyl includes, but is not limited to, azetidinyl, pyrrolidinyl, 2-oxopyrrolidinyl, 2,5-dihydro-1H-pyrrolyl, piperidinyl, 4-piperidonyl, morpholinyl, piperazinyl, 2-oxopiperazinyl, tetrahydropyranyl, 2-oxopiperidinyl, thiomorpholinyl, thiamorpholinyl, perhydroazepinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, dihydropyridinyl, tetrahydropyridinyl, oxazolinyl, oxazolidinyl, isoxazolidinyl, thiazolinyl, thiazolidinyl, quinuclidinyl, isothiazolidinyl, octahydroindolyl, octahydroisoindolyl, decahydroisoquinolyl, tetrahydrofuryl, and tetrahydropyranyl, and the derivatives thereof and N-oxide or a protected derivative thereof.
“Heterocycloalkylalkyl” means an alkyl group, as defined herein, substituted with one or two heterocycloalkyl groups, as defined herein.
“Hydroxyalkyl” means an alkyl radical, as defined herein, substituted with at least one, for example one, two, or three, hydroxy groups, provided that if two hydroxy groups are present they are not both on the same carbon atom. Representative examples include, but are not limited to, hydroxymethyl, 2-hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, 1-(hydroxymethyl)-2-methylpropyl, 2-hydroxybutyl, 3-hydroxybutyl, 4-hydroxybutyl, 2,3-dihydroxypropyl, 1-(hydroxymethyl)-2-hydroxyethyl, 2,3-dihydroxybutyl, 3,4-dihydroxybutyl and 2-(hydroxymethyl)-3-hydroxypropyl, for example 2-hydroxyethyl, 2,3-dihydroxypropyl, or 1-(hydroxymethyl)-2-hydroxyethyl, and the like.
“Hydroxyamino” means a —NH(OH) group.
“Optional” or “optionally” means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances in which it does not. One of ordinary skill in the art would understand that with respect to any molecule described as containing one or more optional substituents, only sterically practical and/or synthetically feasible compounds are meant to be included. “Optionally substituted” refers to all subsequent modifiers in a term. So, for example, in the term “optionally substituted arylC1-8 alkyl,” both the “C1-8 alkyl” portion and the “aryl” portion of the molecule may or may not be substituted. A list of exemplary optional substitutions is presented below in the definition of “substituted.”
“Optionally substituted alkyl” means an alkyl radical, as defined herein, optionally substituted with one or more groups, for example one, two, three, four, or five groups, independently selected from alkylcarbonyl, alkenylcarbonyl, cycloalkylcarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, amino, alkylamino, dialkylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cyano, cyanoalkylaminocarbonyl, alkoxy, alkenyloxy, hydroxy, hydroxyalkoxy, carboxy, alkylcarbonylamino, alkylcarbonyloxy, alkyl-S(O)0-2—, alkenyl-S(O)0-2—, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, alkylsulfonyl-NRc— (where Rc is hydrogen, alkyl, optionally substituted alkenyl, optionally substituted alkynyl, hydroxy, alkoxy, alkenyloxy, or cyanoalkyl), alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylaminoalkyloxy, dialkylaminoalkyloxy, alkoxycarbonyl, alkenyloxycarbonyl, alkoxycarbonylamino, alkylaminocarbonylamino, dialkylaminocarbonylamino, alkoxyalkyloxy, and —C(O)NRaRb (where Ra and Rb are independently hydrogen, alkyl, optionally substituted alkenyl, optionally substituted alkynyl, hydroxy, alkoxy, alkenyloxy, or cyanoalkyl).
“Optionally substituted alkenyl” means an alkenyl radical, as defined herein, optionally substituted with one or more groups, for example one, two, or three groups, independently selected from alkylcarbonyl, alkenylcarbonyl, cycloalkylcarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, amino, alkylamino, dialkylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cyano, cyanoalkylaminocarbonyl, alkoxy, alkenyloxy, hydroxy, hydroxyalkoxy, carboxy, alkylcarbonylamino, alkylcarbonyloxy, alkyl-S(O)0-2—, alkenyl-S(O)0-2—, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, alkylsulfonyl-NRc— (where Rc is hydrogen, optionally substituted alkyl, optionally substituted alkynyl, hydroxy, alkoxy, or alkenyloxy), alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylaminoalkyloxy, dialkylaminoalkyloxy, alkoxycarbonyl, alkenyloxycarbonyl, alkoxycarbonylamino, alkylaminocarbonylamino, dialkylaminocarbonylamino, alkoxyalkyloxy, and —C(O)NRaRb (where Ra and Rb are independently hydrogen, optionally substituted alkyl, alkenyl, optionally substituted alkynyl, hydroxy, alkoxy, or alkenyloxy).
“Optionally substituted aryl” means an aryl group, as defined herein, which is optionally substituted with one, two, three, four, of five groups selected from halo, haloalkyl, haloalkoxy, hydroxy, lower alkyl, lower alkenyl, lower alkynyl, alkoxy, carboxy, carboxy ester, amino, alkylamino, dialkylamino, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl, —C(O)NR′R′′ (where R′ is hydrogen or alkyl and R′′ is hydrogen, alkyl, aryl, heteroaryl, or heterocycloalkyl), —NR′C(O)R′′ (where R′ is hydrogen or alkyl and R′′ is alkyl, aryl, heteroaryl, or heterocycloalkyl), and —NHS(O)2R′ (where R′ is alkyl, aryl, or heteroaryl).
“Optionally substituted heteroaryl” means a heteroaryl group, as defined herein, optionally substituted with one, two, three, four, or five groups selected from halo, haloalkyl, haloalkoxy, lower alkyl, lower alkenyl, lower alkynyl, alkoxy, hydroxy, oxo (valency rules permitting), carboxy, carboxy ester, amino, alkylamino, dialkylamino, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, heteroaryl, optionally substituted aryl, —C(O)NR′R′′ (where R′ is hydrogen or alkyl and R′′ is hydrogen, alkyl, aryl, heteroaryl, or heterocycloalkyl), —NR′C(O)R′′ (where R′ is hydrogen or alkyl and R′′ is alkyl, aryl, heteroaryl, or heterocycloalkyl), and —NHS(O)2R′ (where R′ is alkyl, aryl, or heteroaryl).
“Optionally substituted heterocycloalkyl” means a heterocycloalkyl, as defined herein, optionally substituted with one, two, three, four, or five groups selected from halo, haloalkyl, haloalkoxy, hydroxy, oxo, lower alkyl, lower alkenyl, lower alkynyl, alkoxy, optionally substituted cycloalkyl, heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, alkylaminoalkyl, dialkylaminoalkyl, carboxy, carboxy ester, —C(O)NR′R′′ (where R′ is hydrogen or alkyl and R′′ is hydrogen, alkyl, aryl, heteroaryl, or heterocycloalkyl), —NR′C(O)R′′ (where R′ is hydrogen or alkyl and R′′ is alkyl, aryl, heteroaryl, or heterocycloalkyl), amino, alkylamino, dialkylamino, and —NHS(O)2R′ (where R′ is alkyl, aryl, or heteroaryl).
“Saturated bridged ring system” refers to a bicyclic or polycyclic ring system that is not aromatic. Such a system may contain isolated or conjugated unsaturation, but not aromatic or heteroaromatic rings in its core structure (but may have aromatic substitution thereon). For example, hexahydro-furo[3,2-b]furan, 2,3,3a,4,7,7a-hexahydro-1H-indene, 7-aza-bicyclo[2.2.1]heptane, and 1,2,3,4,4a,5,8,8a-octahydro-naphthalene are all included in the class “saturated bridged ring system.”
“Spirocyclyl” or “spirocyclic ring” refers to a ring originating from a particular annular carbon of another ring. For example, as depicted below, a ring atom of a saturated bridged ring system (rings C and C′), but not a bridgehead atom, can be a shared atom between the saturated bridged ring system and a spirocyclyl (ring D) attached thereto. A spirocyclyl can be carbocyclic or heteroalicyclic.




“Yield” for each of the reactions described herein is expressed as a percentage of the theoretical yield.
Definitions for the Compound of Formula 100
The terms used to describe the scope of formula 100 are defined in WO 2004/006846 (US Nat'l Stage application Ser. No. 10/522,004) which is herein incorporated by reference. For example “optionally substituted alkyl” for formula 100 has the meaning given in WO 2004/006846 (US Nat'l Stage application Ser. No. 10/522,004). Whenever a compound of formula 100 is described in this application, whether by structure or by use of the term “formula 100,” the terms used to describe that compound are defined by WO 2004/006846 (US Nat'l Stage application Ser. No. 10/522,004).
Other Definitions
“AKT inhibitor” includes, for example, LY294002, PKC 412, perifosine, compounds in Table 2a, compounds in Table 2b, and compounds described in WO 2006/071819 and WO05/117909. These references also describe in vitro assays that can be used to determine the inhibitory activity of AKT.
“Alkylating agent” includes, for example, one or more of the following: Chlorambucil, Chlormethine, Cyclophosphamide, Ifosfamide, Melphalan, Carmustine, Streptozocin, Fotemustine, Lomustine, Streptozocin, Carboplatin, Cisplatin, Oxaliplatin, BBR3464, Busulfan, Dacarbazine, Mechlorethamine, Procarbazine, Temozolomide, ThioTEPA, and Uramustine.
“Antibody” includes, for example, one or more of the following: an IGF1R antibody (including, for example, αIGF-1R A12 MoAb, 19D12, h7C10 and CP-751871), an EGFR antibody (including, for example, Cetuximab (Erbitux®) and Panitumumab), an ErbB2 antibody (including, for example, Trastuzumab (Herceptin®)), a VEGF antibody (including, for example, Bevacizumab (Avastin®)), an IgG1 antibody (including, for example, Ibritumomab (tiuxetan)), a CD20 antibody (including, for example, Rituximab and Tositumomab), a CD33 antibody (including, for example, Gemtuzumab and Gemtuzumab ozogamicin), and a CD52 antibody (including, for example, Alemtuzumab).
“Antimetabolite” include, for example, methotrexate, Pemetrexed, Raltitrexed, Cladribine, Clofarabine, Fludarabine, Mercaptopurine, Thioguanine, Capecitabine, Cytarabine, fluorouracil (administered with or without leucovorin or folinic acid), and Gemcitabine.
“Antimicrotubule agent” includes, for example, Vincristine, Vinblastine, Vinorelbine, Vinflunine, and Vindesine.
“Aromatase inhibitor” includes, for example, one or more of the following: Aminoglutethimide, Anastrozole (Arimidex®), Letrozole (Femara®), Exemestane (Aromasin®), and Formestane (Lentaron®).
“Cancer” refers to cellular-proliferative disease states, including but not limited to: Cardiac: sarcoma (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyoma, fibroma, lipoma and teratoma; Lung: bronchogenic carcinoma (squamous cell, undifferentiated small cell, undifferentiated large cell, adenocarcinoma), alveolar (bronchiolar) carcinoma, bronchial adenoma, sarcoma, lymphoma, chondromatous hanlartoma, inesothelioma; Gastrointestinal: esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumors, vipoma), small bowel (adenocarcinoma, lymphoma, carcinoid tumors, Karposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), large bowel (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma); Genitourinary tract: kidney (adenocarcinoma, Wilm's tumor [nephroblastoma], lymphoma, leukemia), bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate (adenocarcinoma, sarcoma), testis (seminoma, teratoma, embryonal carcinoma, teratocarcinoma, choriocarcinoma, sarcoma, interstitial cell carcinoma, fibroma, fibroadenoma, adenomatoid tumors, lipoma); Liver: hepatoma (hepatocellular carcinoma), cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma; Bone: osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticulum cell sarcoma), multiple myeloma, malignant giant cell tumor chordoma, osteochronfroma (osteocartilaginous exostoses), benign chondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma and giant cell tumors; Nervous system: skull (osteoma, hemangioma, granuloma, xanthoma, osteitis deformians), meninges (meningioma, meningiosarcoma, gliomatosis), brain (astrocytoma, medulloblastoma, glioma, ependymoma, germinoma [pinealoma], glioblastorna multiform, oligodendroglioma, schwannoma, retinoblastoma, congenital tumors), spinal cord neurofibroma, meningioma, glioma, sarcoma); Gynecological: uterus (endometrial carcinoma), cervix (cervical carcinoma, pre-tumor cervical dysplasia), ovaries (ovarian carcinoma [serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma], granulosa-thecal cell tumors, Sertoli-Leydig cell tumors, dysgerminoma, malignant teratoma), vulva (squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma), vagina (clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma (embryonal rhabdomyosarcoma], fallopian tubes (carcinoma); Hematologic: blood (myeloid leukemia [acute and chronic], acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative diseases, multiple myeloma, myelodysplastic syndrome), Hodgkin's disease, non-Hodgkin's lymphoma [malignant lymphoma]; Skin: malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Karposi's sarcoma, moles dysplastic nevi, lipoma, angioma, dermatofibroma, keloids, psoriasis; Adrenal Glands: neuroblastoma; and breast cancer. Thus, the term “cancerous cell” as provided herein, includes a cell afflicted by any one of the above-identified conditions.
“Chemotherapeutic agent” includes, but is not limited to, an AKT inhibitor, an alkylating agent, an antimetabolite, an antimicrotubule agent, an aromatase inhibitor, a c-KIT inhibitor, a cMET inhibitor, an EGFR inhibitor, an ErbB2 inhibitor, a Flt-3 inhibitor, an HSP90 inhibitor, an IGF1R inhibitor, a platin, a Raf inhibitor, rapamycin, a Rapamycin analogue, a Receptor Tyrosine Kinase inhibitor, a taxane, a topoisomerase inhibitor, a SRC and/or ABL kinase inhibitor, and a VEGFR inhibitor. A pharmaceutically acceptable salt, solvate, and/or hydrate of a chemotherapeutic agent can be prepared by one of ordinary skill in the art and such salt, solvate, and/or hydrates thereof can be used to practice the invention.
“c-KIT inhibitor” includes, for example, imatinib, sunitinib, nilotinib, AMG 706, sorafenib, compounds in Table 3b, compounds in Table 3c, compounds in Table 8, compounds in Table 9, and compounds described in WO 2006/108059, WO/2005/020921, WO/2006/033943, and WO 2005/030140.
“cMET inhibitor” includes, for example, compounds in Table 3a, compounds in Table 3b, compounds in Table 3c, compounds described in WO06/108059, WO 2006/014325, and WO 2005/030140.
“EGFR inhibitor” includes, for example, one or more of the following: pelitinib, lapatinib (Tykerb®), gefitinib (Iressa®), erlotinib (Tarceva®), Zactima (ZD6474, vandetinib), AEE788 and HKI-272, EKB-569, CI-1033, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, compounds in Table 4, compounds in Table 7, and compounds described in WO 2004/006846 and WO 2004/050681.
“ErbB2 inhibitor” includes, for example, lapatinib (GW572016), PKI-166, canertinib, CI-1033, HKI272, and EKB-569.
“Flt-3 inhibitor” includes, for example, CEP-701, PKC 412, MLN518, sunitinib, sorafenib, compounds in Table 3a, compounds in Table 3b, compounds in Table 3c, compounds in Table 9, and compounds described in WO 2006/108059, WO/2006/033943, WO 2006/014325, and WO 2005/030140.
“Hormone therapy” or “hormonal therapy” includes, for example, treatment with one or more of the following: steroids (e.g. dexamethasone), finasteride, tamoxifen, and an aromatase inhibitor.
“HSP90 inhibitor” includes, for example, 17-AAG, 17-DMAG, Geldanamycin, 5-(2,4-dihydroxy-5-isopropylphenyl)-N-ethyl-4-(4-(morpholinomethyl)phenyl)isoxazole-3-carboxamide [NVP-AUY922 (VER 52296)], 6-chloro-9-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-9H-purin-2-amine (CNF2024, also named BIIB021), compounds disclosed in WO2004072051 (which is herein incorporated by reference), compounds disclosed in WO2005028434 (which is herein incorporated by reference), compounds disclosed in WO2007035620 (which is herein incorporated by reference) and compounds disclosed in WO2006091963 (which is herein incorporated by reference).
“IGF1R inhibitor” includes, for example, Tyrphostin AG 1024, compounds in Table 5a, compounds in Table 5b, and compounds described in WO06/074057.
“Kinase-dependent diseases or conditions” refer to pathologic conditions that depend on the activity of one or more lipid kinases. Kinases either directly or indirectly participate in the signal transduction pathways of a variety of cellular activities including proliferation, adhesion, migration, differentiation and invasion. Diseases associated with kinase activities include tumor growth, the pathologic neovascularization that supports solid tumor growth, and associated with other diseases where excessive local vascularization is involved such as ocular diseases (diabetic retinopathy, age-related macular degeneration, and the like) and inflammation (psoriasis, rheumatoid arthritis, and the like).
While not wishing to be bound to theory, phosphatases can also play a role in “kinase-dependent diseases or conditions” as cognates of kinases; that is, kinases phosphorylate and phosphatases dephosphorylate, for example lipid substrates. Therefore compounds of the invention, while modulating kinase activity as described herein, may also modulate, either directly or indirectly, phosphatase activity. This additional modulation, if present, may be synergistic (or not) to activity of compounds of the invention toward a related or otherwise interdependent kinase or kinase family. In any case, as stated previously, the compounds of the invention are useful for treating diseases characterized in part by abnormal levels of cell proliferation (i.e. tumor growth), programmed cell death (apoptosis), cell migration and invasion and angiogenesis associated with tumor growth.
“Metabolite” refers to the break-down or end product of a compound or its salt produced by metabolism or biotransformation in the animal or human body; for example, biotransformation to a more polar molecule such as by oxidation, reduction, or hydrolysis, or to a conjugate (see Goodman and Gilman, “The Pharmacological Basis of Therapeutics” 8.sup.th Ed., Pergamon Press, Gilman et al. (eds), 1990 for a discussion of biotransformation). As used herein, the metabolite of a compound of the invention or its salt may be the biologically active form of the compound in the body. In one example, a prodrug may be used such that the biologically active form, a metabolite, is released in vivo. In another example, a biologically active metabolite is discovered serendipitously, that is, no prodrug design per se was undertaken. An assay for activity of a metabolite of a compound of the present invention is known to one of skill in the art in light of the present disclosure.
“Patient” for the purposes of the present invention includes humans and other animals, particularly mammals, and other organisms. Thus the methods are applicable to both human therapy and veterinary applications. In another embodiment the patient is a mammal, and in another embodiment the patient is human.
A “pharmaceutically acceptable salt” of a compound means a salt that is pharmaceutically acceptable and that possesses the desired pharmacological activity of the parent compound. It is understood that the pharmaceutically acceptable salts are non-toxic. Additional information on suitable pharmaceutically acceptable salts can be found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, which is incorporated herein by reference or S. M. Berge, et al., “Pharmaceutical Salts,” J. Pharm. Sci., 1977; 66:1-19 both of which are incorporated herein by reference.
Examples of pharmaceutically acceptable acid addition salts include those formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; as well as organic acids such as acetic acid, trifluoroacetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, 3-(4-hydroxybenzoyl)benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, glucoheptonic acid, 4,4′-methylenebis-(3-hydroxy-2-ene-1-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, p-toluenesulfonic acid, and salicylic acid and the like.
Examples of a pharmaceutically acceptable base addition salts include those formed when an acidic proton present in the parent compound is replaced by a metal ion, such as sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like. Preferable salts are the ammonium, potassium, sodium, calcium, and magnesium salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins. Examples of organic bases include isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, tromethamine, N-methylglucamine, polyamine resins, and the like. Exemplary organic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine.
“Platin,” and “platin-containing agent” include, for example, cisplatin, carboplatin, and oxaliplatin.
“Prodrug” refers to compounds that are transformed (typically rapidly) in vivo to yield the parent compound of the above formulae, for example, by hydrolysis in blood. Common examples include, but are not limited to, ester and amide forms of a compound having an active form bearing a carboxylic acid moiety. Examples of pharmaceutically acceptable esters of the compounds of this invention include, but are not limited to, alkyl esters (for example with between about one and about six carbons) the alkyl group is a straight or branched chain. Acceptable esters also include cycloalkyl esters and arylalkyl esters such as, but not limited to benzyl. Examples of pharmaceutically acceptable amides of the compounds of this invention include, but are not limited to, primary amides, and secondary and tertiary alkyl amides (for example with between about one and about six carbons). Amides and esters of the compounds of the present invention may be prepared according to conventional methods. A thorough discussion of prodrugs is provided in T. Higuchi and V. Stella, “Pro-drugs as Novel Delivery Systems,” Vol 14 of the A.C.S. Symposium Series, and in Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987, both of which are incorporated herein by reference for all purposes.
“Raf inhibitor” includes, for example, sorafenib, RAF 265 (CHIR 265), compounds in Table 6, and compounds described in WO 2005/112932. These references also describe in vitro assays that can be used to determine the inhibitory activity of RAF.
“Rapamycin analogue” includes for example, CCI-779, AP23573, RAD 001, TAFA 93, and compounds described in WO 2004/101583 and U.S. Pat. No. 7,160,867 which are each incorporated herein by reference in their entireties.
“Receptor Tyrosine Kinase inhibitor” includes, for example, inhibitors of AKT, EGFR, ErbB2, IGF1R, KIT, Met, Raf, and VEGFR2. Examples of receptor tyrosine kinase inhibitors can be found in WO 2006/108059 (U.S. Nat'l Stage application Ser. No. 11/910,720), WO 2006/074057 (U.S. Nat'l Stage application Ser. No. 11/722,719), WO 2006/071819 (U.S. Nat'l Stage application Ser. No. 11/722,291), WO 2006/014325 (U.S. Nat'l Stage application Ser. No. 11/571,140), WO 2005/117909 (U.S. Nat'l Stage application Ser. No. 11/568,173), WO 2005/030140 (U.S. Nat'l Stage application Ser. No. 10/573,336), WO 2004/050681 U.S. Nat'l Stage application Ser. No. 10/533,555), WO 2005/112932 (U.S. Nat'l Stage application Ser. No. 11/568,789), and WO 2004/006846 (U.S. Nat'l Stage application Ser. No. 10/522,004), each of which is incorporated herein by reference for all purposes. In particular, the applications cited in this paragraph are incorporated for the purpose of providing specific examples and generic embodiments (and the definitions associated with the terms used in the embodiments) of compounds that are useful in the practice of the invention. These references also describe in vitro assays useful in the practice of this invention.
“Taxane” includes, for example, one or more of the following: Paclitaxel (Taxol®) and Docetaxel (Taxotere®).
“Therapeutically effective amount” is an amount of a compound of the invention, that when administered to a patient, ameliorates a symptom of the disease. The amount of a compound of the invention which constitutes a “therapeutically effective amount” will vary depending on the compound, the disease state and its severity, the age of the patient to be treated, and the like. The therapeutically effective amount can be determined routinely by one of ordinary skill in the art having regard to their knowledge and to this disclosure.
“Topoisomerase inhibitor” includes, for example, one or more of the following: amsacrine, camptothecin, etoposide, etoposide phosphate, exatecan, irinotecan, lurtotecan, and teniposide, and topotecan.
“Treating” or “treatment” of a disease, disorder, or syndrome, as used herein, includes (i) preventing the disease, disorder, or syndrome from occurring in a human, i.e. causing the clinical symptoms of the disease, disorder, or syndrome not to develop in an animal that may be exposed to or predisposed to the disease, disorder, or syndrome but does not yet experience or display symptoms of the disease, disorder, or syndrome; (ii) inhibiting the disease, disorder, or syndrome, i.e., arresting its development; and (iii) relieving the disease, disorder, or syndrome, i.e., causing regression of the disease, disorder, or syndrome. As is known in the art, adjustments for systemic versus localized delivery, age, body weight, general health, sex, diet, time of administration, drug interaction and the severity of the condition may be necessary, and will be ascertainable with routine experimentation by one of ordinary skill in the art.
“SRC and/or ABL kinase inhibitor” includes, for example, dasatinib, imatinib (Gleevec®), and compounds described in WO 2006/074057.
“VEGFR inhibitor” includes, for example, one or more of the following: VEGF Trap, ZD6474 (vandetanib, Zactima), sorafenib, Angiozyme, AZD2171 (cediranib), pazopanib, sorafenib, axitinib, SU5416 (semaxanib), PTK787 (vatalanib), AEE778, RAF 265, sunitinib (Sutent), N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, compounds in Table 7, and compounds described in WO 2004/050681 and WO 2004/006846.
Embodiments of the Invention
The following paragraphs present a number of embodiments of compounds of the invention. In each instance, the embodiment includes both the recited compounds as well as individual isomers and mixtures of isomers. In addition, in each instance, the embodiment optionally includes the pharmaceutically acceptable salts, hydrates, and/or solvates of the recited compounds and any individual isomers or mixture of isomers thereof.
For each of the following embodiments, the Compound of Formula I can, for example, be of Formula I(a) or be selected from a Compound in Table 1.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, where growth and/or survival of tumor cells of the cancer is enhanced, at least in part, by the activity of PI3K; in combination with one or more treatments selected from surgery, one or more chemotherapeutic agents, one or more hormone therapies, one or more antibodies, one or more immunotherapies, radioactive iodine therapy, and radiation.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from surgery, one or more chemotherapeutic agents, one or more hormone therapies, one or more antibodies, one or more immunotherapies, radioactive iodine therapy, and radiation; where the cancer is selected from breast cancer, colon cancer, rectal cancer, endometrial cancer, gastric carcinoma (including gastrointestinal carcinoid tumors and gastrointestinal stromal tumors), glioblastoma, hepatocellular carcinoma, small cell lung cancer, non-small cell lung cancer (NSCLC), melanoma, ovarian cancer, cervical cancer, pancreatic cancer, prostate carcinoma, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), non-Hodgkin's lymphoma, and thyroid carcinoma. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from surgery, one or more chemotherapeutic agents, one or more hormone therapies, one or more antibodies, one or more immunotherapies, radioactive iodine therapy, and radiation; where the cancer is selected from prostate cancer, NSCLC, ovarian cancer, cervical cancer, breast cancer, colon cancer, rectal cancer, and glioblastoma. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from surgery, one or more chemotherapeutic agents, one or more hormone therapies, one or more antibodies, one or more immunotherapies, radioactive iodine therapy, and radiation; where the cancer is selected from NSCLC, breast cancer, prostate cancer, glioblastoma, and ovarian cancer.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or more chemotherapeutic agents.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents independently selected from rapamycin, a rapamycin analogue, an alkylating agent, a taxane, a platin, an EGFR inhibitor, and an ErbB2 inhibitor. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents independently selected from rapamycin, temozolomide, paclitaxel, docetaxel, carboplatin, cisplatin, oxaliplatin, gefitinib (Iressa®), erlotinib (Tarceva®), Zactima (ZD6474), HKI-272, pelitinib, canertinib, a compound selected from Table 4, a compound in Table 7, and lapatinib. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents independently selected from rapamycin, temozolomide, paclitaxel, docetaxel, carboplatin, trastuzumab, erlotinib, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, a compound in Table 7, and lapatinib. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents independently selected from rapamycin, paclitaxel, carboplatin, erlotinib, and N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta-[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents independently selected from a platin and a taxane. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents independently selected from carboplatin, cisplatin, oxaliplatin, and paclitaxel.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an AKT inhibitor. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an AKT inhibitor selected from perifosine, PKC 412, a compound in Table 2a, and a compound in Table 2b.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a cMET inhibitor. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a cMET inhibitor selected from a compound in Table 3a, a compound in Table 3b, and a compound in Table 3c.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an EGFR inhibitor. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an EGFR inhibitor selected from lapatinib (Tykerb®), gefitinib (Iressa®), erlotinib (Tarceva®), Zactima (ZD6474), AEE788, HKI-272, EKB-569, CI 1033, a compound selected from Table 4, and a compound in Table 7. In another embodiment, In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an EGFR inhibitor selected from lapatinib (Tykerb®), gefitinib (Iressa®), erlotinib (Tarceva®), Zactima (ZD6474), AEE788, HKI-272, EKB-569, CI 1033, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, and N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an ErbB2 inhibitor. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an ErbB2 inhibitor selected from lapatinib, EKB-569, HKI272, CI 1033, PKI-166, and a compound selected from Table 4.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an HSP90 inhibitor. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an HSP90 inhibitor selected from 17-AAG, 17-DMAG, Geldanamycin, and CNF2024. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an HSP90 inhibitor selected from 17-AAG, 17-DMAG, and Geldanamycin.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an IGF1R inhibitor. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an IGF1R inhibitor selected from Table 5a and Table 5b.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a Raf inhibitor. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a Raf inhibitor selected from sorafenib, RAF 265 (CHIR-265), and a compound in Table 6.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a VEGFR inhibitor. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a VEGFR inhibitor selected from VEGF Trap, ZD6474 (Zactima), cediranib (AZ2171), pazopanib, sunitinib, sorafenib, axitinib, AEE788, RAF 265 (CHIR-265), a compound selected from Table 4, and a compound selected from Table 7.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a cKIT inhibitor. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a cKIT inhibitor selected from imatinib, sunitinib, nilotinib, AMG 706, sorafenib, a compound in Table 3b, a compound in Table 3c, a compound in Table 8, and a compound in Table 9.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a FLT3 inhibitor. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a FLT3 inhibitor selected from CEP-701, PKC 412, sunitinib, MLN518, sunitinib, sorafenib, a compound in Table 3a, a compound in Table 3b, a compound in Table 3c, and a compound in Table 9.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from rapamycin, a rapamycin analogue, PI103, and SF 1126. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from rapamycin, CCI-779, AP23573, RAD 001, TAFA 93, PI103, and SF 1126. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is rapamycin.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is of formula 100:




where q is 1, 2, or 3; E is —NR9—, —O—, or absent and Y is —CH2CH2—, —CH2—, or absent provided that when E is —NR9— or —O—, then Y is —CH2CH2—; R2 is selected from halogen, trihalomethyl, —CN, —NO2, —OR3, and lower alkyl; R8 is selected from —H, lower alkyl, —C(O)OR3, —C(O)N(R3)R4, —SO2R4, and —C(O)R3; R9 is hydrogen or lower alkyl; R3 is hydrogen or R4; R4 is selected from lower alkyl, aryl, lower arylalkyl, heterocyclyl, and lower heterocyclylalkyl; or R3 and R4, when taken together with a common nitrogen to which they are attached, form a five- to seven-membered heterocyclyl, said five- to seven-membered heterocyclyl optionally containing one or more additional heteroatom selected from N, O, S, and P; or a single geometric isomer, stereoisomer, racemate, enantiomer, or diastereomer, thereof and optionally as a pharmaceutically acceptable salt, additionally optionally as a solvate, and additionally as a hydrate thereof. The terms used to describe the scope of formula 100 are defined in WO 2004/006846 (U.S. Nat'l Stage application Ser. No. 10/522,004) which is herein incorporated by reference. Whenever a compound of formula 100 is described in this application, whether by structure or by use of the term “formula 100,” the terms used to describe that compound are defined by WO 2004/006846 (U.S. Nat'l Stage application Ser. No. 10/522,004). In particular, “alkyl” in formula 100 is intended to include linear, branched, or cyclic hydrocarbon structures and combinations thereof, inclusively; “lower alkyl” means alkyl groups of from one to six carbon atoms. “Aryl” in formula 100 means an aromatic six- to fourteen-membered carbocyclic rings which include, for example, benzene, naphthalene, indane, tetralin, fluorene and the like. “Lower arylalkyl” in formula 100 means a residue in which an aryl moiety is attached to a parent structure via one of an alkylene, alkenylene, or alkynylene radical where the “alkyl” portion of the group has one to six carbons; examples include benzyl, phenethyl, phenylvinyl, phenylallyl and the like. In formula 100, “heterocyclyl” means a stable monocyclic, bicyclic or tricyclic three- to fifteen-membered ring radical (including fused or bridged ring systems) that consists of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, phosphorus, oxygen and sulfur where the nitrogen, phosphorus, carbon and sulfur atoms in the heterocyclyl radical may be optionally oxidized to various oxidation states and the nitrogen atom may be optionally quaternized; and the ring radical may be partially or fully saturated or aromatic. “Lower heterocyclylalkyl” means a residue in which a heterocyclyl is attached to a parent structure via one of an alkylene, alkenylene, and alkynylene radical having one to six carbons.

In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 2a. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 2a. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 2a.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 2b. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 2b. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 2b.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 3a. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 3a. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 3a.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 3b. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 3b. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 3b.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 3c. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 3c. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 3c.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 4. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 4. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 4.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, or N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a) in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, or N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, or N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta-[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a) in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta-[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is N-(3,4-dichloro-2-fluorophenyl)-7-({[3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 5ac. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 5a. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 5a.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 5b. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 5b. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 5b.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 6. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 6. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 6.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 7. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 7. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 7.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 8. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 8. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 8.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 9. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 9. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 9.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agent is paclitaxel.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agent is rapamycin.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agent is carboplatin.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agent is erlotinib.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agent is lapatinib.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two antibodies where one of the antibodies is trastuzumab.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two antibodies where one of the antibodies is cetuximab.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two antibodies where one of the antibodies is panitumumab.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two antibodies where one of the antibodies is bevacizumab.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is radiation. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a) in combination with a treatment where the treatment is radiation. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is radiation.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two antibodies. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two antibodies independently selected from an IGF1R antibody (including, for example, αIGF-1R A12 MoAb, αIGF-1R 19D12 MoAb, αIGF-1R h7C10 MoAb and αIGF-1R CP-751871 MoAb), Alemtuzumab, Bevacizumab (Avastin®), Gemtuzumab, Gemtuzumab ozogamicin, Ibritumomab tiuxetan, Panitumumab, Rituximab, Tositumomab, Omnitarg (pertuzimab), an anti-ErbB2 antibodies (including trastuzumab (Herceptin®)), and an anti-EGFR antibodies (including, for example, cetuximab (Erbitux), panitumumab, nimotuzumab, and EMD72000)).
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a) in combination with a treatment where the treatment is one or two antibodies. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a) in combination with a treatment where the treatment is one or two antibodies independently selected from an IGF1R antibody (including, for example, αIGF-1R A12 MoAb, αIGF-1R 19D12 MoAb, αIGF-1R h7C10 MoAb and αIGF-1R CP-751871 MoAb), Alemtuzumab, Bevacizumab (Avastin®), Gemtuzumab, Gemtuzumab ozogamicin, Ibritumomab tiuxetan, Panitumumab, Rituximab, Tositumomab, Omnitarg (pertuzimab), an anti-ErbB2 antibodies (including trastuzumab (Herceptin®)), and an anti-EGFR antibodies (including, for example, cetuximab (Erbitux), panitumumab, nimotuzumab, and EMD72000)).
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two antibodies. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two antibodies independently selected from an IGF1R antibody (including, for example, αIGF-1R A12 MoAb, αIGF-1R 19D12 MoAb, αIGF-1R h7C10 MoAb and αIGF-1R CP-751871 MoAb), Alemtuzumab, Bevacizumab (Avastin®), Gemtuzumab, Gemtuzumab ozogamicin, Ibritumomab tiuxetan, Panitumumab, Rituximab, Tositumomab, Omnitarg (pertuzimab), an anti-ErbB2 antibodies (including trastuzumab (Herceptin®)), and an anti-EGFR antibodies (including, for example, cetuximab (Erbitux), panitumumab, nimotuzumab, and EMD72000)).
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or more chemotherapeutic agents where one of the chemotherapeutic agent is temozolomide. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a) in combination with a treatment where the treatment is one or more chemotherapeutic agents where one of the chemotherapeutic agent is temozolomide. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or more chemotherapeutic agents where one of the chemotherapeutic agent is temozolomide.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is surgery. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a) in combination with a treatment where the treatment is surgery. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is surgery.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two hormone therapies. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I or I(a), as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two hormone therapies independently selected from tamoxifen, Toremifene (Fareston), Fulvestrant (Faslodex), Megestrol acetate (Megace), ovarian ablation, Raloxifene, a luteinizing hormone-releasing hormone (LHRH) analog (including goserelin and leuprolide), Megestrol acetate (Megace), and one or more aromatase inhibitors. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I or I(a), as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two hormone therapies where one of the hormone therapies is an aromatase inhibitor selected from letrozole (Femara), anastrozole (Arimidex), and exemestane (Aromasin). In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I or I(a), as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two hormone therapies independently selected from tamoxifen and an aromatase inhibitor.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two hormone therapies. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where one of the treatments is one or two hormone therapies independently selected from tamoxifen, Toremifene (Fareston), Fulvestrant (Faslodex), Megestrol acetate (Megace), ovarian ablation, Raloxifene, a luteinizing hormone-releasing hormone (LHRH) analog (including goserelin and leuprolide), Megestrol acetate (Megace), and one or two aromatase inhibitors. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where one of the treatments is one or two hormone therapies where one of the hormone therapies is an aromatase inhibitors selected from letrozole (Femara), anastrozole (Arimidex), and exemestane (Aromasin). In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where one of the treatments is one or two hormone therapies independently selected from tamoxifen and an aromatase inhibitor.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where one of the treatments is one antibody selected from an EGFR antibody and an ErbB2 antibody, or the treatment is one or two chemotherapeutic agents independently selected from a rapamycin, rapamycin analogue, an alkylating agent, a taxane, a platin, an EGFR inhibitor, and an ErbB2 inhibitor. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a) in combination with a treatment where one of the treatments is one antibody selected from an EGFR antibody and an ErbB2 antibody, or the treatment is one or two chemotherapeutic agents independently selected from rapamycin, a rapamycin analogue, an alkylating agent, a taxane, a platin, an EGFR inhibitor, and an ErbB2 inhibitor. In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where one of the treatments is one antibody selected from an EGFR antibody and an ErbB2 antibody, or the treatment is one or two chemotherapeutic agents independently selected from rapamycin, a rapamycin analogue, an alkylating agent, a taxane, a platin, an EGFR inhibitor, and an ErbB2 inhibitor.
In another embodiment, the invention is directed to a method of treating acute myelogenous leukemia (AML) which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from bone marrow or peripheral blood stem cell transplantation, radiation, one or two antibodies, and one or two chemotherapeutic agents. In another embodiment, the invention is directed to a method of treating acute myelogenous leukemia (AML) which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or t treatments where one of the treatments is one antibody selected from Gemtuzumab ozogamicin (Mylotarg), αIGF-1R A12 MoAb, αIGF-1R 19D12 MoAb, αIGF-1R h7C10 MoAb, αIGF-1R CP-751871 MoAb and trastuzumab. In another embodiment, the invention is directed to a method of treating acute myelogenous leukemia (AML) which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents selected from Imatinib (i.e. Gleevec®), PKC 412, CEP-701, daunorubicin, doxorubicin, cytarabine (ara-C), an anthracycline drug such as daunorubicin or idarubicin (Daunomycin, Idamycin), 6-thioguanine, and a granulocyte colony-stimulating factor (such as Neupogen or Leukine).
In another embodiment, the invention is directed to a method of treating chronic myelogenous leukemia (CML) which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from bone marrow or peripheral blood stem cell transplantation, radiation, one or two chemotherapeutic agents, immunotherapy, and one or two antibodies. In another embodiment, the invention is directed to a method of treating chronic myelogenous leukemia (CML) which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two of the chemotherapeutic agents selected from Imatinib (i.e. Gleevec®), PKC 412, hydroxyurea (Hydrea), cytosine, cytosine arabinoside, dasatinib, AMN107, VX680 (MK0457), and cytarabine (ara-C). In another embodiment, the invention is directed to a method of treating chronic myelogenous leukemia (CML) which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents selected from Imatinib (i.e. Gleevec®) and dasatinib. In another embodiment, the invention is directed to a method of treating chronic myelogenous leukemia (CML) which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is immunotherapy and the immunotherapy is interferon therapy such as interferon-α.
In another embodiment, the invention is directed to a method of treating prostate cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from surgery (including cryosurgery), radiation, one or two chemotherapeutic agents, one or two antibodies, and one or two hormone therapies. In another embodiment, the invention is directed to a method of treating prostate cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is an antibody selected from αIGF-1R A12 MoAb, αIGF-1R 19D12 MoAb, αIGF-1R h7C10 MoAb, and αIGF-1R CP-751871 MoAb. In another embodiment, the invention is directed to a method of treating prostate cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two of the chemotherapeutic agents independently selected from rapamycin, mitoxantrone, prednisone, docetaxel (Taxotere), doxorubicin, etoposide, vinblastine, paclitaxel, and carboplatin. In another embodiment, the invention is directed to a method of treating prostate cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two of the hormone therapy indepependently selected from androgen deprivation therapy and androgen suppression therapy. In another embodiment, the invention is directed to a method of treating prostate cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a taxanes. In another embodiment, the invention is directed to a method of treating prostate cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents where one of the chemotherapeutic agents is rapamycin.
In another embodiment, the invention is directed to a method of treating melanoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from surgery, radiation, one or two immunotherapies, one or two hormone therapies, and one or two chemotherapeutic agents. In another embodiment, the invention is directed to a method of treating melanoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from an alkylating agent, a taxane, a platin, and a Raf inhibitor. In another embodiment, the invention is directed to a method of treating melanoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from sorafenib, Paclitaxel (Taxol®), Docetaxel (Taxotere®), dacarbazine, rapamycin, imatinib mesylate (Gleevec®), sorafenib, cisplatin, carboplatin, dacarbazine (DTIC), carmustine (BCNU), vinblastine, temozolomide (Temodar), Melphalan, and imiquimod (Aldara). In another embodiment, the invention is directed to a method of treating melanoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two immunotherapies independently selected from ipilimumab, interferon-alpha and interleukin-2. In another embodiment, the invention is directed to a method of treating melanoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is hormone therapy where the hormone therapy is tamoxifen.
In another embodiment, the invention is directed to a method of treating colon or rectal cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from surgery, radiation, one or two antibodies, and one or two chemotherapeutic agents. In another embodiment, the invention is directed to a method of treating colon or rectal cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is surgery selected from local excision, electrofulguration, segmental colon resection, polypectomy, local transanal resection, low anterior resection, abdominoperineal resection, and pelvic exenteration. In another embodiment, the invention is directed to a method of treating colon or rectal cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from a platinum-containing compound (including cisplatin, oxaliplatin, and carboplatin), 5-fluorouracil (5-FU), leucovorin, capecitabine (Xeloda), irinotecan (Camptosar), FOLFOX (Folinic acid, 5-FU, Oxaliplatin), and leucovorin. In another embodiment, the invention is directed to a method of treating colon or rectal cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two antibodies independently selected from cetuximab (Erbitux) and bevacizumab (Avastin).
In another embodiment, the invention is directed to a method of treating pancreatic cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from surgery, radiation, one or two antibodies, and one or two chemotherapeutic agents. In another embodiment, the invention is directed to a method of treating pancreatic cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is selected from one or two chemotherapeutic agents independently selected from platinum-containing compound (including cisplatin, oxaliplatin, and carboplatin), 5-fluorouracil (5-FU), gemcitabine, a taxane (including paclitaxel and docetaxel), topotecan, irinotecan, capecitabine, streptozocin, erlotinib (Tarceva), leucovorin, and capecitabine (Xeloda). In another embodiment, the invention is directed to a method of treating pancreatic cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is an antibody where the antibody is cetuximab.
In another embodiment, the invention is directed to a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from surgery, radiation, one or two chemotherapeutic agents, one or two hormone therapies, and one or two antibodies. In another embodiment, the invention is directed to a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two of the chemotherapeutic agents independently selected from lapatinib (Tykerb®), Paclitaxel (Taxol®), docetaxel, capecitabine, Cyclophosphamide (Cytoxan), CMF (cyclophosphamide, fluoruracil, and methotrexate), methotrexate, fluorouracil, doxorubicin, epirubicin, gemcitabine, carboplatin (Paraplatin), cisplatin (Platinol), vinorelbine (Navelbine), capecitabine (Xeloda), pegylated liposomal doxorubicin (Doxil), albumin-bound paclitaxel (Abraxane), AC (adriamycin and Cyclophosphamide), adriamyclin, and pamidronate or zoledronic acid (to treat bone weakness). In another embodiment, the invention is directed to a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two hormone therapies independently selected from tamoxifen, Toremifene (Fareston), Fulvestrant (Faslodex), Megestrol acetate (Megace), ovarian ablation, Raloxifene, a luteinizing hormone-releasing hormone (LHRH) analogs (including goserelin and leuprolide), Megestrol acetate (Megace), and one or more aromatase inhibitors. In another embodiment, the invention is directed to a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two hormone therapies and one of the hormone therapies is an aromatase inhibitors selected from letrozole (Femara), anastrozole (Arimidex), and exemestane (Aromasin). In another embodiment, the invention is directed to a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two antibodies independently selected from αIGF-1R A12 MoAb, αIGF-1R 19D12 MoAb, αIGF-1R h7C10 MoAb, αIGF-1R CP-751871 MoAb, bevacizumab (Avastin), and trastuzumab.
In another embodiment, the invention is directed to a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents and one of the chemotherapeutic agents is erlotinib.
In another embodiment, the invention is directed to a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two of the chemotherapeutic agents and one or two of the chemotherapeutic agents are independently selected from rapamycin, lapatinib, erlotinib, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof, and N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof.
In another embodiment, the invention is directed to a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two of the antibodies. In another embodiment, the invention is directed to a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two antibodies and one of the antibodies is trastuzumab.
In another embodiment, the invention is directed to a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two of the chemotherapeutic agents and one of the chemotherapeutic agents is selected from N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, and N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine; optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof.
In another embodiment, the invention is directed to a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two of the chemotherapeutic agents and one of the chemotherapeutic agents is N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta-[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof.
In another embodiment, the invention is directed to a method of treating non-small cell lung cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from surgery, radiation, one or more antibodies, and one or more chemotherapeutic agents. In another embodiment, the invention is directed to a method of treating non-small cell lung cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from cisplatin, oxaliplatin, carboplatin, Zactima (ZD6474), Paclitaxel, Docetaxel (Taxotere®), Gemcitabine (Gemzar®), Vinorelbine, Irinotecan, Etoposide, Vinblastine, Erlotinib (Tarceva®), gefitinib (Iressa), and Pemetrexed. In another embodiment, the invention is directed to a method of treating non-small cell lung cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is an antibody and the antibody is Bevacizumab. In another embodiment, the invention is directed to a method of treating non-small cell lung cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from cisplatin, oxaliplatin, carboplatin, Paclitaxel, Docetaxel (Taxotere®), and erlotinib (Tarceva®).
In another embodiment, the invention is directed to a method of treating non-small cell lung cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents and one of the chemotherapeutic agents is carboplatin.
In another embodiment, the invention is directed to a method of treating non-small cell lung cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents and one of the chemotherapeutic agents is selected from N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, and N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine; optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof. In another embodiment, the invention is directed to a method of treating non-small cell lung cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents and one of the chemotherapeutic agents is N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta-[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof.
In another embodiment, the invention is directed to a method of treating small cell lung cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from surgery, radiation, and one or two chemotherapeutic agents. In another embodiment, the invention is directed to a method of treating small cell lung cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapy agents independently selected from a platin (such as cisplatin, oxaliplatin, and carboplatin), gefitinib, vinorelbine, docetaxel, paclitaxel, etoposide, fosfamide, ifosfamide, cyclophosphamide, cyclophosphamide/doxorubicin/vincristine (CAV), doxorubicin, vincristine, gemcitabine, paclitaxel, vinorelbine, topotecan, irinotecan, methotrexate, and docetaxel.
In another embodiment, the invention is directed to a method of treating papillary or anaplastic thyroid cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from surgery, radiation, radioactive iodine therapy, one or two hormone therapies, and one or two chemotherapeutic agents. In another embodiment, the invention is directed to a method of treating papillary or anaplastic thyroid cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from thyroid hormone pills, Doxorubucin and a platin. In another embodiment, the invention is directed to a method of treating papillary or anaplastic thyroid cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is hormone therapy and the hormone therapy is radioiodine ablation.
In another embodiment, the invention is directed to a method of treating endometrial cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from surgery, radiation, one or two hormone therapies, and one or two chemotherapeutic agents. In another embodiment, the invention is directed to a method of treating endometrial cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two hormone therapies independently selected from megestrol acetate, Tamoxifen, and a progestin including medroxyprogesterone acetate (Provera) and megestrol acetate (Megace). In another embodiment, the invention is directed to a method of treating endometrial cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from a platinum-containing compound (including cisplatin, oxaliplatin, and carboplatin, more for example cisplatin), a taxane (including paclitaxel), doxorubicin (Adriamycin), cyclophosphamide, fluorouracil (5-FU), methotrexate, and vinblastine.
In another embodiment, the invention is directed to a method of treating ovarian cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from surgery, radiation, one or two antibodies, and one or two chemotherapeutic agents. In another embodiment, the invention is directed to a method of treating ovarian cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is an antibody and the antibody is bevacizumab. In another embodiment, the invention is directed to a method of treating ovarian cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from a platinum-containing compound (including cisplatin, oxaliplatin and carboplatin), a taxane (including paclitaxel and docetaxel), topotecan, an anthracyclines (including doxorubicin and liposomal doxorubicin), gemcitabine, cyclophosphamide, vinorelbine (Navelbine), hexamethylmelamine, ifosfamide, etoposide, bleomycin, vinblastine, ifosfamide, vincristine, and cyclophosphamide. In another embodiment, the invention is directed to a method of treating ovarian cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from a platin and a taxane. In another embodiment, the invention is directed to a method of treating ovarian cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from cisplatin, oxaliplatin, carboplatin, paclitaxel, and docetaxel.
In another embodiment, the invention is directed to a method of treating glioblastoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from surgery, radiation, one or two chemotherapeutic agents, one or two anti-seizure agents, and one or two agents to reduce swelling. In another embodiment, the invention is directed to a method of treating glioblastoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is radiation selected from external beam radiation, interstitial radiotherapy, and stereotactic radiosurgery. In another embodiment, the invention is directed to a method of treating glioblastoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from carmustine (BCNU), Erlotinib (Tarceva), bevacizumab, gefitinib (Iressa), rapamycin, temozolomide, cisplatin, BCNU, lomustine, procarbazine, and vincristine. In another embodiment, the invention is directed to a method of treating glioblastoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is an anti-seizure agent and the anti-seizure agent is diphenylhydantoin (Dilantin). In another embodiment, the invention is directed to a method of treating glioblastoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is an agents to reduce swelling and the agent is dexamethasone (Decadron). In another embodiment, the invention is directed to a method of treating glioblastoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents. In another embodiment, the invention is directed to a method of treating glioblastoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from erlotinib and temozolomide.
In another embodiment, the invention is directed to a method of treating cervical cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from surgery, radiation, and one or two chemotherapeutic agents. In another embodiment, the invention is directed to a method of treating cervical cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is surgery selected from cryosurgery, laser surgery, loop electrosurgical excision, conization, simple hysterectomy, and radical hysterectomy and pelvic lymph node dissection. In another embodiment, the invention is directed to a method of treating cervical cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is radiation selected from called external beam radiation therapy and brachytherapy. In another embodiment, the invention is directed to a method of treating cervical cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from a platinum compound (such as cisplatin, carboplatin, and oxaliplatin), paclitaxel, topotecan, ifosfamide, gemcitabine, vinorelbine, and fluorouracil.
In another embodiment, the invention is directed to a method of treating a gastrointestinal carcinoid tumor which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from surgery, radiation, immunotherapy, and one or two chemotherapeutic agents. In another embodiment, the invention is directed to a method of treating a gastrointestinal carcinoid tumor which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is surgery selected from excision and electrofulguration. In another embodiment, the invention is directed to a method of treating a gastrointestinal carcinoid tumor which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from cyproheptadine, SOM230, octreotide and lanreotide. In another embodiment, the invention is directed to a method of treating a gastrointestinal carcinoid tumor which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is immunotherapy and the immunotherapy is an interferon.
In another embodiment, the invention is directed to a method of treating a gastrointestinal stromal tumor which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from surgery, radiation, and one or two chemotherapeutic agents. In another embodiment, the invention is directed to a method of treating a gastrointestinal stromal tumor which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from imatinib mesylate (Gleevec), sunitinib (Sutent), and nilotinib (AMN107).
In another embodiment, the invention is directed to a method of treating hepatocellular carcinoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from surgery, radiofrequency ablation, ethanol ablation, cryosurgery, hepatic artery embolization, chemoembolization, radiation, and one or two chemotherapeutic agents. In another embodiment, the invention is directed to a method of treating hepatocellular carcinoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is surgery selected from resection and transplantation. In another embodiment, the invention is directed to a method of treating hepatocellular carcinoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from sorafenib, 5-fluorouracil and cisplatin.
In another embodiment, the invention is directed to a method of treating non-Hodgkin's lymphoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments independently selected from radiation, one or two chemotherapeutic agents, interferon therapy, one or two antibodies, and bone marrow or peripheral blood stem cell transplantation. In another embodiment, the invention is directed to a method of treating non-Hodgkin's lymphoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents selected from CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone), chlorambucil, fludarabine, and etoposide. In another embodiment, the invention is directed to a method of treating non-Hodgkin's lymphoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is an antibody selected from rituximab, ibritumomab tiuxetan, tositumomab, and alemtuzumab. In another embodiment, the invention is directed to a method of treating non-Hodgkin's lymphoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is an antibody and the anitbody is rituximab.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is radiation and another treatment is surgery.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is radiation and another treatment is one or two chemotherapeutic agents.
In another embodiment, the invention is directed to a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with one or more treatments where one of the treatments is surgery and another treatment is one or two chemotherapeutic agents.
For each of the foregoing embodiments, the Compound of Formula I is selected from any of the following embodiments, including from the Representative Compounds in Table 1.
One embodiment (A) of the invention is directed to a compound of Formula I where W1, W2, W3, and W4 are —C(R1)═; or one or two of W1, W2, W3, and W4 are independently —N═ and the remaining are —C(R1)═; where each R1 is independently hydrogen, alkyl, haloalkyl, nitro, alkoxy, haloalkoxy, halo, hydroxy, cyano, amino, alkylamino, or dialkylamino; and all other groups are as defined in the Summary of the Invention. In another embodiment, W1, W2, W3, and W4 are —C(R1)═ and each R1 is independently hydrogen or alkyl; or one of W1 and W4 is —N═ and the other is —C(H)═. In another embodiment, W1, W2, W3, and W4 are —C(R1)═ where each R1 is independently hydrogen or alkyl. In another embodiment, R1 is hydrogen.
Another embodiment (B) of the invention is a Compound of Formula I where R50 is hydrogen, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, hydroxy, alkoxy, alkenyloxy, haloalkoxy, nitro, amino, alkylamino, dialkylamino, —N(R55)C(O)—C1-C6-alkylene-N(R55a)R55b, alkylcarbonyl, alkenylcarbonyl, carboxy, alkoxycarbonyl, cyano, alkylthio, —S(O)2NR55R55a, or alkylcarbonylamino; where R55 and R55b are independently hydrogen, alkyl, or alkenyl and R55a is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy; and all other groups are as defined in the Summary of the Invention. In another embodiment, R50 is hydrogen.
Another embodiment (C) of the invention is a Compound of Formula I where R51 is hydrogen or alkyl; and all other groups are as defined in the Summary of the Invention. In another embodiment, R51 is alkyl. In another embodiment, R51 is methyl.
Another embodiment (D) of the invention is a Compound of Formula I where R52 is hydrogen or halo; and all other groups are as defined in the Summary of the Invention. In another embodiment R52 is hydrogen or fluoro. In another embodiment, R52 is hydrogen.
Another embodiment (E) of the invention is a Compound of Formula I where R53 is hydrogen, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, hydroxy, alkoxy, alkenyloxy, haloalkoxy, nitro, amino, alkylamino, dialkylamino, —N(R55)C(O)—C1-C6-alkylene-N(R55a)R55b, alkylcarbonyl, alkenylcarbonyl, carboxy, alkoxycarbonyl, cyano, alkylthio, —S(O)2NR55R55a, or alkylcarbonylamino; where R55 and R55b are independently hydrogen, alkyl, or alkenyl and R55a is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy; and all other groups are as defined in the Summary of the Invention. In another embodiment, R53 is hydrogen, alkoxy, nitro, amino, or —N(R55)C(O)—C1-C6-alkylene-N(R55a)R55b. In another embodiment, R53 is hydrogen, methoxy, nitro, amino, or —NHC(O)CH2N(CH3)2. In another embodiment, R53 is hydrogen or methoxy.
Another embodiment (F) of the invention is a Compound of Formula I where R54 is hydrogen, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, hydroxy, alkoxy, alkenyloxy, haloalkoxy, nitro, amino, alkylamino, dialkylamino, —N(R55)C(O)—C1-C6-alkylene-N(R55a)R55b, alkylcarbonyl, alkenylcarbonyl, carboxy, alkoxycarbonyl, cyano, alkylthio, —S(O)2NR55R55a, or alkylcarbonylamino; where R55 and R55′′ are independently hydrogen, alkyl, or alkenyl and R55a is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy; and all other groups are as defined in the Summary of the Invention. In another embodiment, R54 is hydrogen, alkyl, alkoxy, or halo. In another embodiment, R54 is hydrogen, methyl, methoxy, bromo, or chloro. In another embodiment, R54 is hydrogen, methoxy, or chloro.
Another embodiment (G) of the invention is directed to a compound of Formula I where R50, R52, and R53 are hydrogen and R54 is halo or alkoxy; R50, R52, and R54 are hydrogen and R53 is alkoxy; or R50 and R52 are hydrogen and R53 and R54 together with the carbons to which they are attached form a 6-membered heteroaryl; and all other groups are as defined in the Summary of the Invention. In another embodiment, R50, R52, and R53 are hydrogen and R54 is chloro or methoxy; R50, R52, and R54 are hydrogen and R53 is methoxy; or R50 and R52 are hydrogen and R53 and R54 together with the carbons to which they are attached form pyridinyl. Even more specifically, R50, R52, and R53 are hydrogen and R54 is chloro or methoxy; or R50, R52, and R54 are hydrogen and R53 is methoxy.
In another embodiment (G1) of embodiment G is a compound of Formula I where R51 is methyl.
Another embodiment (H) of the invention is a compound of Formula I where B is phenyl substituted with R3a and optionally further substituted with one, two, or three R3; and all other groups are as defined in the Summary of the Invention. In another embodiment, B is phenyl substituted with R3a. In another embodiment the Compound is of Formula I(a):




In another embodiment, B is phenyl substituted with R3a as depicted in Ia and is not further substituted with R3.

Another embodiment of the Invention (J) is directed to a compound of Formula I where B is heteroaryl optionally substituted with one, two, or three R3. In another embodiment, B is thien-3-yl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, oxazolyl, isoxazolyl, pyrrolyl, imidazolyl, pyrazolyl, or thiazolyl, each of which is optionally substituted with one or two R3. In another embodiment, B is thien-3-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, imidazol-2-yl, pyrrol-2-yl, pyrrol-3-yl, imidazol-4-yl, imidazol-5-yl, pyrazol-3-yl, pyrazol-4-yl, or pyrazol-5-yl, each of which is optionally substituted with one or two R3. In another embodiment, B is thien-3-yl, pyridin-3-yl, pyridin-4-yl, isoxazol-4-yl, or pyrazol-4-yl, each of which is optionally substituted with one or two R3. In another embodiment, B is pyridin-3-yl, 2-hydroxy-pyridin-5-yl, isoxazol-4-yl, or pyrazol-4-yl, each of which is optionally substituted with one or two R3.
Another embodiment (K) provides a compound of Formula I or Ia where R3a is cyano; hydroxyamino; carboxy; alkylsulfonyl, aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; —N(R7)C(O)—C1-C6-alkylene-N(R7a)(R7b); —C(O)NR8R8a; —NR9C(O)R9a; —C(O)N(R10—C1-C6-alkylene-N(R10a)R10b; —NR11C(O)NR11aR11b where R11a; —C(O)R12; —NR13C(O)OR13a; —C(O)N(R14)N(R14a)(R14b); —S(O)2N(R15)—C1-C6-alkylene-N(R15a)R15b; —C(O)N(R16)—C1-C6-alkylene-C(O)OR16a; heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; —N(R17)— C(═N(R17b)(R17a))(NR17cR17d); —N(R18)C(O)—C1-C6-alkylene-N(R18b)C(O)R18a; —C(O)N(R19)—C1-C6-alkylene-C(O)R19a; —N(R22)C(O)—C1-C6-alkylene-N(R22b)—N(R22c)(R22a); —C0-C6-alkylene-N(R23)—C1-C6-alkylene-N(R23b)R23a; or —NR24C(O)—C1-C6-alkylene-OR24a; where each of the alkylene in R3a is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, amino, alkylamino, and dialkylamino; and all other groups are as defined in the Summary of the Invention.
In another embodiment, R3a is —NHC(O)CH2NH(CH3), —NHC(O)CH2NH(CH2CH3), —NHC(O)CH(CH3)NH2, —NHC(O)C(CH3)2NH2, —NHC(O)CH2N(CH3)2, —NHC(O)CH2N(CH3)CH2CH2N(CH3)2, —NHC (O)CH(NH2)CH2CH3, —NHC(O)CH2N(CH3)CH2CH2N(CH3)2, —NHC(O)CH(CH3)NH(CH3), —NHC(O)CH2NH2, —NHC(O)H, —NHC(O)CH2(azetidin-1-yl), —NHC(O)(pyrrolidin-2-yl), —NHC(O)CH(NH2)CH2OH, —NHC(O)(azetidin-4-yl), —NHC(O)C(CH3)2NH(CH3), —NH2, —NHC(O)CH2NH(CH2CH2CH3), —NHC(O)CH2CH2NH2, —NHOH, —NHC(O)(piperidin-3-yl), —NHC(O)CH2(4-methyl-1,4-diazepan-1-yl), —NHC(O)CH(NH2)(CH2CH3), —NHC(O)CH2NH(CH2CH(OH)(CH3)), —NHC(O)CH2NHCH2CH2F, —NHC(O)CH2NH(OCH2CH(CH3)2), —NHC(O)(1-aminocycloprop-1-yl), —NHC(O)CH2NH(CH2cyclopropyl), —NHC(O)CH2(3-(dimethylamino)-azetidin-1-yl), —NHC(O)(piperidin-2-yl), —NHC(O)(morpholin-4-yl), —NHC(O)CH2(pyrrolidin-1-yl), —NHC(O)CH(NH2)CH2CH2CH2CH2N(CH3)2, —NHC(O)CH2N(CH3)(CH2CH3), —NHC(O)CH2(imidazol-5-yl), —NHC(O)(1-aminocyclopent-1-yl), —NHC(O)CH2NH(CH2CH(CH3)2), —NHC(O)CH2N(CH3)(CH2CH3), —NHC(O)(N-(imidazol-4-ylmethyl)-azetidin-3-yl), —NHC(O)(N-ethyl-azetidin-3-yl), —NHCH2N(CH3)CH2CH2N(CH3)2, —NHC(O)CH2N(CH3)(N-methyl-pyrrolidin-3-yl), —NHC(O)CH2N(CH3)(CH2CH2N(CH3)2), —NHC(O)CH2(3-hydroxy-pyrrolidin-1-yl), —NHC(O)(1-amino-cyclobut-1-yl), —NHC(O)CH2NH(CH2)3CH3, —NHC(O)CH2(3-piperidin-1-ylazetidin-1yl), —NHC(O)NH2, —NHC(O)(1-hydroxycyclopropyl), —NHC(O)CH2NHN(CH3)2, —NHC(O)NH(CH2)2N(CH3)2, —NHC(O)CH2OH, —NHC(O)(pyridazin-4-yl), —NHC(O)(N-methyl-piperidin-4-yl), —NHC(O)CH2NHCH(CH3)3, —NHC(O)CH2(3-dimethylamino-pyrrolidin-1yl), —NHC(O)CH2NH(CH2)2N(CH3)2, —NHC(O)(1-cyclopropylmethyl-azetidin-3-yl), —NHC(O)CH2NH(CH3)3, —NHC(O)(imidazol-2-yl), —NHC(O)(imidazol-4-yl), —NHC(O)(1,2-oxazol-5-yl), —NHC(O)CH2NHCH2CF3, —NHC(O)CH2CH2(piperidin-1-yl), —NHC(O)(3-oxo-cyclopent-1-yl), —NHC(O)(2-hydroxy-pyridin-6-yl), —NHC(O)CH2NH(3-fluoro-4-hydroxyphenyl), —NHC(O)(CH2)3N(CH3)2, —NHC(O)(1-(furan-2-ylmethyl)-azetidin-3-yl), —NHC(O)(pyrimidin-5-yl), —NHC(O)(pyrrol-2-yl), —NHC(O)CH2N(CH3)CH(CH3)2, —NHC(O)CH2N(CH2CH3)2, —NHC(O)CH2(3-methyl-1,2-oxazol-5-yl), —NHC(O)CH2NHCH2(3-hydroxyphenyl), —NHC(O)(N-methyl-pyrrol-2-yl), —NHC(O)(2-amino-tetrahydropyran-2-yl), —NHC(O)CH2(4-methylamino-piperidin-1-yl), —NHC(O)(piperidin-1-yl), —NHC(O)(N-methyl-pyrrolidin-2-yl), —NHC(O)(thien-3-yl), —NHC(O)(N-(cyclopropylcarbonyl)azetidin-3-yl), —NHC(O)CH2(4-methylpiperazin-1-yl), —NHC(O)(N-benzylazetidin-3-yl), —NHC(O)(2-chloro-pyridin-3-yl), —NHC(O)CH2(Pyridin-4-yl), —NHC(O)CH2N(CH3)(CH2CH═CH2), —NHC(O)CH2NH(benzyl), —NHC(O)CH2OCH3, —NHC(O)[1-(C(O)CH2CH3)-azetidin-3-yl], —NHC(O)(pyridin-3-yl), —NHC(O)CH2NHCH2CH2OCH3, —NHC(O)(1-[C(O)CH3]piperidin-4-yl), —NHC(O)CH2(2-methyl-pyrrolidin-1-yl), —NHC(O)(furan-3-yl), —NHC(O)CH2N(CH3)2, —NHC(O)(2-chloro-pyridin-5-yl), —NHC(O)(2-chlorophenyl), —NHC(O)CH2(pyridin-2-yl), —NHC(O)CH2(3-dimethylamino-azetidin-1-yl), —NHC(O)CH2(pyridin-3-yl), —NHC(O)CH2(2-chlorophenyl), —NHC(O)CH2N(CH3)CH2CH2CH2N(CH3)2, —NHC(O)CH2N(CH2CH3)CH2CH2OH, —NHC(O)CH2(2-benzyl-pyrrolidin-1-yl), —NHC(O)(furan-2-yl, —NHC(O)(2-chloro-pyridin-4-yl), —NHC(O)CH2NHC(O)CH3, —NHC(O)CH2CH2CH3, —NHC(O)(4-chlorophenyl), —NHC(O)(4-methyl-phenyl), —NHC(O)CH2NHC(O)O(CH3)3, —NHC(O)(benzo[d][1,3]dioxol-5-yl), —NHC(O)CH2NHOCH2(2-methoxyphenyl), —NHC(O)(pyridin-4-yl), —NHC(O)CH2[4-(3,4-dichlorophenyl)-piperazin-1-yl], —NHC(O)CH2CH2(pyridin-3-yl), —NHC(O)(tetrahydrofuran-3-yl), —NHC(O)CH2NHCH2(2-methylphenyl), —NHC(O)CH(CH3)CH2CH3, —NHC(O)CH2(3-fluorophenyl), —NHC(O)CH2C(CH3)2phenyl, —NHC(O)(2-methyl-cycloprop-1-yl), —NHC(O)(2-methyl-4-methoxyphenyl), —NHC(O)(2-methylpyridin-3-yl), —NHC(O)(4-methoxyphenyl), —NHC(O)CH2(4-ethylpiperazin-1-yl), —NHC(O)(thien-2-yl), —NHC(O)(3-fluoro-2-methylphenyl), —NHC(O)(2-bromo-thien-3-yl), —NHC(O)(4-fluorophenyl), —NHC(O)CH2(3-methylpiperidin-1-yl), —NHC(O)CH(CH3)2, —NHC(O)(CH2)3CH3, —NHC(O)CH2OCH2CH3, —NHC(O)CH2NH(2-fluorophenyl), —NHC(O)(3-dimethylaminophenyl), —NHC(O)CH2(4-methylpiperidin-1-yl), —NHC(O)CH2NH(2-n-propylphenyl), —NHC(O)phenyl, —NHC(O)(pyrazin2-yl), —NHC(O)(3-fluoro-4-methoxyphenyl), —NHC(O)C(CH3)2CH2CH3, —NHC(O)CH2O(4-fluorophenyl), —NHC(O)(1-methylcarbonyl-azetidin-3-yl), —NHC(O)CH2NH(4-methylphenyl), —NHC(O)CH2NH(phenyl), —NHC(O)CH2(4-allyl-piperazin-1-yl), —NHC(O)(2-methylphenyl), —NHC(O)CH2CH2OCH3, —NHC(O)(3-methyl-furan-2-yl), —NHC(O)C(CH3)3, —NHC(O)CH2NHObenzyl, —NHC(O)CH2NH(3-chlorophenyl), —NHC(O)cyclobutyl, —NHC(O)CH2(3-methoxyphenyl), —NHC(O)(1-methylcycloprop-1-yl), —NHC(O)(3-fluorophenyl), —NHC(O)(4-dimethylaminophenyl), —NHC(O)(3,4-dichlorophenyl), —NHC(O)CH2NHCH2(2-methylthiophenyl), —NHC(O)CH2(2-fluorophenyl), —NHC(O)CH2N(CH2CH3)CH(CH3)2, —NHC(O)(thiazol-4-yl), —NHC(O)CH2N(CH3)benzyl, —NHC(O)CH2NHCH2(thien-2-yl), —NHC(O)CH2NHCH2(pyridin-2-yl), —NHC(O)(3-methoxyphenyl), —NHC(O)CH2NHCH2(3-chloro-4-methylphenyl), —NHC(O)CH(CH3)CH2CH2CH3, —NHC(O)CH2(4-chlorophenyl), —NHC(O)(3-fluoro-4-methylphenyl), —NHC(O)CH2O(2-methylphenyl), —NHC(O)CH2(cyclohexyl), —NHC(O)(2-phenyl-cycloprop-1-yl), —NHC(O)(3-chlorophenyl), —NHC(O)CH2(2-methoxyphenyl), —NHC(O)CH2CH2(3-methoxyphenyl), —NHC(O)CH2NH(2-fluoro-4-methylphenyl), —NHC(O)CH2NHCH2(3-fluoro-phenyl), —NHC(O)CH2(4-methoxy-phenyl), —NHC(O)benzyl, —NHC(O)(2,4-dichlorophenyl), —NHC(O)(3-oxo-cyclohex-1-yl), —NHC(O)CH2NH(3-fluorophenyl), —NHC(O)CH2(3-chlorophenyl), —NHC(O)CH2NHCH2CH(CH3)phenyl, —NHC(O)CH2NHCH2(2,4-dimethylphenyl), —NHC(O)CH2(2-methyl-piperidin-1-yl), —NHC(O)CH2NH(2-methoxyphenyl), —NHC(O)CH2(1,2,3,4-tetrahydroisoquinolin-2-yl), —NHC(O)CH2CH2CH═CH2, —NHC(O)CH2NH(2-methylphenyl), —NHC(O)CH2(4-oxo-piperidin-1-yl), —NHC(O)(2-fluorophenyl), —NHC(O)CH2NHCH(CH3)phenyl, —NHC(O)(2-fluoro-6-methoxyphenyl), —NHC(O)CH2NH(2-isopropylphenyl), —NHC(O)CH2CH2(2-methoxyphenyl), —NHC(O)CH2CH2CH(CH3)2, —NHC(O)CH2(2-phenyl-morpholin-4-yl), —NHC(O)CH2CH2(4-methoxyphenyl), —NHC(O)CH2N(allyl)cyclopentyl, —NHC(O)CH2N(CH3)CH2CH2OCH3, —NHC(O)CH2CH2C(O)cyclopropyl, —NHC(O)CH2NH(3-tert-butylphenyl), —NHC(O)CH2N(n-propyl)(cyclopropylmethyl), —NHC(O)CH2(2-oxo-cyclopentyl), —NHC(O)CH2NH(4-chlorophenyl), —NHC(O)CH2(4-piperidin-1-ylpiperidin-1-yl), —NHC(O)CH2(4-cyclopentylpiperazin-1-yl), —NHC(O)CH2(2-methylphenyl), —NHC(O)CH2NHCH2(3-fluoro-6-methylphenyl), —NHC(O)CH2C(CH3)3, —NHC(O)CH2NH(2-chlorophenyl), —NHC(O)(3-fluoro-6-methylphenyl), —NHC(O)(4-fluoro-3-methylphenyl), —NHC(O)(2,3-dichlorophenyl), —NHC(O)CH2O phenyl, —NHC(O)CH2NH(2,3-dimethylphenyl), —NHC(O)(2-fluoro-5-methylphenyl), —NHC(O)CH2NHOCH2(4-methylphenyl), —NHC(O)CH2(4-isopropylpiperazin-1-yl), —NHC(O)CH2(4-fluorophenyl), —NHC(O)CH2CH(CH3)2, —NHC(O)(2-methoxy-4-methylphenyl), —NHC(O)CH2(4-n-propylpiperidin-1-yl), —NHC(O)CH2O(3-methylphenyl), —NHC(O)(tetrahydrofuran-2-yl), —NHC(O)CH2(3-hydroxymethylpiperidin-1-yl), —NHC(O)(1-tert-butoxycarbonylpiperidin-2-yl), —NHC(O)CH2N(CH3)CH2(pyridin-3-yl), —NHC(O)CH2N(CH2CH3)phenyl, —NHC(O)CH2OCH2CH2OCH3, —NHC(O)CH2CH2(cyclopentyl), —NHC(O)(2,5-dichlorophenyl), —NHC(O)CH2(4-methylcarbonylpiperazin-1-yl), —NHC(O)(5-fluoro-2-methoxyphenyl), —NHC(O)CH2N(CH2CH3)cyclohexyl, —NHC(O)(5-methyl-1,2-oxazol-3-yl), —NHC(O)(3-methylpyridin-3-yl), —NHC(O)(2-methoxypyridin-3-yl), —NHC(O)(3,5-dichlorophenyl), —NHC(O)CH2(thiazolidin3-yl), —NHC(O)CH2(4-[C(O)H]-piperazin-1-yl), —NHC(O)CH2(2-pyridin-4-ylpiperidin-1-yl), —NHC(O)(2-methoxyphenyl), —NHC(O)CH2N(CH3)CH2CH(CH3)2, —NHC(O)CH2(4-[C(O)H]-homopiperazin-1-yl), —NHC(O)(1-phenylcycloprop-1-yl), —NHC(O)CH2(2,6-dimethylmorpholin-4-yl), NHC(O)CH2(2-phenylpyrrolidin-1-yl), —NHC(O)CH2(morpholin-4-yl), —C(O)NHCH(CH3)CH2N(CH3)2, —C(O)NHCH2CH2N(CH3)2, —C(O)NH(pyrrolidin-3-yl), —C(O)NHCH2CH2(pyrrolidin-1-yl), —C(O)NHCH2CH2NH2, —C(O)N(CH3)CH2CH2N(CH3)2, —C(O)NHCH2(piperidin-2-yl), —C(O)NH(1-methylazetidin-3-yl), —C(O)NHCH2CH2(piperidin-1-yl), —C(O)NHCH2CH2N(CH2CH3)2, —C(O)NH(1-methylpiperidin-3-yl), —C(O)NH(piperidin-3-yl), —C(O)NHCH2(1-methylpiperidin-3-yl), —C(O)NHCH2CH2N(CH2CH2OH)2, —C(O)NH(1-ethylpiperidin-3-yl), —C(O)NH2, —C(O)(3-aminopyrrolidin-1-yl), —C(O)(3-methylaminopyrrolidin-1-yl), —C(O)OH, —C(O)NHCH2CH2(morpholin-4-yl), —C(O)NHCH2(1-ethylpyrrolidin-2-yl), —C(O)(4-amino-3-oxo-pyrazolidin-1-yl), —C(O)NHCH3, —C(O)(3-aminocyclobut-1-yl), —C(O)NHCH2(pyridin-3-yl), —C(O)NHCH2CH2OH, —C(O)NH(3-oxo-pyrazolidin-4-yl), —NHCH2CH2(imidazol-4-yl), —C(O)(3-dimethylaminopyrrolidin-1-yl), —C(O)NHCH2(pyridin-4-yl), —C(O)N(CH3)(1-methyl-pyrrolidin-3-yl), —C(O)(3-diethylaminopyrrolidin-1-yl), —C(O)NH(pyrrol-1-yl), —C(O)NHCH2CH2CH2(pyrrolidin-1-yl), —C(O)N(CH3)CH2CH2CN, —C(O)NHCH2CH2OCH3, —C(O)N(CH2CH3)CH2CH2CN, —C(O)(3-aminopiperidin-1-yl), —C(O)NHCH2CH2CH2N(CH3)2, —C(O)NH(morpholin-4-yl), —C(O)NHN(CH3)2, —C(O)NHCH2CH2CH2(imidazol-1-yl), —C(O)NHCH2CH2CH2N(CH2CH3)2, —C(O)NHCH2CH2CN, —C(O)NHCH2CH2C(O)OCH3, —C(O)NHCH2CH2SCH3, —C(O)NHCH2CH2SCH2CH3, —C(O)N(CH2CH3)CH2CH2N(CH3)2, —C(O)NHCH2CH2CH2(2-oxo-pyrrolidin-1-yl), —C(O)NHCH2CH2(pyridin-4-yl), —C(O)NHCH2CH2CH2OCH2CH3, —C(O)NHCH2CH2CH2(morpholin-4-yl), —C(O)NHCH2CH2CH2OCH3, —C(O)N(CH3)CH2CH2CH2N(CH3)2, —C(O)NHCH2CH2CH2OCH2CH2CH3, —C(O)NHCH2CH2C(O)OCH2CH3, —C(O)NHCH2CH2CH2OCH(CH3)2, —C(O)NHC(CH3)2CH2(piperidin-1-yl), —C(O)N(CH3)CH2CH2CH3, —C(O)NH(piperidin-1-yl), —C(O)NHCH(CH3)CH2OCH3, —C(O)NHC(CH3)2CH2(morpholin-4-yl), —C(O)(2-dimethylaminomethylpiperidin-1-yl), —C(O)NH(CH2)3—O—(CH2)3CH3, —C(O)NHCH(CH3)(CH2)3N(CH2CH3)2, —C(O)NHC(CH3)2C(O)(piperidin-1-yl), —C(O)(4-methylpiperazin-1-yl), —C(O)(2-piperidin-1-ylmethyl-piperidin-1-yl), cyano, —NHCH3, —CH(CH3)NHCH2CH2N(CH3)2, —C(O)CH3, —S(O)2NHCH2CH2N(CH3)2, —S(O)2NH(CH2)3N(CH3)2, 5-(N,N-dimethylaminomethyl)-1,3,4-oxadiazol-2-yl, —NHCH2CH2N(CH3)2, —N(CH3)2, —OCH2CH2N(CH3)2, —NHC[N(CH3)2][═N(CH3)2], —OCH F2, —S(O)2CH3, —OCF3, or —NHC(O)CH2(4-dimethylaminopiperidin-1-yl).
In another embodiment (L), the compound of Formula I or Ia is that where R1a is hydroxyamino, —N(R7)C(O)—C1-C6-alkylene-N(R7a)(R7b), —C(O)NR8R8a, —NR9C(O)R9a, —C(O)N(R10—C1-C6-alkylene-N(R10a)R10b, —NR11C(O)NR11aR11b, —N(R22)C(O)—C1-C6-alkyene-N(R22b)—N(R22c)(R22a), —NR13C(O)OR13a, —N(R18)C(O)—C1-C6-alkylene-N(R18b)C(O)R18a, —NR24C(O)—C1-C6-alkylene-OR24a, or —N(R20)C(O)—C1-C6-alkylene-C(O)R20a; where each of the alkylene in R3a is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino; and all other groups are as defined in the Summary of the Invention. In another embodiment, R3a is —NHC(O)CH2NH(CH3), —NHC(O)CH(CH3)NH2, —NHC(O)C(CH3)2NH2, —NHC(O)CH2N(C H3)2, —NHC(O)CH2N(CH3)CH2CH2N(CH3)2, —NHC(O)CH(NH2)CH2CH3, —NHC(O)CH2N(C H3)CH2CH2N(CH3)2, —NHC(O)CH(CH3)NH(CH3), —NHC(O)H, —NHC(O)CH2(azetidin-1-yl), —NHC(O)(pyrrolidin-2-yl), —NHC(O)CH(NH2)CH2OH, —NHC(O)(azetidin-4-yl), —NHC(O)C(CH3)2NH(CH3), —NH2, —NHC(O)CH2NH(CH2CH2CH3), —NHC(O)CH2CH2NH2, —NHOH, or —NHC(O)(piperidin-3-yl).
In another embodiment (M) the compound is of Formula I or Ia and R3a—N(R7)C(O)—C1-C6-alkylene-N(R7a)(R7b); and R7 is hydrogen or alkyl and R7a and R7b are independently hydrogen, alkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; and all other groups are as defined in the Summary of the Invention. In another embodiment, R3a is —NHC(O)CH2NH(CH3), —NHC(O)CH(CH3)NH2, —NHC(O)C(CH3)2NH2, —NHC(O)CH2N(CH3)2, —NHC(O)CH2N(CH3)CH2CH2N(CH3)2, —NHC(O)CH(NH2)CH2CH3, —NHC(O)CH2N(CH3)CH2CH2N(CH3)2, or —NHC(O)CH(CH3)NH(CH3).
Embodiment (N) provides a compound of Formula I where each R3 is independently halo; cyano; alkyl; alkenyl; alkoxy; hydroxyamino; carboxy; alkylsulfonyl, aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; —N(R7)C(O)—C1-C6-alkylene-N(R7a)(R7b); —C(O)NR8R8a; —NR9C(O)R9a; —C(O)N(R10)—C1-C6-alkylene-N(R10a)R10b; —(NR11C(O)NR11aR11b where R11a; —C(O)R12; —NR13C(O)OR13a; —C(O)N(R14)N(R14a)(R14b); —S(O)2N(R15)—C1-C6-alkylene-N(R15a)R15b; —C(O)N(R16)—C1-C6-alkylene-C(O)OR16a; heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; —N(R17)—C(═N(R17b)(R17a))(NR17c)(R17d); —N(R18)C(O)—C1-C6-alkylene-N(R18b)C(O)R18a; —C(O)N(R19)—C1-C6-alkylene-C(O)R19a; —N(R22)C(O)—C1-C6-alkylene-N(R22b)—N(R22c)(R22a); —C0-C6-alkylene-N(R23)—C1-C6-alkylene-N(R23b)R23a; or —NR24C(O)—C1-C6-alkylene-OR24a; where each of the alkylene in R3 is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, amino, alkylamino, and dialkylamino; and all other groups are as defined in the Summary of the Invention.
In another embodiment, each R3 is independently methyl, bromo, chloro, fluoro, —NHC(O)CH2NH(CH3), —NHC(O)CH2NH(CH2CH3), —NHC(O)CH(CH3)NH2, —NHC(O)C(CH3)2NH2, —NHC(O)CH2N(CH3)2, —NHC(O)CH2N(CH3)CH2CH2N(CH3)2, —NHC(O)CH(NH2)CH2CH3, —NHC(O)CH2N(CH3)CH2CH2N(CH3)2, —NHC(O)CH(CH3)NH(CH3), —NHC(O)CH2NH2, —NHC(O)H, —NHC(O)CH2(azetidin-1-yl), —NHC(O)(pyrrolidin-2-yl), —NHC(O)CH(NH2)CH2OH, —NHC(O)(azetidin-4-yl), —NHC(O)C(CH3)2NH(CH3), —NH2, —NHC(O)CH2NH(CH2CH2CH3), —NHC(O)CH2CH2NH2, —NHOH, —NHC(O)(piperidin-3-yl), —NHC(O)CH2(4-methyl-1,4-diazepan-1-yl), —NHC(O)CH(NH2)(CH2CH3), —NHC(O)CH2NH(CH2CH(OH)(CH3)), —NHC(O)CH2NHCH2CH2F, —NHC(O)CH2NH(OCH2CH(CH3)2), —NHC(O)(1-aminocycloprop-1-yl), —NHC(O)CH2NH(CH2cyclopropyl), —NHC(O)CH2(3-(dimethylamino)-azetidin-1-yl), —NHC(O)(piperidin-2-yl), —NHC(O)(morpholin-4-yl), —NHC(O)CH2(pyrrolidin-1-yl), —NHC(O)CH(NH2)CH2CH2CH2CH2N(CH3)2, —NHC(O)CH2N(CH3)(CH2CH3), —NHC(O)CH2(imidazol-5-yl), —NHC(O)(1-aminocyclopent-1-yl), —NHC(O)CH2NH(CH2CH(CH3)2), —NHC(O)CH2N(CH3)(CH2CH3), —NHC(O)(N-(imidazol-4-ylmethyl)-azetidin-3-yl), —NHC(O)(N-ethyl-azetidin-3-yl), —NHCH2N(CH3)CH2CH2N(CH3)2, —NHC(O)CH2N(CH3)(N-methyl-pyrrolidin-3-yl), —NHC(O)CH2N(CH3)(CH2CH2N(CH3)2), —NHC(O)CH2(3-hydroxy-pyrrolidin-1-yl), —NHC(O)(1-amino-cyclobut-1-yl), —NHC(O)CH2NH(CH2)3CH3, —NHC(O)CH2(3-piperidin-1-ylazetidin-1-yl), —NHC(O)NH2, —NHC(O)(1-hydroxycyclopropyl), —NHC(O)CH2NHN(CH3)2, —NHC(O)NH(CH2)2N(CH3)2, —NHC(O)CH2 OH, —NHC(O)(pyridazin-4-yl), —NHC(O)(N-methyl-piperidin-4-yl), —NHC(O)CH2NHCH(CH3)3, —NHC(O)CH2(3-dimethylamino-pyrolidin-1-yl), —NHC(O)CH2NH(CH2)2N(CH3)2, —NHC(O)(1-cyclopropylmethyl-azetidin-3-yl), —NHC(O)CH2NH(CH3)3, —NHC(O)(imidazol-2-yl), —NHC(O)(imidazol-4-yl), —NHC(O)(1,2-oxazol-5-yl), —NHC(O)CH2NHCH2CF3, —NHC(O)CH2CH2(piperidin-1-yl), —NHC(O)(3-oxo-cyclopent-1-yl), —NHC(O)(2-hydroxy-pyridin-6-yl), —NHC(O)CH2NH(3-fluoro-4-hydroxyphenyl), —NHC(O)(CH2)3N(CH3)2, —NHC(O)(1-(furan-2-ylmethyl)-azetidin-3-yl), —NHC(O)(pyrimidin-5-yl), —NHC(O)(pyrrol-2-yl), —NHC(O)CH2N(CH3)CH(CH3)2, —NHC(O)CH2N(CH2CH3)2, —NHC(O)CH2(3-methyl-1,2-oxazol-5-yl), —NHC(O)CH2NHCH2(3-hydroxyphenyl), —NHC(O)(N-methyl-pyrrol-2-yl), —NHC(O)(2-amino-tetrahydropyran-2-yl), —NHC(O)CH2(4-methylamino-piperidin-1-yl), —NHC(O)(piperidin-1-yl), —NHC(O)(N-methyl-pyrrolidin-2-yl), —NHC(O)(thien-3-yl), —NHC(O)(N-(cyclopropylcarbonyl)azetidin-3-yl), —NHC(O)CH2(4-methylpiperazin-1-yl), —NHC(O)(N-benzylazetidin-3-yl), —NHC(O)(2-chloro-pyridin-3-yl), —NHC(O)CH2(pyridin-4-yl), —NHC(O)CH2N(CH3)(CH2CH═CH2), —NHC(O)CH2NH(benzyl), —NHC(O)CH2OCH3, —NHC(O)[1-(C(O)CH2CH3)-azetidin-3-yl], —NHC(O)(pyridin-3-yl), —NHC(O)CH2NHCH2CH2OCH3, —NHC(O)(1-[C(O)CH3]piperidin-4-yl), —NHC(O)CH2(2-methyl-pyrrolidin-1-yl), —NHC(O)(furan-3-yl), —NHC(O)CH2N(CH3)2, —NHC(O)(2-chloro-pyridin-5-yl), —NHC(O)(2-chlorophenyl), —NHC(O)CH2(pyridin-2-yl), —NHC(O)CH2(3-dimethylamino-azetidin-1-yl), —NHC(O)CH2(pyridin-3-yl), —NHC(O)CH2(2-chlorophenyl), —NHC(O)CH2N(CH3)CH2CH2CH2N(CH3)2, —NHC(O)CH2N(CH2CH3)CH2CH2OH, —NHC(O)CH2(2-benzyl-pyrrolidin-1-yl), —NHC(O)(furan-2-yl, —NHC(O)(2-chloro-pyridin-4-yl), —NHC(O)CH2NHC(O)CH3, —NHC(O)CH2CH2CH3, —NHC(O)(4-chlorophenyl), —NHC(O)(4-methyl-phenyl), —NHC(O)CH2NHC(O)O(CH3)3, —NHC(O)(benzo[d][1,3]dioxol-5-yl), —NHC(O)CH2NHOCH2(2-methoxyphenyl), —NHC(O)(pyridin-4-yl), —NHC(O)CH2[4-(3,4-dichlorophenyl)-piperazin-1-yl], —NHC(O)CH2CH2(pyridin-3-yl), —NHC(O)(tetrahydrofuran-3-yl), —NHC(O)CH2NHCH2(2-methylphenyl), —NHC(O)CH(CH3)CH2CH3, —NHC(O)CH2(3-fluorophenyl), —NHC(O)CH2C(CH3)2-phenyl, —NHC(O)(2-methyl-cycloprop-1-yl), —NHC(O)(2-methyl-4-methoxyphenyl), —NHC(O)(2-methylpyridin-3-yl), —NHC(O)(4-methoxyphenyl), —NHC(O)CH2(4-ethylpiperazin-1-yl), —NHC(O)(thien-2-yl), —NHC(O)(3-fluoro-2-methylphenyl), —NHC(O)(2-bromo-thien-3-yl), —NHC(O)(4-fluorophenyl), —NHC(O)CH2(3-methylpiperidin-1-yl), —NHC(O)CH(CH3)2, —NHC(O)(CH2)3CH3, —NHC(O)CH2OCH2CH3, —NHC(O)CH2NH(2-fluorophenyl), —NHC(O)(3-dimethylaminophenyl), —NHC(O)CH2(4-methylpiperidin-1-yl), —NHC(O)CH2NH(2-n-propylphenyl), —NHC(O)phenyl, —NHC(O)(pyrazin2-yl), —NHC(O)(3-fluoro-4-methoxyphenyl), —NHC(O)C(CH3)2CH2CH3, —NHC(O)CH2O(4-fluorophenyl), —NHC(O)(1-methylcarbonyl-azetidin-3-yl), —NHC(O)CH2NH(4-methylphenyl), —NHC(O)CH2NH(phenyl), —NHC(O)CH2(4-allyl-piperazin-1-yl), —NHC(O)(2-methylphenyl), —NHC(O)CH2CH2OCH3, —NHC(O)(3-methyl-furan-2-yl), —NHC(O)C(CH3)3, —NHC(O)CH2NHObenzyl, —NHC(O)CH2NH(3-chlorophenyl), —NHC(O)cyclobutyl, —NHC(O)CH2(3-methoxyphenyl), —NHC(O)(1-methylcycloprop-1-yl), —NHC(O)(3-fluorophenyl), —NHC(O)(4-dimethylaminophenyl), —NHC(O)(3,4-dichlorophenyl), —NHC(O)CH2NHCH2(2-methylthiophenyl), —NHC(O)CH2(2-fluorophenyl), —NHC(O)CH2N(CH2CH3)CH(CH3)2, —NHC(O)(thiazol-4-yl), —NHC(O)CH2N(CH3)benzyl, —NHC(O)CH2NHCH2(thien-2-yl), —NHC(O)CH2NHCH2(pyridin-2-yl), —NHC(O)(3-methoxyphenyl), —NHC(O)CH2NHCH2(3-chloro-4-methylphenyl), —NHC(O)CH(CH3)CH2CH2CH3, —NHC(O)CH2(4-chlorophenyl), —NHC(O)(3-fluoro-4-methylphenyl), —NHC(O)CH2O(2-methylphenyl), —NHC(O)CH2(cyclohexyl), —NHC(O)(2-phenyl-cycloprop-1-yl), —NHC(O)(3-chlorophenyl), —NHC(O)CH2(2-methoxyphenyl), —NHC(O)CH2CH2(3-methoxyphenyl), —NHC(O)CH2NH(2-fluoro-4-methyl-phenyl), —NHC(O)CH2NHCH2(3-fluoro-phenyl), —NHC(O)CH2(4-methoxyphenyl), —NHC(O)benzyl, —NHC(O)(2,4-dichlorophenyl), —NHC(O)(3-oxo-cyclohex-1-yl), —NHC(O)CH2NH(3-fluorophenyl), —NHC(O)CH2(3-chlorophenyl), —NHC(O)CH2NHCH2CH(CH3)phenyl, —NHC(O)CH2NHCH2(2,4-dimethylphenyl), —NHC(O)CH2(2-methyl-piperidin-1-yl), —NHC(O)CH2NH(2-methoxyphenyl), —NHC(O)CH2(1,2,3,4-tetrahydroisoquinolin-2-yl), —NHC(O)CH2CH2CH═CH2, —NHC(O)CH2NH(2-methylphenyl), —NHC(O)CH2(4-oxo-piperidin-1-yl), —NHC(O)(2-fluorophenyl), —NHC(O)CH2NHCH(CH3)phenyl, —NHC(O)(2-fluoro-6-methoxyphenyl), —NHC(O)CH2NH(2-isopropylphenyl), —NHC(O)CH2CH2(2-methoxyphenyl), —NHC(O)CH2CH2CH(CH3)2, —NHC(O)CH2(2-phenyl-morpholin-4-yl), —NHC(O)CH2CH2(4-methoxyphenyl), —NHC(O)CH2N(allyl)cyclopentyl, —NHC(O)CH2N(CH3)CH2CH2OCH3, —NHC(O)CH2CH2C(O)cyclopropyl, —NHC(O)CH2NH(3-tert-butylphenyl), —NHC(O)CH2N(n-propyl)(cyclopropylmethyl), —NHC(O)CH2(2-oxo-cyclopentyl), —NHC(O)CH2NH(4-chlorophenyl), —NHC(O)CH2(4-piperidin-1-ylpiperidin-1-yl), —NHC(O)CH2(4-cyclopentylpiperazin-1-yl), —NHC(O)CH2(2-methylphenyl), —NHC(O)CH2NHCH2(3-fluoro-6-methylphenyl), —NHC(O)CH2C(CH3)3, —NHC(O)CH2NH(2-chlorophenyl), —NHC(O)(3-fluoro-6-methylphenyl), —NHC(O)(4-fluoro-3-methylphenyl), —NHC(O)(2,3-dichlorophenyl), —NHC(O)CH2O phenyl, —NHC(O)CH2NH(2,3-dimethylphenyl), —NHC(O)(2-fluoro-5-methylphenyl), —NHC(O)CH2NHOCH2(4-methylphenyl), —NHC(O)CH2(4-isopropylpiperazin-1-yl), —NHC(O)CH2(4-fluorophenyl), —NHC(O)CH2CH(CH3)2, —NHC(O)(2-methoxy-4-methylphenyl), —NHC(O)CH2(4-n-propylpiperidin-1-yl), —NHC(O)CH2O(3-methylphenyl), —NHC(O)(tetrahydrofuran-2-yl), —NHC(O)CH2(3-hydroxymethylpiperidin-1-yl), —NHC(O)(1-tert-butoxycarbonylpiperidin-2-yl), —NHC(O)CH2N(CH3)CH2(pyridin-3-yl), —NHC(O)CH2N(CH2CH3)phenyl, —NHC(O)CH2OCH2CH2OCH3, —NHC(O)CH2CH2(cyclopentyl), —NHC(O)(2,5-dichlorophenyl), —NHC(O)CH2(4-methylcarbonylpiperazin-1-yl), —NHC(O)(5-fluoro-2-methoxyphenyl), —NHC(O)CH2N(CH2CH3)cyclohexyl, —NHC(O)(5-methyl-1,2-oxazol-3-yl), —NHC(O)(3-methylpyridin-3-yl), —NHC(O)(2-methoxypyridin-3-yl), —NHC(O)(3,5-dichlorophenyl), —NHC(O)CH2(thiazolidin3-yl), —NHC(O)CH2(4-[C(O)H]-piperazin-1-yl), —NHC(O)CH2(2-pyridin-4-ylpiperidin-1-yl), —NHC(O)(2-methoxyphenyl), —NHC(O)CH2N(CH3)CH2CH(CH3)2, —NHC(O)CH2(4-[C(O)H]-homopiperazin-1-yl), —NHC(O)(1-phenylcycloprop-1-yl), —NHC(O)CH2(2,6-dimethylmorpholin-4-yl), NHC(O)CH2(2-phenylpyrrolidin-1-yl), —NHC(O)CH2(morpholin-4-yl), —C(O)NHCH(CH3)CH2N(CH3)2, —C(O)NHCH2CH2N(CH3)2, —C(O)NH(pyrrolidin-3-yl), —C(O)NHCH2CH2(pyrrolidin-1-yl), —C(O)NHCH2CH2NH2, —C(O)N(CH3)CH2CH2N(CH3)2, —C(O)NHCH2(piperidin-2-yl), —C(O)NH(1-methylazetidin-3-yl), —C(O)NHCH2CH2(piperidin-1-yl), —C(O)NHCH2CH2N(CH2CH3)2, —C(O)NH(1-methylpiperidin-3-yl), —C(O)NH(piperidin-3-yl), —C(O)NHCH2(1-methylpiperidin-3-yl), —C(O)NHCH2CH2N(CH2CH2OH)2, —C(O)NH(1-ethylpiperidin-3-yl), —C(O)NH2, —C(O)(3-aminopyrrolidin-1-yl), —C(O)(3-methylaminopyrrolidin-1-yl), —C(O)OH, —C(O)NHCH2CH2(morpholin-4-yl), —C(O)NHCH2(1-ethylpyrrolidin-2-yl), —C(O)(4-amino-3-oxo-pyrazolidin-1-yl), —C(O)NHCH3, —C(O)(3-aminocyclobut-1-yl), —C(O)NHCH2(pyridin-3-yl), —C(O)NHCH2CH2OH, —C(O)NH(3-oxo-pyrazolidin-4-yl), —NHCH2CH2(imidazol-4-yl), —C(O)(3-dimethylaminopyrrolidin-1-yl), —C(O)NHCH2(pyridin-4-yl), —C(O)N(CH3)(1-methyl-pyrrolidin-3-yl), —C(O)(3-diethylaminopyrrolidin-1-yl), —C(O)NH(pyrrol-1-yl), —C(O)NHCH2CH2CH2(pyrrolidin-1-yl), —C(O)N(CH3)CH2CH2CN, —C(O)NHCH2CH2OCH3, —C(O)N(CH2CH3)CH2CH2CN, —C(O)(3-aminopiperidin-1-yl), —C(O)NHCH2CH2CH2N(CH3)2, —C(O)NH(morpholin-4-yl), —C(O)NHN(CH3)2, —C(O)NHCH2CH2CH2(imidazol-1-yl), —C(O)NHCH2CH2CH2N(CH2CH3)2, —C(O)NHCH2CH2CN, —C(O)NHCH2CH2C(O)OCH3, —C(O)NHCH2CH2SCH3, —C(O)NHCH2CH2SCH2CH3, —C(O)N(CH2CH3)CH2CH2N(CH3)2, —C(O)NHCH2CH2CH2(2-oxo-pyrrolidin-1-yl), —C(O)NHCH2CH2(pyridin-4-yl), —C(O)NHCH2CH2CH2OCH2CH3, —C(O)NHCH2CH2CH2(morpholin-4-yl), —C(O)NHCH2CH2CH2OCH3, —C(O)N(CH3)CH2CH2CH2N(CH3)2, —C(O)NHCH2CH2CH2OCH2CH2CH3, —C(O)NHCH2CH2C(O)OCH2CH3, —C(O)NHCH2CH2CH2OCH(CH3)2, —C(O)NHC(CH3)2CH2(piperidin-1-yl), —C(O)N(CH3)CH2CH2CH3, —C(O)NH(piperidin-1-yl), —C(O)NHCH(CH3)CH2OCH3, —C(O)NHC(CH3)2CH2(morpholin-4-yl), —C(O)(2-dimethylaminomethylpiperidin-1-yl), —C(O)NH(CH2)3—O—(CH2)3CH3, —C(O)NHCH(CH3)(CH2)3N(CH2CH3)2, —C(O)NHC(CH3)2C(O)(piperidin-1-yl), —C(O)(4-methylpiperazin-1-yl), —C(O)(2-piperidin-1-ylmethyl-piperidin-1-yl), cyano, —NHCH3, —CH(CH3)NHCH2CH2N(CH3)2, —C(O)CH3, —S(O)2NHCH2CH2N(CH3)2, —S(O)2NH(CH2)3N(CH3)2, 5-(N,N-dimethylaminomethyl)-1,3,4-oxadiazol-2-yl, —NHCH2CH2N(CH3)2, —N(CH3)2, —OCH2CH2N(CH3)2, —NHC[N(CH3)2][═N(CH3)2], —OCH F2, —CF3, —S(O)2CH3, —OCF3, —NHC(O)CH2(4-dimethylaminopiperidin-1-yl), or methoxy.
In another embodiment (P), the Compound of Formula I is that where each R3 is independently halo, alkyl, hydroxyamino, —N(R7)C(O)—C1-C6-alkylene-N(R7a)(R7b), —C(O)NR8R8a, —NR9C(O)R9a, —C(O)N(R10)—C1-C6-alkylene-N(R10a)R10b—NR11C(O)NR11aR11b, —N(R22)C(O)—C1-C6-alkylene-N(R22b)— NR22c)(R22a), —NR13C(O)OR13a, —N(R18)C(O)—C1-C6-alkylene-N(R18b)C(O)R18a, —NR24C(O)—C1-C6-alkylene-OR24a, or —N(R20)C(O)—C1-C6-alkylene-C(O)R20a; where each of the alkylene in R3 is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino; and all other groups are as defined in the Summary of the Invention. In another embodiment, each R3 is independently methyl, chloro, —NHC(O)CH2NH(CH3), —NHC(O)CH(CH3)NH2, —NHC(O)C(CH3)2NH2, —NHC(O)CH2N(CH3)2, —NHC(O)CH2N(CH3)CH2CH2N(CH3)2, —NHC(O)CH(NH2)CH2CH3, —NHC(O)CH2N(CH3)CH2CH2N(CH3)2, —NHC(O)CH(CH3)NH(CH3), —NHC(O)H, —NHC(O)CH2(azetidin-1-yl), —NHC(O)(pyrrolidin-2-yl), —NHC(O)CH(NH2)CH2OH, —NHC(O)(azetidin-4-yl), —NHC(O)C(CH3)2NH(CH3), —NH2, —NHC(O)CH2NH(CH2CH2CH3), —NHC(O)CH2CH2NH2, —NHOH, or —NHC(O)(piperidin-3-yl).
In another embodiment (Q), the Compound of Formula I is that where R3 is alkyl or —N(R7)C(O)—C1-C6-alkylene-N(R7a)(R7b); and R7 is hydrogen or alkyl and R7a and R7b are independently hydrogen, alkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; and all other groups are as defined in the Summary of the Invention. In another embodiment, each R3 is independently methyl, —NHC(O)CH2NH(CH3), —NHC(O)CH(CH3)NH2, —NHC(O)C(CH3)2NH2, —NHC(O)—CH2N(CH3)2, —NHC(O)CH2N(CH3)CH2CH2N(CH3)2, —NHC(O)CH(NH2)CH2CH3, —NHC(O)CH2N(CH3)CH2CH2N(CH3)2, or —NHC(O)CH(CH3)NH(CH3).
In another embodiment (R), the Compound of Formula I is that where B is phenyl, R3 is not present or R3 is halo, alkyl, or alkoxy; R3a is —C(O)NR8R8a, —NR9C(O)R9a, —N(R7)C(O)—C1-C6-alkylene-N(R7a)(R7b), or —C(O)N(R10)—C1-C6-alkylene-N(R10a)R10b where each of the alkylene in R3a is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino; and all other groups are as defined in the Summary of the Invention.
In another embodiment (R1) of embodiment R, the compound is that where R50, R52, and R53 are hydrogen and R54 is halo or alkoxy; R50, R52, and R54 are hydrogen and R53 is alkoxy; or R50 and R52 are hydrogen and R53 and R54 together with the carbons to which they are attached form a 6-membered heteroaryl; and all other groups are as defined in the Summary of the Invention. In another embodiment, R50, R52, and R53 are hydrogen and R54 is halo or alkoxy; or R50, R52, and R54 are hydrogen and R53 is alkoxy.
In another embodiment of (R2) of embodiment R, the compound is that where R51 is methyl.
In another embodiment (S), the compound of Formula Ia:




is that where R3 is not present or R3 is alkyl and R3a is —N(R7)C(O)—C1-C6-alkylene-N(R7a)(R7b), —C(O)NR8R8a, —NR9C(O)R9a, or)-C(O)N(R10)—C1-C6-alkylene-N(R10a)R10b; where each of the alkylene in R3a is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino; and all other groups are as defined in the Summary of the Invention. In another embodiment, R3 is not present or is methyl. In another embodiment, R3 is not present.

In another embodiment (S1) of embodiment S is that where R7 is hydrogen or alkyl and R7a, and R7b are independently hydrogen, alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; R8 is hydrogen or alkyl and R8a is heterocycloalkyl or heterocycloalkylalkyl; R9 is hydrogen or alkyl and R9a is hydrogen, heterocycloalkyl, or heterocycloalkylalkyl; and R10, R10a, and R10b are independently hydrogen, alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl.
In another embodiment (S2) of embodiment S is that where R50, R52, and R53 are hydrogen and R54 is halo or alkoxy; or R50, R52, and R54 are hydrogen and R53 is alkoxy; or R50 and R52 are hydrogen and R53 and R54 together with the carbons to which they are attached form a 6-membered heteroaryl. In another embodiment, R50, R52, and R53 are hydrogen and R54 is halo or alkoxy; or R50, R52, and R54 are hydrogen and R53 is alkoxy.
In another embodiment of (S3) of embodiment S, the compound is that where R51 is methyl.
In another embodiment (T), the Compound of Formula I is that where B is heteroaryl, one R3 is halo, alkyl, or alkoxy and a second R3 is —C(O)NR8R8a, —NR9C(O)R9a, —N(R7)C(O)—C1-C6-alkylene-N(R7a)(R7b), or)-C(O)N(R10)—C1-C6-alkylene-N(R10a)R10b where each of the alkylene in R3 is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino; and all other groups are as defined in the Summary of the Invention.
In another embodiment (T1) of embodiment T, the compound is that where R7 is hydrogen or alkyl and R7a, and R7b are independently hydrogen, alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; R8 is hydrogen or alkyl and R8a is heterocycloalkyl or heterocycloalkylalkyl; R9 is hydrogen or alkyl and R9a is hydrogen, heterocycloalkyl, or heterocycloalkylalkyl; R10, R10a, and R10b are independently hydrogen, alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl.
In another embodiment U, the compound of Formula I is that where B is




each R3 (when R3 is present) is independently halo, alkyl, alkoxy, aminoalkyloxy, alkylaminoalkyloxy, dialkylaminoalkyloxy, alkylamino, dialkylamino, —C(O)NR8R8a, —NR9C(O)R9a, —N(R7)C(O)—C1-C6-alkylene-N(R7a)(R7b), or —C(O)N(R10)—C1-C6-alkylene-N(R10a)R10b; and all other groups are as defined in the Summary of the Invention.

In another embodiment (U1) of embodiment U, the compound of Formula I is that where R50, R52, and R53 are hydrogen and R54 is halo or alkoxy; R50, R52, and R54 are hydrogen and R53 is alkoxy; or R50 and R52 are hydrogen and R53 and R54 together with the carbons to which they are attached form a 6-membered heteroaryl; and all other groups are as defined in the Summary of the Invention. In another embodiment, R50, R52, and R53 are hydrogen and R54 is halo or alkoxy; or R50, R52, and R54 are hydrogen and R53 is alkoxy.
In another embodiment (U2) of embodiment U1, the compound of Formula I is that where R51 is methyl.
In another embodiment (U3) of embodiment U, the Compound of Formula I is that where R7 is hydrogen or alkyl and R7a, and R7b are independently hydrogen, alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; R8 is hydrogen or alkyl and R8a is heterocycloalkyl or heterocycloalkylalkyl; R9 is hydrogen or alkyl and R9a is hydrogen, heterocycloalkyl, or heterocycloalkylalkyl; R10, R10a, and R10b are independently hydrogen, alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl
In another embodiment of the Invention (V) the Compound of Formula I is that where W1, W2, W3, and W4 are —C(H)═; or W2 and W3 are —C(H)═ and one of W1 and W4 is —N═ and the other is —C(H)═;

    R50 is hydrogen;
    R51 is hydrogen or alkyl;
    R52 is hydrogen;
    R53 is hydrogen, alkoxy, nitro, amino, or —N(R55)C(O)—C1-C6-alkylene-N(R55a)R55b; and R54 is hydrogen, alkyl, alkoxy, or halo; or R53 and R54 together with the carbons to which they are attached form a 6-membered heteroaryl;
    B is phenyl substituted with R3a and optionally further substituted with one R3; or
    B is heteroaryl optionally substituted with one or two R3;
    R3a is cyano; hydroxyamino; carboxy; alkylsulfonyl, aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; —N(R7)C(O)—C1-C6-alkylene-N(R7a)(R7b); —C(O)NR8R8a; —NR9C(O)R9a; —C(O)N(R10)—C1-C6-alkylene-N(R10a)R10b; —NR11C(O)NR11aR11b where R11a; —C(O)R12; —NR13C(O)OR13a; —C(O)N(R14)N(R14a)(R14b); —S(O)2N(R15)—C1-C6-alkylene-N(R15a)R15b; —C(O)N(R16)—C1-C6-alkylene-C(O)OR16a; heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; —N(R17)— C(═N(R17b)(R17a))(NR17cR17d); —N(R18)C(O)—C1-C6-alkylene-N(R18b)C(O)R18a; —C(O)N(R19)—C1-C6-alkylene-C(O)R19a; —N(R22)C(O)—C1-C6-alkylene-N(R22b)—N(R22c)(R22a); —C0-C6-alkylene-N(R23)—C1-C6-alkylene-N(R23b)R23a; or —NR24C(O)—C1-C6-alkylene-OR24a; where each of the alkylene in R3a is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino;
    each R3 (when R3 is present) is independently halo; cyano; alkyl; alkenyl; alkoxy; hydroxyamino; carboxy; alkylsulfonyl, aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; —N(R7)C(O)—C1-C6-alkylene-N(R7a)(R7b); —C(O)NR8R8a; —NR9C(O)R9a; —C(O)N(R10)—C1-C6-alkylene-N(R10a)R10b; —NR11C(O)NR11aR11b where R11a; —C(O)R12; —NR13C(O)OR13a; —C(O)N(R14)N(R14a)(R14b); —S(O)2N(R15)—C1-C6-alkylene-N(R15a)R15b; —C(O)N(R16)—C1-C6-alkylene-C(O)OR16a; heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; —N(R17)— C(═N(R17NR17a))(NR17cR17d); —N(R18)C(O)—C1-C6-alkylene-N(R18b)C(O)R18a; —C(O)N(R19)—C1-C6-alkylene-C(O)R19a; —N(R22)C(O)—C1-C6-alkylene-N(R22b)—N(R22c)(R22a); —N(R23b)R23a; or —NR24C(O)—C1-C6-alkylene-N(R23)—C1-C6-alkylene or —NR24C(O)—C1-C6-alkylene-OR24a; where each of the alkylene in R3 is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino;
    provided that when R50 and R52 are hydrogen, R51 is hydrogen or methyl, R53 is hydrogen or methoxy, and R54 is hydrogen or methoxy, then B is not 2,3-dihydro-1,4-benzodioxinyl, thien-2-yl, or thien-2-yl substituted with one R3 where R3 is halo.


Another embodiment (W) of the invention is a Compound of Formula I where R50, R53, and R54 are independently hydrogen, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, hydroxy, alkoxy, alkenyloxy, haloalkoxy, nitro, amino, alkylamino, dialkylamino, —N(R55)C(O)—C1-C6-alkylene-N(R55a)R55b, alkylcarbonyl, alkenylcarbonyl, carboxy, alkoxycarbonyl, cyano, alkylthio, —S(O)2NR55R55a, or alkylcarbonylamino and where R55 and R55b are independently hydrogen, alkyl, or alkenyl and R55a is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy; or R53 and R54 together with the carbons to which they are attached form a 5- or 6-membered heteroaryl or 5- or 6-membered heterocycloalkyl.
Another embodiment (X) of the invention is a Compound of Formula I where R53 and R54 together with the carbons to which they are attached form a 5- or 6-membered heteroaryl or 5- or 6-membered heterocycloalkyl.
Representative Compounds
Representative compounds of Formula I and/or II are depicted below. The examples are merely illustrative and do not limit the scope of the invention in any way. Compounds of the invention are named according to systematic application of the nomenclature rules agreed upon by the International Union of Pure and Applied Chemistry (IUPAC), International Union of Biochemistry and Molecular Biology (IUBMB), and the Chemical Abstracts Service (CAS). Names in Table 1 were generated using ACD/Labs naming software 8.00 release, product version 8.08 with the exception of Compound 374 which was named using ChemDraw v. 9.0.1.
The Compounds in Table 1 can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 1 can be used to practice the invention. In particular, the invention can be practiced with one or two pharmaceutically acceptable salts of a Compound of Table 1 which salt(s) are formed with one or two acids independently selected from hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, acetic acid, trifluoroacetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, 3-(4-hydroxybenzoyl)benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, glucoheptonic acid, 4,4′-methylenebis-(3-hydroxy-2-ene-1-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, p-toluenesulfonic acid, and salicylic acid. In particular, the invention can be practiced with one or two pharmaceutically acceptable salts of a Compound of Table 1 which salt(s) are formed with one or two bases independently selected from sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, tromethamine, and N-methylglucamine. Any individual compound (and any optional salt, optional solvate, and optional hydrate thereof) in Table 1 can be used in combination with any of the above embodiments.









TABLE 1





Cpd. 




No.
Structure
Name

















1




N-(4-{[(3-{[4-(methoxy)phenyl] amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)  acetamide


 


2




4-bromo-N-[3-(phenylamino) quinoxalin-2-yl]benzene sulfonamide


 


3




4-bromo-N-{3-[(2- methylphenyl)amino] quinoxalin-2-yl}benzene sulfonamide


 


4




4-bromo-N-(3-{[4- (methoxy)phenyl]amino} quinoxalin-2-yl)benzene sulfonamide


 


5




4-chloro-N-{3-[(4- chlorophenyl)amino]-6- (methoxy)quinoxalin-2- yl}benzenesulfonamide


 


6




N-(4-{[3-{[(4-chlorophenyl) sulfonyl]amino}-7-(methoxy) quinoxalin-2-yl]amino} phenyl)acetamide


 


7




4-chloro-N-{6-(methoxy)-3-[(2- oxo-2,3-dihydro-1H- benzimidazol-5-yl)amino] quinoxalin-2-yl} benzenesulfonamide


 


8




N-{4-[(3-{[(4-chlorophenyl) sulfonyl]amino}quinoxalin-2- yl)amino]phenyl}acetamide


 


9




N-(3-{[4-(ethyloxy)phenyl] amino}quinoxalin-2-yl)-4- methylbenzene sulfonamide


 


10




N-{3-[(3,4-dimethylphenyl) amino]-6-methylquinoxalin- 2-yl}-4-methylbenzene sulfonamide


 


11




N-(3-{[3-(dimethylamino) phenyl]amino}quinoxalin-2- yl)-4-methylbenzene  sulfonamide


 


12




4-methyl-N-{6-methyl-3-[(4- methylphenyl)amino]quinoxalin- 2-yl} benzene sulfonamide


 


13




N-{3-[(4-hydroxyphenyl) amino]-6-methylquinoxalin- 2-yl}-4-methylbenzene sulfonamide


 


14




N-{3-[(2,5-dimethylphenyl) amino]quinoxalin-2-yl}-4- methylbenzenesulfonamide


 


15




4-chloro-N-[3-(naphthalen- 2-ylamino)quinoxalin-2- yl]benzenesulfonamide


 


16




N-{3-[(3-aminophenyl)amino] quinoxalin-2-yl}-4- chlorobenzenesulfonamide


 


17




N-(3-{[4-(aminosulfonyl)phenyl] amino}quinoxalin-2-yl)-3- nitrobenzenesulfonamide


 


18




4-chloro-N-{3-[(4-chlorophenyl) amino]quinoxalin-2-yl} benzenesulfonamide


 


19




4-chloro-N-{3-[(4-methylphenyl) amino]quinoxalin-2-yl} benzenesulfonamide


 


20




4-chloro-N-{3-[(2-methylphenyl) amino]quinoxalin-2-yl} benzenesulfonamide


 


21




methyl 4-[(3-{[(4-chlorophenyl) sulfonyl]amino} quinoxalin-2- yl)amino]benzoate


 


22




methyl 2-chloro-5-[(3-{[(4- methylphenyl)sulfonyl]amino} quinoxalin-2-yl)amino]benzoate


 


23




N-{4-[(7-methyl-3-{[(4- methylphenyl)sulfonyl]amino} quinoxalin-2-yl) amino]phenyl}acetamide


 


24




4-methyl-N-(6-methyl-3-{[2- (methoxy)phenyl]amino} quinoxalin-2-yl) benzenesulfonamide


 


25




N-{3-[(phenylmethyl) amino]quinoxalin-2-yl} benzenesulfonamide


 


26




4-({3-[(phenylsulfonyl)amino] quinoxalin-2-yl}amino) benzoic acid


 


27




3-({3-[(phenylsulfonyl)amino] quinoxalin-2-yl}amino) benzenesulfonamide


 


28




N-{3-[(1,5-dimethyl-3-oxo-2- phenyl-2,3-dihydro-1H-pyrazol- 4-yl)amino]quinoxalin-2-yl} benzenesulfonamide


 


29




N-{3-[(4-hydroxyphenyl) amino]quinoxalin-2-yl} benzenesulfonamide


 


30




N-{3-[(4-hydroxyphenyl) amino]quinoxalin-2-yl}-4- methylbenzenesulfonamide


 


31




N-(3-{[4-(aminosulfonyl)phenyl] amino}quinoxalin-2-yl)-4- methylbenzenesulfonamide


 


32




3-[(3-{[(4-methylphenyl) sulfonyl]amino}quinoxalin-2- yl)amino]benzoic acid


 


33




N-[4-({[3-(phenylamino) quinoxalin-2-yl]amino}sulfonyl) phenyl]acetamide


 


34




N-(4-{[(3-{[4-(aminosulfonyl) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl) acetamide


 


35




N-[4-({[3-(naphthalen-1- ylamino)quinoxalin-2-yl] amino}sulfonyl)phenyl] acetamide


 


36




N-{4-[(3-{[(4-methylphenyl) sulfonyl]amino}quinoxalin-2- yl)amino]phenyl}acetamide


 


37




N-(3-{[3-(aminosulfonyl) phenyl]amino}quinoxalin-2-yl)- 4-bromobenzenesulfonamide


 


38




N-{3-[(3-hydroxyphenyl)amino] quinoxalin-2-yl}-4- methylbenzenesulfonamide


 


39




4-[(3-{[(4-chlorophenyl) sulfonyl]amino}quinoxalin-2- yl)amino]-2-hydroxybenzoic acid


 


40




N-(3-{[4-(methoxy)phenyl] amino}quinoxalin-2-yl)-3- nitrobenzenesulfonamide


 


41




3-[(3-{[(4-chlorophenyl) sulfonyl]amino}quinoxalin- 2-yl)amino]benzoic acid


 


42




N-(3-{[4-(aminosulfonyl) phenyl]amino}quinoxalin-2-yl)- 4-chlorobenzenesulfonamide


 


43




N-(3-{[3-(aminosulfonyl) phenyl]amino}quinoxalin-2-yl)- 4-chlorobenzenesulfonamide


 


44




N-[3-(naphthalen-2-ylamino) quinoxalin-2-yl]-4- nitrobenzenesulfonamide


 


45




N-(3-{[3-(methoxy)phenyl] amino}quinoxalin-2-yl) benzenesulfonamide


 


46




N-{3-[(4-bromophenyl)amino] quinoxalin-2-yl}-3- nitrobenzenesulfonamide


 


47




3-[(3-{[(4-nitrophenyl)sulfonyl] amino}quinoxalin-2- yl)amino]benzoic acid


 


48




4-nitro-N-[3-(phenylamino) quinoxalin-2-yl] benzenesulfonamide


 


49




4-chloro-N-[3- (phenylamino)quinoxalin- 2-yl]benzenesulfonamide


 


50




3-nitro-N-[3-(phenylamino) quinoxalin-2-yl] benzenesulfonamide


 


51




4-[(3-{[(4-nitrophenyl)sulfonyl] amino}quinoxalin-2-yl)amino] benzoic acid


 


52




N-[3-(naphthalen-2-ylamino) quinoxalin-2-yl]-3- nitrobenzenesulfonamide


 


53




4-methyl-N-(3-{[3-(methoxy) phenyl]amino}quinoxalin-2-yl) benzenesulfonamide


 


54




N-(3-{[3-chloro-4-(methoxy) phenyl]amino}quinoxalin-2- yl)benzenesulfonamide


 


55




N-{3-[(3-chloro-4-fluorophenyl) amino]quinoxalin-2-yl} benzenesulfonamide


 


56




methyl 2-chloro-5-({3- [(phenylsulfonyl)amino] quinoxalin-2-yl}amino)benzoate


 


57




4-chloro-N-{3-[(3- hydroxyphenyl)amino]quinoxalin- 2-yl}benzenesulfonamide


 


58




4-methyl-N-[6-methyl-3- (phenylamino)quinoxalin-2-yl] benzenesulfonamide


 


59




N-{4-[({3-[(4-methylphenyl) amino]quinoxalin-2-yl}amino) sulfonyl]phenyl}acetamide


 


60




1-methylethyl 4-[(3-{[(4- chlorophenyl)sulfonyl] amino}-7-methylquinoxalin- 2-yl)amino]benzoate


 


61




N-{3-[(4-methylphenyl)amino] quinoxalin-2-yl} benzenesulfonamide


 


62




N-{3-[(3-methylphenyl)amino] quinoxalin-2-yl} benzenesulfonamide


 


63




N-{3-[(4-bromophenyl)amino] quinoxalin-2-yl}-4- methylbenzenesulfonamide


 


64




4-methyl-N-{3-[(3-methylphenyl) amino]quinoxalin-2-yl} benzenesulfonamide


 


65




4-methyl-N-[3-(naphthalen-1- ylamino)quinoxalin-2-yl] benzenesulfonamide


 


66




N-{4-[({3-[(4-chlorophenyl) amino]quinoxalin-2-yl}amino) sulfonyl]phenyl}acetamide


 


67




N-(4-{[(3-{[3-(aminosulfonyl) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl) acetamide


 


68




4-methyl-N-{3-[(phenylmethyl) amino]quinoxalin-2-yl} benzenesulfonamide


 


69




4-[(3-{[(4-bromophenyl) sulfonyl]amino}quinoxalin- 2-yl)amino]-2- hydroxybenzoic acid


 


70




4-bromo-N-{3-[(4- methylphenyl)amino]quinoxalin- 2-yl}benzenesulfonamide


 


71




4-bromo-N-{3-[(3-methylphenyl) amino]quinoxalin-2-yl} benzenesulfonamide


 


72




N-{4-[({3-[(2-hydroxyethyl) amino]quinoxalin-2-yl}amino) sulfonyl]phenyl}acetamide


 


73




4-bromo-N-[3-(naphthalen- 1-ylamino)quinoxalin-2-yl] benzenesulfonamide


 


74




4-[(3-{[(4-chlorophenyl) sulfonyl]amino}quinoxalin-2- yl)amino]benzoic acid


 


75




3-[(3-{[(3-nitrophenyl)sulfonyl] amino}quinoxalin-2-yl)amino] benzoic acid


 


76




N-{3-[(2-methylphenyl)amino] quinoxalin-2-yl} benzenesulfonamide


 


77




4-({3-[(phenylsulfonyl)amino] quinoxalin-2-yl}amino) benzenesulfonamide


 


78




N-[3-(naphthalen-1-ylamino) quinoxalin-2-yl]-3- nitrobenzenesulfonamide


 


79




N-(3-{[3-(aminosulfonyl) phenyl]amino}quinoxalin-2-yl)- 3-nitrobenzenesulfonamide


 


80




N-{3-[(4-bromophenyl)amino] quinoxalin-2-yl}-4- nitrobenzenesulfonamide


 


81




4-chloro-N-[3-(naphthalen-1- ylamino)quinoxalin-2-yl] benzenesulfonamide


 


82




N-{4-[({3-[(phenylmethyl) amino]quinoxalin-2-yl}amino) sulfonyl]phenyl}acetamide


 


83




N-[4-({[3-(butylamino) quinoxalin-2-yl]amino} sulfonyl)phenyl]acetamide


 


84




N-[3-(butylamino)quinoxalin-2- yl]-4-methylbenzenesulfonamide


 


85




N-[3-(cyclohexylamino) quinoxalin-2-yl] benzenesulfonamide


 


86




1-(phenylsulfonyl)-3-[4- (pyrrolidin-1-ylsulfonyl) phenyl]-2,3-dihydro-1H- imidazo[4,5-b]quinoxaline


 


87




1-(phenylsulfonyl)-3-[4- (piperidin-1-ylsulfonyl)phenyl]- 2,3-dihydro-1H-imidazo[4,5-b] quinoxaline


 


88




2,5-dichloro-N-[3-(3,4- dihydroquinolin-1(2H)- yl)quinoxalin-2-yl] benzenesulfonamide


 


89




ethyl 2-[(3-{[(4- methylphenyl)sulfonyl]amino} quinoxalin-2-yl)amino]-4,5,6,7- tetrahydro-1-benzothiophene-3- carboxylate


 


90




2,5-dichloro-N-{3-[(2-morpholin- 4-ylphenyl)amino]quinoxalin- 2-yl}benzenesulfonamide


 


91




N-{4-[({3-[(3-methylphenyl) amino]quinoxalin-2-yl}amino) sulfonyl]phenyl}acetamide


 


92




4-chloro-N-{3-[(3-chloro-4- piperidin-1-ylphenyl)amino]- 6-methylquinoxalin-2- yl}benzenesulfonamide


 


93




3-nitro-N-[3-(quinolin-6- ylamino)quinoxalin-2- yl]benzenesulfonamide


 


94




butyl N-{[4-({3-[(phenylsulfonyl) amino]quinoxalin-2-yl}amino) phenyl]carbonyl}glycinate


 


95




4-nitro-N-(3-{[3-(trifluoromethyl) phenyl]amino}quinoxalin-2- yl)benzenesulfonamide


 


96




N-[4-({3-[(phenylsulfonyl) amino]quinoxalin-2-yl} amino)phenyl]acetamide


 


97




N-{3-[(3-{[(4-methylphenyl) sulfonyl]amino}quinoxalin-2- yl)amino]phenyl}acetamide


 


98




ethyl 3,3,3-trifluoro-2-hydroxy- 2-{4-[(3-{[(4-methylphenyl) sulfonyl]amino}quinoxalin-2-yl) amino]phenyl}propanoate 


 


99




N-{3-[(4-{[(2,6- dimethylpyrimidin-4-yl)amino] sulfonyl}phenyl)amino] quinoxalin-2-yl}-3- nitrobenzenesulfonamide


 


100




4-chloro-N-{3-[(3,4- dimethylphenyl)amino]-6- methylquinoxalin-2-yl} benzenesulfonamide


 


101




4-chloro-N-(6-methyl-3-{[3- (methoxy)phenyl]amino} quinoxalin-2-yl) benzenesulfonamide


 


102




butyl 4-[(3-{[(4-chlorophenyl) sulfonyl]amino}-7- methylquinoxalin-2-yl)amino] benzoate


 


103




4-chloro-N-{3-[(3-chloro-4- methylphenyl)amino]quinoxalin- 2-yl}benzenesulfonamide


 


104




1-methylethyl 4-[(3-{[(4- chlorophenyl)sulfonyl]amino} quinoxalin-2-yl)amino] benzoate


 


105




N-{3-[(2,5-dimethylphenyl) amino]-6-nitroquinoxalin-2- yl}-4-methylbenzenesulfonamide


 


106




N-[3-(cyclohexylamino)-6- nitroquinoxalin-2-yl]-4- methylbenzenesulfonamide


 


107




N-{3-[(2,4-dimethylphenyl) amino]quinoxalin-2-yl}-4- methylbenzenesulfonamide


 


108




N-(3-{[4-(ethyloxy)phenyl] amino}-6-methylquinoxalin-2- yl)-4-methylbenzenesulfonamide


 


109




3-({3-[({4-[hydroxy(oxido) amino]phenyl}sulfonyl)amino] quinoxalin-2-yl}amino) benzoic acid


 


110




N-{[4-({3-[(phenylsulfonyl) amino]quinoxalin-2-yl}amino) phenyl]carbonyl}glycine


 


111




N-{3-[(3-{[(4-chlorophenyl) sulfonyl]amino}-7- methylquinoxalin-2-yl)amino] phenyl}acetamide


 


112




4-chloro-N-{3-[(3,5-dimethyl- 1H-pyrazol-4-yl)amino]-6- methylquinoxalin-2-yl} benzenesulfonamide


 


113




4-bromo-N-{3-[(4′- nitrobiphenyl-3-yl)amino] quinoxalin-2-yl} benzenesulfonamide


 


114




4-bromo-N-{3-[(2-chlorophenyl) amino]quinoxalin-2- yl}benzenesulfonamide


 


115




N-{3-[(4-butylphenyl)amino]- 6-methylquinoxalin-2-yl}-4- chlorobenzenesulfonamide


 


116




N-{4-[(3-{[(4-chlorophenyl) sulfonyl]amino}-7- methylquinoxalin-2-yl) amino]phenyl}acetamide


 


117




4-chloro-N-{6-methyl-3-[(2- oxo-2,3-dihydro-1H- benzimidazol-5-yl)amino] quinoxalin-2-yl} benzenesulfonamide


 


118




propyl 4-[(3-{[(4-chlorophenyl) sulfonyl]amino}-7- methylquinoxalin-2-yl)amino] benzoate


 


119




4-chloro-N-{3-[(4-fluorophenyl) amino]quinoxalin-2-yl} benzenesulfonamide


 


120




N-[4-({[3-(naphthalen-2- ylamino)quinoxalin-2-yl] amino}sulfonyl)phenyl] acetamide


 


121




4-bromo-N-(3-{[4- (phenylamino)phenyl] amino}quinoxalin-2-yl) benzenesulfonamide


 


122




2-hydroxy-4-({3- [(phenylsulfonyl)amino] quinoxalin-2- yl}amino)benzoic acid


 


123




N-(3-{[3-(aminosulfonyl) phenyl]amino}quinoxalin-2- yl)-4-methylbenzenesulfonamide


 


124




4-[(3-{[(3-nitrophenyl)sulfonyl] amino}quinoxalin-2- yl)amino]benzoic acid


 


125




N-(3-{[3-(butyloxy)phenyl] amino}quinoxalin-2-yl)-4- methylbenzenesulfonamide


 


126




N-{3-[(4-fluorophenyl)amino] quinoxalin-2-yl}-3- nitrobenzenesulfonamide


 


127




4-{[3-({[4-(acetylamino)phenyl] sulfonyl}amino)quinoxalin- 2-yl]amino}-2- hydroxybenzoic acid


 


128




N-[3-(naphthalen-1-ylamino) quinoxalin-2-yl]-4- nitrobenzenesulfonamide


 


129




4-[(3-{[(4-bromophenyl) sulfonyl]amino}quinoxalin-2- yl)amino]benzoic acid


 


130




N-{4-[({3-[(3-hydroxyphenyl) amino]quinoxalin-2-yl}amino) sulfonyl]phenyl}acetamide


 


131




3-[(3-{[(4-bromophenyl) sulfonyl]amino}quinoxalin-2- yl)amino]benzoic acid


 


132




4-bromo-N-(3-{[3- (butyloxy)phenyl]amino} quinoxalin-2-yl) benzenesulfonamide


 


133




4-bromo-N-(3-{[3- (trifluoromethyl)phenyl] amino}quinoxalin-2-yl) benzenesulfonamide


 


134




4-methyl-N-{3-[(4′-nitrobiphenyl- 3-yl)amino]quinoxalin-2-yl} benzenesulfonamide


 


135




4-chloro-N-{3-[(3-fluorophenyl) amino]quinoxalin-2-yl} benzenesulfonamide


 


136




N-{3-[(2-chlorophenyl)amino] quinoxalin-2-yl} benzenesulfonamide


 


137




4-bromo-N-[3-(quinolin-5- ylamino)quinoxalin-2- yl]benzenesulfonamide


 


138




N-{3-[(3-fluorophenyl)amino] quinoxalin-2-yl}-4- methylbenzenesulfonamide


 


139




N-{3-[(4-fluorophenyl)amino] quinoxalin-2-yl}-4- methylbenzenesulfonamide


 


140




3-nitro-N-(3-{[3- (trifluoromethyl)phenyl] amino}quinoxalin-2- yl)benzenesulfonamide


 


141




2-hydroxy-4-[(3-{[(3- nitrophenyl)sulfonyl]amino} quinoxalin-2-yl)amino] benzoic acid


 


142




N-{3-[(3-chlorophenyl)amino] quinoxalin-2-yl}-4- methylbenzenesulfonamide


 


143




N-[3-(1,3-benzodioxol-5-ylamino) quinoxalin-2-yl]-4- bromobenzenesulfonamide


 


144




N-{3-[(3-acetylphenyl)amino] quinoxalin-2-yl}-4- chlorobenzenesulfonamide


 


145




3-nitro-N-(3-{[4-(9H-xanthen- 9-yl)phenyl]amino}quinoxalin- 2-yl)benzenesulfonamide


 


146




4-chloro-N-{3-[(4′-nitrobiphenyl- 3-yl)amino]quinoxalin-2- yl}benzenesulfonamide


 


147




N-[3-(2,1,3-benzothiadiazol-5- ylamino)quinoxalin-2- yl]-4-tolylsulfonamide


 


148




N-{3-[(2-methyl-1,3-dioxo-2,3- dihydro-1H-isoindol-5-yl) amino]quinoxalin-2- yl}benzenesulfonamide


 


149




4-methyl-N-[3-(quinolin-5- ylamino)quinoxalin-2-yl] benzenesulfonamide


 


150




4-methyl-N-{3-[(1-oxo-1,3- dihydro-2-benzofuran-5-yl) amino]quinoxalin-2-yl} benzenesulfonamide


 


151




4-chloro-N-{3-[(2-chlorophenyl) amino]quinoxalin-2-yl] benzenesulfonamide


 


152




2-hydroxy-5-[(3-{[(4- methylphenyl)sulfonyl]amino} quinoxalin-2- yl)amino]benzoic acid


 


153




N-(3-{[3,5-bis(1,1- dimethylethyl)-4- hydroxyphenyl]amino} quinoxalin-2-yl) benzenesulfonamide


 


154




N-[3-({2- [(trifluoromethyl) thio]phenyl} amino)quinoxalin-2-yl] benzenesulfonamide


 


155




N-{4-[({3-[(4- hydroxyphenyl)amino] quinoxalin-2-yl}amino) sulfonyl]phenyl}acetamide


 


156




N-[3-(1,3-benzodioxol- 5-ylamino)quinoxalin- 2-yl]-4- methylbenzenesulfonamide


 


157




N-(3-{[2,5- bis(methoxy)phenyl] amino}quinoxalin-2-yl) benzenesulfonamide


 


158




N-{3-[(2,4- dichlorophenyl)amino] quinoxalin-2-yl} benzenesulfonamide


 


159




N-[4-({[3-(2,3-dihydro-1,4- benzodioxin-6-ylamino) quinoxalin-2-yl]amino}sulfonyl) phenyl]acetamide


 


160




4-chloro-N-{3-[(3,4- dimethylphenyl)amino] quinoxalin-2-yl} benzenesulfonamide


 


161




N-(3-{[2,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-3- nitrobenzenesulfonamide


 


162




4-bromo-N-{3-[(3,4- dimethylphenyl)amino] quinoxalin-2-yl} benzenesulfonamide


 


163




5-{[3-({[4-(acetylamino)phenyl] sulfonyl}amino)quinoxalin-2- yl]amino}-2- hydroxybenzoic acid


 


164




N-(3-{[2,5-bis(methoxy) phenyl]amino}quinoxalin-2-yl)- 4-chlorobenzenesulfonamide


 


165




N-(3-{[2,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-4- methylbenzenesulfonamide


 


166




N-{3-[(2,4-dichlorophenyl) amino]quinoxalin-2-yl}-4- methylbenzenesulfonamide


 


167




4-bromo-N-{3-[(3-fluorophenyl) amino]quinoxalin-2-yl} benzenesulfonamide


 


168




4-{[3-({[4-(acetylamino) phenyl]sulfonyl}amino) quinoxalin-2-yl]amino} benzoic acid


 


169




N-{3-[(2-fluorophenyl) amino]quinoxalin-2-yl}-4- methylbenzenesulfonamide


 


170




N-[3-(2,3-dihydro-1,4- benzodioxin-6-ylamino) quinoxalin-2-yl]-4- methylbenzenesulfonamide


 


171




N-{3-[(3,4-dimethylphenyl) amino]quinoxalin-2-yl} benzenesulfonamide


 


172




4-methyl-N-(3-{[3- (trifluoromethyl)phenyl] amino}quinoxalin-2-yl) benzenesulfonamide


 


173




5-[(3-{[(4-chlorophenyl) sulfonyl]amino}quinoxalin- 2-yl)amino]-2- hydroxybenzoic acid


 


174




3-nitro-N-{3-[(1-oxo-1,3- dihydro-2-benzofuran-5-yl) amino]quinoxalin-2-yl} benzenesulfonamide


 


175




N-{4-[({3-[(2-bromo-4- methylphenyl)amino] quinoxalin-2-yl}amino) sulfonyl]phenyl}acetamide


 


176




N-{3-[(2-fluorophenyl)amino] quinoxalin-2-yl}-4- nitrobenzenesulfonamide


 


177




N-{3-[(2-methyl-1,3-dioxo- 2,3-dihydro-1H-isoindol-5-yl) amino]quinoxalin-2-yl}-3- nitrobenzenesulfonamide


 


178




4-chloro-N-{3-[(1-oxo-1,3- dihydro-2-benzofuran-5-yl) amino]quinoxalin-2- yl}benzenesulfonamide


 


179




N-{3-[(1-oxo-1,3-dihydro-2- benzofuran-5-yl)amino] quinoxalin-2-yl} benzenesulfonamide


 


180




N-{3-[(2-fluorophenyl)amino] quinoxalin-2-yl}-3- nitrobenzenesulfonamide


 


181




N-[2-(butyloxy)-2-hydroxyethyl]- 4-({3-[(phenylsulfonyl)amino] quinoxalin-2-yl}amino) benzamide


 


182




3-nitro-N-(3-{[4- (phenylamino)phenyl]amino} quinoxalin-2- yl)benzenesulfonamide


 


183




4-bromo-N-{3-[(4-fluorophenyl) amino]quinoxalin-2-yl} benzenesulfonamide


 


184




4-methyl-N-[3-({2- [(trifluoromethyl)thio] phenyl}amino) quinoxalin-2-yl] benzenesulfonamide


 


185




N-[4-({3-[2-(methoxy)phenyl]- 2,3-dihydro-1H-imidazo[4,5-b] quinoxalin-1-yl}sulfonyl) phenyl]acetamide


 


186




4-(3-{[4-(acetylamino)phenyl] sulfonyl}-2,3-dihydro-1H- imidazo[4,5-b]quinoxalin-1- yl)benzoic acid


 


187




1-naphthalen-2-yl-3-[(3- nitrophenyl)sulfonyl]-2,3- dihydro-1H-imidazo[4,5- b]quinoxaline


 


188




N-[4-({3-[4-(methoxy)phenyl]- 2,3-dihydro-1H-imidazo[4,5- b]quinoxalin-1-yl}sulfonyl) phenyl]acetamide


 


189




1-(3-methylphenyl)-3-[(4- methylphenyl)sulfonyl]-2,3- dihydro-1H-imidazo [4,5-b]quinoxaline


 


190




N-(4-{[3-(4-methylphenyl)-2,3- dihydro-1H-imidazo[4,5-b] quinoxalin-1-yl]sulfonyl} phenyl)acetamide


 


191




N-{4-[(3-phenyl-2,3-dihydro-1H- imidazo[4,5-b]quinoxalin-1-yl) sulfonyl]phenyl}acetamide


 


192




N-(4-{[3-(3-methylphenyl)- 2,3-dihydro-1H-imidazo[4,5-b] quinoxalin-1-yl]sulfonyl} phenyl)acetamide


 


193




1-[4-(methoxy)phenyl]-3-[(4- methylphenyl)sulfonyl]-2,3- dihydro-1H-imidazo[4,5-b] quinoxaline


 


194




N-(4-{[3-(2-methylphenyl)- 2,3-dihydro-1H-imidazo [4,5-b]quinoxalin-1-yl]sulfonyl} phenyl)acetamide


 


195




1-(3-methylphenyl)-3-[(3- nitrophenyl)sulfonyl]-2,3- dihydro-1H-imidazo[4,5-b] quinoxaline


 


196




1-(4-methylphenyl)-3-[(3- nitrophenyl)sulfonyl]-2,3- dihydro-1H-imidazo[4,5-b] quinoxaline


 


197




N-{3-[(4-methylphenyl)amino] quinoxalin-2-yl}-3-(1H-tetrazol- 1-yl)benzenesulfonamide


 


198




N-(3-{[2-(ethyloxy)phenyl] amino}quinoxalin-2-yl)-4- methylbenzenesulfonamide


 


199




N-{4-[({3-[(4-ethylphenyl) amino]quinoxalin-2-yl}amino) sulfonyl]phenyl}acetamide


 


200




4-bromo-N-(3-{[3-(methoxy) phenyl]amino}quinoxalin-2- yl)benzenesulfonamide


 


201




N-(4-{[(3-{[4-(ethyloxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl} phenyl)acetamide


 


202




N-{4-[({3-[(2-ethylphenyl) amino]quinoxalin-2-yl}amino) sulfonyl]phenyl}acetamide


 


203




N-(4-{[(3-{[2-(ethyloxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl) acetamide


 


204




N-{3-[(4-nitrophenyl)amino] quinoxalin-2-yl} benzenesulfonamide


 


205




4-(ethyloxy)-N-(3-{[4-(methoxy) phenyl]amino}quinoxalin-2- yl)benzenesulfonamide


 


206




methyl N-acetyl-N-[4-({3- [(phenylsulfonyl)amino] quinoxalin-2-yl}amino) phenyl]-beta-alaninate


 


207




methyl N-acetyl-N-{4-[(3-{[(4- chlorophenyl)sulfonyl]amino} quinoxalin-2-yl)amino]phenyl}- beta-alaninate


 


208




N-{3-[(3-chloro-5-methylphenyl) amino]quinoxalin-2-yl}- 4-methylbenzenesulfonamide


 


209




N-{3-[(3-acetylphenyl)amino] quinoxalin-2-yl}-3- nitrobenzenesulfonamide


 


210




4-{[3-({[4-(acetylamino)phenyl] sulfonyl}amino)quinoxalin-2- yl]amino}-N-[4-(methoxy) phenyl]benzamide


 


211




2-hydroxy-5-({3- [(phenylsulfonyl)amino] quinoxalin-2-yl}amino) benzoic acid


 


212




N-[3-(2,3-dihydro-1,4- benzodioxin-6-ylamino) quinoxalin-2-yl]-3- nitrobenzenesulfonamide


 


213




N-[4-(methoxy)phenyl]- 4-[(3-{[(4-nitrophenyl) sulfonyl]amino}quinoxalin-2- yl)amino]benzamide


 


214




4-chloro-N-{3-[(2-oxo-2,3- dihydro-1H-benzimidazol-5-yl) amino]quinoxalin-2- yl}benzenesulfonamide


 


215




4-methyl-N-{3- [methyl(phenylmethyl) amino]quinoxalin-2- yl}benzenesulfonamide


 


216




N-[3-(3,4- dihydroisoquinolin-2(1H)- yl)quinoxalin-2-yl]-2- methylbenzenesulfonamide


 


217




N-[4-({[3-(2,1,3-benzothiadiazol- 5-ylamino)quinoxalin-2-yl] amino}sulfonyl)phenyl] acetamide


 


218




4-bromo-N-{3-[(4- phenylquinolin-8-yl)amino] quinoxalin-2-yl} benzenesulfonamide


 


219




4-methyl-N-{3-[(4- phenylquinolin-8-yl)amino] quinoxalin-2-yl} benzenesulfonamide


 


220




1-[(4-chlorophenyl) sulfonyl]-3-[4-(pyrrolidin- 1-ylsulfonyl)phenyl]-2,3- dihydro-1H-imidazo [4,5-b]quinoxaline


 


221




1-(4-morpholin-4-ylphenyl)-3- (phenylsulfonyl)-2,3-dihydro- 1H-imidazo[4,5-b]quinoxaline


 


222




methyl 4,5-dimethyl-2-({3- [(phenylsulfonyl)amino] quinoxalin-2-yl}amino) thiophene-3-carboxylate


 


223




ethyl 6-methyl-2-[(3-{[(2- methylphenyl)sulfonyl] amino}quinoxalin-2-yl) amino]-4,5,6,7-tetrahydro- 1-benzothiophene-3- carboxylate


 


224




ethyl 2-{[3-({[4- (acetylamino)phenyl] sulfonyl}amino)quinoxalin- 2-yl]amino}-6-phenyl- 4,5,6,7-tetrahydro-1- benzothiophene-3- carboxylate


 


225




ethyl 6-methyl-2-[(3-{[(4- methylphenyl)sulfonyl] amino}quinoxalin-2-yl) amino]-4,5,6,7-tetrahydro- 1-benzothiophene-3- carboxylate


 


226




propyl 4-[(3-{[(4- chlorophenyl)sulfonyl] amino}quinoxalin-2- yl)amino]benzoate


 


227




N-{3-[(4-butylphenyl) amino]quinoxalin-2-yl}-4- chlorobenzenesulfonamide


 


228




N-{3-[(2- chlorophenyl)amino] quinoxalin-2-yl}-4- methylbenzenesulfonamide


 


229




N-{3-[(2,3- dimethylphenyl)amino] quinoxalin-2-yl}-4- methylbenzenesulfonamide


 


230




N-{3-[(3,4- dimethylphenyl)amino] quinoxalin-2-yl}-3- nitrobenzenesulfonamide


 


231




N-{4-[({3-[(2,3- dimethylphenyl)amino] quinoxalin-2-yl}amino) sulfonyl]phenyl}acetamide


 


232




4-chloro-N-{3-[(2,3- dimethylphenyl)amino] quinoxalin-2-yl} benzenesulfonamide


 


233




3-nitro-N-(3-{[3,4,5- tris(methoxy)phenyl] amino}quinoxalin-2- yl)benzenesulfonamide


 


234




4-chloro-N-{3-[(2,4- dichlorophenyl)amino] quinoxalin-2-yl} benzenesulfonamide


 


235




N-{3-[(2,3- dimethylphenyl)amino] quinoxalin-2-yl}-3- nitrobenzenesulfonamide


 


236




N-{4-[({3-[(3,4- dimethylphenyl)amino] quinoxalin-2- yl}amino)sulfonyl] phenyl}acetamide


 


237




ethyl 2-[(3-{[(4- chlorophenyl)sulfonyl] amino}quinoxalin-2- yl)amino]-5,6-dihydro-4H- cyclopenta[b]thiophene- 3-carboxylate


 


238




4-chloro-N-(3-{[4-chloro- 3-(morpholin-4- ylsulfonyl)phenyl]amino} quinoxalin-2-yl) benzenesulfonamide


 


239




ethyl 2-[(3-{[(2- methylphenyl)sulfonyl] amino}quinoxalin-2- yl)amino]-4,5,6,7- tetrahydro-1- benzothiophene-3- carboxylate


 


240




4-bromo-N-{3-[(2,4- dichlorophenyl)amino] quinoxalin-2- yl}benzenesulfonamide


 


241




ethyl 5-ethyl-2-[(3-{[(3- nitrophenyl)sulfonyl] amino}quinoxalin-2-yl) amino]thiophene-3- carboxylate


 


242




N-(3-{[3-(morpholin-4- ylsulfonyl)phenyl] amino}quinoxalin-2- yl)benzenesulfonamide


 


243




ethyl 2-[(3-{[(4- bromophenyl)sulfonyl] amino}quinoxalin-2-yl) amino]-4,5,6,7-tetrahydro- 1-benzothiophene-3- carboxylate


 


244




4-methyl-N-(3-{[3- (piperidin-1-ylsulfonyl) phenyl]amino}quinoxalin- 2-yl)benzenesulfonamide


 


245




4-chloro-N-(3-{[4- (morpholin-4-ylsulfonyl) phenyl]amino}quinoxalin- 2-yl)benzenesulfonamide


 


246




4-chloro-N-(3-{[3- (morpholin-4-ylsulfonyl) phenyl]amino}quinoxalin- 2-yl)benzenesulfonamide


 


247




4-methyl-N-[3-(quinolin- 6-ylamino)quinoxalin- 2-yl]benzenesulfonamide


 


248




N-(3-{[3-(piperidin-1- ylsulfonyl)phenyl] amino}quinoxalin-2- yl)benzenesulfonamide


 


249




N-(3-{[4- (phenylamino)phenyl] amino}quinoxalin-2- yl)benzenesulfonamide


 


250




N-(3-{[2,5-bis(methoxy) phenyl]amino} quinoxalin-2-yl)-4- bromobenzenesulfonamide


 


251




ethyl 2-[(3-{[(3- nitrophenyl)sulfonyl] amino}quinoxalin-2-yl) amino]-5,6-dihydro-4H- cyclopenta[b]thiophene- 3-carboxylate


 


252




N-{3-[(4′-nitrobiphenyl- 4-yl)amino]quinoxalin- 2-yl}benzenesulfonamide


 


253




ethyl 2-[(3-{[(3- nitrophenyl)sulfonyl] amino}quinoxalin-2-yl) amino]-4,5,6,7-tetrahydro- 1-benzothiophene-3- carboxylate


 


254




N-(3-{[4-chloro-3- (morpholin-4- ylsulfonyl)phenyl] amino}quinoxalin-2- yl)benzenesulfonamide


 


255




ethyl 5-ethyl-2-({3- [(phenylsulfonyl)amino] quinoxalin-2-yl}amino) thiophene-3-carboxylate


 


256




N-[4-({[3-(quinolin-6- ylamino)quinoxalin-2- yl]amino}sulfonyl) phenyl]acetamide


 


257




ethyl 2-[(3-{[(2- methylphenyl)sulfonyl] amino}quinoxalin-2- yl)amino]-5,6-dihydro- 4H-cyclopenta[b] thiophene-3-carboxylate


 


258




3,4-dichloro-N-[3- (naphthalen-1-ylamino) quinoxalin-2-yl] benzenesulfonamide


 


259




ethyl 2-{[3-({[4- (acetylamino)-3,5- dibromophenyl]sulfonyl} amino)quinoxalin-2-yl] amino}-4,5,6,7-tetrahydro- 1-benzothiophene-3- carboxylate


 


260




ethyl 2-[(3-{[(2-chloro-5- nitrophenyl)sulfonyl] amino}quinoxalin-2-yl) amino]-4,5,6,7-tetrahydro- 1-benzothiophene-3- carboxylate


 


261




N-{3-[(3-fluorophenyl) amino]quinoxalin-2- yl}benzenesulfonamide


 


262




N-(3-{[4-(morpholin-4- ylsulfonyl)phenyl]amino} quinoxalin-2-yl) benzenesulfonamide


 


263




ethyl 2-{[3-({[4- (acetylamino)phenyl] sulfonyl}amino) quinoxalin-2-yl]amino}- 4,5,6,7-tetrahydro-1- benzothiophene-3- carboxylate


 


264




ethyl 2-[(3-{[(4- chlorophenyl)sulfonyl] amino}quinoxalin-2-yl) amino]-5-ethylthiophene- 3-carboxylate


 


265




N,N-diethyl-4-[(3-{[(4- methylphenyl)sulfonyl] amino}quinoxalin-2- yl)amino] benzenesulfonamide


 


266




ethyl 2-{[3-({[4- (acetylamino)phenyl] sulfonyl}amino) quinoxalin-2-yl]amino}- 5-ethylthiophene-3- carboxylate


 


267




ethyl 2-[(3-{[(4- chlorophenyl)sulfonyl] amino}quinoxalin-2-yl) amino]-4,5,6,7-tetrahydro- 1-benzothiophene-3- carboxylate


 


268




ethyl 2-({3- [(phenylsulfonyl)amino] quinoxalin-2-yl}amino)- 4,5,6,7-tetrahydro-1- benzothiophene-3- carboxylate


 


269




N-[4-(methoxy)phenyl]-4- [(3-{[(3-nitrophenyl) sulfonyl]amino}quinoxalin- 2-yl)amino]benzamide


 


270




N-{3-({4-[(4-aminophenyl) oxy]phenyl}amino) quinoxalin-2-yl]-4- chlorobenzenesulfonamide


 


271




N-[4-({[3-({4-[(4- aminophenyl)oxy]phenyl} amino)quinoxalin-2-yl] amino}sulfonyl)phenyl] acetamide


 


272




(2E)-3-{3-[(3-{[(4- methylphenyl)sulfonyl] amino}quinoxalin-2-yl) amino]phenyl} prop-2-enoic acid


 


273




N-{3-[(9-ethyl-9H- carbazol-3-yl)amino] quinoxalin-2-yl}-3- nitrobenzenesulfonamide


 


274




N-[3-({4-[(4- aminophenyl)oxy]phenyl} amino)quinoxalin-2- yl]benzenesulfonamide


 


275




4-bromo-N-{3-[(9-ethyl- 9H-carbazol-3-yl) amino]quinoxalin-2-yl} benzenesulfonamide


 


276




N-{3-[(9-ethyl-9H- carbazol-3-yl)amino] quinoxalin-2-yl} benzenesulfonamide


 


277




N-{3-[(2-iodophenyl) amino]quinoxalin-2- yl}benzenesulfonamide


 


278




N-{3-[(1- phenylethyl)amino] quinoxalin-2- yl}benzenesulfonamide


 


279




4-bromo-N-{3-[(4- bromophenyl)amino] quinoxalin-2- yl}benzenesulfonamide


 


280




4-bromo-N-{3-[(4- chlorophenyl)amino] quinoxalin-2- yl}benzenesulfonamide


 


281




4-bromo-N-[3-(naphthalen- 2-ylamino)quinoxalin-2- yl]benzenesulfonamide


 


282




N-{3-[(2,3- dimethylphenyl)amino]-6- methylquinoxalin-2-yl}-4- methylbenzenesulfonamide


 


283




4-chloro-N-{3-[(2- iodophenyl)amino] quinoxalin-2- yl}benzenesulfonamide


 


284




N-(3-{[4-(octyloxy)phenyl] amino}quinoxalin-2- yl)benzenesulfonamide


 


285




N-[3-(2,1,3- benzothiadiazol-5-ylamino) quinoxalin-2-yl]-3- nitrobenzenesulfonamide


 


286




N-{3-[(2-bromo-4- methylphenyl)amino] quinoxalin-2- yl}benzenesulfonamide


 


287




N-[3-({4-[(3-aminophenyl) sulfonyl]phenyl}amino) quinoxalin-2-yl]-4- chlorobenzenesulfonamide


 


288




N-[3-({2-[(difluoromethyl) oxy]phenyl}amino) quinoxalin-2-yl]-3- nitrobenzenesulfonamide


 


289




8-[(3-{[(4- methylphenyl)sulfonyl] amino}quinoxalin-2- yl)amino]quinoline-2- carboxylic acid


 


290




ethyl 3,3,3-trifluoro-2- hydroxy-2-{4-[(3-{[(3- nitrophenyl)sulfonyl] amino}quinoxalin-2-yl) amino]phenyl}propanoate


 


291




N-[3-(quinolin-6- ylamino)quinoxalin-2- yl]benzenesulfonamide


 


292




4-{[3-({[4-(acetylamino) phenyl]sulfonyl}amino) quinoxalin-2-yl]amino} phenyl thiocyanate


 


293




1-[3-({[4-(acetylamino) phenyl]sulfonyl}amino) quinoxalin-2-yl]-4- methylpyridinium


 


294




N-{3-[(2-chlorophenyl) amino]quinoxalin-2-yl}-3- nitrobenzenesulfonamide


 


295




4-methyl-N-[3- (phenylamino)quinoxalin- 2-yl]benzenesulfonamide


 


296




4-methyl-N-{3-[(2- methylphenyl)amino] quinoxalin-2- yl}benzenesulfonamide


 


297




4-methyl-N-{3-[(4- methylphenyl)amino] quinoxalin-2- yl}benzenesulfonamide


 


298




N-{3-[(4- chlorophenyl)amino] quinoxalin-2-yl}-4- methylbenzenesulfonamide


 


299




4-methyl-N-[3- (naphthalen-2-ylamino) quinoxalin-2-yl] benzenesulfonamide


 


300




N-{4-[({3-[(4- bromophenyl)amino] quinoxalin-2-yl}amino) sulfonyl]phenyl} acetamide


 


301




N-{4-[({3-[(2- methylphenyl)amino] quinoxalin-2-yl}amino) sulfonyl]phenyl} acetamide


 


302




N-{3-[bis (phenylmethyl)amino] quinoxalin-2-yl} benzenesulfonamide


 


303




4-[(3-{[(4- methylphenyl)sulfonyl] amino}quinoxalin-2- yl)amino]benzoic acid


 


304




2-hydroxy-4-[(3-{[(4- methylphenyl)sulfonyl] amino}quinoxalin-2- yl)amino]benzoic acid


 


305




4-bromo-N-(3-{[2- (methoxy)phenyl]amino} quinoxalin-2- yl)benzenesulfonamide


 


306




N-{3-[(3-hydroxyphenyl) amino]quinoxalin-2- yl}benzenesulfonamide


 


307




N-[3-(naphthalen-1- ylamino)quinoxalin-2- yl]benzenesulfonamide


 


308




3-methyl-1-(3-{[(4- methylphenyl)sulfonyl] amino}quinoxalin-2- yl)pyridinium


 


309




N-(3-{[3-{[(4- chlorophenyl)sulfonyl] amino}-7-(methoxy) quinoxalin-2-yl] amino}phenyl)acetamide


 


310




N-{3-[(3-{[(4- chlorophenyl)sulfonyl] amino}quinoxalin-2-yl) amino]phenyl}acetamide


 


311




N-{3-[(4-bromophenyl) amino]quinoxalin-2-yl}-4- chlorobenzenesulfonamide


 


312




N-{3-[(2,4- dimethylphenyl)amino]-6- methylquinoxalin-2-yl}-4- methylbenzenesulfonamide


 


313




N-{3-[(3,4- dimethylphenyl)amino] quinoxalin-2-yl}-4- methylbenzenesulfonamide


 


314




N-{3-[(2,5- dimethylphenyl)amino]-6- methylquinoxalin-2-yl}-4- methylbenzenesulfonamide


 


315




ethyl 4-[(3-{[(4- chlorophenyl)sulfonyl] amino}quinoxalin-2- yl)amino]benzoate


 


316




4-chloro-N-{3-[(4- ethylphenyl)amino] quinoxalin-2- yl}benzenesulfonamide


 


317




4-chloro-N-(6-methyl-3- {[4-(methoxy)phenyl] amino}quinoxalin-2- yl)benzenesulfonamide


 


318




4-chloro-N-{3-[(4- chlorophenyl)amino]- 6-methylquinoxalin-2- yl}benzenesulfonamide


 


319




N-(3-{[4-chloro-2,5- bis(methoxy)phenyl] amino}quinoxalin-2- yl)benzenesulfonamide


 


320




N-(3-{[3,5- bis(methoxy)phenyl] amino}quinoxalin-2- yl)benzenesulfonamide


 


321




N-(3-{[3,5-bis(methoxy) phenyl]amino} quinoxalin-2-yl)-4- methylbenzenesulfonamide


 


322




N-(3-{[3,5-bis(methoxy) phenyl]amino} quinoxalin-2-yl)-3- nitrobenzenesulfonamide


 


323




N-(3-{[2-methyl-5- (methoxy)phenyl] amino}quinoxalin-2- yl)benzenesulfonamide


 


324




N-[3-(2-Chloro-5- methoxy-phenylamino)- quinoxalin-2-yl]- benzensulfonamide


 


325




3-amino-N-(3-{[3,5- bis(methoxy)phenyl] amino}quinoxalin-2- yl)benzenesulfonamide


 


326




N-(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)-4- chlorobenzenesulfonamide


 


327




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)acetamide


 


328




N-(3-{[4-chloro-3- (methoxy)phenyl] amino}quinoxalin-2-yl) benzenesulfonamide


 


329




N-(3-{[4-fluoro-3-(methoxy) phenyl]amino}quinoxalin- 2-yl)benzenesulfonamide 


 


330




3-amino-N-(3-{[2,5- bis(methoxy)phenyl] amino}quinoxalin-2- yl)benzenesulfonamide


 


331




N-(3-{[3,5-bis(methoxy) phenyl]amino} quinoxalin-2-yl)-4- bromobenzenesulfonamide


 


332




N-(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)-3- nitrobenzenesulfonamide


 


333




3-amino-N-(3-{[2-chloro- 5-(methoxy)phenyl] amino}quinoxalin-2- yl)benzenesulfonamide


 


334




N-(3-{[(3-{[3,5- bis(methoxy)phenyl] amino}quinoxalin-2- yl)amino]sulfonyl}  phenyl)-N-2-,N-2- dimethylglycinamide


 


335




N-(3-{[2,5-bis(methoxy) phenyl]amino}-7- methylquinoxalin-2- yl)benzenesulfonamide


 


336




N-(3-{[2,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)-4-(methoxy) benzenesulfonamide


 


337




N-(3-{[2,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)-3- bromobenzenesulfonamide


 


338




N-(3-{[2,5-bis(methoxy) phenyl]amino} quinoxalin-2-yl)-3- fluorobenzenesulfonamide


 


339




N-(3-{[3,5- bis(methoxy)phenyl] amino}quinoxalin-2-yl)-2- fluorobenzenesulfonamide


 


340




N-(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)-4-(methoxy) benzenesulfonamide


 


341




N-(3-{[3,5-bis(methoxy) phenyl]amino} quinoxalin-2-yl)-3- bromobenzenesulfonamide


 


342




N-(3-{[(3-{[3,5-bis (methoxy)phenyl] amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)-1- methylpiperidine-4- carboxamide


 


343




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-3- piperidin-1-ylpropanamide


 


344




N-(3-{[(3-{[3,5- bis(methoxy)phenyl] amino}quinoxalin-2- yl)amino]sulfonyl} phenyl)-4-(dimethylamino) butanamide


 


345




N-(3-{[3,5- bis(methoxy)phenyl] amino}quinoxalin-2- yl)-3-(hydroxyamino) benzenesulfonamide


 


346




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2- morpholin-4-ylacetamide


 


347




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}-4-methylphenyl)- N-2-methylglycinamide


 


348




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}-4-methylphenyl)- L-alaninamide


 


349




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}-4-methylphenyl)- 2-methylalaninamide


 


350




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}-4-methylphenyl)- N-2-,N-2- dimethylglycinamide


 


351




N-(3-{[(3-{[3,5- bis(methoxy)phenyl] amino}quinoxalin-2- yl)amino]sulfonyl} phenyl)-D-alaninamide


 


352




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2- methylglycinamide


 


353




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}-4-methylphenyl)- D-alaninamide


 


354




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2- methylglycinamide


 


355




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-L- alaninamide


 


356




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-D- alaninamide


 


357




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2- methylalaninamide


 


358




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2- methylalaninamide


 


359




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}-4- methylphenyl)-N-2-,N-2- dimethylglycinamide


 


360




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2-[2- (dimethylamino)ethyl]- N-2-methylglycinamide


 


361




(2S)-2-amino-N-(3-{[(3- {[2-chloro-5-(methoxy) phenyl]amino}quinoxalin- 2-yl)amino]sulfonyl} phenyl)butanamide


 


362




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2-[2- (dimethylamino)ethyl]-N- 2-methylglycinamide


 


363




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2-,N-2- dimethylglycinamide


 


364




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2- methyl-L-alaninamide


 


365




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl) glycinamide


 


366




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl) glycinamide


 


367




N-(2-chloro-5-{[(3-{[2- chloro-5-(methoxy)phenyl] amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)- N-2-methylglycinamide


 


368




2-(dimethylamino)- N-(3-(N-(3-(3-(2- (dimethylamino)acetamido)- 5-methoxyphenylamino) quinoxalin-2-yl)sulfamoyl) phenyl)acetamide


 


369




N-(3-{[(3-{[2-acetyl-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2-,N-2- dimethylglycinamide


 


370




N-(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)-3- (formylamino) benzenesulfonamide


 


371




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2- ethylglycinamide


 


372




N-(5-{[(3-{[3,5- bis(methoxy)phenyl] amino}quinoxalin-2- yl)amino]sulfonyl}-2- methylphenyl)glycinamide


 


373




2-azetidin-1-yl-N-(3-{[(3- {[2-chloro-5-(methoxy) phenyl]amino}quinoxalin- 2-yl)amino]sulfonyl} phenyl)acetamide


 


374




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-L- prolinamide


 


375




N-(3-{[(3-{[2-bromo-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2- methylglycinamide


 


376




N-2-,N-2-dimethyl-N-(3- {[(3-{[6-(methoxy) quinolin-8-yl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl) glycinamide


 


377




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-L- alaninamide


 


378




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2- methyl-D-alaninamide


 


379




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-L- prolinamide


 


380




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-D- serinamide


 


381




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl) azetidine-3-carboxamide


 


382




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2-,2- dimethylalaninamide


 


383




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2- methyl-D-alaninamide


 


384




N-(3-{[(3-{[2-bromo-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2-, N-2-dimethylglycinamide


 


385




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2- propylglycinamide


 


386




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2- methyl-L-alaninamide


 


387




N-(5-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}-2-methylphenyl)- beta-alaninamide


 


388




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl) piperidine-3-carboxamide


 


389




N-(3-{[(3-{[3,5- bis(methoxy)phenyl] amino}quinoxalin-2- yl)amino]sulfonyl} phenyl)-2-(4-methyl-1,4- diazepan-1-yl)acetamide


 


390




(2S)-2-amino-N-(3-{[(3- {[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl) amino]sulfonyl} phenyl)butanamide


 


391




N-(3-{[(3-{[3,5-bis (methoxy)phenyl] amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)- N-2-(2-hydroxypropyl) glycinamide


 


392




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2-(2- fluoroethyl)glycinamide


 


393




3-amino-N-(2-{[3,5-bis (methoxy)phenyl]amino} pyrido[2,3-b]pyrazin-3-yl) benzenesulfonamide


 


394




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2-[(2- methylpropyl)oxy] glycinamide


 


395




1-amino-N-(3-{[(3-{[2- chloro-5-(methoxy)phenyl] amino}quinoxalin-2-yl) amino]sulfonyl}phenyl) cyclopropanecarboxamide


 


396




N-(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)-3-(formylamino) benzenesulfonamide


 


397




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2- (cyclopropylmethyl) glycinamide


 


398




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-D- prolinamide


 


399




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2-[3- (dimethylamino)azetidin- 1-yl]acetamide


 


400




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-D- prolinamide


 


401




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl) piperidine-2-carboxamide


 


402




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl) morpholine-4-carboxamide


 


403




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2- pyrrolidin-1-ylacetamide


 


404




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-6-,N-6- dimethyl-L-lysinamide


 


405




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2- ethyl-N-2- methylglycinamide


 


406




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2-(1H- imidazol-4-yl)acetamide


 


407




1-amino-N-(3-{[(3-{[2- chloro-5-(methoxy)phenyl] amino}quinoxalin-2- yl)amino]sulfonyl}phenyl) cyclopentanecarboxamide


 


408




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2-(2- methylpropyl)glycinamide


 


409




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2- ethyl-N-2- methylglycinamide


 


410




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-1-(1H- imidazol-4-ylmethyl) azetidine-3-carboxamide


 


411




N-(5-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}-2-methylphenyl)- N-2-,N-2- dimethylglycinamide


 


412




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-1- ethylazetidine-3- carboxamide


 


413




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2- methyl-N-2-(1- methylpyrrolidin-3- yl)glycinamide


 


414




N-(3-{[(2-{[3,5-bis (methoxy)phenyl]amino} pyrido[2,3-b]pyrazin-3- yl)amino]sulfonyl} phenyl)-N-2-[2- (dimethylamino)ethyl]-N- 2-methylglycinamide


 


415




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2-[(3S)- 3-hydroxypyrrolidin- 1-yl]acetamide


 


416




1-amino-N-(3-{[(3-{[3,5- bis(methoxy)phenyl] amino}quinoxalin-2-yl) amino]sulfonyl}phenyl) cyclobutanecarboxamide


 


417




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2- butylglycinamide


 


418




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2-(3- piperidin-1-ylazetidin-1- yl)acetamide


 


419




3-[(aminocarbonyl)amino]- N-(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)benzenesulfonamide


 


420




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)-1- hydroxycyclopropanecarboxamide


 


421




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- (2,2-dimethylhydrazino) acetamide


 


422




N-(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)-3-[({[2-(dimethylamino) ethyl]amino}carbonyl)amino] benzenesulfonamide


 


423




N-(3-{[(3-{[3-fluoro-5-(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)-N-2- methylglycinamide


 


424




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)-2- hydroxyacetamide


 


425




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}phenyl) pyridazine-4-carboxamide


 


426




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)-N-2- (1-methylethyl)glycinamide


 


427




1-amino-N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl) cyclopentanecarboxamide


 


428




1-amino-N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl) cyclopropanecarboxamide


 


429




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)-2-[3- (dimethylamino) pyrrolidin-1-yl]acetamide


 


430




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)amino]sulfonyl}phenyl)- N-2-[2-(dimethylamino)ethyl] glycinamide


 


431




2-(dimethylamino)ethyl(3- {[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)amino]sulfonyl} phenyl)carbamate


 


432




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-1- (cyclopropylmethyl) azetidine-3-carboxamide


 


433




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2- (1,1-dimethylethyl) glycinamide


 


434




N-2-methyl-N-(3-{[(3-{[3- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl) glycinamide


 


435




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)-1H- imidazole-2-carboxamide


 


436




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl) isoxazole-5-carboxamide


 


437




N-(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2-(2,2,2- trifluoroethyl)glycinamide


 


438




3-amino-N-(3-{[2-methyl- 5-(methoxy)phenyl]amino} quinoxalin-2- yl)benzenesulfonamide


 


439




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)-3- oxocyclopentanecarboxamide


 


440




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)amino]sulfonyl}phenyl)-6- hydroxypyridine-2-carboxamide


 


441




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N-2- (3-fluoro-4-hydroxyphenyl) glycinamide


 


442




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-1- (furan-2-ylmethyl)azetidine- 3-carboxamide


 


443




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl) pyrimidine-5-carboxamide


 


444




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-1H- pyrrole-2-carboxamide


 


445




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)amino]sulfonyl}phenyl)- N-2-methyl-N-2-(1- methylethyl)glycinamide


 


446




N-(3-{[(3-{[3-fluoro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2-,N-2- dimethylglycinamide


 


447




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-1H- imidazole-4-carboxamide


 


448




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2-,N-2- diethylglycinamide


 


449




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2-(3- methylisoxazol-5-yl) acetamide


 


450




N-2-,N-2-dimethyl-N-(3- {[(3-{[2-methyl-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl) glycinamide


 


451




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)amino]sulfonyl}phenyl)- N-2-[(3-hydroxyphenyl)methyl] glycinamide


 


452




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)amino]sulfonyl}phenyl)- 1-methyl-1H-pyrrole-2- carboxamide


 


453




4-amino-N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)tetrahydro- 2H-pyran-4-carboxamide


 


454




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)- 2-[4-(methylamino)piperidin- 1-yl]acetamide


 


455




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)amino]sulfonyl}phenyl)-2- piperidin-1-ylacetamide


 


456




N-(4-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)amino]sulfonyl}phenyl)- N-2-,N-2-dimethylglycinamide


 


457




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)amino]sulfonyl}phenyl)- 1-methyl-L-prolinamide


 


458




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)amino]sulfonyl}phenyl) thiophene-3-carboxamide


 


459




3-amino-N-{3-[(2-chloro-5- hydroxyphenyl)amino] quinoxalin-2-yl} benzenesulfonamide


 


460




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)amino]sulfonyl}phenyl)-1- (cyclopropylcarbonyl) azetidine-3-carboxamide


 


461




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)amino]sulfonyl}phenyl)- 2-(4-methylpiperazin-1-yl) acetamide


 


462




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino(quinoxalin- 2-yl)amino]sulfonyl}phenyl)-1- (phenylmethyl)azetidine-3- carboxamide


 


463




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- y])amino]sulfonyl}phenyl)-2- chloropyridine-3-carboxamide


 


464




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)amino]sulfonyl}phenyl)-2- pyridin-4-ylacetamide


 


465




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-methyl-N-2-prop-2-en- 1-ylglycinamide


 


466




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N-2- (phenylmethyl)glycinamide


 


467




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- (methoxy)acetamide


 


468




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)amino]sulfonyl}phenyl)- 1-propanoylazetidine-3- carboxamide


 


469




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl) amino]sulfonyl}phenyl) pyridine-3-carboxamide


 


470




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2-[2- (methoxy)ethyl]glycinamide


 


471




1-acetyl-N-3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl) piperidine-4-carboxamide 


 


472




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2-(2- methylpyrrolidin-1-yl) acetamide


 


473




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)furan- 3-carboxamide


 


474




N-2-,N-2-dimethyl-N-(3- {[(3-{[3-(methoxy)phenyl] amino}quinoxalin-2-yl) amino]sulfonyl}phenyl) glycinamide


 


475




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-6- chloropyridine-3- carboxamide


 


476




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2- chlorobenzamide


 


477




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2- pyridin-2-ylacetamide


 


478




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2-[3- (dimethylamino) azetidin-1-yl]acetamide


 


479




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2- pyridin-3-ylacetamide


 


480




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2-(2- chlorophenyl)acetamide


 


481




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2-[3- (dimethylamino)propyl]-N- 2-methylglycinamide


 


482




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2- ethyl-N-2-(2-hydroxyethyl) glycinamide


 


483




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2-[2- (phenylmethyl) pyrrolidin-1-yl]acetamide


 


484




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl) propanamide


 


485




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)furan- 2-carboxamide


 


486




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2- chloropyridine-4- carboxamide


 


487




N-2-acetyl-N-(3-{[(3-{[3,5- bis(methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)glycinamide


 


488




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)butanamide


 


489




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-4- chlorobenzamide


 


490




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-4- methylbenzamide


 


491




1,1-dimethylethyl{2-[(3- {[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin- 2-yl)amino]sulfonyl} phenyl)amino]-2-oxoethyl}  carbamate


 


492




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-1,3- benzodioxole-5-carboxamide


 


493




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2-({[2- (methoxy)phenyl]methyl} oxy)glycinamide


 


494




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl) pyridine-4-carboxamide


 


495




N-(3-{[(3-{[4-fluoro-3- (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2-, N-2-dimethylglycinamide


 


496




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2-[4-(3,4- dichlorophenyl)piperazin- 1-yl]acetamide


 


497




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino}  quinoxalin-2-yl)amino] sulfonyl}phenyl)-3- pyridin-3-ylpropanamide


 


498




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl) tetrahydrofuran-3- carboxamide


 


499




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-N-2- [(2-methylphenyl) methyl]glycinamide


 


500




N-(3-{[(3-{[3,5- bis(methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2- methylbutanamide


 


501




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2-(3- fluorophenyl)acetamide


 


502




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-(1-methyl-1-phenylethyl) glycinamide


 


503




N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino] sulfonyl}phenyl)-2- methylcyclopropanecarboxamide


 


504




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- methyl-4-(methoxy)benzamide


 


505




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- methylpyridine-3-carboxamide


 


506




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-4- (methoxy)benzamide


 


507




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- (4-ethylpiperazin-1-yl)acetamide


 


508




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl) thiophene-2-carboxamide


 


509




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-3- fluoro-2-methylbenzamide


 


510




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- bromothiophene-3-carboxamide


 


511




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-4- fluorobenzamide


 


512




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2-(3- methylpiperidin-1-yl)acetamide


 


513




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- methylpropanamide


 


514




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl) pentanamide


 


515




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- (ethyloxy)acetamide


 


516




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-(2-fluorophenyl)glycinamide


 


517




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-3- (dimethylamino)benzamide


 


518




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2-(4- methylpiperidin-1-yl)acetamide


 


519




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-(2-propylphenyl)glycinamide


 


520




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl) benzamide


 


521




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl) pyrazine-2-carboxamide


 


522




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-3- fluoro-4-(methoxy)benzamide


 


523




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2,2- dimethylbutanamide


 


524




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- [(4-fluorophenyl)oxy]acetamide


 


525




1-acetyl-N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino]sulfonyl} phenyl)azetidine-3-carboxamide


 


526




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)-N-2- (4-methylphenyl)glycinamide


 


527




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-phenylglycinamide


 


528




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)- 2-(4-prop-2-en-1-ylpiperazin- 1-yl)acetamide


 


529




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- methylbenzamide


 


530




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-3- (methoxy)propanamide


 


531




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-3- methylfuran-2-carboxamide


 


532




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)- 2,2-dimethylpropanamide


 


533




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N-2- [(phenylmethyl)oxy]glycinamide


 


534




N-(3-[({3-[(2-chloro-5- hydroxyphenyl)amino] quinoxalin-2-yl}amino)sulfonyl] phenyl}-N-2-,N-2- dimethylglycinamide


 


535




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)-N-2- (3-chlorophenyl)glycinamide


 


536




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl) cyclobutanecarboxamide


 


537




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2-[3- (methoxy)phenyl]acetamide


 


538




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-1- methylcyclopropanecarboxamide


 


539




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-3- fluorobenzamide


 


540




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-4- (dimethylamino)benzamide


 


541




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-3,4- dichlorobenzamide


 


542




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N-2- {[2-(methylthio)phenyl]methyl} glycinamide


 


543




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- (2-fluorophenyl)acetamide


 


544




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-ethyl-N-2-(1-methylethyl) glycinamide


 


545




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-1,3- thiazole-4-carboxamide


 


546




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-methyl-N-2-(phenylmethyl) glycinamide


 


547




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-(2-thienylmethyl)glycinamide


 


548




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N-2- (pyridin-2-ylmethyl)glycinamide


 


549




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-3- (methoxy)benzamide


 


550




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-[(3-chloro-4-methylphenyl) methyl]glycinamide


 


551




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- methylpentanamide


 


552




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- (4-chlorophenyl)acetamide


 


553




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-3- fluoro-4-methylbenzamide


 


554




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)-2-[(2- methylphenyl)oxy]acetamide


 


555




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- cyclohexylacetamide


 


556




(1R,2R)-N-(3-{[(3-{[3,5-bis (methoxy)phenyl]amino} quinoxalin-2-yl)amino]sulfonyl} phenyl)-2- phenylcyclopropanecarboxamide


 


557




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-3- chlorobenzamide


 


558




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2-[2- (methoxy)phenyl]acetamide


 


559




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-3-[3- (methoxy)phenyl]propanamide


 


560




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-(2-fluoro-4-methylphenyl) glycinamide


 


561




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-[(3-fluorophenyl)methyl] glycinamide


 


562




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- [4-(methoxy)phenyl]acetamide


 


563




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- phenylacetamide


 


564




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2,4- dichlorobenzamide


 


565




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-3- oxocyclohexanecarboxamide


 


566




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N-2- (3-fluorophenyl)glycinamide


 


567




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- (3-chlorophenyl)acetamide


 


568




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N-2- (2-phenylpropyl)glycinamide


 


569




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N-2- [(2,4-dimethylphenyl)methyl] glycinamide


 


570




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2-(2- methylpiperidin-1-yl)acetamide


 


571




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-[2-(methoxy)phenyl] glycinamide


 


572




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- (3,4-dihydroisoquinolin- 2-(1H)-yl)acetamide


 


573




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl) pent-4-enamide


 


574




N-3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-(2-methylphenyl)glycinamide


 


575




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)- 2-(4-oxopiperidin-1-yl)acetamide


 


576




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- fluorobenzamide


 


577




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- y])amino]sulfonyl}phenyl)-N- 2-(1-phenylethyl)glycinamide


 


578




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- fluoro-6-(methoxy)benzamide


 


579




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N-2- [2-(1-methylethyl)phenyl] glycinamide


 


580




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)-3-[2- (methoxy)phenyl]propanamide


 


581




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)- 4-methylpentanamide


 


582




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2-(2- phenylmorpholin-4-yl)acetamide


 


583




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)-3-[4- (methoxy)phenyl]propanamide


 


584




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-cyclopentyl-N-2-prop-2-en- 1-ylglycinamide


 


585




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-methyl-N-2-[2-(methoxy) ethyl]glycinamide


 


586




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-4- cyclopropyl-4-oxobutanamide


 


587




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-[3-(1,1-dimethylethyl) phenyl]glycinamide


 


588




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-(cyclopropylmethyl)-N- 2-propylglycinamide


 


589




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- (2-oxocyclopentyl)acetamide


 


590




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-(4-chlorophenyl)glycinamide


 


591




2-(1,4′-bipiperidin-1′-yl)-N-(3- {[(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)amino] sulfonyl}phenyl)acetamide


 


592




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)- 2-(4-cyclopentylpiperazin- 1-yl)acetamide


 


593




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)- 2-(2-methylphenyl)acetamide


 


594




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-[(5-fluoro-2-methylphenyl) methyl]glycinamide


 


595




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-3,3- dimethylbutanamide


 


596




N-(3-{[(3-{[3,5-bis(methyloxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N2- (2-chlorophenyl)glycinamide


 


597




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-5- fluoro-2-methylbenzamide


 


598




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)- 4-fluoro-3-methylbenzamide


 


599




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)- 2,3-dichlorobenzamide


 


600




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- (phenyloxy)acetamide


 


601




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)-N-2- (2,3-dimethylphenyl)glycinamide


 


602




3-amino-N-(3-{[3,5-bis(methoxy) phenyl]amino}pyrido[2,3-b] pyrazin-2-yl)benzenesulfonamide


 


603




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)- 2-fluoro-5-methylbenzamide


 


604




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N-2- {[(4-methylphenyl)methyl]oxy} glycinamide


 


605




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- [4-(1-methylethyl)piperazin- 1-yl]acetamide


 


606




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)- 2-(4-fluorophenyl)acetamide


 


607




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-3- methylbutanamide


 


608




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-4- methyl-2-(methoxy)benzamide


 


609




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)-2-(4- propylpiperidin-1-yl)acetamide


 


610




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- [(3-methylphenyl)oxy]acetamide


 


611




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl) tetrahydrofuran-2-carboxamide


 


612




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- [3-(hydroxymethyl)piperidin- 1-yl]acetamide


 


613




1,1-dimethylethyl2-{[(3-{[(3- {[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)amino] sulfonyl}phenyl)amino]carbonyl} piperidine-1-carboxylate


 


614




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-methyl-N-2-(pyridin-3- ylmethyl)glycinamide


 


615




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-N- 2-ethyl-N-2-phenylglycinamide


 


616




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)-2-{[2- (methoxy)ethyl]oxy}acetamide


 


617




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)- 3-cyclopentylpropanamide


 


618




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)- 2,5-dichlorobenzamide


 


619




2-(4-acetylpiperazin-1-yl)-N-(3- {[(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)amino] sulfonyl}phenyl)acetamide


 


620




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-5- fluoro-2-(methoxy)benzamide


 


621




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)-N-2- cyclohexyl-N-2-ethylglycinamide


 


622




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-5- methylisoxazole-3-carboxamide


 


623




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-3- methylpyridine-2-carboxamide


 


624




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}phenyl)-2- (methoxy)pyridine-3- carboxamide


 


625




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-3,5- dichlorobenzamide


 


626




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- (1,3-thiazolidin-3-yl)acetamide


 


627




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2-(4- formylpiperazin-1-yl)acetamide


 


628




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- (2-pyridin-4-ylpiperidin-1- yl)acetamide


 


629




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)- 2-(methoxy)benzamide


 


630




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)- N-2-methyl-N-2-(2- methylpropyl)glycinamide


 


631




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- (4-formyl-1,4-diazepan-1- yl)acetamide


 


632




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-1- phenylcyclopropanecarboxamide


 


633




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- (2,6-dimethylmorpholin-4- yl)acetamide


 


634




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2- (2-phenylpyrrolidin-1-yl) acetamide


 


635




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[2- (dimethylamino)-1-methylethyl] benzamide


 


636




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[2- (dimethylamino)ethyl]benzamide


 


637




5-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[2- (dimethylamino)ethyl]-2- fluorobenzamide


 


638




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-pyrrolidin- 3-ylbenzamide


 


639




3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[2- (dimethylamino)ethyl] benzamide


 


640




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-(2- pyrrolidin-1-ylethyl)benzamide


 


641




N-(2-aminoethyl)-3-{[(3-{[2- chloro-5-(methoxy)phenyl] amino}quinoxalin-2-yl) amino]sulfonyl}benzamide


 


642




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[2- (dimethylamino)ethyl]-N- methylbenzamide


 


643




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N- (piperidin-2-ylmethyl) benzamide


 


644




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-(1- methylazetidin-3-yl)benzamide


 


645




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-(2- piperidin-1-ylethyl)benzamide


 


646




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[2- (diethylamino)ethyl]benzamide


 


647




3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[2- (dimethylamino)ethyl]-N- methylbenzamide


 


648




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-(1- methylpiperidin-3-yl)benzamide


 


649




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-piperidin- 3-ylbenzamide


 


650




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[(1- methylpiperidin-2-yl)methyl] benzamide


 


651




N-{2-[bis(2-hydroxyethyl) amino]ethyl}-3-{[(3-{[2- chloro-5-(methoxy)phenyl] amino}quinoxalin-2- yl)amino]sulfonyl}benzamide


 


652




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-(1- ethylpiperidin-3-yl)benzamide


 


653




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}benzamide


 


654




3-[(3-aminopyrrolidin-1-yl) carbonyl]-N-(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl) benzenesulfonamide


 


655




5-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[2- (dimethylamino)ethyl]-2- (methoxy)benzamide


 


656




N-(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2-yl)- 3-{[3-(methylamino)pyrrolidin-1- yl]carbonyl}benzenesulfonamide


 


657




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}benzoicacid


 


658




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-(2- morpholin-4-ylethyl)benzamide


 


659




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[(1- ethylpyrrolidin-2-yl)methyl] benzamide


 


660




3-[(4-amino-3-oxopyrazolidin- 1-yl)carbonyl]-N-(3-{[2-chloro- 5-(methoxy)phenyl]amino} quinoxalin-2-yl) benzenesulfonamide


 


661




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}-N- methylbenzamide


 


662




3-[(3-aminoazetidin-1-yl) carbonyl]-N-(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl) benzenesulfonamide


 


663




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-(pyridin- 3-ylmethyl)benzamide


 


664




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-(pyridin- 2-ylmethyl)benzamide


 


665




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-(2- hydroxyethyl)benzamide


 


666




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-(3- oxopyrazolidin-4-yl)benzamide


 


667




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[2-(1H- imidazol-4-yl)ethyl]benzamide


 


668




N-(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)-3-{[3-(dimethylamino) pyrrolidin-1-yl]carbonyl} benzenesulfonamide


 


669




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N- (pyridin-4-ylmethyl)benzamide


 


670




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-methyl- N-(1-methylpyrrolidin-3-yl) benzamide


 


671




N-(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2-yl)- 3-{[3-(diethylamino)pyrrolidin- 1-yl]carbonyl} benzenesulfonamide


 


672




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-1H- pyrrol-1-ylbenzamide


 


673




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-(3- pyrrolidin-1-ylpropyl)benzamide


 


674




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}-N-(2- cyanoethyl)-N-methylbenzamide


 


675




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[2- (methoxy)ethyl]benzamide


 


676




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-(2- cyanoethyl)-N-ethylbenzamide


 


677




3-[(3-aminopiperidin-1-yl) carbonyl]-N-(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl) benzenesulfonamide


 


678




3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfony}benzoicacid


 


679




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}-N-[3- (dimethylamino)propyl] benzamide


 


680




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N- morpholin-4-ylbenzamide


 


681




N-(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)-3-[(2,2-dimethylhydrazino) carbonyl]benzenesulfonamide


 


682




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[3-(1H- imidazol-1-yl)propyl]benzamide


 


683




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[3- (diethylamino)propyl]benzamide


 


684




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-(2- cyanoethyl)benzamide


 


685




methylN-[(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino]sulfonyl} phenyl)carbonyl]-beta-alaninate


 


686




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[2- (methylthio)ethyl]benzamide


 


687




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[2- (ethylthio)ethyl]benzamide


 


688




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[2- (dimethylamino)ethyl]- N-ethylbenzamide


 


689




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N[3-(2- oxopyrrolidin-1-yl)propyl] benzamide


 


690




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-(2- pyridin-4-ylethyl)benzamide


 


691




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[3- (ethyloxy)propyl]benzamide


 


692




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-(3- morpholin-4-ylpropyl) benzamide


 


693




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[3- (methoxy)propyl]benzamide


 


694




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[3- (dimethylamino)propyl]-N- methylbenzamide


 


695




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[3- (propyloxy)propyl]benzamide


 


696




ethylN-[(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino]sulfonyl} phenyl)carbonyl]-beta-alaninate


 


697




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-{3-[(1- methylethyl)oxy]propyl} benzamide


 


698




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-(1,1- dimethyl-2-piperidin-1- ylethyl)benzamide


 


699




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-methyl- N-propylbenzamide


 


700




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N- piperidin-1-ylbenzamide


 


701




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[1- methyl-2-(methoxy)ethyl] benzamide


 


702




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2-yl) amino]sulfonyl}-N-(1,1- dimethyl-2-morpholin-4-ylethyl) benzamide


 


703




N-(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)-3-({2-[(dimethylamino) methyl]piperidin-1-yl}carbonyl) benzenesulfonamide


 


704




N-[3-(butyloxy)propyl]-3-{[(3- {[2-chloro-5-(methoxy)phenyl] amino}quinoxalin-2-yl) amino]sulfonyl}benzamide


 


705




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-[4- (diethylamino)-1-methylbutyl] benzamide


 


706




3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}-N-(1,1-dimethyl- 2-oxo-2-piperidin-1-ylethyl) benzamide


 


707




N-(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)-3-[(4-methylpiperazin-1- yl)carbonyl]benzenesulfonamide


 


708




N-(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)-3-{[2-(piperidin-1-ylmethyl) piperidin-1-yl]carbonyl} benzenesulfonamide


 


709




N-(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)-6-oxo-1,6-dihydropyridine- 3-sulfonamide


 


710




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)- 6-oxo-1,6-dihydropyridine-3- sulfonamide


 


711




3-amino-N-(3-{[6-(methoxy) quinolin-8-yl]amino}quinoxalin- 2-yl)benzenesulfonamide


 


712




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl) thiophene-2-sulfonamide


 


713




N-(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)-3-cyanobenzenesulfonamide


 


714




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-3- (methylamino) benzenesulfonamide


 


715




N-(2-{[3,5-bis(methoxy)phenyl] amino}pyrido[2,3-b]pyrazin-3- yl)-3-nitrobenzenesulfonamide


 


716




N-(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)-3-(1-{[2-(dimethylamino) ethyl]amino}ethyl) benzenesulfonamide


 


717




3-amino-N-(3-{[3-(methoxy)-5- nitrophenyl]amino}quinoxalin- 2-yl)benzenesulfonamide


 


718




3-acetyl-N-(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl) benzenesulfonamide


 


719




3-amino-N-(3-{[3-fluoro-5- (methoxy)phenyl]amino} quinoxalin-2-yl) benzenesulfonamide


 


720




N-(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2-yl)- N′-[2-(dimethylamino)ethyl] benzene-1,3-disulfonamide


 


721




N-(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2-yl)- N′-[3-(dimethylamino)propyl] benzene-1,3-disulfonamide


 


722




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-6- chloropyridine-3-sulfonamide


 


723




N-(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2- yl)-3-{5-[(dimethylamino) methyl]-1,3,4-oxadiazol-2- yl}benzenesulfonamide


 


724




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-6-{[2- (dimethylamino)ethyl]amino} pyridine-3-sulfonamide


 


725




3-amino-N-(3-{[3-amino-5- (methoxy)phenyl]amino} quinoxalin-2-yl) benzenesulfonamide


 


726




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-3- (dimethylamino) benzenesulfonamide


 


727




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-6- {[2-(dimethylamino)ethyl] oxy}pyridine-3-sulfonamide


 


728




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-6- (dimethylamino)pyridine-3- sulfonamide


 


729




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)- 4-cyanobenzenesulfonamide


 


730




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)- 4-fluorobenzenesulfonamide


 


731




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-4-fluoro- 2-methylbenzenesulfonamide


 


732




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)- 2-methylbenzenesulfonamide


 


733




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)- 3-cyanobenzenesulfonamide


 


734




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-3,5- difluorobenzenesulfonamide


 


735




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)- 2-chlorobenzenesulfonamide


 


736




N-(4-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl) acetamide


 


737




N-(3-{[6-(methoxy)quinolin-8- yl]amino}quinoxalin-2-yl)-3- nitrobenzenesulfonamide


 


738




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-3-(2H- tetrazol-5-yl)benzenesulfonamide


 


739




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl) naphthalene-1-sulfonamide


 


740




N-{[(3-{[(3-{[2-chloro-5- (methoxy)phenyl]amino} quinoxalin-2-yl)amino]sulfonyl}- 4-methylphenyl)amino] (dimethylamino)methylidene}- N-methylmethanaminium


 


741




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)- 3-fluorobenzenesulfonamide


 


742




N-(3-{[2-bromo-5-(methoxy) phenyl]amino}quinoxalin-2-yl)- 3-nitrobenzensulfonamide


 


743




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-4- [(difluoromethyl)oxy] benzenesulfonamide


 


744




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-2- (trifluoromethyl) benzenesulfonamide


 


745




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-3-chloro- 4-fluorobenzensulfonamide


 


746




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-4- (trifluoromethyl) benzenesulfonamide


 


747




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-3- (methylsulfonyl) benzenesulfonamide


 


748




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-2,5- dichlorthiophene-3-sulfonamide


 


749




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-3,5- dichlorobenzenesulfonamide


 


750




N-(3-{[2-methyl-5-(methoxy) phenyl]amino}quinoxalin-2-yl)- 3-nitrobenzenesulfonamide


 


751




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-4- [(trifluoromethyl)oxy] benzensulfonamide


 


752




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-2-[4- (dimethylamino)piperidin-1-yl] acetamide


 


753




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-5- chloro-2-(methoxy) benzenesulfonamide


 


754




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-3- (trifluoromethyl) benzenesulfonamide


 


755




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-2,5-bis (methoxy)benzenesulfonamide


 


756




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-3,5- dimethylisoxazole-4-sulfonamide


 


757




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-5-bromo- 2-(methoxy)benzenesulfonamide


 


758




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-4- fluoro-3-(trifluoromethyl) benzenesulfonamide


 


759




N-(3-{[3-fluoro-5-(methoxy) phenyl]amino}quinoxalin-2-yl)- 3-nitrobenzenesulfonamide


 


760




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-3-fluoro- 4-methylbenzenesulfonamide


 


761




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-3-chloro- 4-methylbenzenesulfonamide


 


762




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-2,5- dimethylthiophene-3-sulfonamide


 


763




N-(3-{[3-(methoxy)phenyl] amino}quinoxalin-2-yl)-3- nitrobenzenesulfonamide


 


764




N-{3-[(2-chloro-5- hydroxyphenyl)amino]quinoxalin- 2-yl}-3-nitrobenzenesulfonamide


 


765




N-(3-{[(3-{[3,5-bis(methoxy) phenyl]amino}quinoxalin-2- yl)amino]sulfonyl}phenyl)-4- methyl-3-(methoxy)benzamide


 


766




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-1- phenylmethanesulfonamide


 


767




N-(3-{[3-(methoxy)-5- nitrophenyl]amino}quinoxalin-2- yl)-3-nitrobenzenesulfonamide


 


768




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-1-(3- chlorophenyl) methanesulfonamide


 


769




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-4,5- dichlorothiophene-2-sulfonamide


 


770




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-5- chloro-1,3-dimethyl-1H- pyrazole-4-sulfonamide


 


771




N-(3-{[3,5-bis(methoxy)phenyl] amino}quinoxalin-2-yl)-3,5-bis (trifluoromethyl) benzenesulfonamide









The Compounds in Table 2a can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 2a can be used to practice the invention.











Cmpd No.
Name
















1
3-(azetidin-3-ylidenemethyl)-4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-



pyrazolo[3,4-d]pyrimidine


2
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(3-fluoropyridin-4-yl)-1H-pyrazolo[3,4-



d]pyrimidine


3
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(3-chloropyridin-4-yl)-1H-pyrazolo[3,4-



d]pyrimidine


4
2-({5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-



methylphenyl}oxy)-N,N-dimethylethanamine


5
2-({5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-



methylphenyl}oxy)-N,N-diethylethanamine


6
4-(4-{5-chloro-2-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-3-ethyl-



1H-pyrazolo[3,4-d]pyrimidine


7
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-piperazin-1-yl-1H-pyrazolo[3,4-



d]pyrimidine


8
N-(3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-



yl}prop-2-yn-1-yl)acetamide


9
N,N-diethyl-2-({3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-



yl]phenyl}oxy)ethanamine


10
3-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-chloro-2-



methylphenyl}-N,N-diethylpropan-1-amine


11
3-bromo-4-{4-[5-chloro-2-methyl-3-(3-pyrrolidin-1-ylpropyl)phenyl]piperazin-1-yl}-1H-



pyrazolo[3,4-d]pyrimidine


12
3-bromo-4-(4-{5-chloro-2-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-



1H-pyrazolo[3,4-d]pyrimidine


13
2-({3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-chloro-2-



methylphenyl}oxy)-N,N-diethylethanamine


14
4-[4-(5-chloro-2-methyl-3-{[2-(1-methylpiperidin-4-yl)ethyl]oxy}phenyl)piperazin-1-yl]-



3-ethyl-1H-pyrazolo[3,4-d]pyrimidine


15
5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-



pyrrolidin-1-ylethyl)aniline


16
4-(4-{5-chloro-2-methyl-3-[(2-morpholin-4-ylethyl)oxy]phenyl}piperazin-1-yl)-3-ethyl-



1H-pyrazolo[3,4-d]pyrimidine


17
4-(4-{5-chloro-2-methyl-3-[(2-piperidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-3-ethyl-1H-



pyrazolo[3,4-d]pyrimidine


18
3-bromo-4-{4-[5-chloro-2-methyl-3-(3-morpholin-4-ylpropyl)phenyl]piperazin-1-yl}-1H-



pyrazolo[3,4-d]pyrimidine


19
3-bromo-4-(4-{5-chloro-2-methyl-3-[3-(4-methylpiperazin-1-yl)propyl]phenyl}piperazin-



1-yl)-1H-pyrazolo[3,4-d]pyrimidine


20
3-bromo-4-(4-{5-chloro-2-methyl-3-[(2-piperidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-



1H-pyrazolo[3,4-d]pyrimidine


21
3-bromo-4-(4-{5-chloro-2-methyl-3-[(2-morpholin-4-ylethyl)oxy]phenyl}piperazin-1-yl)-



1H-pyrazolo[3,4-d]pyrimidine


22
4-{4-[5-chloro-2-methyl-3-(3-morpholin-4-ylpropyl)phenyl]piperazin-1-yl}-3-ethyl-1H-



pyrazolo[3,4-d]pyrimidine


23
N′-{5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-



methylphenyl}-N,N-diethylethane-1,2-diamine


24
4-{4-[5-chloro-2-methyl-3-(3-piperidin-1-ylpropyl)phenyl]piperazin-1-yl}-3-ethyl-1H-



pyrazolo[3,4-d]pyrimidine


25
4-[4-(5-chloro-3-{[2-(4-ethylpiperazin-1-yl)ethyl]oxy}-2-methylphenyl)piperazin-1-yl]-3-



ethyl-1H-pyrazolo[3,4-d]pyrimidine


26
4-(4-{5-chloro-2-methyl-3-[(3-morpholin-4-ylpropyl)oxy]phenyl}piperazin-1-yl)-3-ethyl-



1H-pyrazolo[3,4-d]pyrimidine


27
3-bromo-4-{4-[5-chloro-2-methyl-3-(3-piperidin-1-ylpropyl)phenyl]piperazin-1-yl}-1H-



pyrazolo[3,4-d]pyrimidine


28
N′-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-chloro-2-



methylphenyl}-N,N-diethylethane-1,2-diamine


29
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-chloro-2-methyl-N-(2-



pyrrolidin-1-ylethyl)aniline


30
4-[4-(5-chloro-2-methyl-3-{[2-(4-methylpiperazin-1-yl)ethyl]oxy}phenyl)piperazin-1-yl]-



3-ethyl-1H-pyrazolo[3,4-d]pyrimidine


31
4-[4-(5-chloro-2-methyl-3-{[(1-methylpiperidin-4-yl)methyl]oxy}phenyl)piperazin-1-yl]-3-



ethyl-1H-pyrazolo[3,4-d]pyrimidine


32
N,N-diethyl-2-({3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-



methylphenyl}oxy)ethanamine


33
2-[(5-chloro-3-{4-[1-(1,1-dimethylethyl)-3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidin-



4-yl]piperazin-1-yl}-2-methylphenyl)oxy]-N,N-diethylethanamine


34
2-[(5-chloro-2-methyl-3-{4-[3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-



yl]piperazin-1-yl}phenyl)oxy]-N,N-diethylethanamine


35
4-(4-{5-chloro-2-methyl-3-[(3-pyrrolidin-1-ylpropyl)oxy]phenyl}piperazin-1-yl)-3-ethyl-



1H-pyrazolo[3,4-d]pyrimidine


36
4-[4-(5-chloro-2-methyl-3-{[3-(4-methylpiperazin-1-yl)propyl]oxy}phenyl)piperazin-1-yl]-



3-ethyl-1H-pyrazolo[3,4-d]pyrimidine


37
3-bromo-4-(4-{5-chloro-2-methyl-3-[(3-piperidin-1-ylpropyl)oxy]phenyl}piperazin-1-yl)-



1H-pyrazolo[3,4-d]pyrimidine


38
3-bromo-4-(4-{5-chloro-2-methyl-3-[(3-morpholin-4-ylpropyl)oxy]phenyl}piperazin-1-yl)-



1H-pyrazolo[3,4-d]pyrimidine


39
4-(4-{5-chloro-2-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-3-



(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine


40
4-(4-{5-chloro-2-methyl-3-[(3-morpholin-4-ylpropyl)oxy]phenyl}piperazin-1-yl)-3-



(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine


41
4-(4-{5-chloro-2-methyl-3-[(2-morpholin-4-ylethyl)oxy]phenyl}piperazin-1-yl)-3-



(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine


42
4-(4-{5-chloro-2-methyl-3-[(3-piperidin-1-ylpropyl)oxy]phenyl}piperazin-1-yl)-3-ethyl-



1H-pyrazolo[3,4-d]pyrimidine


43
4-[4-(5-chloro-3-{[3-(4-ethylpiperazin-1-yl)propyl]oxy}-2-methylphenyl)piperazin-1-yl]-3-



ethyl-1H-pyrazolo[3,4-d]pyrimidine


44
5-chloro-2-methyl-3-[4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-(2-



pyrrolidin-1-ylethyl)aniline


45
5-chloro-2-methyl-3-[4-(3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-(2-



pyrrolidin-1-ylethyl)aniline


46
N′-(5-chloro-2-methyl-3-{4-[3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-



yl]piperazin-1-yl}phenyl)-N,N-dimethylethane-1,2-diamine


47
3-({5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-



methylphenyl}oxy)-N,N-diethylpropan-1-amine


48
N′-(5-chloro-2-methyl-3-{4-[3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-



yl]piperazin-1-yl}phenyl)-N,N-diethylethane-1,2-diamine


49
5-chloro-2-methyl-N-(2-pyrrolidin-1-ylethyl)-3-{4-[3-(trifluoromethyl)-1H-pyrazolo[3,4-



d]pyrimidin-4-yl]piperazin-1-yl}aniline


50
3-bromo-4-(4-{4-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-1H-



pyrazolo[3,4-d]pyrimidine


51
4-(4-{4-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-



d]pyrimidine


52
3-methyl-4-(4-{4-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-1H-



pyrazolo[3,4-d]pyrimidine


53
4-(4-{5-chloro-2-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-1H-



pyrazolo[3,4-d]pyrimidine


54
4-(4-{5-chloro-2-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-3-methyl-



1H-pyrazolo[3,4-d]pyrimidine


55
4-(4-{5-chloro-2-methyl-3-[(2-piperidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-3-



(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine


56
3-[(5-chloro-2-methyl-3-{4-[3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-



yl]piperazin-1-yl}phenyl)oxy]-N,N-diethylpropan-1-amine


57
5-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-



pyrrolidin-1-ylethyl)aniline


58
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-fluoro-2-methyl-N-(2-



pyrrolidin-1-ylethyl)aniline


59
4-{4-[5-chloro-2-methyl-3-(3-pyrrolidin-1-ylpropyl)phenyl]piperazin-1-yl}-1H-



pyrazolo[3,4-d]pyrimidine


60
3-bromo-4-{4-[5-fluoro-2-methyl-3-(3-pyrrolidin-1-ylpropyl)phenyl]piperazin-1-yl}-1H-



pyrazolo[3,4-d]pyrimidine


61
4-{4-[5-chloro-2-methyl-3-(3-pyrrolidin-1-ylpropyl)phenyl]piperazin-1-yl}-3-



(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine


62
4-(4-{5-chloro-2-methyl-3-[3-(4-methylpiperazin-1-yl)propyl]phenyl}piperazin-1-yl)-3-



ethyl-1H-pyrazolo[3,4-d]pyrimidine


63
3-bromo-4-(4-pyridin-2-ylpiperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine


64
3-bromo-4-[4-(2,4-dimethylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


65
3-bromo-4-{4-[3-(methyloxy)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine


66
3-bromo-4-{4-[2-(methyloxy)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine


67
3-bromo-4-{4-[4-methyl-3-(3-pyrrolidin-1-ylpropyl)phenyl]piperazin-1-yl}-1H-



pyrazolo[3,4-d]pyrimidine


68
4-(4-{5-chloro-2-methyl-3-[(3-pyrrolidin-1-ylpropyl)oxy]phenyl}piperazin-1-yl)-3-



(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine


69
4-(4-{5-chloro-2-methyl-3-[(3-piperidin-1-ylpropyl)oxy]phenyl}piperazin-1-yl)-3-



(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine


70
4-[4-(5-chloro-2-methyl-3-{[3-(4-methylpiperazin-1-yl)propyl]oxy}phenyl)piperazin-1-yl]-



3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine


71
4-[4-(5-chloro-3-{[3-(4-ethylpiperazin-1-yl)propyl]oxy}-2-methylphenyl)piperazin-1-yl]-3-



(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine


72
3-bromo-4-[4-(5-chloro-2-methyl-3-{[2-(4-methylpiperazin-1-



yl)ethyl]oxy}phenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


73
4-[4-(5-chloro-2-methyl-3-{[2-(4-methylpiperazin-1-yl)ethyl]oxy}phenyl)piperazin-1-yl]-



3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine


74
3-bromo-4-[4-(5-chloro-3-{[2-(4-ethylpiperazin-1-yl)ethyl]oxy}-2-



methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


75
3-bromo-4-[4-(3,4-dichlorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


76
3-bromo-4-[4-(3,4-difluorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


77
3-bromo-4-[4-(2,4-dichlorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


78
3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-fluoro-2-methyl-N-(2-



pyrrolidin-1-ylethyl)aniline


79
5-fluoro-2-methyl-N-(2-pyrrolidin-1-ylethyl)-3-{4-[3-(trifluoromethyl)-1H-pyrazolo[3,4-



d]pyrimidin-4-yl]piperazin-1-yl}aniline


80
4-{4-[3,5-bis(methyloxy)phenyl]piperazin-1-yl}-3-bromo-1H-pyrazolo[3,4-d]pyrimidine


81
4-[4-(5-chloro-3-{[2-(4-ethylpiperazin-1-yl)ethyl]oxy}-2-methylphenyl)piperazin-1-yl]-3-



(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine


82
N-{5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-



methylphenyl}-N,N′,N′-trimethylethane-1,2-diamine


83
3-({3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-chloro-2-



methylphenyl}oxy)-N,N-diethylpropan-1-amine


84
3-bromo-4-(4-{5-chloro-2-methyl-3-[(3-pyrrolidin-1-ylpropyl)oxy]phenyl}piperazin-1-yl)-



1H-pyrazolo[3,4-d]pyrimidine


85
3-bromo-4-[4-(5-chloro-2-methyl-3-{[3-(4-methylpiperazin-1-



yl)propyl]oxy}phenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


86
3-bromo-4-[4-(5-chloro-3-{[3-(4-ethylpiperazin-1-yl)propyl]oxy}-2-



methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


87
3-(5-chloro-2-methyl-3-{4-[3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-



yl]piperazin-1-yl}phenyl)-N,N-diethylpropan-1-amine


88
3-bromo-4-[4-(5-chloro-2-methyl-3-{[(1-methylpiperidin-4-



yl)methyl]oxy}phenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


89
3-bromo-4-[4-(5-chloro-2-methyl-3-{[2-(1-methylpiperidin-4-



yl)ethyl]oxy}phenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


90
4-[4-(5-chloro-2-methyl-3-{[(1-methylpiperidin-4-yl)methyl]oxy}phenyl)piperazin-1-yl]-3-



(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine


91
4-[4-(5-chloro-2-methyl-3-{[2-(1-methylpiperidin-4-yl)ethyl]oxy}phenyl)piperazin-1-yl]-



3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine


92
4-(4-{5-chloro-2-methyl-3-[3-(4-methylpiperazin-1-yl)propyl]phenyl}piperazin-1-yl)-3-



(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine


93
3-bromo-4-[4-(3-chloro-4-fluorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


94
1-{4-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]phenyl}ethanone


95
3-bromo-4-[4-(2,5-dichlorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


96
3-bromo-4-[4-(3,4-dimethylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


97
3-bromo-4-[4-(4-nitrophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


98
3-ethyl-4-(4-phenylpiperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine


99
3-ethyl-4-{4-[3-(methyloxy)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine


100
4-{4-[5-chloro-2-methyl-3-(3-piperidin-1-ylpropyl)phenyl]piperazin-1-yl}-3-



(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine


101
4-[4-(3,6-dimethylpyrazin-2-yl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine


102
1-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]isoquinoline


103
3-bromo-4-[4-(2,6-dimethylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


104
3-bromo-4-{4-[4-(ethyloxy)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine


105
3-bromo-4-[4-(2-ethylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


106
4-{4-[2,4-bis(methyloxy)phenyl]piperazin-1-yl}-3-bromo-1H-pyrazolo[3,4-d]pyrimidine


107
3-bromo-4-(4-pyrazin-2-ylpiperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine


108
3-bromo-4-(4-pyrimidin-2-ylpiperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine


109
4-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-



(trifluoromethyl)quinoline


110
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]pyrazine-2-carbonitrile


111
4-[4-(4,6-dimethylpyrimidin-2-yl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine


112
ethyl 4-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-



(trifluoromethyl)pyrimidine-5-carboxylate


113
4-{4-[3-chloro-5-(methyloxy)phenyl]piperazin-1-yl}-3-ethyl-1H-pyrazolo[3,4-



d]pyrimidine


114
4-[4-(3-bromo-2-chloro-5-fluorophenyl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-



d]pyrimidine


115
2-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]pyridine-3-carboxamide


116
3-ethyl-4-{4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}-1H-pyrazolo[3,4-



d]pyrimidine


117
3-bromo-4-{4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}-1H-pyrazolo[3,4-



d]pyrimidine


118
3-bromo-4-{4-[4-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl}-1H-pyrazolo[3,4-



d]pyrimidine


119
2-({3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]pyrazin-2-yl}oxy)-



N,N-dimethylethanamine


120
4-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methylquinoline


121
3-bromo-4-[4-(2-nitrophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


122
2-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]benzonitrile


123
4-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]benzonitrile


124
3-bromo-4-{4-[4-(trifluoromethyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine


125
3-bromo-4-(4-{4-[(phenylmethyl)oxy]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-



d]pyrimidine


126
4-{4-[5-chloro-2-methyl-3-(methyloxy)phenyl]piperazin-1-yl}-3-ethyl-1H-pyrazolo[3,4-



d]pyrimidine


127
2-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]pyridine-3-carbonitrile


128
3-bromo-4-[4-(3,5-dichlorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


129
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-chloro-5-fluoro-N-(2-



pyrrolidin-1-ylethyl)aniline


130
2-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-fluoro-N-(2-



pyrrolidin-1-ylethyl)aniline


131
3-bromo-4-[4-(2,5-difluorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


132
4-[4-(2,5-difluorophenyl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine


133
3-bromo-4-{4-[3-(methyloxy)pyrazin-2-yl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine


134
3-bromo-4-[4-(3-chlorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


135
3-bromo-4-{4-[3-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}-1H-pyrazolo[3,4-



d]pyrimidine


136
3-bromo-4-{4-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}-1H-pyrazolo[3,4-



d]pyrimidine


137
4-(4-{5-chloro-2-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-3-(1-



methylethyl)-1H-pyrazolo[3,4-d]pyrimidine


138
5-chloro-2-methyl-3-{4-[3-(1-methylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperazin-1-



yl}-N-(2-pyrrolidin-1-ylethyl)aniline


139
2-({3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]phenyl}oxy)-N-



ethylacetamide


140
2-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N,N-diethylpyrimidin-4-



amine


141
3-bromo-4-[4-(3-{[(3-methylphenyl)methyl]oxy}phenyl)piperazin-1-yl]-1H-pyrazolo[3,4-



d]pyrimidine


142
3-bromo-4-(4-{3-[(2-piperidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-



d]pyrimidine


143
3-bromo-4-[4-(4-furan-2-ylpyrimidin-2-yl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


144
6-{2-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]pyrimidin-4-yl}-2H-



1,4-benzoxazin-3(4H)-one


145
3-ethyl-4-{4-[2-methyl-3-(methyloxy)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-



d]pyrimidine


146
N′-{5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-



methylphenyl}-N-methyl-N-(1-methylethyl)ethane-1,2-diamine


147
N′-{5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-



methylphenyl}-N-ethyl-N-methylethane-1,2-diamine


148
N′-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-chloro-2-



methylphenyl}-N,N-dimethylethane-1,2-diamine


149
3-({6-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-chloro-5-



methylpyrimidin-4-yl}oxy)-N,N-diethylpropan-1-amine


150
3-bromo-4-[4-(2,3-dichlorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


151
3-bromo-4-{4-[2-(trifluoromethyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine


152
3-bromo-4-(4-phenylpiperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine


153
3-bromo-4-[4-(4-fluorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


154
3-bromo-4-[4-(4-chlorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


155
3-bromo-4-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine


156
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-amine


157
3-bromo-4-[4-(4-bromophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


158
3-bromo-4-[3-methyl-4-(3-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


159
4-[4-(3-bromo-5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-



amine


160
4-(4-{5-chloro-2-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-3-



cyclopropyl-1H-pyrazolo[3,4-d]pyrimidine


161
5-chloro-3-[4-(3-cyclopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-



N-(2-pyrrolidin-1-ylethyl)aniline


162
5-chloro-2-methyl-3-{4-[3-(2-methylpropyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperazin-



1-yl}-N-(2-pyrrolidin-1-ylethyl)aniline


163
4-(4-{5-chloro-2-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-3-(2-



methylpropyl)-1H-pyrazolo[3,4-d]pyrimidine


164
3-bromo-4-[(3S)-4-(5-chloro-2-methylphenyl)-3-methylpiperazin-1-yl]-1H-pyrazolo[3,4-



d]pyrimidine


165
5-bromo-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methylaniline


166
2-({3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]phenyl}oxy)-N-



cyclopropylacetamide


167
3-bromo-4-(4-{3-[(2-piperidin-1-ylethyl)oxy]pyrazin-2-yl}piperazin-1-yl)-1H-



pyrazolo[3,4-d]pyrimidine


168
4-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-6,7-



bis(methyloxy)quinazoline


169
2-({3-chloro-5-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]phenyl}oxy)-



N,N-diethylethanamine


170
4-{4-[2-chloro-5-(trifluoromethyl)phenyl]piperazin-1-yl}-3-ethyl-1H-pyrazolo[3,4-



d]pyrimidine


171
3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-[(2-



methylpropyl)oxy]-N-(2-pyrrolidin-1-ylethyl)aniline


172
3-({4-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-6-chloro-5-



methylpyrimidin-2-yl}oxy)-N,N-diethylpropan-1-amine


173
3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-



[(phenylmethyl)oxy]-N-(2-pyrrolidin-1-ylethyl)aniline


174
3-bromo-4-[(3R)-4-(5-chloro-2-methylphenyl)-3-methylpiperazin-1-yl]-1H-pyrazolo[3,4-



d]pyrimidine


175
3-[(2S)-4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-2-methylpiperazin-1-yl]-4-methyl-



N-phenylbenzamide


176
3-[(2S)-4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-2-methylpiperazin-1-yl]-4-methyl-



N-(phenylmethyl)benzamide


177
methyl 3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methylbenzoate


178
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methylbenzoic acid


179
(2E)-3-(4-{4-[5-chloro-2-methyl-3-(3-pyrrolidin-1-ylpropyl)phenyl]piperazin-1-yl}-1H-



pyrazolo[3,4-d]pyrimidin-3-yl)prop-2-enoic acid


180
3-(4-{4-[5-chloro-2-methyl-3-(3-pyrrolidin-1-ylpropyl)phenyl]piperazin-1-yl}-1H-



pyrazolo[3,4-d]pyrimidin-3-yl)prop-2-yn-1-ol


181
4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1-(5-chloro-2-methylphenyl)piperazin-2-



one


182
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-[(2-



methylpropyl)oxy]-N-(2-pyrrolidin-1-ylethyl)aniline


183
N′-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-[(2-



methylpropyl)oxy]phenyl}-N,N-diethylethane-1,2-diamine


184
methyl 3-bromo-5-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-



methylbenzoate


185
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-N-



phenylbenzamide


186
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N,4-dimethylbenzamide


187
2-({3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]phenyl}oxy)-N,N-



diethylethanamine


188
methyl 3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-



pyrrolidin-1-ylethyl)amino]benzoate


189
3-bromo-5-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-N-



phenylbenzamide


190
3-bromo-5-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-N-



phenylbenzamide


191
N′-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-chloro-2-



methylphenyl}-N-methyl-N-(1-methylethyl)ethane-1,2-diamine


192
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-N-phenyl-5-[(2-



pyrrolidin-1-ylethyl)amino]benzamide


193
N′-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-[(2-



methylpropyl)oxy]phenyl}-N,N-dimethylethane-1,2-diamine


194
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N,N,4-



trimethylbenzamide


195
3-[4-(3-chloro-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-N-(2-



methylpropyl)benzamide


196
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N,N,4-trimethyl-5-[(2-



pyrrolidin-1-ylethyl)amino]benzamide


197
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-2-oxopiperazin-1-yl]-4-methyl-N-



phenylbenzamide


198
3-[(2R)-4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-2-(hydroxymethyl)piperazin-1-yl]-



4-methyl-N-phenylbenzamide


199
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-(pyrrolidin-1-



ylcarbonyl)-N-(2-pyrrolidin-1-ylethyl)aniline


200
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N,4-dimethyl-5-[(2-



pyrrolidin-1-ylethyl)amino]benzamide


201
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-(4-chlorophenyl)-4-



methyl-5-[(2-pyrrolidin-1-ylethyl)amino]benzamide


202
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-(2-chlorophenyl)-4-



methyl-5-[(2-pyrrolidin-1-ylethyl)amino]benzamide


203
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-



[(cyclopropylmethyl)oxy]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline


204
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-[(3-



methylbutyl)oxy]-N-(2-pyrrolidin-1-ylethyl)aniline


205
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-[(2-ethylbutyl)oxy]-2-



methyl-N-(2-pyrrolidin-1-ylethyl)aniline


206
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-(butyloxy)-2-methyl-N-



(2-pyrrolidin-1-ylethyl)aniline


207
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-N-(1-



methylethyl)-5-[(2-pyrrolidin-1-ylethyl)amino]benzamide


208
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N,4-dimethyl-N-(1-



methylethyl)-5-[(2-pyrrolidin-1-ylethyl)amino]benzamide


209
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-



[(cyclobutylmethyl)oxy]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline


210
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-(ethyloxy)-2-methyl-N-



(2-pyrrolidin-1-ylethyl)aniline


211
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-[2-



(dimethylamino)ethyl]-4-methylbenzamide


212
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-(1,1-dimethylethyl)-4-



methyl-5-[(2-pyrrolidin-1-ylethyl)amino]benzamide


213
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-N-pyridin-3-yl-



5-[(2-pyrrolidin-1-ylethyl)amino]benzamide


214
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-[(2-fluoro-2-



methylpropyl)oxy]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline


215
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-



[(cyclohexylmethyl)oxy]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline


216
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-



[(cyclopentylmethyl)oxy]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline


217
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-ethyl-4-methyl-5-[(2-



pyrrolidin-1-ylethyl)amino]benzamide


218
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-[(1-



methylethyl)oxy]-N-(2-pyrrolidin-1-ylethyl)aniline


219
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-[(2,2-



dimethylpropyl)oxy]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline


220
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-



pyrrolidin-1-ylethyl)-5-[(tetrahydrofuran-2-ylmethyl)oxy]aniline


221
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-{[2-



(methyloxy)ethyl]oxy}-N-(2-pyrrolidin-1-ylethyl)aniline


222
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-(propyloxy)-



N-(2-pyrrolidin-1-ylethyl)aniline


223
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-{[2-



(dimethylamino)ethyl]amino}-4-methyl-N-phenylbenzamide


224
N′-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-[(2-fluoro-2-



methylpropyl)oxy]-2-methylphenyl}-N,N-dimethylethane-1,2-diamine


225
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-{[2-



(dimethylamino)ethyl]amino}-4-methyl-N-(1-methylethyl)benzamide


226
1-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-



pyrrolidin-1-ylethyl)amino]phenyl}pentan-1-one


227
N′-(3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-{[2,3-difluoro-2-



(fluoromethyl)propyl]oxy}-2-methylphenyl)-N,N-dimethylethane-1,2-diamine


228
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-{[2,3-difluoro-2-



(fluoromethyl)propyl]oxy}-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline


229
5-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-N-(2-



pyrrolidin-1-ylethyl)biphenyl-3-amine


230
1-(3-{5-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methylbiphenyl-



3-yl}propyl)pyridinium


231
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-



pyrrolidin-1-ylethyl)-5-(1,3-thiazol-2-yl)aniline


232
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-



pyrrolidin-1-ylethyl)amino]benzoic acid


233
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-



(phenylethynyl)-N-(2-pyrrolidin-1-ylethyl)aniline


234
{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-



pyrrolidin-1-ylethyl)amino]phenyl}(phenyl)methanone


235
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-ethynyl-2-methyl-N-(2-



pyrrolidin-1-ylethyl)aniline


236
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-(3,3-dimethylbut-1-yn-



1-yl)-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline


237
3-bromo-4-{4-[5-{[2,3-difluoro-2-(fluoromethyl)propyl]oxy}-2-methyl-3-(3-pyrrolidin-1-



ylpropyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine


238
3-bromo-4-{4-[2-methyl-5-[(2-methylpropyl)oxy]-3-(3-pyrrolidin-1-



ylpropyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine


239
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-(3-phenyl-



1,2,4-oxadiazol-5-yl)-N-(2-pyrrolidin-1-ylethyl)aniline


240
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-(3-methyl-



1,2,4-oxadiazol-5-yl)-N-(2-pyrrolidin-1-ylethyl)aniline


241
1-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-



pyrrolidin-1-ylethyl)amino]phenyl}propan-1-one


242
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-(3,3-dimethylbutyl)-2-



methyl-N-(2-pyrrolidin-1-ylethyl)aniline


243
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-ethyl-2-methyl-N-(2-



pyrrolidin-1-ylethyl)aniline


244
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-



pyrrolidin-1-ylethyl)-5-[2-(trimethylsilyl)ethyl]aniline


245
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-(2-



phenylethyl)-N-(2-pyrrolidin-1-ylethyl)aniline


246
1-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-



pyrrolidin-1-ylethyl)amino]phenyl}butan-1-one


247
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N,4-dimethyl-N-



(methyloxy)-5-[(2-pyrrolidin-1-ylethyl)amino]benzamide


248
3-bromo-4-[4-(3-bromo-5-{[2,3-difluoro-2-(fluoromethyl)propyl]oxy}-2-



methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


249
4-[4-(3-bromo-5-{[2,3-difluoro-2-(fluoromethyl)propyl]oxy}-2-methylphenyl)piperazin-1-



yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine


250
1-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-



pyrrolidin-1-ylethyl)amino]phenyl}ethanone


251
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-[(difluoromethyl)oxy]-



2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline


252
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-



{[(difluoromethyl)oxy]methyl}-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline


253
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-(methyloxy)-



N-(2-pyrrolidin-1-ylethyl)aniline


254
5-{[2,3-difluoro-2-(fluoromethyl)propyl]oxy}-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-



4-yl)piperazin-1-yl]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline


255
2-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-3,5,6-trifluoro-N-(3-



methylbutyl)pyridin-4-amine


256
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-



[(cyclopropylmethyl)oxy]-4-methyl-5-[(2-pyrrolidin-1-ylethyl)amino]benzamide


257
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-(5-methyl-



1,2,4-oxadiazol-3-yl)-N-(2-pyrrolidin-1-ylethyl)aniline


258
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-(ethylsulfonyl)-2-



methyl-N-(2-pyrrolidin-1-ylethyl)aniline


259
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-



(methylsulfonyl)-N-(2-pyrrolidin-1-ylethyl)aniline


260
1-{3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-



pyrrolidin-1-ylethyl)amino]phenyl}pentan-1-one


261
3-bromo-4-[4-(5-{[2,3-difluoro-2-(fluoromethyl)propyl]oxy}-2-methylphenyl)piperazin-1-



yl]-1H-pyrazolo[3,4-d]pyrimidine


262
6-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-3,5-difluoro-N~4~-(3-



methylbutyl)-N~2~-(2-pyrrolidin-1-ylethyl)pyridine-2,4-diamine


263
3-bromo-5-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-(2-pyrrolidin-



1-ylethyl)aniline


264
3-bromo-4-[4-(3′,4′,6-trifluoro-4-methylbiphenyl-3-yl)piperazin-1-yl]-1H-pyrazolo[3,4-



d]pyrimidine


265
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-chloro-N-(2-pyrrolidin-



1-ylethyl)aniline


266
{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-



pyrrolidin-1-ylethyl)amino]phenyl}methanol


267
3-bromo-4-(4-{4-methyl-2′-[(2-pyrrolidin-1-ylethyl)oxy]biphenyl-3-yl}piperazin-1-yl)-1H-



pyrazolo[3,4-d]pyrimidine


268
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-{[(2,2-



difluorocyclopropyl)methyl]oxy}-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline


269
5-bromo-3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-



pyrrolidin-1-ylethyl)aniline


270
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-[(ethyloxy)methyl]-2-



methyl-N-(2-pyrrolidin-1-ylethyl)aniline


271
3-[4-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-1-methyl-6-



(trifluoromethyl)-1H-benzimidazol-2-yl]propan-1-ol


272
1-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-



pyrrolidin-1-ylethyl)amino]phenyl}-4,4,4-trifluorobutan-1-one


273
{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-



pyrrolidin-1-ylethyl)amino]phenyl}(cyclopropyl)methanone


274
3-({3′-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4′-methylbiphenyl-2-



yl}oxy)-N,N-dimethylpropan-1-amine


275
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-(1,1-difluorobutyl)-2-



methyl-N-(2-pyrrolidin-1-ylethyl)aniline


276
3-bromo-4-(4-{4-methyl-2′-[(3-morpholin-4-ylpropyl)oxy]biphenyl-3-yl}piperazin-1-yl)-



1H-pyrazolo[3,4-d]pyrimidine


277
3-bromo-4-(4-{4-methyl-2′-[(2-morpholin-4-ylethyl)oxy]biphenyl-3-yl}piperazin-1-yl)-1H-



pyrazolo[3,4-d]pyrimidine


278
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-



pyrrolidin-1-ylethyl)-5-{[(2,2,2-trifluoroethyl)oxy]methyl}aniline


279
1-[2-({3′-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4′-



methylbiphenyl-2-yl}oxy)ethyl]pyrrolidine-2,5-dione


280
3-bromo-4-(4-{3′-fluoro-4-methyl-2′-[(2-pyrrolidin-1-ylethyl)oxy]biphenyl-3-yl}piperazin-



1-yl)-1H-pyrazolo[3,4-d]pyrimidine


281
1-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-[(2-pyrrolidin-1-



ylethyl)amino]phenyl}butan-1-one


282
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-



pyrrolidin-1-ylethyl)-5-[(3,3,3-trifluoropropyl)oxy]aniline


283
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-



pyrrolidin-1-ylethyl)-5-[(2,2,2-trifluoroethyl)oxy]aniline


284
1-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-



pyrrolidin-1-ylethyl)amino]phenyl}butan-1-ol


285
3-bromo-4-(4-{4-chloro-2′-[(2-pyrrolidin-1-ylethyl)oxy]biphenyl-3-yl}piperazin-1-yl)-1H-



pyrazolo[3,4-d]pyrimidine


286
3-[4-(4-{5-{[2,3-difluoro-2-(fluoromethyl)propyl]oxy}-2-methyl-3-[(2-pyrrolidin-1-



ylethyl)amino]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]prop-2-yn-1-ol


287
3-bromo-4-(4-{4-chloro-4′-fluoro-2′-[(2-pyrrolidin-1-ylethyl)oxy]biphenyl-3-yl}piperazin-



1-yl)-1H-pyrazolo[3,4-d]pyrimidine


288
3-bromo-4-(4-{4-methyl-3′-[(2-pyrrolidin-1-ylethyl)oxy]biphenyl-3-yl}piperazin-1-yl)-1H-



pyrazolo[3,4-d]pyrimidine


289
(2E)-3-[4-(4-{5-{[2,3-difluoro-2-(fluoromethyl)propyl]oxy}-2-methyl-3-[(2-pyrrolidin-1-



ylethyl)amino]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]prop-2-enoic acid


290
3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-



pyrrolidin-1-ylethyl)-5-[4,4,4-trifluoro-1,1-bis(methyloxy)butyl]aniline


291
6-(4-phenylpiperazin-1-yl)-9H-purine


292
6-[4-(3-chlorophenyl)piperazin-1-yl]-9H-purine


293
4-(4-phenylpiperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine


294
4-[4-(3-chlorophenyl)piperazin-1-yl]-7H-pyrrolo[2,3-d]pyrimidine


295
4-(4-phenylpiperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine


296
4-[4-(3-chlorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


297
6-[4-(2-chlorophenyl)piperazin-1-yl]-9H-purine


298
6-[4-(2-fluorophenyl)piperazin-1-yl]-9H-purine


299
4-[4-(2-methylphenyl)piperazin-1-yl]-7H-pyrrolo[2,3-d]pyrimidine


300
4-{4-[2-(methyloxy)phenyl]piperazin-1-yl}-7H-pyrrolo[2,3-d]pyrimidine


301
4-{4-[3-(methyloxy)phenyl]piperazin-1-yl}-7H-pyrrolo[2,3-d]pyrimidine


302
4-{4-[4-(methyloxy)phenyl]piperazin-1-yl}-7H-pyrrolo[2,3-d]pyrimidine


303
4-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}-7H-pyrrolo[2,3-d]pyrimidine


304
6-{4-[4-(methyloxy)phenyl]piperazin-1-yl}-9H-purine


305
6-{4-[2-(methyloxy)phenyl]piperazin-1-yl}-9H-purine


306
6-[4-(4-chlorophenyl)piperazin-1-yl]-9H-purine


307
6-[4-(4-fluorophenyl)piperazin-1-yl]-9H-purine


308
4-[4-(4-chlorophenyl)piperazin-1-yl]-7H-pyrrolo[2,3-d]pyrimidine


309
4-[4-(2-chlorophenyl)piperazin-1-yl]-7H-pyrrolo[2,3-d]pyrimidine


310
4-[4-(4-fluorophenyl)piperazin-1-yl]-7H-pyrrolo[2,3-d]pyrimidine


311
4-[4-(2-fluorophenyl)piperazin-1-yl]-7H-pyrrolo[2,3-d]pyrimidine


312
6-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}-9H-purine


313
6-[4-(2-methylphenyl)piperazin-1-yl]-9H-purine


314
4-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine


315
4-[4-(2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


316
4-[4-(3-chlorophenyl)piperazin-1-yl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidine


317
3-methyl-4-[4-(2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


318
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


319
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidine


320
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-methyl-6-phenyl-1H-pyrazolo[3,4-



d]pyrimidine


321
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine


322
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-6-methyl-1H-pyrazolo[3,4-d]pyrimidine


323
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-6-ethyl-1H-pyrazolo[3,4-d]pyrimidine


324
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-6-(1-methylethyl)-1H-pyrazolo[3,4-



d]pyrimidine


325
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-phenyl-1H-pyrazolo[3,4-d]pyrimidine


326
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-({[2-(methyloxy)ethyl]oxy}methyl)-1H-



pyrazolo[3,4-d]pyrimidine


327
3-bromo-4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


328
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-propyl-1H-pyrazolo[3,4-d]pyrimidine


329
4-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-



yl}phenol


330
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-N-phenyl-1H-pyrazolo[3,4-d]pyrimidin-3-



amine


331
4-[4-(3-chlorophenyl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine


332
4-{4-[5-chloro-2-(methyloxy)phenyl]piperazin-1-yl}-3-ethyl-1H-pyrazolo[3,4-



d]pyrimidine


333
3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-



yl}phenol


334
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-{3-[(phenylmethyl)oxy]phenyl}-1H-



pyrazolo[3,4-d]pyrimidine


335
3-(1,3-benzodioxol-5-yl)-4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-



d]pyrimidine


336
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(2-thienyl)-1H-pyrazolo[3,4-d]pyrimidine


337
3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-



yl}aniline


338
3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-



yl}benzoic acid


339
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(4-methylphenyl)-1H-pyrazolo[3,4-



d]pyrimidine


340
N-(4-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-



yl}phenyl)acetamide


341
4-[4-(3-chlorophenyl)-1,4-diazepan-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine


342
4-[5-(3-chlorophenyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]-3-ethyl-1H-pyrazolo[3,4-



d]pyrimidine


343
4-(4-{3-chloro-4-[(2-morpholin-4-ylethyl)oxy]phenyl}piperazin-1-yl)-3-ethyl-1H-



pyrazolo[3,4-d]pyrimidine


344
methyl 1-(3-chlorophenyl)-4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazine-2-



carboxylate


345
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(3-methylbut-2-en-1-yl)-1H-pyrazolo[3,4-



d]pyrimidine


346
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(trifluoromethyl)-1H-pyrazolo[3,4-



d]pyrimidine


347
methyl 4-(3-chlorophenyl)-1-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazine-2-



carboxylate


348
4-(4-{3-chloro-4-[(2-piperidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-3-ethyl-1H-



pyrazolo[3,4-d]pyrimidine


349
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(1-methylethyl)-1H-pyrazolo[3,4-



d]pyrimidine


350
1-(3-chlorophenyl)-4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazine-2-carboxylic



acid


351
1-(3-chlorophenyl)-4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-methylpiperazine-2-



carboxamide


352
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(phenylmethyl)-1H-pyrazolo[3,4-



d]pyrimidine


353
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(2-methylpropyl)-1H-pyrazolo[3,4-



d]pyrimidine


354
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-[4-(methyloxy)phenyl]-1H-pyrazolo[3,4-



d]pyrimidine


355
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(4-fluorophenyl)-1H-pyrazolo[3,4-



d]pyrimidine


356
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-[4-(phenyloxy)phenyl]-1H-pyrazolo[3,4-



d]pyrimidine


357
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-{4-[(piperidin-4-ylmethyl)oxy]phenyl}-



1H-pyrazolo[3,4-d]pyrimidine


358
1-(3-chlorophenyl)-N-[2-(dimethylamino)ethyl]-4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-



yl)piperazine-2-carboxamide


359
4-[4-(5-chloro-2-methyl-3-morpholin-4-ylphenyl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-



d]pyrimidine


360
4-(3-chlorophenyl)-1-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-methylpiperazine-2-



carboxamide


361
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-[2-(methyloxy)phenyl]-1H-pyrazolo[3,4-



d]pyrimidine


362
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-pyridin-4-yl-1H-pyrazolo[3,4-



d]pyrimidine


363
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-[3-(methyloxy)phenyl]-1H-pyrazolo[3,4-



d]pyrimidine


364
4-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-



yl}benzonitrile


365
[5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-



(methyloxy)phenyl]methanol


366
methyl 5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-



(methyloxy)benzoate


367
(2E)-3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-



yl}prop-2-enoic acid


368
3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-



yl}propanoic acid


369
3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-



yl}propan-1-ol


370
methyl (2E)-3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-



d]pyrimidin-3-yl}prop-2-enoate


371
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-{4-[(2-morpholin-4-ylethyl)oxy]phenyl}-



1H-pyrazolo[3,4-d]pyrimidine


372
5-chloro-N-[2-(dimethylamino)ethyl]-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-



yl)piperazin-1-yl]-2-(methyloxy)benzamide


373
4-(4-{5-chloro-2-(methyloxy)-3-[(4-methylpiperazin-1-yl)carbonyl]phenyl}piperazin-1-yl)-



3-ethyl-1H-pyrazolo[3,4-d]pyrimidine


374
2-(dimethylamino)ethyl 5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-



yl)piperazin-1-yl]-2-(methyloxy)benzoate


375
1-[5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-



(methyloxy)phenyl]-N,N-dimethylmethanamine


376
N′-{[5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-



(methyloxy)phenyl]methyl}-N,N-dimethylethane-1,2-diamine


377
[1-(3-chlorophenyl)-4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-2-yl]methanol


378
3-[(4-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-



yl}phenyl)oxy]-N,N-dimethylpropan-1-amine


379
2-chloro-4-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-methylphenol


380
1-(3-chlorophenyl)-4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-(1-methylpiperidin-4-



yl)piperazine-2-carboxamide


381
1-(3-chlorophenyl)-4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-(2-morpholin-4-



ylethyl)piperazine-2-carboxamide


382
2-{[5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-



(methyloxy)phenyl]oxy}-N,N-dimethylethanamine


383
3-{5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-



methylphenyl}-N,N-dimethylprop-2-yn-1-amine


384
N′-{5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-



methylphenyl}-N,N-dimethylethane-1,2-diamine


385
1,1-dimethylethyl (2E)-3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-



pyrazolo[3,4-d]pyrimidin-3-yl}prop-2-enoate


386
3-({2-chloro-4-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-



methylphenyl}oxy)-N,N-dimethylpropan-1-amine


387
2-({2-chloro-4-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-



methylphenyl}oxy)-N,N-dimethylethanamine


388
4-{4-[5-chloro-2-methyl-4-(methyloxy)phenyl]piperazin-1-yl}-3-ethyl-1H-pyrazolo[3,4-



d]pyrimidine


389
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(4-methylpiperazin-1-yl)-1H-



pyrazolo[3,4-d]pyrimidine


390
3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-N,N-



diethylprop-2-yn-1-amine


391
3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}prop-



2-yn-1-ol


392
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(piperidin-4-ylmethyl)-1H-pyrazolo[3,4-



d]pyrimidine


393
phenylmethyl (3aR,6aS)-5-({4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-



pyrazolo[3,4-d]pyrimidin-3-yl}methylidene)hexahydrocyclopenta[c]pyrrole-2(1H)-



carboxylate


394
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-[(E)-(3aR,6aS)-



hexahydrocyclopenta[c]pyrrol-5(1H)-ylidenemethyl]-1H-pyrazolo[3,4-d]pyrimidine


395
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(3-pyrrolidin-1-ylprop-1-yn-1-yl)-1H-



pyrazolo[3,4-d]pyrimidine


396
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-[3-(4-methylpiperazin-1-yl)prop-1-yn-1-



yl]-1H-pyrazolo[3,4-d]pyrimidine


397
3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-N,N-



diethylpropan-1-amine


398
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(3-pyrrolidin-1-ylpropyl)-1H-



pyrazolo[3,4-d]pyrimidine


399
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-



pyrazolo[3,4-d]pyrimidine


400
3-{5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-



methylphenyl}-N,N-diethylpropan-1-amine


401
4-{4-[5-chloro-2-methyl-3-(3-pyrrolidin-1-ylpropyl)phenyl]piperazin-1-yl}-3-ethyl-1H-



pyrazolo[3,4-d]pyrimidine









The Compounds in Table 2b can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 2b can be used to practice the invention.











Entry
Name
















1
[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-



chlorophenyl)methanol


2
2-{[[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-



chlorophenyl)methyl]oxy}-N,N-dimethylethanamine


3
3-{[[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-



chlorophenyl)methyl]oxy}-N,N-dimethylpropan-1-amine


4
3-bromo-4-{4-[(4-bromophenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-



d]pyrimidine


5
{4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1-[(4-



chlorophenyl)methyl]piperazin-2-yl}methanol


6
N′-[[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-



chlorophenyl)methyl]-N,N-diethylethane-1,2-diamine


7
3-bromo-4-(4-{[4-(1,1-dimethylethyl)phenyl]methyl}piperazin-1-yl)-1H-



pyrazolo[3,4-d]pyrimidine


8
4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1-[(4-



chlorophenyl)methyl]piperazin-2-one


9
2-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-(4-



chlorophenyl)-N-[2-(dimethylamino)ethyl]acetamide


10
N-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-N-(4-



chlorophenyl)-N′,N′-diethylpropane-1,3-diamine


11
3-bromo-4-(4-{[4-(trifluoromethyl)phenyl]methyl}piperazin-1-yl)-1H-



pyrazolo[3,4-d]pyrimidine


12
N-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-N-(4-



chlorophenyl)-N′-[2-(dimethylamino)ethyl]urea


13
N-[[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-



chlorophenyl)methyl]-N′-[2-(dimethylamino)ethyl]urea


14
2-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-2-oxopiperazin-1-yl]-2-(4-



chlorophenyl)-N-[2-(dimethylamino)ethyl]acetamide


15
2-(dimethylamino)ethyl [1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-



yl)piperidin-4-yl](4-chlorophenyl)carbamate


16
3-bromo-4-{4-[(4-chloro-3-fluorophenyl)methyl]piperazin-1-yl}-1H-



pyrazolo[3,4-d]pyrimidine


17
3-bromo-4-{4-[(4-chloro-2-fluorophenyl)methyl]piperazin-1-yl}-1H-



pyrazolo[3,4-d]pyrimidine


18
N-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-N-(4-



chlorophenyl)-N′,N′-diethylethane-1,2-diamine


19
3-bromo-4-{4-[(4-chlorophenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-



d]pyrimidine


20
[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-



fluorophenyl)methanone


21
N-[[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-



chlorophenyl)methyl]-N′,N′-diethyl-N-methylethane-1,2-diamine


22
[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-



fluorophenyl)methanol


23
3-bromo-4-(4-{[2-fluoro-4-(trifluoromethyl)phenyl]methyl}piperazin-1-yl)-1H-



pyrazolo[3,4-d]pyrimidine


24
N-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-N-(4-



chlorophenyl)-N~3~,N~3~-diethyl-beta-alaninamide


25
2-{[[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-



fluorophenyl)methyl]oxy}-N,N-dimethylethanamine


26
N-[[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-



chlorophenyl)methyl]-N~3~,N~3~-diethyl-beta-alaninamide


27
3-bromo-4-{4-[(3,4-dichlorophenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-



d]pyrimidine


28
N-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-N-(4-



chlorophenyl)-N′-[2-(dimethylamino)ethyl]ethanediamide


29
N-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-N-(4-



chlorophenyl)-2-(diethylamino)ethanesulfonamide


30
4-[4-(biphenyl-4-ylmethyl)piperazin-1-yl]-3-bromo-1H-pyrazolo[3,4-



d]pyrimidine


31
3-bromo-4-{(3S)-4-[(4-chlorophenyl)methyl]-3-methylpiperazin-1-yl}-1H-



pyrazolo[3,4-d]pyrimidine


32
3-bromo-4-(4-{[4-(methyloxy)phenyl]methyl}piperazin-1-yl)-1H-pyrazolo[3,4-



d]pyrimidine


33
4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-[3-



(trifluoromethyl)phenyl]piperazine-1-carboxamide


34
3-bromo-4-{4-[(4-fluorophenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-



d]pyrimidine


35
N-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-N-(4-



chlorophenyl)pent-4-enamide


36
3-bromo-4-[4-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)piperazin-1-yl]-1H-



pyrazolo[3,4-d]pyrimidine


37
4-[4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl]-3-bromo-1H-pyrazolo[3,4-



d]pyrimidine


38
[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-



chlorophenyl)methanone


39
3-bromo-4-(4-{[4-(phenyloxy)phenyl]methyl}piperazin-1-yl)-1H-pyrazolo[3,4-



d]pyrimidine


40
3-bromo-4-{4-[(3,4-dichlorophenyl)methyl]piperidin-1-yl}-1H-pyrazolo[3,4-



d]pyrimidine


41
4-{[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]methyl}-N,N-



dimethylaniline


42
methyl 4-{[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-



yl]methyl}benzoate


43
3-bromo-4-{4-[(2E)-3-phenylprop-2-enoyl]piperazin-1-yl}-1H-pyrazolo[3,4-



d]pyrimidine


44
1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-4-[(4-chlorophenyl)methyl]-N-



[3-(diethylamino)propyl]piperidine-4-carboxamide


45
3-bromo-4-{4-[(2-bromophenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-



d]pyrimidine


46
3-bromo-4-{4-[(2-chlorophenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-



d]pyrimidine


47
3-bromo-4-{4-[(2,4-dichlorophenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-



d]pyrimidine


48
3-bromo-4-{4-[(2-chloro-4-fluorophenyl)methyl]piperazin-1-yl}-1H-



pyrazolo[3,4-d]pyrimidine


49
1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-4-(4-chlorophenyl)-N-[3-



(diethylamino)propyl]piperidine-4-carboxamide


50
3-bromo-4-[4-(phenylmethyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


51
2-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-pyridin-2-



ylacetamide


52
3-bromo-4-[4-(1H-imidazol-2-ylmethyl)piperazin-1-yl]-1H-pyrazolo[3,4-



d]pyrimidine


53
3-bromo-4-(4-{[3-(phenyloxy)phenyl]methyl}piperazin-1-yl)-1H-pyrazolo[3,4-



d]pyrimidine


54
3-bromo-4-{4-[(3-methylphenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-



d]pyrimidine


55
3-{[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-



yl]methyl}benzonitrile


56
3-bromo-4-{4-[(2-chloro-6-fluorophenyl)methyl]piperazin-1-yl}-1H-



pyrazolo[3,4-d]pyrimidine


57
3-bromo-4-[4-(1-phenylethyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


58
3-bromo-4-[4-(pyridin-4-ylmethyl)piperazin-1-yl]-1H-pyrazolo[3,4-



d]pyrimidine


59
1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-(4-chlorophenyl)piperidin-4-



amine


60
3-bromo-4-[4-(pyridin-3-ylmethyl)piperazin-1-yl]-1H-pyrazolo[3,4-



d]pyrimidine


61
3-bromo-4-(4-{[2,3,4-tris(methyloxy)phenyl]methyl}piperazin-1-yl)-1H-



pyrazolo[3,4-d]pyrimidine


62
3-bromo-4-[4-({3-[(phenylmethyl)oxy]phenyl}methyl)piperazin-1-yl]-1H-



pyrazolo[3,4-d]pyrimidine


63
3-bromo-4-[4-(naphthalen-1-ylmethyl)piperazin-1-yl]-1H-pyrazolo[3,4-



d]pyrimidine


64
3-bromo-4-(4-{[5-(4-chlorophenyl)furan-2-yl]methyl}piperazin-1-yl)-1H-



pyrazolo[3,4-d]pyrimidine


65
3-bromo-4-[4-({4-[(4-fluorophenyl)oxy]-3-nitrophenyl}methyl)piperazin-1-yl]-



1H-pyrazolo[3,4-d]pyrimidine


66
3-bromo-4-[4-(furan-2-ylcarbonyl)piperazin-1-yl]-1H-pyrazolo[3,4-



d]pyrimidine


67
3-bromo-4-[4-(1H-indol-6-ylcarbonyl)piperazin-1-yl]-1H-pyrazolo[3,4-



d]pyrimidine


68
3-bromo-4-{4-[2-(2-thienyl)ethyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine


69
3-bromo-4-[4-(3-pyrrolidin-1-ylpropyl)piperazin-1-yl]-1H-pyrazolo[3,4-



d]pyrimidine


70
3-bromo-4-[4-(cyclohexylmethyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


71
3-bromo-4-{4-[(10-chloroanthracen-9-yl)methyl]piperazin-1-yl}-1H-



pyrazolo[3,4-d]pyrimidine


72
3-bromo-4-[4-(1-methylpropyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine


73
4-(4-{[4,6-bis(methyloxy)pyrimidin-2-yl]methyl}piperazin-1-yl)-3-bromo-1H-



pyrazolo[3,4-d]pyrimidine


74
3-bromo-4-{4-[2-(methyloxy)ethyl]piperazin-1-yl}-1H-pyrazolo[3,4-



d]pyrimidine


75
3-bromo-4-[4-(2-morpholin-4-yl-2-oxoethyl)piperazin-1-yl]-1H-pyrazolo[3,4-



d]pyrimidine


76
3-bromo-4-{4-[3-(methyloxy)propyl]piperazin-1-yl}-1H-pyrazolo[3,4-



d]pyrimidine


77
4-{4-[[4,6-bis(methyloxy)pyrimidin-2-yl](phenyl)methyl]piperazin-1-yl}-3-



bromo-1H-pyrazolo[3,4-d]pyrimidine


78
3-bromo-4-[4-(6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl)piperazin-1-yl]-



1H-pyrazolo[3,4-d]pyrimidine


79
3-bromo-4-[4-({4-[(phenylmethyl)oxy]phenyl}methyl)piperazin-1-yl]-1H-



pyrazolo[3,4-d]pyrimidine


80
3-bromo-4-[4-({3-chloro-4-[(phenylmethyl)oxy]phenyl}methyl)piperazin-1-yl]-



1H-pyrazolo[3,4-d]pyrimidine


81
4-{[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]methyl}-N-(3-



morpholin-4-ylpropyl)benzamide


82
4-{[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]methyl}-N-[3-



(methyloxy)propyl]benzamide


83
2-[({4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1-[(4-



chlorophenyl)methyl]piperazin-2-yl}methyl)oxy]-N,N-dimethylethanamine


84
3-bromo-4-[4-({4-[(4-chlorophenyl)oxy]-3-nitrophenyl}methyl)piperazin-1-yl]-



1H-pyrazolo[3,4-d]pyrimidine


85
2-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N,N-



dimethylacetamide


86
2-{[(R)-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-



chlorophenyl)methyl]oxy}-N,N-dimethylethanamine


87
N-(4-bromo-3-fluorophenyl)-N-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-



yl)piperidin-4-yl]-N′-[2-(dimethylamino)ethyl]urea


88
2-({(R)-(4-chlorophenyl)[1-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-



yl)piperidin-4-yl]methyl}oxy)-N,N-dimethylethanamine


89
2-{[(S)-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-



chlorophenyl)methyl]oxy}-N,N-dimethylethanamine


90
3-bromo-4-(4-{(R)-(4-chlorophenyl)[(2-pyrrolidin-1-



ylethyl)oxy]methyl}piperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine


91
1-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-1-(4-



chlorophenyl)-4-(dimethylamino)butan-1-ol


92
2-{[(R)-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-



chloro-3-fluorophenyl)methyl]oxy}-N,N-dimethylethanamine


93
3-bromo-4-(4-{(R)-(4-chlorophenyl)[(2-piperidin-1-



ylethyl)oxy]methyl}piperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine


94
4-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-4-(4-



chlorophenyl)-N,N-dimethylbutan-1-amine


95
3-bromo-4-(4-{(R)-(4-chlorophenyl)[(2-morpholin-4-



ylethyl)oxy]methyl}piperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine


96
1-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-1-(4-



fluorophenyl)-N-(furan-2-ylmethyl)-N-methylmethanamine


97
1-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-1-(4-



fluorophenyl)-N-methyl-N-(pyridin-2-ylmethyl)methanamine


98
4-{[{[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-



fluorophenyl)methyl}(methyl)amino]methyl}-N,N-dimethylaniline


99
[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl](1H-indol-6-



yl)methanol


100
3-bromo-4-(4-{(R)-(4-chloro-3-fluorophenyl)[(2-pyrrolidin-1-



ylethyl)oxy]methyl}piperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine


101
3-bromo-4-{4-[(4-chlorophenyl)oxy]piperidin-1-yl}-1H-pyrazolo[3,4-



d]pyrimidine


102
2-{[(R)-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-



chlorophenyl)methyl]oxy}-N,N-diethylethanamine


103
2-{[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]oxy}-5-



chloro-N-(2-pyrrolidin-1-ylethyl)aniline









The Compounds in Table 3a can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 3a can be used to practice the invention.











Cmpd No.
Name
















1
N-(4-fluorophenyl)-N′-[3-fluoro-4-(7H-pyrrolo[2,3-



d]pyrimidin-4-yloxy)phenyl]propanediamide


2
N-(4-fluorophenyl)-N′-[3-fluoro-4-(7H-pyrrolo[2,3-



d]pyrimidin-4-yloxy)phenyl]cyclopropane-1,1-dicarboxamide


3
N-({[3-fluoro-4-(7H-pyrrolo[2,3-d]pyrimidin-4-



yloxy)phenyl]amino}carbonothioyl)-2-phenylacetamide


4
N-(4-fluorophenyl)-N′-(4-{[1-(tetrahydro-2H-pyran-2-yl)-1H-



pyrazolo[3,4-d]pyrimidin-4-yl]oxy}phenyl)cyclopropane-1,1-



dicarboxamide


5
2-phenyl-N-{[(4-{[1-(tetrahydro-2H-pyran-2-yl)-1H-



pyrazolo[3,4-d]pyrimidin-4-



yl]oxy}phenyl)amino]carbonothioyl}acetamide


6
N-(4-fluorophenyl)-N′-[4-(1H-pyrazolo[3,4-d]pyrimidin-4-



yloxy)phenyl]cyclopropane-1,1-dicarboxamide


7
2-phenyl-N-({[4-(1H-pyrazolo[3,4-d]pyrimidin-4-



yloxy)phenyl]amino}carbonothioyl)acetamide


8
N-(4-fluorophenyl)-N′-(4-{[9-(tetrahydro-2H-pyran-2-yl)-9H-



purin-6-yl]oxy}phenyl)cyclopropane-1,1-dicarboxamide


9
2-phenyl-N-{[(4-{[9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-



yl]oxy}phenyl)amino]carbonothioyl}acetamide


10
N-(4-fluorophenyl)-N′-[4-(9H-purin-6-



yloxy)phenyl]cyclopropane-1,1-dicarboxamide


11
2-phenyl-N-({[4-(9H-purin-6-



yloxy)phenyl]amino}carbonothioyl)acetamide


12
N-{3-fluoro-4-[(6-{[(2-morpholin-4-ylethyl)amino]carbonyl}-



7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy]phenyl}-N′-(4-



fluorophenyl)cyclopropane-1,1-dicarboxamide









The Compounds in Table 3b can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 3b can be used to practice the invention.











Entry
Name
















1
N-[({3-fluoro-4-[(6-(methyloxy)-7-{[(3aR,6aS)-



octahydrocyclopenta[c]pyrrol-5-ylmethyl]oxy}quinazolin-4-



yl)oxy]phenyl}amino)carbonothioyl]-2-phenylacetamide


2
N-{[(3-fluoro-4-{[7-({[(3aR,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-



5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-



yl]oxy}phenyl)amino]carbonothioyl}-2-phenylacetamide


3
N-{[(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-



fluorophenyl)(methyl)amino]carbonothioyl}-2-phenylacetamide


4
1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)imidazolidin-2-one


5
1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-3-



(phenylmethyl)imidazolidin-2-one


6
1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-3-



(phenylacetyl)imidazolidin-2-one


7
ethyl [(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-



fluorophenyl)amino](oxo)acetate


8
N-{[(4-{[6,7-bis(methyloxy)quinazolin-4-yl]amino}-3-



fluorophenyl)amino]carbonothioyl}-2-phenylacetamide


9
N′-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N-methyl-



N-(2-phenylethyl)sulfamide


10
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-3-



(phenylmethyl)-1,2,4-oxadiazol-5-amine


11
1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)piperidin-2-



one


12
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-



(phenylmethyl)ethanediamide


13
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-4-phenyl-



1,3-thiazol-2-amine


14
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-(2-



phenylethyl)ethanediamide


15
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-1-



phenylmethanesulfonamide


16
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-2-



phenylethanesulfonamide


17
4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluoro-N-



(phenylmethyl)benzenesulfonamide


18
4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluoro-N-methyl-N-



(phenylmethyl)benzenesulfonamide


19
4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluoro-N-(2-



phenylethyl)benzenesulfonamide


20
4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluoro-N-methyl-N-(2-



phenylethyl)benzenesulfonamide


21
4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluoro-N-(3-



phenylpropyl)benzenesulfonamide


22
1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)pyrrolidin-2-



one


23
4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl (phenylmethyl)carbamate


24
4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl (2-phenylethyl)carbamate


25
4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluoro-N-methyl-N-(3-



phenylpropyl)benzenesulfonamide


26
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-



phenylethanediamide


27
N-{[(3-fluoro-4-{[7-{[(2-methyloctahydrocyclopenta[c]pyrrol-5-



yl)methyl]oxy}-6-(methyloxy)quinolin-4-



yl]oxy}phenyl)amino]carbonothioyl}-2-phenylacetamide


28
N-[(Z)-[(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-



fluorophenyl)amino](imino)methyl]-2-phenylacetamide


29
4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluoro-N-[2-



(phenyloxy)ethyl]benzenesulfonamide


30
N,N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-bis-(3-



phenylpropane-1-sulfonamide)


31
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-3-



phenylpropane-1-sulfonamide


32
N2-[(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)sulfonyl]-



N1-phenylglycinamide


33
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}pyridin-3-yl)-2-



phenylacetamide


34
N-{[(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}pyridin-3-



yl)amino]carbonothioyl}-2-phenylacetamide


35
6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-1,3-benzothiazol-2-amine


36
6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-1,3-benzothiazol-2-



amine


37
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-1,3-benzothiazol-2-



yl)-2-phenylacetamide


38
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-(2-



morpholin-4-ylethyl)ethanediamide


39
benzyl-{[4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenylcarbamoyl]-



methyl}-carbamic acid tert-butyl ester


40
N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N2-



(phenylmethyl)glycinamide


41
N2-acetyl-N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-



N2-(phenylmethyl)glycinamide


42
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-1,3-benzothiazol-2-yl)-2-



phenylacetamide


43
benzyl-{[6-(6,7-dimethoxy-quinolin-4-yloxy)-pyridin-3-ylcarbamoyl]-



methyl}-carbamic acid tert-butyl ester


44
N1-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}pyridin-3-yl)-N2-



(phenylmethyl)glycinamide


45
N2-acetyl-N1-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}pyridin-3-yl)-N2-



(phenylmethyl)glycinamide


46
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}pyridin-3-yl)-3-



phenylpropanamide


47
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}pyridin-3-yl)-4-



phenylbutanamide


48
N1-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}pyridin-3-yl)-N2-methyl-



N2-(phenylmethyl)glycinamide


49
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-{2-[4-



(methyloxy)phenyl]ethyl}ethanediamide


50
N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N2-



methyl-N2-(phenylmethyl)glycinamide


51
4-[(2-amino-1,3-benzothiazol-6-yl)oxy]-6,7-bis(methyloxy)-1-(2-oxo-2-



phenylethyl)quinolinium


52
N-{[(4-{[6,7-bis(methyloxy)quinolin-4-



yl]amino}phenyl)amino]carbonothioyl}-2-phenylacetamide


53
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-1,3-benzothiazol-2-



yl)-3-phenylpropanamide


54
N-{[(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-



yl)amino]carbonothioyl}-2-phenylacetamide


55
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-(2,3-



dihydro-1H-inden-1-yl)ethanediamide


56
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-(2,3-



dihydro-1H-inden-2-yl)ethanediamide


57
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-(1,2,3,4-



tetrahydronaphthalen-1-yl)ethanediamide


58
N′-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N-(2-



phenylethyl)-N-(phenylmethyl)sulfamide


59
N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N2-



(trifluoroacetyl)glycinamide


60
N-{[4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenylcarbamoyl]-



methyl}-benzamide


61
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}pyridin-3-yl)-N′-(4-



fluorophenyl)propanediamide


62
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-[(2S)-



1,2,3,4-tetrahydronaphthalen-2-yl]ethanediamide


63
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-[2-(4-



methylphenyl)ethyl]ethanediamide


64
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-(2-



phenylpropyl)ethanediamide


65
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-[2-(4-



chlorophenyl)ethyl]ethanediamide


66
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N,N′-



bis(phenylmethyl)sulfamide


67
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N,N′-bis(2-



phenylethyl)sulfamide


68
ethyl [(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-



yl)amino](oxo)acetate


69
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N′-(2-



phenylethyl)ethanediamide


70
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N′-(4-



fluorophenyl)propanediamide


71
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-(1,2,3,4-



tetrahydronaphthalen-2-yl)ethanediamide


72
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-[2-(1-



methylpyrrolidin-2-yl)ethyl]ethanediamide


73
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-[2-



(phenyloxy)ethyl]ethanediamide


74
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-[2-



hydroxy-1-(phenylmethyl)ethyl]urea


75
1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-3-[(4-



methylphenyl)sulfonyl]-4-(phenylmethyl)imidazolidin-2-one


76
N′-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N-methyl-



N-(2-phenylethyl)ethanediamide


77
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-{[3-



(trifluoromethyl)phenyl]methyl}ethanediamide


78
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-{2-[3-



(trifluoromethyl)phenyl]ethyl}ethanediamide


79
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-3-oxo-



4-phenylbutanamide


80
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-2-[3-



(trifluoromethyl)phenyl]acetamide


81
6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-N-[2-



(phenyloxy)ethyl]-1,3-benzothiazol-2-amine


82
6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-N-(2-piperidin-1-



ylethyl)-1,3-benzothiazol-2-amine


83
6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-N-methyl-N-(2-



phenylethyl)-1,3-benzothiazol-2-amine


84
6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-N-(2-pyrrolidin-1-



ylethyl)-1,3-benzothiazol-2-amine


85
6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-N-{[3-



(trifluoromethyl)phenyl]methyl}-1,3-benzothiazol-2-amine


86
6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-N-{2-[3-



(trifluoromethyl)phenyl]ethyl}-1,3-benzothiazol-2-amine


87
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N′-[3-



(trifluoromethyl)phenyl]propanediamide


88
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-1,3-benzothiazol-2-



yl)-2-[3-(trifluoromethyl)phenyl]acetamide


89
N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N2-{[3-



(trifluoromethyl)phenyl]methyl}glycinamide


90
N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N2-(2-



phenylethyl)glycinamide


91
N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N2-{2-[3-



(trifluoromethyl)phenyl]ethyl}glycinamide


92
benzyl-{[5-chloro-6-(6,7-dimethoxy-quinolin-4-yloxy)-pyridin-3-



ylcarbamoyl]-methyl}-carbamic acid tert-butyl ester


93
N1-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N2-



(phenylmethyl)glycinamide


94
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-1,3-benzothiazol-2-



yl)-2-[3,5-bis(trifluoromethyl)phenyl]acetamide


95
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-1,3-benzothiazol-2-



yl)-2-[2-chloro-5-(trifluoromethyl)phenyl]acetamide


96
N-{3-fluoro-4-[(6-(methyloxy)-7-{[(1-methylpiperidin-4-



yl)methyl]oxy}quinolin-4-yl)oxy]phenyl}-N′-(2-



phenylethyl)ethanediamide


97
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-(1,2,3,4-



tetrahydroisoquinolin-1-ylmethyl)ethanediamide


98
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-[(2-



methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)methyl]ethanediamide


99
N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N2-



methyl-N2-{[3-(trifluoromethyl)phenyl]methyl}glycinamide


100
N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N2-



methyl-N2-{2-[3-(trifluoromethyl)phenyl]ethyl}glycinamide


101
N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N2-



methyl-N2-(2-phenylethyl)glycinamide


102
1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-4-



(phenylmethyl)imidazolidin-2-one


103
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}pyridazin-3-yl)-N′-(4-



fluorophenyl)propanediamide


104
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N′-(2-



chlorophenyl)propanediamide


105
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N′-(3-



chlorophenyl)propanediamide


106
N1-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N2-



methyl-N2-(phenylmethyl)glycinamide


107
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N′-(4-



chlorophenyl)propanediamide


108
(2E)-N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-2-



[(methyloxy)imino]propanamide


109
(2E)-N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-2-



[(ethyloxy)imino]propanamide


110
(2E)-N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-2-



{[(phenylmethyl)oxy]imino}propanamide


111
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-1-



(phenylmethyl)prolinamide


112
1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-3-[(4-



methylphenyl)sulfonyl]-4-(phenylmethyl)imidazolidin-2-one


113
1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-4-



(phenylmethyl)imidazolidin-2-one


114
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-4-(phenylmethyl)-



4,5-dihydro-1,3-oxazol-2-amine


115
6,7-bis(methyloxy)-4-({4-[4-(phenylmethyl)piperazin-1-



yl]phenyl}oxy)quinoline


116
1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-4-



(phenylmethyl)piperazin-2-one


117
N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N2-



(phenylmethyl)alaninamide


118
N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N2-methyl-N2-



(phenylmethyl)alaninamide


119
N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N2-



(phenylmethyl)leucinamide


120
N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N2-methyl-N2-



(phenylmethyl)leucinamide


121
N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N2-



(phenylmethyl)valinamide


122
4-(6,7-dimethoxy-quinolin-4-ylamino)-N-(3-phenyl-propyl)-benzamide


123
4-benzyl-1-[4-(6,7-dimethoxy-quinolin-4-yloxy)-phenyl]-tetrahydro-



pyrimidin-2-one


124
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-phenethyl-oxalamide


125
2-(Benzyl-methyl-amino)-N-[4-(6,7-dimethoxy-quinolin-4-yloxy)-phenyl]-



3-methyl-butyramide



(note: Alphabetic order of prefixes ignored while selecting parent chain)


126
N-[4-(6,7-Dimethoxy-quinolin-4-yloxy)-phenyl]-2-phenoxyimino-



propionamide


127
2-Benzyloxyimino-N-[4-(6,7-dimethoxy-quinolin-4-yloxy)-phenyl]-2-



phenyl-acetamide


128
4-[4-(4-Benzyl-piperidin-1-yl)-phenoxy]-6,7-dimethoxy-quinoline


129
N-[4-(6,7-Dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-N′-(2-isopropyl-



1,2,3,4-tetrahydro-isoquinolin-1-ylmethyl)-oxalamide


130
N-[4-(6,7-Dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-N′-(2-ethyl-



1,2,3,4-tetrahydro-isoquinolin-1-ylmethyl)-oxalamide


131
4-(4-{3-Chloro-5-[2-(4-fluoro-phenylcarbamoyl)-acetylamino]-pyridin-2-



yloxy}-6-methoxy-quinolin-7-yloxymethyl)-piperidine-1-carboxylic acid



tert-butyl ester


132
N-{5-Chloro-6-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



pyridin-3-yl}-N′-(4-fluoro-phenyl)-malonamide


133
N-{5-Chloro-6-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-



4-yloxy]-pyridin-3-yl}-N′-(4-fluoro-phenyl)-malonamide


134
N-{4-[7-(3-Diethylamino-propoxy)-6-methoxy-quinolin-4-yloxy]-3-fluoro-



phenyl}-N′-phenethyl-oxalamide


135
N-{3-Fluoro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinolin-4-



yloxy]-phenyl}-N′-phenethyl-oxalamide


136
N-{3-Fluoro-4-[6-methoxy-7-(3-piperidin-1-yl-propoxy)-quinolin-4-



yloxy]-phenyl}-N′-phenethyl-oxalamide


137
N-{4-[7-(2-Diethylamino-ethoxy)-6-methoxy-quinolin-4-yloxy]-3-fluoro-



phenyl}-N′-phenethyl-oxalamide


138
N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-



4-yloxy]-phenyl}-N′-methyl-N′-phenethyl-oxalamide


139
N-{3-Fluoro-4-[6-methoxy-7-(2-methyl-octahydro-cyclopenta[c]pyrrol-5-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-N′-phenethyl-oxalamide


140
N-{3-Fluoro-4-[6-methoxy-7-(2-methyl-octahydro-cyclopenta[c]pyrrol-5-



ylmethoxy)-quinazolin-4-yloxy]-phenyl}-N′-phenethyl-oxalamide


141
2-(3,4-Dihydro-1H-isoquinolin-2-yl)-N-{3-fluoro-4-[6-methoxy-7-(1-



methyl-piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-2-oxo-



acetamide


142
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-2-oxo-2-(3-phenyl-pyrrolidin-1-yl)-acetamide


143
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-2-oxo-2-(2-phenyl-morpholin-4-yl)-acetamide


144
N-(2-Dimethylamino-2-phenyl-ethyl)-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


145
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(2-oxo-2-phenyl-ethyl)-oxalamide


146
N-[5-Chloro-6-(6,7-dimethoxy-quinolin-4-yloxy)-pyridin-3-yl]-2,2-



difluoro-N′-(4-fluoro-phenyl)-malonamide


147
N-Benzyl-N′-{3-fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-



quinolin-4-yloxy]-phenyl}-oxalamide


148
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-[2-(2-fluoro-phenyl)-ethyl]-oxalamide


149
N-[2-(3-Chloro-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


150
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-[2-(2-methoxy-phenyl)-ethyl]-oxalamide


151
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(2-pyridin-3-yl-ethyl)-oxalamide


152
N-Benzyl-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-



4-yloxy]-phenyl}-oxalamide


153
N-[2-(2,5-Dimethoxy-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


154
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-[2-(2-trifluoromethyl-phenyl)-ethyl]-oxalamide


155
N-[2-(2-Ethoxy-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


156
N-[2-(2,4-Dimethyl-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


157
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(1S-phenyl-2-p-tolyl-ethyl)-oxalamide


158
N-[2-(4-Chloro-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


159
N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-



4-yloxy]-phenyl}-oxalamic acid


160
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-[2-(3-fluoro-phenyl)-ethyl]-oxalamide


161
N-[2-(2-Chloro-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


162
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-[2-(3-methoxy-phenyl)-ethyl]-oxalamide


163
N-(1,2-Diphenyl-ethyl)-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


164
N-[2-(2,4-Dichloro-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-



4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


165
N-[2-(3,4-Dimethoxy-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


166
N-[2-(4-Ethyl-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


167
N-[2-(4-Ethoxy-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


168
N-[2-(4-Ethoxy-3-methoxy-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


169
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-[2-(4-phenoxy-phenyl)-ethyl]-oxalamide


170
N-[2-(3-Ethoxy-4-methoxy-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


171
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(2-pyridin-2-yl-ethyl)-oxalamide


172
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(2-pyridin-4-yl-ethyl)-oxalamide


173
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-[2-(4-fluoro-phenyl)-ethyl]-oxalamide


174
N-[2-(2-Bromo-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


175
N-[2-(2-Chloro-6-fluoro-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


176
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(2R-phenyl-propyl)-oxalamide


177
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-indan-1-yl-oxalamide


178
N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-



4-yloxy]-phenyl}-N′-isobutyl-oxalamide


179
N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-



4-yloxy]-phenyl}-N′-(3-methyl-butyl)-oxalamide


180
N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-



4-yloxy]-phenyl}-N′-(2R-phenyl-propyl)-oxalamide


181
N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-



4-yloxy]-phenyl}-N′-(2-phenyl-propyl)-oxalamide


182
N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-



4-yloxy]-phenyl}-N′-indan-2-yl-oxalamide


183
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(1R-phenyl-ethyl)-oxalamide


184
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(1S-phenyl-ethyl)-oxalamide


185
N-[2-(3-Bromo-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


186
N-[2-(2,6-Dichloro-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-



4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


187
N-[2-(2,4-Dichloro-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-



4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


188
N-(2-Benzo[1,3]dioxol-5-yl-ethyl)-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


189
N-[2-(3-Bromo-4-methoxy-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


190
N-[2-(3,5-Dimethoxy-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


191
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(2-o-tolyl-ethyl)-oxalamide


192
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(2-m-tolyl-ethyl)-oxalamide


193
N-[2-(3-Ethoxy-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


194
N-[2-(3,4-Dimethyl-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


195
N-[2-(2,5-Dimethyl-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


196
N-[2-(3-Chloro-4-propoxy-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


197
N-[2-(4-Butoxy-3-chloro-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


198
N-[2-(4-tert-Butyl-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-



4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


199
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-[2-(4-sulfamoyl-phenyl)-ethyl]-oxalamide


200
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-oxalamide


201
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-[2-(3-hydroxy-4-methoxy-phenyl)-ethyl]-oxalamide


202
N-(2,4-Dichloro-benzyl)-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


203
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(4-fluoro-2-trifluoromethyl-benzyl)-oxalamide


204
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(1-p-tolyl-ethyl)-oxalamide


205
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(3-fluoro-4-trifluoromethyl-benzyl)-oxalamide


206
N-(3-Chloro-4-fluoro-benzyl)-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


207
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-[1-(3-methoxy-phenyl)-ethyl]-oxalamide


208
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(1-naphthalen-2-yl-ethyl)-oxalamide


209
N-(4-Chloro-3-trifluoromethyl-benzyl)-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


210
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(1-p-tolyl-ethyl)-oxalamide


211
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(6-trifluoromethyl-pyridin-3-ylmethyl)-oxalamide


212
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(2-methyl-benzyl)-oxalamide


213
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(3-methyl-benzyl)-oxalamide


214
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(4-fluoro-3-trifluoromethyl-benzyl)-oxalamide


215
N-(3,5-Dichloro-benzyl)-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


216
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(1R,2,3,4-tetrahydro-naphthalen-1-yl)-oxalamide


217
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(1S,2,3,4-tetrahydro-naphthalen-1-yl)-oxalamide


218
N-Cyclopentyl-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-



quinolin-4-yloxy]-phenyl}-oxalamide


219
N-[1-(4-Bromo-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


220
N-(2-Fluoro-benzyl)-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


221
N-[2-(3,4-Dichloro-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-



4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


222
N-(4-Fluoro-benzyl)-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


223
N-(2,3-Difluoro-benzyl)-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


224
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(2-phenoxy-ethyl)-oxalamide


225
N-(2,2-Diphenyl-ethyl)-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


226
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-[2-(4-methoxy-phenyl)-ethyl]-oxalamide


227
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(2-phenyl-propyl)-oxalamide


228
N-[2-(4-Bromo-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


229
N-{4-[7-(1-Ethyl-piperidin-4-ylmethoxy)-6-methoxy-quinolin-4-yloxy]-3-



fluoro-phenyl}-2-oxo-2-(2-phenyl-morpholin-4-yl)-acetamide


230
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(3-fluoro-5-trifluoromethyl-benzyl)-oxalamide


231
N-(3,5-Difluoro-benzyl)-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


232
N-(2-Chloro-5-trifluoromethyl-benzyl)-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


233
N-[4-(6,7-Dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-N′-(2-



dimethylamino-2-phenyl-ethyl)-oxalamide


234
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(4-methoxy-benzyl)-oxalamide


235
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(4-trifluoromethyl-benzyl)-oxalamide


236
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(3-methoxy-benzyl)-oxalamide


237
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(3-trifluoromethyl-benzyl)-oxalamide


238
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(3-trifluoromethoxy-benzyl)-oxalamide


239
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(2-methoxy-benzyl)-oxalamide


240
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(2-trifluoromethyl-benzyl)-oxalamide


241
N-(3-Chloro-benzyl)-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


242
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(2-trifluoromethoxy-benzyl)-oxalamide


243
N-(2-Chloro-benzyl)-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


244
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(4-trifluoromethoxy-benzyl)-oxalamide


245
N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-



4-yloxy]-phenyl}-N′-(4-methoxy-benzyl)-oxalamide


246
N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-



4-yloxy]-phenyl}-N′-(4-trifluoromethyl-benzyl)-oxalamide


247
N-{4-[7-(Azetidin-3-ylmethoxy)-6-methoxy-quinolin-4-yloxy]-3-fluoro-



phenyl}-N′-phenethyl-oxalamide


248
N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-azetidin-3-ylmethoxy)-quinolin-4-



yloxy]-phenyl}-N′-phenethyl-oxalamide


249
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(2-hydroxy-2-phenyl-ethyl)-oxalamide


250
N-[5-Chloro-6-(6,7-dimethoxy-quinolin-4-yloxy)-pyridin-3-yl]-N′-(2,4-



difluoro-phenyl)-malonamide


251
N-[5-Chloro-6-(6,7-dimethoxy-quinolin-4-yloxy)-pyridin-3-yl]-N′-(4-



fluoro-phenyl)-N′-methyl-malonamide


252
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(1R-phenyl-propyl)-oxalamide


253
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(1R-phenyl-propyl)-oxalamide


254
N-(3,4-Difluoro-benzyl)-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


255
N-(2,6-Difluoro-benzyl)-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


256
N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-



4-yloxy]-phenyl}-N′-[2-(4-fluoro-phenyl)-ethyl]-oxalamide


257
N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-



4-yloxy]-phenyl}-N′-phenyl-oxalamide


258
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(3-fluoro-phenyl)-oxalamide


259
N-(4-Chloro-3-fluoro-phenyl)-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


260
N-(3,4-Dimethoxy-phenyl)-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


261
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(3-methyl-butyl)-oxalamide


262
N-(3,3-Dimethyl-butyl)-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


263
N-{5-Chloro-6-[6-methoxy-7-(3-piperidin-1-yl-propoxy)-quinolin-4-



yloxy]-pyridin-3-yl}-N′-(4-fluoro-phenyl)-malonamide


264
N-{5-Chloro-6-[6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinolin-4-



yloxy]-pyridin-3-yl}-N′-(4-fluoro-phenyl)-malonamide


265
N-{5-Chloro-6-[7-(3-diethylamino-propoxy)-6-methoxy-quinolin-4-



yloxy]-pyridin-3-yl}-N′-(4-fluoro-phenyl)-malonamide


266
N-(4-Chloro-benzyl)-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


267
N-(3,5-Dimethoxy-benzyl)-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


268
N-(4-Butyl-benzyl)-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-



quinolin-4-yloxy]-phenyl}-oxalamide


269
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(2-p-tolyl-ethyl)-oxalamide


270
N-(3,5-Bis-trifluoromethyl-benzyl)-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


271
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-pyrazin-2-ylmethyl-oxalamide


272
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-pyridin-2-ylmethyl-oxalamide


273
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinazolin-4-



yloxy]-phenyl}-N′-phenethyl-oxalamide


274
N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-



quinazolin-4-yloxy]-phenyl}-N′-phenethyl-oxalamide


275
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(2-fluoro-3-trifluoromethyl-benzyl)-oxalamide


276
N-[2-(2-Bromo-6-methoxy-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


277
N-[2-(3,4-Dimethoxy-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N-methyl-oxalamide


278
N-[2-(5-Bromo-2-methoxy-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


279
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(2-fluoro-5-trifluoromethyl-benzyl)-oxalamide


280
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-[1-(4-fluoro-phenyl)-ethyl]-oxalamide


281
N-(1S-Benzyl-2-oxo-2-pyrrolidin-1-yl-ethyl)-N′-{3-fluoro-4-[6-methoxy-7-



(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


282
N-{3-Fluoro-4-[6-methoxy-7-(octahydro-cyclopenta[c]pyrrol-5-



ylmethoxy)-quinazolin-4-yloxy]-phenyl}-N′-phenethyl-oxalamide


283
N-[2-(4-Amino-phenyl)-ethyl]-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


284
2-(4-Benzyl-piperidin-1-yl)-N-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-2-oxo-acetamide


285
N-[4-(6,7-Dimethoxy-quinolin-4-yloxy)-phenyl]-N′-(4-fluoro-phenyl)-



malonamide


286
N-[5-Chloro-6-(6,7-dimethoxy-quinolin-4-yloxy)-pyridin-3-yl]-N′-(3-



fluoro-phenyl)-malonamide


287
N-[5-Chloro-6-(6,7-dimethoxy-quinolin-4-yloxy)-pyridin-3-yl]-N′-phenyl-



malonamide


288
N-[5-Chloro-6-(6,7-dimethoxy-quinolin-4-yloxy)-pyridin-3-yl]-N′-(4-



fluoro-phenyl)-2,2-dimethyl-malonamide


289
N-Ethyl-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-



yloxy]-phenyl}-oxalamide


290
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-isopropyl-oxalamide


291
N-Butyl-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-



yloxy]-phenyl}-oxalamide


292
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(2-methoxy-ethyl)-oxalamide


293
N-Cyclopropylmethyl-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-



ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide


294
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-N′-(2-morpholin-4-yl-ethyl)-oxalamide


295
N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-



phenyl}-2-oxo-2-pyrrolidin-1-yl-acetamide


296
N-Ethyl-N′-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-



yloxy]-phenyl}-N-methyl-oxalamide









The Compounds in Table 3c can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 3c can be used to practice the invention.











Entry
Name
















1
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N′-(4-



fluorophenyl)cyclopropane-1,1-dicarboxamide


2
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N′-(4-



fluorophenyl)cyclobutane-1,1-dicarboxamide


3
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N′-



(phenylmethyl)cyclopropane-1,1-dicarboxamide


4
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N′-



phenylcyclopropane-1,1-dicarboxamide


5
N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-



yl}oxy)phenyl]-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide


6
N-[3-fluoro-4-({6-(methyloxy)-7-[(3-piperidin-1-ylpropyl)oxy]quinolin-4-



yl}oxy)phenyl]-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide


7
N-[3-fluoro-4-({6-(methyloxy)-7-[(3-piperidin-1-ylpropyl)oxy]quinolin-4-



yl}oxy)phenyl]-N′-(4-fluorophenyl)cyclobutane-1,1-dicarboxamide


8
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N′-(2-



phenylethyl)cyclopropane-1,1-dicarboxamide


9
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-2-methylpyridin-3-yl)-N′-(4-



fluorophenyl)cyclopropane-1,1-dicarboxamide


10
N-{4-[(7-chloroquinolin-4-yl)oxy]-3-fluorophenyl}-N′-(4-



fluorophenyl)cyclopropane-1,1-dicarboxamide


11
N-{4-[(7-chloroquinolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl)cyclopropane-



1,1-dicarboxamide


12
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-



fluorophenyl)cyclopropane-1,1-dicarboxamide


13
N-(4-{[6,7-bis(methyloxy)quinazolin-4-yl]oxy}phenyl)-N′-(4-



fluorophenyl)cyclopropane-1,1-dicarboxamide


14
N-(4-{[6,7-bis(methyloxy)quinazolin-4-yl]oxy}-3-fluorophenyl)-N′-(4-



fluorophenyl)cyclopropane-1,1-dicarboxamide


15
N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinazolin-4-



yl}oxy)phenyl]-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide


16
N-{5-chloro-6-[(6-(methyloxy)-7-{[(1-methylpiperidin-4-



yl)methyl]oxy}quinolin-4-yl)oxy]pyridin-3-yl}-N′-(4-



fluorophenyl)cyclopropane-1,1-dicarboxamide


17
N-[5-chloro-6-({6-(methyloxy)-7-[(piperidin-4-ylmethyl)oxy]quinolin-4-



yl}oxy)pyridin-3-yl]-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide


18
N-[5-chloro-6-({6-(methyloxy)-7-[(phenylmethyl)oxy]quinolin-4-



yl}oxy)pyridin-3-yl]-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide


19
N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-



fluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide


20
N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-



fluorophenyl)-N′-(4-fluorophenyl)cyclobutane-1,1-dicarboxamide


21
N-{3-fluoro-4-[(6-(methyloxy)-7-{[(1-methylpiperidin-4-



yl)methyl]oxy}quinazolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl)cyclopropane-



1,1-dicarboxamide


22
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-2-methylphenyl)-N′-(4-



fluorophenyl)cyclopropane-1,1-dicarboxamide


23
N-(4-fluorophenyl)-N′-[2-methyl-6-({6-(methyloxy)-7-[(3-morpholin-4-



ylpropyl)oxy]quinolin-4-yl}oxy)pyridin-3-yl]cyclopropane-1,1-dicarboxamide


24
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-(4-



fluorophenyl)cyclopropane-1,1-dicarboxamide


25
N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloro-2-methylpyridin-3-yl)-



N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide


26
N-[3-fluoro-4-({7-(methyloxy)-6-[(3-morpholin-4-ylpropyl)oxy]quinazolin-4-



yl}oxy)phenyl]-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide


27
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3,5-difluorophenyl)-N′-(4-



fluorophenyl)cyclopropane-1,1-dicarboxamide


28
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-2,5-difluorophenyl)-N′-(4-



fluorophenyl)cyclopropane-1,1-dicarboxamide


29
N-[3-fluoro-4-({7-(methyloxy)-6-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-



yl}oxy)phenyl]-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide


30
N-{3-fluoro-4-[(6-(methyloxy)-7-(2-methyl octahydrocyclo-penta[c]pyrrol-5-



ylmethoxy)quinazolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl)cyclopropane-1,1-



dicarboxamide


31
N-{3-fluoro-4-[(7-(methyloxy)-6-{[(1-methylpiperidin-4-



yl)methyl]oxy}quinazolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl)cyclopropane-



1,1-dicarboxamide


32
N-[5-fluoro-2-methyl-4-({6-(methyloxy)-7-[(3-morpholin-4-



ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N′-(4-fluorophenyl)cyclopropane-1,1-



dicarboxamide


33
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-2,3,5-trifluorophenyl)-N′-(4-



fluorophenyl)cyclopropane-1,1-dicarboxamide


34
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-2-methylphenyl)-N′-(4-



fluorophenyl)cyclopropane-1,1-dicarboxamide


35
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-2-chloro-5-methylphenyl)-N′-(4-



fluorophenyl)cyclopropane-1,1-dicarboxamide


36
N-(3-fluoro-4-{[6-hydroxy-7-(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-



fluorophenyl)cyclopropane-1,1-dicarboxamide


37
N-(4-fluorophenyl)-N′-[2-methyl-4-({6-(methyloxy)-7-[(3-morpholin-4-



ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]cyclopropane-1,1-dicarboxamide


38
N-[3-fluoro-4-({6-(methyloxy)-7-[(3-piperazin-1-ylpropyl)oxy]quinolin-4-



yl}oxy)phenyl]-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide


39
N-{3-fluoro-4-[(6-(methyloxy)-7-{[3-(4-methylpiperazin-1-



yl)propyl]oxy}quinolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl)cyclopropane-



1,1-dicarboxamide


40
N-{3-fluoro-4-[(6-(methyloxy)-7-{[(1-methylpiperidin-4-



yl)methyl]oxy}quinolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl)cyclopropane-



1,1-dicarboxamide


41
N-(4-fluorophenyl)-N′-[4-({6-(methyloxy)-7-[(3-morpholin-4-



ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]cyclopropane-1,1-dicarboxamide


42
N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-



fluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide


43
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-2-chloro-5-fluorophenyl)-N′-(4-



fluorophenyl)cyclopropane-1,1-dicarboxamide


44
N-(4-{[6,7-bis(methyloxy)-2-(methylthio)quinolin-4-yl]oxy}-3-fluorophenyl)-



N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide


45
N-(4-fluorophenyl)-N′-(4-{[2-methyl-6,7-bis(methyloxy)quinazolin-4-



yl]oxy}phenyl)cyclopropane-1,1-dicarboxamide


46
N-(4-{[2-amino-6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-(4-



fluorophenyl)cyclopropane-1,1-dicarboxamide


47
N-(3-fluoro-4-{[2-(methylamino)-6,7-bis(methyloxy)quinolin-4-



yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide


48
(1S,2R)-N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-



ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N′-(4-fluorophenyl)-2-



methylcyclopropane-1,1-dicarboxamide


49
(1R,2R)-N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-



ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N′-(4-fluorophenyl)-2-



methylcyclopropane-1,1-dicarboxamide


50
N-(4-{[6-{[3-(diethylamino)propyl]oxy}-7-(methyloxy)quinolin-4-yl]oxy}-3-



fluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide


51
N-(4-{[6-{[2-(diethylamino)ethyl]oxy}-7-(methyloxy)quinolin-4-yl]oxy}-3-



fluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide


52
1,1-dimethylethyl 4-(3-{[4-[(2-fluoro-4-{[(1-{[(4-



fluorophenyl)amino]carbonyl}cyclopropyl)carbonyl]amino}phenyl)oxy]-6-



(methyloxy)quinolin-7-yl]oxy}propyl)piperazine-1-carboxylate


53
(1R,2R)-N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-



ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N′-(4-fluorophenyl)-2-



methylcyclopropane-1,1-dicarboxamide


54
(1R,2R)-N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinazolin-4-



yl]oxy}-3-fluorophenyl)-N′-(4-fluorophenyl)-2-methylcyclopropane-1,1-



dicarboxamide


55
N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinazolin-4-yl]oxy}-3-



fluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide


56
N-(4-{[7-{[3-(4-acetylpiperazin-1-yl)propyl]oxy}-6-(methyloxy)quinolin-4-



yl]oxy}-3-fluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide


57
1,1-dimethylethyl 4-(3-{[4-[(2-fluoro-4-{[((1R,2R)-1-{[(4-



fluorophenyl)amino]carbonyl}-2-



methylcyclopropyl)carbonyl]amino}phenyl)oxy]-6-(methyloxy)quinolin-7-



yl]oxy}propyl)piperazine-1-carboxylate


58
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)-1-



(phenylmethyl)azetidine-3,3-dicarboxamide


59
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-



fluorophenyl)azetidine-3,3-dicarboxamide


60
(1R,2S)-N-{3-fluoro-4-[(6-(methyloxy)-7-{[3-(4-methylpiperazin-1-



yl)propyl]oxy}quinolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl)-2-



methylcyclopropane-1,1-dicarboxamide


61
(1R,2R)-N-{3-fluoro-4-[(6-(methyloxy)-7-{[3-(4-methylpiperazin-1-



yl)propyl]oxy}quinolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl)-2-



methylcyclopropane-1,1-dicarboxamide


62
(1R,2R)-N-[3-fluoro-4-({6-(methyloxy)-7-[(3-piperazin-1-



ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N′-(4-fluorophenyl)-2-



methylcyclopropane-1,1-dicarboxamide


63
N-(3-fluoro-4-{[7-({3-[4-(1-methylethyl)piperazin-1-yl]propyl}oxy)-6-



(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-



dicarboxamide


64
N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinazolin-4-yl]oxy}-3-



fluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide


65
(1R,2R)-N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinolin-4-



yl]oxy}-3-fluorophenyl)-N′-(4-fluorophenyl)-2-methylcyclopropane-1,1-



dicarboxamide


66
(1R,2R)-N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinolin-4-



yl]oxy}-3-fluorophenyl)-N′-(4-fluorophenyl)-2-methylcyclopropane-1,1-



dicarboxamide


67
(1R,2S)-N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinolin-4-



yl]oxy}-3-fluorophenyl)-N′-(4-fluorophenyl)-2-methylcyclopropane-1,1-



dicarboxamide


68
(1R,2S)-N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinolin-4-



yl]oxy}-3-fluorophenyl)-N′-(4-fluorophenyl)-2-methylcyclopropane-1,1-



dicarboxamide


69
N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinazolin-4-yl]oxy}-3-



fluorophenyl)-N′-(4-fluorophenyl)cyclobutane-1,1-dicarboxamide


70
(1R,2S)-N-[3-fluoro-4-({6-(methyloxy)-7-[(3-piperazin-1-



ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N′-(4-fluorophenyl)-2-



methylcyclopropane-1,1-dicarboxamide


71
(1R,2R,3S)-N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-



ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N′-(4-fluorophenyl)-2,3-



dimethylcyclopropane-1,1-dicarboxamide


72
(1R,2R,3S)-N-{3-fluoro-4-[(6-(methyloxy)-7-{[3-(4-methylpiperazin-1-



yl)propyl]oxy}quinolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl)-2,3-



dimethylcyclopropane-1,1-dicarboxamide


73
(1R,2R,3S)-N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-



ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N′-(4-fluorophenyl)-2,3-



dimethylcyclopropane-1,1-dicarboxamide


74
(1R,2R,3S)-N-{3-fluoro-4-[(6-(methyloxy)-7-{[3-(4-methylpiperazin-1-



yl)propyl]oxy}quinazolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl)-2,3-



dimethylcyclopropane-1,1-dicarboxamide


75
N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinazolin-4-



yl}oxy)phenyl]-N′-(4-fluorophenyl)cyclobutane-1,1-dicarboxamide


76
(2R,3R)-N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-



ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N′-(4-fluorophenyl)-2,3-



dimethylcyclopropane-1,1-dicarboxamide


77
(2R,3R)-N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinolin-4-



yl]oxy}-3-fluorophenyl)-N′-(4-fluorophenyl)-2,3-dimethylcyclopropane-1,1-



dicarboxamide


78
N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-



fluorophenyl)-N′-(4-fluorophenyl)-2,2-dimethylcyclopropane-1,1-



dicarboxamide


79
N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinazolin-4-



yl}oxy)phenyl]-N′-(4-fluorophenyl)-2,2-dimethylcyclopropane-1,1-



dicarboxamide


80
(1R,2R,3S)-N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinolin-4-



yl]oxy}-3-fluorophenyl)-N′-(4-fluorophenyl)-2,3-dimethylcyclopropane-1,1-



dicarboxamide


81
N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-



fluorophenyl)-N′-(4-fluorophenyl)-2,2-dimethylcyclopropane-1,1-



dicarboxamide


82
(1R,2R,3S)-N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinolin-4-



yl]oxy}-3-fluorophenyl)-N′-(4-fluorophenyl)-2,3-dimethylcyclopropane-1,1-



dicarboxamide


83
N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-



yl}oxy)phenyl]-N′-(4-fluorophenyl)-2,2-dimethylcyclopropane-1,1-



dicarboxamide


84
N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinazolin-4-yl]oxy}-3-



fluorophenyl)-N′-(4-fluorophenyl)-2,2-dimethylcyclopropane-1,1-



dicarboxamide


85
N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinazolin-4-yl]oxy}-3-



fluorophenyl)-N′-(4-fluorophenyl)-2,2-dimethylcyclopropane-1,1-



dicarboxamide


86
N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinazolin-4-yl]oxy}-3-



fluorophenyl)-N′-(4-fluorophenyl)cyclobutane-1,1-dicarboxamide


87
N-{3-fluoro-4-[(6-(methyloxy)-7-{[3-(4-methylpiperazin-1-



yl)propyl]oxy}quinazolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl)cyclobutane-



1,1-dicarboxamide


88
N-[3-fluoro-4-({6-(methyloxy)-7-[(3-piperazin-1-ylpropyl)oxy]quinazolin-4-



yl}oxy)phenyl]-N′-(4-fluorophenyl)cyclobutane-1,1-dicarboxamide


89
(2R,3R)-N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-



ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N′-(4-fluorophenyl)-2,3-



dimethylcyclopropane-1,1-dicarboxamide


90
N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-



fluorophenyl)-N′-(4-fluorophenyl)cyclobutane-1,1-dicarboxamide


91
N-{3-fluoro-4-[(6-(methyloxy)-7-{[3-(4-methylpiperazin-1-



yl)propyl]oxy}quinolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl)cyclobutane-1,1-



dicarboxamide


92
(1R,2R)-N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinazolin-4-



yl]oxy}-3-fluorophenyl)-N′-(4-fluorophenyl)-2-methylcyclopropane-1,1-



dicarboxamide


93
(1R,2R)-N-{3-fluoro-4-[(6-(methyloxy)-7-{[3-(4-methylpiperazin-1-



yl)propyl]oxy}quinazolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl)-2-



methylcyclopropane-1,1-dicarboxamide


94
(2R,3R)-N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinazolin-4-



yl]oxy}-3-fluorophenyl)-N′-(4-fluorophenyl)-2,3-dimethylcyclopropane-1,1-



dicarboxamide


95
(2R,3R)-N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinazolin-4-



yl]oxy}-3-fluorophenyl)-N′-(4-fluorophenyl)-2,3-dimethylcyclopropane-1,1-



dicarboxamide


96
(1R,2R)-N-[3-fluoro-4-({6-(methyloxy)-7-[(3-piperazin-1-



ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N′-(4-fluorophenyl)-2-



methylcyclopropane-1,1-dicarboxamide


97
(2R,3R)-N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinolin-4-



yl]oxy}-3-fluorophenyl)-N′-(4-fluorophenyl)-2,3-dimethylcyclopropane-1,1-



dicarboxamide


98
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-[(4-



fluorophenyl)methyl]cyclopropane-1,1-dicarboxamide


99
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(2-morpholin-4-



ylethyl)cyclopropane-1,1-dicarboxamide


100
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-[2-(piperidin-1-



ylmethyl)phenyl]cyclopropane-1,1-dicarboxamide


101
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-[2-(pyrrolidin-1-



ylmethyl)phenyl]cyclopropane-1,1-dicarboxamide


102
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-[3-(morpholin-4-



ylmethyl)phenyl]cyclopropane-1,1-dicarboxamide


103
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-[2-(morpholin-4-



ylmethyl)phenyl]cyclopropane-1,1-dicarboxamide


104
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-phenylcyclopropane-



1,1-dicarboxamide


105
N-[3-(aminomethyl)phenyl]-N′-(4-{[6,7-bis(methyloxy)quinolin-4-



yl]oxy}phenyl)cyclopropane-1,1-dicarboxamide


106
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-[3-(piperidin-1-



ylmethyl)phenyl]cyclopropane-1,1-dicarboxamide


107
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-[3-(pyrrolidin-1-



ylmethyl)phenyl]cyclopropane-1,1-dicarboxamide









The Compounds in Table 4 can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 4 can be used to practice the invention. In particular, the invention can be practiced with one or two pharmaceutically acceptable salts of a Compound of Table 4 which salt(s) are formed with one or two acids independently selected from hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, acetic acid, trifluoroacetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, 3-(4-hydroxybenzoyl)benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, glucoheptonic acid, 4,4′-methylenebis-(3-hydroxy-2-ene-1-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, p-toluenesulfonic acid, and salicylic acid.











Entry
Name
















1
N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-(1-



methylethyl)octahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-



(methyloxy)quinazolin-4-amine


2
N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-(1-



methylethyl)octahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-



(methyloxy)quinazolin-4-amine


3
7-({[(3aR,5r,6aS)-2-acetyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-N-(4-



bromo-3-chloro-2-fluorophenyl)-6-(methyloxy)quinazolin-4-amine


4
N-(4-bromo-3-chloro-2-fluorophenyl)-6-(methyloxy)-7-{[(3aR,5r,6aS)-



octahydrocyclopenta[c]pyrrol-5-ylmethyl]oxy}quinazolin-4-amine


5
ethyl (3aR,6aS)-5-({[4-[(4-bromo-3-chloro-2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]oxy}methyl)hexahydrocyclopenta[c]pyrrole-2(1H)-



carboxylate


6
N-(4-bromo-3-chloro-2-fluorophenyl)-6-(methyloxy)-7-({[(3aR,5r,6aS)-2-



(methylsulfonyl)octahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)quinazolin-4-



amine


7
N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-



ethyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-



amine


8
N-(3,4-dichloro-2-fluorophenyl)-6-(methyloxy)-7-({[(3aR,5r,6aS)-2-(2-



methylpropyl)octahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)quinazolin-4-amine


9
N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-



methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-



4-amine


10
N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-



methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-



4-amine


11
N-(3-chloro-2,4-difluorophenyl)-7-({[(3aR,5s,6aS)-2-



methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-



4-amine


12
N-(4,5-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-



methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-



4-amine


13
N-(4-bromo-5-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-



methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-



4-amine


14
N-(4-bromo-2,3-dichlorophenyl)-7-({[(3aR,5s,6aS)-2-



methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-



4-amine


15
N-(3,4-dichlorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-



5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


16
N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-



ethyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-



amine


17
N-(4-bromo-3-chloro-2-fluorophenyl)-6-(methyloxy)-7-({[(3aR,5r,6aS)-2-(2-



methylpropyl)octahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)quinazolin-4-amine


18
N-(4-bromo-2,3-dichlorophenyl)-7-{[(3R,9aS)-hexahydro-1H-[1,4]oxazino[3,4-



c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


19
N-(4,5-dichloro-2-fluorophenyl)-7-{[(3R,9aS)-hexahydro-1H-[1,4]oxazino[3,4-



c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


20
N-(4-bromo-5-chloro-2-fluorophenyl)-7-{[(3R,9aS)-hexahydro-1H-



[1,4]oxazino[3,4-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


21
N-(3-chloro-2,4-difluorophenyl)-7-{[(3R,9aS)-hexahydro-1H-[1,4]oxazino[3,4-



c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


22
N-(3,4-dichloro-2-fluorophenyl)-7-{[(3S,9aS)-hexahydro-1H-[1,4]oxazino[3,4-



c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


23
N-(4-bromo-3-chloro-2-fluorophenyl)-7-{[(3S,9aS)-hexahydro-1H-



[1,4]oxazino[3,4-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


24
N-(3-chloro-2,4-difluorophenyl)-7-{[(3S,9aS)-hexahydro-1H-[1,4]oxazino[3,4-



c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


25
N-(3,4-dichlorophenyl)-7-[(hexahydro-1H-[1,4]oxazino[3,4-c][1,4]oxazin-3-



ylmethyl)oxy]-6-(methyloxy)quinazolin-4-amine


26
N-(4,5-dichloro-2-fluorophenyl)-7-{[(3S,9aS)-hexahydro-1H-[1,4]oxazino[3,4-



c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


27
N-(4-bromo-2,3-dichlorophenyl)-7-{[(3S,9aS)-hexahydro-1H-[1,4]oxazino[3,4-



c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


28
N-(4-bromo-5-chloro-2-fluorophenyl)-7-{[(3S,9aS)-hexahydro-1H-



[1,4]oxazino[3,4-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


29
N-(3,4-dichloro-2-fluorophenyl)-7-{[(3R,9aS)-hexahydro-1H-[1,4]oxazino[3,4-



c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


30
N-(4-bromo-3-chloro-2-fluorophenyl)-7-{[(3R,9aS)-hexahydro-1H-



[1,4]oxazino[3,4-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


31
N-(3,4-dichlorophenyl)-7-{[(3R,8aR)-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-3-



ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


32
N-(4-bromo-5-chloro-2-fluorophenyl)-7-{[(3S,8aS)-hexahydro-1H-pyrrolo[2,1-



c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


33
N-(3,4-dichlorophenyl)-7-{[(3S,8aR)-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-3-



ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


34
N-(3,4-dichlorophenyl)-7-{[(3S,8aS)-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-3-



ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


35
N-(3,4-dichlorophenyl)-7-{[(3R,8aS)-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-3-



ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


36
N-(3,4-dichloro-2-fluorophenyl)-7-{[(3S,8aS)-hexahydro-1H-pyrrolo[2,1-



c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


37
N-(4-bromo-3-chloro-2-fluorophenyl)-7-{[(3S,8aS)-hexahydro-1H-pyrrolo[2,1-



c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


38
N-(3-chloro-2,4-difluorophenyl)-7-{[(3S,8aS)-hexahydro-1H-pyrrolo[2,1-



c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


39
N-(4-bromo-2,3-dichlorophenyl)-7-{[(3S,8aS)-hexahydro-1H-pyrrolo[2,1-



c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


40
N-(4,5-dichloro-2-fluorophenyl)-7-{[(3S,8aS)-hexahydro-1H-pyrrolo[2,1-



c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine


41
1,4:3,6-dianhydro-5-({[4-[(4-bromo-5-chloro-2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]oxy}methyl)-5-deoxy-2-O-methyl-D-xylo-hexitol


42
1,4:3,6-dianhydro-5-deoxy-5-({[4-[(3,4-dichlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]oxy}methyl)-2-O-methyl-D-glucitol


43
1,4:3,6-dianhydro-5-deoxy-5-({[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]oxy}methyl)-2-O-methyl-D-xylo-hexitol


44
1,4:3,6-dianhydro-5-({[4-[(4-bromo-3-chloro-2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]oxy}methyl)-5-deoxy-2-O-methyl-D-xylo-hexitol


45
1,4:3,6-dianhydro-5-({[4-[(3-chloro-2,4-difluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]oxy}methyl)-5-deoxy-2-O-methyl-D-xylo-hexitol


46
1,4:3,6-dianhydro-5-({[4-[(4-bromo-2,3-dichlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]oxy}methyl)-5-deoxy-2-O-methyl-D-glucitol


47
1,4:3,6-dianhydro-2-deoxy-2-({[4-[(3,4-dichlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]oxy}methyl)-5-O-methyl-D-threo-hexitol


48
1,4:3,6-dianhydro-5-deoxy-5-({[4-[(4,5-dichloro-2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]oxy}methyl)-2-O-methyl-D-glucitol


49
(3S,9aS)-3-({[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)hexahydro-2H-pyrido[1,2-a]pyrazin-1(6H)-one


50
(3S,9aR)-3-({[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)hexahydro-2H-pyrido[1,2-a]pyrazin-1(6H)-one


51
(3S,8aS)-3-({[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)hexahydropyrrolo[1,2-a]pyrazin-1(2H)-one


52
(3S,8aR)-3-({[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)hexahydropyrrolo[1,2-a]pyrazin-1(2H)-one


53
(3S,8aS)-3-({[4-[(4-bromo-3-chloro-2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]oxy}methyl)hexahydropyrrolo[1,2-a]pyrazin-1(2H)-



one


54
(3S,8aS)-3-({[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)-2-methylhexahydropyrrolo[1,2-a]pyrazin-1(2H)-one


55
N-(3,4-dichlorophenyl)-7-({2-[(8-methyl-8-azabicyclo[3.2.1]oct-3-



yl)amino]ethyl}oxy)-6-(methyloxy)quinazolin-4-amine


56
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(8aR)-tetrahydro-1H-[1,3]thiazolo[4,3-



c][1,4]oxazin-6-ylmethyl]oxy}quinazolin-4-amine


57
N-(3,4-dichlorophenyl)-7-{[2-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)ethyl]oxy}-6-



(methyloxy)quinazolin-4-amine


58
N-(3,4-dichlorophenyl)-7-{[(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


59
N-(3,4-dichlorophenyl)-7-{[(3aR,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-



yl]oxy}-6-(methyloxy)quinazolin-4-amine


60
N-(3,4-dichlorophenyl)-7-[(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)oxy]-6-



(methyloxy)quinazolin-4-amine


61
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-5-chloro-2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol


62
1,4:3,6-dianhydro-2-O-[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol


63
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chloro-2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol


64
1,4:3,6-dianhydro-2-O-methyl-5-O-{6-(methyloxy)-4-[(2,3,4-



trichlorophenyl)amino]quinazolin-7-yl}-L-iditol


65
1,4:3,6-dianhydro-5-O-[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-



7-yl]-2-O-methyl-D-xylo-hexitol


66
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-2,3-dichlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol


67
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)-



quinazolin-7-yl]-sorbose ethylene glycol acetal


68
1,4:3,6-dianhydro-2-O-[4-[(3-chloro-2,4-difluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol


69
1,4:3,6-dianhydro-2-O-[4-[(4,5-dichloro-2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol


70
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-O-(difluoromethyl)-L-iditol


71
1,4:3,6-dianhydro-2-O-[4-[(3-chloro-2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol


72
1,4:3,6-dianhydro-2-O-[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-



7-yl]-5-O-methyl-L-iditol


73
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol


74
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-O-ethyl-L-iditol


75
1,4:3,6-dianhydro-2-O-[4-[(3-bromo-2-methylphenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol


76
1,4:3,6-dianhydro-2-O-[4-[(3-chloro-2-methylphenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol


77
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-deoxy-D-xylo-hexitol


78
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-O-methyl-D-glucitol


79
methyl 3,6-anhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-O-methyl-alpha-L-idofuranoside


80
3,6-anhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-



7-yl]-1,2-O-(1-methylethylidene)-beta-L-xylo-hexofuranose


81
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-deoxy-5-methylidene-D-xylo-hexitol


82
methyl 3,6-anhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-O-methyl-beta-L-idofuranoside


83
N-(3,4-dichloro-2-fluorophenyl)-6-(methyloxy)-7-[(octahydro-2H-quinolizin-3-



ylmethyl)oxy]quinazolin-4-amine


84
1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-{6-(methyloxy)-4-[(2,3,4-



trifluorophenyl)amino]quinazolin-7-yl}-D-iditol


85
1,4:3,6-dianhydro-5-O-[4-[(2-chloro-4-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


86
1,4:3,6-dianhydro-5-O-[4-[(2-bromo-4-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


87
1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(2,6-difluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol


88
1,4:3,6-dianhydro-5-O-[4-[(3-chloro-2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


89
1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-[4-{[4-fluoro-3-



(trifluoromethyl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-D-iditol


90
1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(2,4-difluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol


91
1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(2,5-difluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol


92
1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(2,3-difluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol


93
1,4:3,6-dianhydro-5-O-[4-[(5-chloro-2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


94
1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(3,5-difluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol


95
1,4:3,6-dianhydro-5-O-[4-[(3-chloro-4-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


96
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-2-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


97
1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol


98
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-5-chloro-2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


99
1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-{6-(methyloxy)-4-[(2,4,5-



trifluorophenyl)amino]quinazolin-7-yl}-D-iditol


100
1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-{6-(methyloxy)-4-[(2,4,6-



trifluorophenyl)amino]quinazolin-7-yl}-D-iditol


101
1,4:3,6-dianhydro-5-O-[4-({4-[(4-chlorophenyl)oxy]-3,5-difluorophenyl}amino)-



6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


102
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chloro-2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


103
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-2,3-dichlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


104
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chloro-5-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


105
1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(4,5-dichloro-2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol


106
1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-{6-(methyloxy)-4-[(2,3,4-



trichlorophenyl)amino]quinazolin-7-yl}-D-iditol


107
1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-{6-(methyloxy)-4-[(3,4,5-



trichlorophenyl)amino]quinazolin-7-yl}-D-iditol


108
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


109
1,4:3,6-dianhydro-5-O-[4-[(4-chloro-2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


110
1,4:3,6-dianhydro-5-O-[4-[(3-chloro-2-methylphenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


111
1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(3,4-difluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol


112
1,4:3,6-dianhydro-5-O-[4-[(2-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]-2-deoxy-2-fluoro-D-iditol


113
1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-[4-[(2-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-D-iditol


114
1,4:3,6-dianhydro-5-O-[4-[(3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]-2-deoxy-2-fluoro-D-iditol


115
1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-[4-[(4-fluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-D-iditol


116
1,4:3,6-dianhydro-5-O-[4-[(4-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]-2-deoxy-2-fluoro-D-iditol


117
1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(2,4-dichlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol


118
1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(2,5-dichlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol


119
1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(3,4-dichlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol


120
1,4:3,6-dianhydro-5-O-[4-[(2-bromo-4,6-difluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


121
1,4:3,6-dianhydro-5-O-[4-{[4-chloro-3-(trifluoromethyl)phenyl]amino}-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


122
1,4:3,6-dianhydro-5-O-[4-{[2-chloro-5-(trifluoromethyl)phenyl]amino}-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


123
1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-[4-{[2-fluoro-3-



(trifluoromethyl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-D-iditol


124
1,4:3,6-dianhydro-5-O-[4-{[2-bromo-5-(trifluoromethyl)phenyl]amino}-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


125
1,4:3,6-dianhydro-5-O-[4-{[2-bromo-4-(trifluoromethyl)phenyl]amino}-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


126
1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-[4-{[4-fluoro-2-



(trifluoromethyl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-D-iditol


127
1,4:3,6-dianhydro-5-O-[4-{[3-bromo-5-(trifluoromethyl)phenyl]amino}-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


128
1,4:3,6-dianhydro-5-O-[4-[(2-bromophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]-2-deoxy-2-fluoro-D-iditol


129
1,4:3,6-dianhydro-5-O-[4-[(3-bromophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]-2-deoxy-2-fluoro-D-iditol


130
1,4:3,6-dianhydro-5-O-[4-[(4-bromophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]-2-deoxy-2-fluoro-D-iditol


131
1,4:3,6-dianhydro-5-O-[4-[(3-bromo-4-methylphenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


132
1,4:3,6-dianhydro-5-O-[4-[(5-chloro-2-methylphenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


133
1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(3,5-dimethylphenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol


134
1,4:3,6-dianhydro-5-O-[4-{[2,5-bis(methyloxy)phenyl]amino}-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


135
1,4:3,6-dianhydro-5-O-[4-{[5-chloro-2,4-bis(methyloxy)phenyl]amino}-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


136
1,4:3,6-dianhydro-5-O-[4-{[4-chloro-2,5-bis(methyloxy)phenyl]amino}-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


137
1,4:3,6-dianhydro-5-O-[4-[(3-chloro-2,4-difluorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol


138
N-(3,4-dichlorophenyl)-7-[({5-[(dimethylamino)methyl]-1,2,4-oxadiazol-3-



yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine


139
N-(3,4-dichlorophenyl)-7-[({3-[(dimethylamino)methyl]-1,2,4-oxadiazol-5-



yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine


140
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({3-[(4-methylpiperazin-1-yl)methyl]-



1,2,4-oxadiazol-5-yl}methyl)oxy]quinazolin-4-amine


141
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(5-piperidin-4-yl-1,2,4-oxadiazol-3-



yl)methyl]oxy}quinazolin-4-amine


142
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[5-(1-methylpiperidin-4-yl)-1,2,4-



oxadiazol-3-yl]methyl}oxy)quinazolin-4-amine


143
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[3-(morpholin-4-ylmethyl)-1,2,4-



oxadiazol-5-yl]methyl}oxy)quinazolin-4-amine


144
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(morpholin-2-ylmethyl)oxy]quinazolin-



4-amine


145
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(5-piperidin-2-yl-1,2,4-oxadiazol-3-



yl)methyl]oxy}quinazolin-4-amine


146
N-(3,4-dichlorophenyl)-7-[({2-[(dimethylamino)methyl]-1,3-thiazol-4-



yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine


147
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(phenylmethyl)morpholin-2-



yl]methyl}oxy)quinazolin-4-amine


148
1,1-dimethylethyl 2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)morpholine-4-carboxylate


149
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[2-(morpholin-4-ylmethyl)-1,3-thiazol-



4-yl]methyl}oxy)quinazolin-4-amine


150
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({2-[(4-methylpiperazin-1-yl)methyl]-



1,3-thiazol-4-yl}methyl)oxy]quinazolin-4-amine


151
N-(3,4-dichlorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


152
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(1,4-oxazepan-2-



ylmethyl)oxy]quinazolin-4-amine


153
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(5-piperidin-3-yl-1,2,4-oxadiazol-3-



yl)methyl]oxy}quinazolin-4-amine


154
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[5-(1-methylpiperidin-2-yl)-1,2,4-



oxadiazol-3-yl]methyl}oxy)quinazolin-4-amine


155
N-(3,4-dichlorophenyl)-7-{[(4-methyl-1,4-oxazepan-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


156
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[5-(1-methylpiperidin-3-yl)-1,2,4-



oxadiazol-3-yl]methyl}oxy)quinazolin-4-amine


157
N-(3,4-dichlorophenyl)-7-({[5-(1,1-dimethylethyl)-1,2,4-oxadiazol-3-



yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


158
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(2-phenyl-1,3-thiazol-4-



yl)methyl]oxy}quinazolin-4-amine


159
7-[(2,1,3-benzothiadiazol-4-ylmethyl)oxy]-N-(3,4-dichlorophenyl)-6-



(methyloxy)quinazolin-4-amine


160
N-(3,4-dichlorophenyl)-7-{[(5-methylisoxazol-3-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


161
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(5-methyl-4-phenylisoxazol-3-



yl)methyl]oxy}quinazolin-4-amine


162
7-[(1,3-benzothiazol-2-ylmethyl)oxy]-N-(3,4-dichlorophenyl)-6-



(methyloxy)quinazolin-4-amine


163
7-[(2,1,3-benzoxadiazol-5-ylmethyl)oxy]-N-(3,4-dichlorophenyl)-6-



(methyloxy)quinazolin-4-amine


164
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[2-(2-thienyl)-1,3-thiazol-4-



yl]methyl}oxy)quinazolin-4-amine


165
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(1-phenyl-1H-pyrazol-4-



yl)methyl]oxy}quinazolin-4-amine


166
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({5-[3-(trifluoromethyl)phenyl]-1,2,4-



oxadiazol-3-yl}methyl)oxy]quinazolin-4-amine


167
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({5-[4-(trifluoromethyl)phenyl]-1,2,4-



oxadiazol-3-yl}methyl)oxy]quinazolin-4-amine


168
7-({[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]methyl}oxy)-N-(3,4-



dichlorophenyl)-6-(methyloxy)quinazolin-4-amine


169
7-({[6-bromo-2-(methyloxy)naphthalen-1-yl]methyl}oxy)-N-(3,4-dichlorophenyl)-



6-(methyloxy)quinazolin-4-amine


170
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(1,3-thiazol-4-ylmethyl)oxy]quinazolin-



4-amine


171
7-{[(6-chloropyridin-3-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-



(methyloxy)quinazolin-4-amine


172
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(pyridin-4-ylmethyl)oxy]quinazolin-4-



amine


173
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(2-methyl-1,3-thiazol-4-



yl)methyl]oxy}quinazolin-4-amine


174
7-{[(6-chloro-4H-1,3-benzodioxin-8-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-



(methyloxy)quinazolin-4-amine


175
7-{[(5-chloro-1-methyl-3-phenyl-1H-pyrazol-4-yl)methyl]oxy}-N-(3,4-



dichlorophenyl)-6-(methyloxy)quinazolin-4-amine


176
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[1-methyl-3-(trifluoromethyl)-1H-



thieno[2,3-c]pyrazol-5-yl]methyl}oxy)quinazolin-4-amine


177
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(3-phenylisoxazol-5-



yl)methyl]oxy}quinazolin-4-amine


178
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(2,4,6-



trimethylphenyl)methyl]oxy}quinazolin-4-amine


179
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(pyridin-3-ylmethyl)oxy]quinazolin-4-



amine


180
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({3-[4-(methyloxy)phenyl]isoxazol-5-



yl}methyl)oxy]quinazolin-4-amine


181
N-(3,4-dichlorophenyl)-7-({[5-[(2,4-dichlorophenyl)oxy]-1-methyl-3-



(trifluoromethyl)-1H-pyrazol-4-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


182
7-[(cyclopropylmethyl)oxy]-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-



amine


183
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(tetrahydrofuran-2-



ylmethyl)oxy]quinazolin-4-amine


184
7-(cyclopentyloxy)-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine


185
7-[(2-cyclohexylethyl)oxy]-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-



amine


186
7-[(cyclohexylmethyl)oxy]-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-



amine


187
7-[(cyclobutylmethyl)oxy]-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-



amine


188
N-(3,4-dichlorophenyl)-7-{[2-(1,3-dioxolan-2-yl)ethyl]oxy}-6-



(methyloxy)quinazolin-4-amine


189
N-(3,4-dichlorophenyl)-7-{[2-(1,3-dioxan-2-yl)ethyl]oxy}-6-



(methyloxy)quinazolin-4-amine


190
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(2-morpholin-4-ylethyl)oxy]quinazolin-



4-amine


191
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(2-pyrrolidin-1-ylethyl)oxy]quinazolin-



4-amine


192
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(2-piperidin-1-ylethyl)oxy]quinazolin-4-



amine


193
2-(2-{[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}ethyl)-



1H-isoindole-1,3(2H)-dione


194
methyl 6-O-[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-alpha-



D-glucopyranoside


195
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(2-morpholin-4-yl-2-



oxoethyl)oxy]quinazolin-4-amine


196
1,1-dimethylethyl 2-[3-({[4-[(3,4-dichlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]oxy}methyl)-1,2,4-oxadiazol-5-yl]piperidine-1-



carboxylate


197
1,1-dimethylethyl 4-[3-({[4-[(3,4-dichlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]oxy}methyl)-1,2,4-oxadiazol-5-yl]piperidine-1-



carboxylate


198
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(4-pyrrolidin-1-ylphenyl)-1,3-



thiazol-2-yl]methyl}oxy)quinazolin-4-amine


199
N-(3,4-dichlorophenyl)-7-[({4-[4-(diethylamino)phenyl]-1,3-thiazol-2-



yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine


200
5-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)-1,3-thiazol-4-yl]-2-hydroxybenzamide


201
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-pyridin-3-yl-1,3-thiazol-2-



yl)methyl]oxy}quinazolin-4-amine


202
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-pyridin-2-yl-1,3-thiazol-2-



yl)methyl]oxy}quinazolin-4-amine


203
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-pyridin-4-yl-1,3-thiazol-2-



yl)methyl]oxy}quinazolin-4-amine


204
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(2-morpholin-4-yl-1,3-thiazol-4-



yl)methyl]oxy}quinazolin-4-amine


205
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(3-morpholin-4-yl-1,2,4-oxadiazol-5-



yl)methyl]oxy}quinazolin-4-amine


206
N-(3,4-dichlorophenyl)-7-({[3-(dimethylamino)-1,2,4-oxadiazol-5-



yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


207
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({4-[(4-methylpiperazin-1-yl)methyl]-



1,3-thiazol-2-yl}methyl)oxy]quinazolin-4-amine


208
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(4,5,6,7-tetrahydro[1,3]thiazolo[5,4-



c]pyridin-2-ylmethyl)oxy]quinazolin-4-amine


209
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(morpholin-4-ylmethyl)-1,3-thiazol-



2-yl]methyl}oxy)quinazolin-4-amine


210
N-(3,4-dichlorophenyl)-7-[({4-[(4-methyl-1,4-diazepan-1-yl)methyl]-1,3-thiazol-2-



yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine


211
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(5-{[(phenylmethyl)oxy]methyl}-1,2,4-



oxadiazol-3-yl)methyl]oxy}quinazolin-4-amine


212
N-(3,4-dichlorophenyl)-7-{[(4-ethylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


213
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(2-piperidin-4-yl-1,3-thiazol-4-



yl)methyl]oxy}quinazolin-4-amine


214
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[2-(1-methylpiperidin-4-yl)-1,3-thiazol-



4-yl]methyl}oxy)quinazolin-4-amine


215
1,1-dimethylethyl 4-[5-({[4-[(3,4-dichlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]oxy}methyl)-1,2,4-oxadiazol-3-yl]piperazine-1-



carboxylate


217
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(3-piperazin-1-yl-1,2,4-oxadiazol-5-



yl)methyl]oxy}quinazolin-4-amine


218
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[3-(4-methylpiperazin-1-yl)-1,2,4-



oxadiazol-5-yl]methyl}oxy)quinazolin-4-amine


219
N-(3,4-dichlorophenyl)-7-({[5-(1-ethylpiperidin-2-yl)-1,2,4-oxadiazol-3-



yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


220
N-(3,4-dichlorophenyl)-7-({[3-(4-ethylpiperazin-1-yl)-1,2,4-oxadiazol-5-



yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


221
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({5-[4-(methyloxy)phenyl]-1,2,4-



oxadiazol-3-yl}methyl)oxy]quinazolin-4-amine


222
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({2-[4-(trifluoromethyl)phenyl]-1,3-



thiazol-4-yl}methyl)oxy]quinazolin-4-amine


223
7-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}oxy)-N-(3,4-dichlorophenyl)-6-



(methyloxy)quinazolin-4-amine


224
N-(3,4-dichlorophenyl)-7-({[5-(3,5-dimethylisoxazol-4-yl)-1,2,4-oxadiazol-3-



yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


225
7-{[(5-chloro-1-benzothien-3-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-



(methyloxy)quinazolin-4-amine


226
N-(3,4-dichlorophenyl)-7-[({3-[4-(1,1-dimethylethyl)phenyl]-1,2,4-oxadiazol-5-



yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine


227
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({5-[2-(methyloxy)phenyl]-1,2,4-



oxadiazol-3-yl}methyl)oxy]quinazolin-4-amine


228
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[5-(4-methylphenyl)-1,3,4-oxadiazol-2-



yl]methyl}oxy)quinazolin-4-amine


229
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[1-(phenylmethyl)-1H-imidazol-2-



yl]methyl}oxy)quinazolin-4-amine


230
N-(3,4-dichlorophenyl)-7-({[3-(2,6-dichlorophenyl)-5-methylisoxazol-4-



yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


231
N-(3,4-dichlorophenyl)-7-{[(6-fluoro-4H-1,3-benzodioxin-8-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


232
7-{[(3,5-dibromophenyl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-



(methyloxy)quinazolin-4-amine


233
N-(3,4-dichlorophenyl)-7-{[(2,6-difluorophenyl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


234
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({3-[(pyridin-2-ylsulfonyl)methyl]-



1,2,4-oxadiazol-5-yl}methyl)oxy]quinazolin-4-amine


235
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(5-phenyl-1,2,4-oxadiazol-3-



yl)methyl]oxy}quinazolin-4-amine


236
7-({[4-chloro-2-(trifluoromethyl)quinolin-6-yl]methyl}oxy)-N-(3,4-



dichlorophenyl)-6-(methyloxy)quinazolin-4-amine


237
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[2-(1-methylpyrrolidin-2-



yl)ethyl]oxy}quinazolin-4-amine


238
N-(3,4-dichlorophenyl)-7-({[5-(1-ethylpiperidin-4-yl)-1,2,4-oxadiazol-3-



yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


239
N-(3,4-dichlorophenyl)-7-({[5-(1-ethylpiperidin-3-yl)-1,2,4-oxadiazol-3-



yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


240
N-(3,4-dichlorophenyl)-7-({[2-(dimethylamino)-1,3-thiazol-4-yl]methyl}oxy)-6-



(methyloxy)quinazolin-4-amine


241
N-(3,4-dichlorophenyl)-7-{[(4-ethyl-1,4-oxazepan-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


242
N-(3,4-dichlorophenyl)-7-({[2-(1-ethylpiperidin-4-yl)-1,3-thiazol-4-



yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


243
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({3-[(2S)-pyrrolidin-2-yl]-1,2,4-



oxadiazol-5-yl}methyl)oxy]quinazolin-4-amine


244
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({2-[(2S)-pyrrolidin-2-yl]-1,3-thiazol-4-



yl}methyl)oxy]quinazolin-4-amine


245
[4-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-



1,3-thiazol-2-yl]methyl benzoate


246
[4-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-



1,3-thiazol-2-yl]methanol


247
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(5-methyl-4,5,6,7-



tetrahydro[1,3]thiazolo[5,4-c]pyridin-2-yl)methyl]oxy}quinazolin-4-amine


248
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({2-[(4S)-1,3-thiazolidin-4-yl]-1,3-



thiazol-4-yl}methyl)oxy]quinazolin-4-amine


249
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(2-piperidin-2-yl-1,3-thiazol-4-



yl)methyl]oxy}quinazolin-4-amine


250
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[2-(1-methylpiperidin-2-yl)-1,3-thiazol-



4-yl]methyl}oxy)quinazolin-4-amine


251
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(2-piperidin-3-yl-1,3-thiazol-4-



yl)methyl]oxy}quinazolin-4-amine


252
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[2-(1-methylpiperidin-3-yl)-1,3-thiazol-



4-yl]methyl}oxy)quinazolin-4-amine


253
N-(3,4-dichlorophenyl)-7-({[2-(1-ethylpiperidin-2-yl)-1,3-thiazol-4-



yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


254
N-(3,4-dichlorophenyl)-7-({[2-(1-ethylpiperidin-3-yl)-1,3-thiazol-4-



yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


255
N-(3,4-dichlorophenyl)-7-[({3-[(2S)-1-ethylpyrrolidin-2-yl]-1,2,4-oxadiazol-5-



yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine


256
N-(3,4-dichlorophenyl)-7-[({2-[(2S)-1-ethylpyrrolidin-2-yl]-1,3-thiazol-4-



yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine


257
N-(3,4-dichlorophenyl)-7-{[(5-ethyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridin-



2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine


258
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-propyl-1,4-oxazepan-2-



yl)methyl]oxy}quinazolin-4-amine


259
7-({[4-(cyclopropylmethyl)-1,4-oxazepan-2-yl]methyl}oxy)-N-(3,4-



dichlorophenyl)-6-(methyloxy)quinazolin-4-amine


260
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({4-[2-(methyloxy)ethyl]-1,4-oxazepan-



2-yl}methyl)oxy]quinazolin-4-amine


261
N-(3,4-dichlorophenyl)-7-({[4-(1-methylethyl)-1,4-oxazepan-2-yl]methyl}oxy)-6-



(methyloxy)quinazolin-4-amine


262
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(2-piperazin-1-yl-1,3-thiazol-4-



yl)methyl]oxy}quinazolin-4-amine


263
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(5-pyrrolidin-2-yl-1,2,4-oxadiazol-3-



yl)methyl]oxy}quinazolin-4-amine


264
N-(3,4-dichlorophenyl)-7-({[5-(1-ethylpyrrolidin-2-yl)-1,2,4-oxadiazol-3-



yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


265
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({3-[(2S)-1-methylpyrrolidin-2-yl]-



1,2,4-oxadiazol-5-yl}methyl)oxy]quinazolin-4-amine


266
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({2-[(2S)-1-methylpyrrolidin-2-yl]-1,3-



thiazol-4-yl}methyl)oxy]quinazolin-4-amine


267
N-(3,4-dichlorophenyl)-7-({[2-(4-ethylpiperazin-1-yl)-1,3-thiazol-4-



yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


268
N-(3,4-dichlorophenyl)-7-{[(1,4-dimethylpiperazin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


269
7-{[(4-cyclopentylmorpholin-2-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-



(methyloxy)quinazolin-4-amine


270
N-(3,4-dichlorophenyl)-7-({[4-(1-methylethyl)morpholin-2-yl]methyl}oxy)-6-



(methyloxy)quinazolin-4-amine


271
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(3-phenylpropyl)morpholin-2-



yl]methyl}oxy)quinazolin-4-amine


272
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({4-[2-(methyloxy)ethyl]morpholin-2-



yl}methyl)oxy]quinazolin-4-amine


273
ethyl 2-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)morpholin-4-yl]propanoate


274
N-(3,4-dichlorophenyl)-7-{[(4-hex-5-en-1-ylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


275
2-({2-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)morpholin-4-yl]ethyl}oxy)ethanol


276
methyl 3-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)morpholin-4-yl]propanoate


277
6-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)morpholin-4-yl]hexanenitrile


278
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(tetrahydro-2H-pyran-2-



ylmethyl)morpholin-2-yl]methyl}oxy)quinazolin-4-amine


279
4-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)morpholin-4-yl]butanenitrile


280
N-(3,4-dichlorophenyl)-7-[({4-[(4-fluorophenyl)methyl]morpholin-2-



yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine


281
methyl 5-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)morpholin-4-yl]pentanoate


282
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-oct-7-en-1-ylmorpholin-2-



yl)methyl]oxy}quinazolin-4-amine


283
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-propylmorpholin-2-



yl)methyl]oxy}quinazolin-4-amine


284
6-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)morpholin-4-yl]hexan-1-ol


285
7-{[(4-acetylmorpholin-2-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-



(methyloxy)quinazolin-4-amine


286
7-({[4-(cyclopropylmethyl)morpholin-2-yl]methyl}oxy)-N-(3,4-dichlorophenyl)-6-



(methyloxy)quinazolin-4-amine


287
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-prop-2-yn-1-ylmorpholin-2-



yl)methyl]oxy}quinazolin-4-amine


288
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-pyridin-4-ylmorpholin-2-



yl)methyl]oxy}quinazolin-4-amine


289
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(pyridin-2-ylmethyl)morpholin-2-



yl]methyl}oxy)quinazolin-4-amine


290
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-pent-2-yn-1-ylmorpholin-2-



yl)methyl]oxy}quinazolin-4-amine


291
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[2-(4-methylpiperazin-1-yl)-1,3-



thiazol-4-yl]methyl}oxy)quinazolin-4-amine


292
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[5-(1-methylpyrrolidin-2-yl)-1,2,4-



oxadiazol-3-yl]methyl}oxy)quinazolin-4-amine


293
N-(3-chloro-4-fluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


294
7-{[(4-butyl-1,4-oxazepan-2-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-



(methyloxy) quinazolin-4-amine


295
(3,4-dichlorophenyl)[7-(methyloxy)-6-({[4-(2-methylpropyl)-1,4-oxazepan-2-



yl]methyl}oxy) quinazolin-4-amine


296
7-{[(4-acetyl-1-ethylpiperazin-2-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-



(methyloxy)quinazolin-4-amine


297
(3,4-dichlorophenyl)(6-(methyloxy)-7-{[(4-pentyl-1,4-oxazepan-2-yl)methyl]oxy}



quinazolin-4-amine


298
(3,4-dichlorophenyl)[6-(methyloxy)-7-({[4-(tetrahydro-2H-pyran-2-ylmethyl)-1,4-



oxazepan-2-yl]methyl}oxy)quinazolin-4-amine


299
(3,4-dichlorophenyl)[6-(methyloxy)-7-({[4-(3-thienylmethyl)-1,4-oxazepan-2-



yl]methyl}oxy) quinazolin-4-amine


300
N-[4-chloro-2,5-bis(methyloxy)phenyl]-7-{[(4-methylmorpholin-2-



yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine


301
N-(3-bromo-2-methylphenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


302
7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)-N-(3,4,5-



trichlorophenyl)quinazolin-4-amine


303
N-(3-chloro-2-methylphenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


304
N-(3,4-dichlorophenyl)-7-{[(4-ethanimidoyl-1,4-oxazepan-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


305
N-(4-bromo-2-fluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


306
N-(5-chloro-2-fluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


307
N-(4-chloro-2-fluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


308
N-(2,4-dichlorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


309
N-(2,4-dibromophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


310
7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)-N-(2,3,4-



trichlorophenyl)quinazolin-4-amine


311
N-(3,4-dichlorophenyl)-7-{[(1-ethyl-4-methylpiperazin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


312
N′-cyano-2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)morpholine-4-carboximidamide


313
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[2-(pyrrolidin-1-ylmethyl)-1,3-thiazol-



4-yl]methyl}oxy)quinazolin-4-amine


314
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(tetrahydro-2H-pyran-4-



yl)morpholin-2-yl]methyl}oxy)quinazolin-4-amine


315
N-(3,4-dichlorophenyl)-7-({[4-(2-ethylbutyl)morpholin-2-yl]methyl}oxy)-6-



(methyloxy)quinazolin-4-amine


316
7-({[4-(cyclohexylmethyl)morpholin-2-yl]methyl}oxy)-N-(3,4-dichlorophenyl)-6-



(methyloxy)quinazolin-4-amine


317
2-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)morpholin-4-yl]ethanol


318
7-{[(4-but-2-yn-1-ylmorpholin-2-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-



(methyloxy)quinazolin-4-amine


319
7-{[(4-cyclobutylmorpholin-2-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-



(methyloxy)quinazolin-4-amine


320
N-(3,4-dichlorophenyl)-7-[({4-[2-(1,3-dioxolan-2-yl)ethyl]morpholin-2-



yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine


321
7-({[4-(2-cyclohexylethyl)morpholin-2-yl]methyl}oxy)-N-(3,4-dichlorophenyl)-6-



(methyloxy)quinazolin-4-amine


322
N-(3,4-dichlorophenyl)-7-[({4-[2-(1,3-dioxan-2-yl)ethyl]morpholin-2-



yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine


323
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-pent-4-en-1-ylmorpholin-2-



yl)methyl]oxy}quinazolin-4-amine


324
N-(3,4-dichlorophenyl)-7-[({4-[(2R)-2-methylbutyl]morpholin-2-yl}methyl)oxy]-



6-(methyloxy)quinazolin-4-amine


325
N-(3,4-dichlorophenyl)-7-({[4-(4-fluorobutyl)morpholin-2-yl]methyl}oxy)-6-



(methyloxy)quinazolin-4-amine


326
3-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)morpholin-4-yl]butan-2-one


327
1-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)morpholin-4-yl]butan-2-one


328
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-pentylmorpholin-2-



yl)methyl]oxy}quinazolin-4-amine


329
N-(3,4-dichlorophenyl)-7-{[(4-hexylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


330
N-(3,4-dichlorophenyl)-7-{[(4-heptylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


331
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-octylmorpholin-2-



yl)methyl]oxy}quinazolin-4-amine


332
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(2-phenylethyl)morpholin-2-



yl]methyl}oxy)quinazolin-4-amine


333
7-{[(4-butylmorpholin-2-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-



(methyloxy)quinazolin-4-amine


334
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-prop-2-en-1-ylmorpholin-2-



yl)methyl]oxy}quinazolin-4-amine


335
2-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)morpholin-4-yl]-1-phenylethanone


336
N-(3,4-dichlorophenyl)-7-({[4-(2-fluoroethyl)morpholin-2-yl]methyl}oxy)-6-



(methyloxy)quinazolin-4-amine


337
N-(3,4-dichlorophenyl)-7-({[4-(3-methylbut-2-en-1-yl)morpholin-2-



yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


338
7-[({4-[(2E)-3-bromoprop-2-en-1-yl]morpholin-2-yl}methyl)oxy]-N-(3,4-



dichlorophenyl)-6-(methyloxy)quinazolin-4-amine


339
2-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)morpholin-4-yl]acetamide


340
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({4-[3-(tetrahydro-2H-pyran-2-



yloxy)propyl]-1,4-oxazepan-2-yl}methyl)oxy]quinazolin-4-amine


341
N-(3,4-dichlorophenyl)-7-({[4-(3-methylbutyl)-1,4-oxazepan-2-yl]methyl}oxy)-6-



(methyloxy)quinazolin-4-amine


342
7-({[4-(cyclohexylmethyl)-1,4-oxazepan-2-yl]methyl}oxy)-4-[(3,4-



dichlorophenyl)methyl]-6-(methyloxy)quinazoline


343
7-({[4-(2-cyclohexylethyl)-1,4-oxazepan-2-yl]methyl}oxy)-4-[(3,4-



dichlorophenyl)methyl]-6-(methyloxy)quinazoline


345
N-(3,4-dichlorophenyl)-7-({[4-(2-ethylbutyl)-1,4-oxazepan-2-yl]methyl}oxy)-6-



(methyloxy)quinazolin-4-amine


346
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(methylsulfonyl)-1,4-oxazepan-2-



yl]methyl}oxy)quinazolin-4-amine


347
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(1-methylpiperidin-4-yl)morpholin-



2-yl]methyl}oxy)quinazolin-4-amine


348
N-(3-chloro-2-fluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


349
N′-cyano-2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)-1,4-oxazepane-4-carboximidamide


350
N-(3-bromo-4-methylphenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


351
N-(3,4-dichlorophenyl)-7-{[(1,4-diethylpiperazin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


352
4-({[4-[(4-bromo-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)-N′-cyanopiperidine-1-carboximidamide


353
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(methylsulfonyl)morpholin-2-



yl]methyl}oxy)quinazolin-4-amine


354
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({4-[(phenylmethyl)sulfonyl]morpholin-



2-yl}methyl)oxy]quinazolin-4-amine


355
N-(3,4-dichlorophenyl)-7-[({4-[(4-fluorophenyl)sulfonyl]morpholin-2-



yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine


356
N-(3,4-dichlorophenyl)-7-({[4-(ethylsulfonyl)morpholin-2-yl]methyl}oxy)-6-



(methyloxy)quinazolin-4-amine


357
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(phenylsulfonyl)morpholin-2-



yl]methyl}oxy)quinazolin-4-amine


358
7-[({4-[(3-chloropropyl)sulfonyl]morpholin-2-yl}methyl)oxy]-N-(3,4-



dichlorophenyl)-6-(methyloxy)quinazolin-4-amine


359
7-({[4-(butylsulfonyl)morpholin-2-yl]methyl}oxy)-N-(3,4-dichlorophenyl)-6-



(methyloxy)quinazolin-4-amine


360
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({4-[(4-



methylphenyl)sulfonyl]morpholin-2-yl}methyl)oxy]quinazolin-4-amine


361
N-(3,4-dichlorophenyl)-7-[({4-[(3,5-dimethylisoxazol-4-yl)carbonyl]morpholin-2-



yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine


362
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-{[3-



(methyloxy)phenyl]acetyl}morpholin-2-yl)methyl]oxy}quinazolin-4-amine


363
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(2-methylpentanoyl)morpholin-2-



yl]methyl}oxy)quinazolin-4-amine


364
7-[({4-[(4-butylphenyl)carbonyl]morpholin-2-yl}methyl)oxy]-N-(3,4-



dichlorophenyl)-6-(methyloxy)quinazolin-4-amine


365
7-[({4-[(4-chlorophenyl)acetyl]morpholin-2-yl}methyl)oxy]-N-(3,4-



dichlorophenyl)-6-(methyloxy)quinazolin-4-amine


366
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(2-propylpentanoyl)morpholin-2-



yl]methyl}oxy)quinazolin-4-amine


367
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(4-methylpentanoyl)morpholin-2-



yl]methyl}oxy)quinazolin-4-amine


368
N-(3,4-dichlorophenyl)-7-[({4-[(2,5-difluorophenyl)carbonyl]morpholin-2-



yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine


369
7-({[4-(cyclopentylcarbonyl)morpholin-2-yl]methyl}oxy)-N-(3,4-dichlorophenyl)-



6-(methyloxy)quinazolin-4-amine


370
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(2-phenylbutanoyl)morpholin-2-



yl]methyl}oxy)quinazolin-4-amine


371
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({4-[(2,3,6-



trifluorophenyl)carbonyl]morpholin-2-yl}methyl)oxy]quinazolin-4-amine


372
N-(3,4-dichlorophenyl)-7-({[4-(furan-3-ylcarbonyl)morpholin-2-yl]methyl}oxy)-6-



(methyloxy)quinazolin-4-amine


373
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-propanoylmorpholin-2-



yl)methyl]oxy}quinazolin-4-amine


374
N-(3,4-dichlorophenyl)-7-{[(4-hexanoylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


375
N-(3,4-dichlorophenyl)-7-({[4-(2-ethylhexanoyl)morpholin-2-yl]methyl}oxy)-6-



(methyloxy)quinazolin-4-amine


376
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(3-phenylpropanoyl)morpholin-2-



yl]methyl}oxy)quinazolin-4-amine


377
N-(3,4-dichlorophenyl)-7-({[4-(2,2-dimethylpropanoyl)morpholin-2-



yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


378
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(naphthalen-1-



ylcarbonyl)morpholin-2-yl]methyl}oxy)quinazolin-4-amine


379
7-[({4-[(2-chloropyridin-3-yl)carbonyl]morpholin-2-yl}methyl)oxy]-N-(3,4-



dichlorophenyl)-6-(methyloxy)quinazolin-4-amine


380
7-[({4-[(6-chloropyridin-3-yl)carbonyl]morpholin-2-yl}methyl)oxy]-N-(3,4-



dichlorophenyl)-6-(methyloxy)quinazolin-4-amine


381
7-({[4-(1,3-benzodioxol-5-ylcarbonyl)morpholin-2-yl]methyl}oxy)-N-(3,4-



dichlorophenyl)-6-(methyloxy)quinazolin-4-amine


382
N-(3,4-dichlorophenyl)-6-[(1-methylethyl)oxy]-7-[(morpholin-2-



ylmethyl)oxy]quinazolin-4-amine


383
N-(3,4-dichlorophenyl)-6-{[2-(methyloxy)ethyl]oxy}-7-[(morpholin-2-



ylmethyl)oxy]quinazolin-4-amine


384
N-(3,4-dichlorophenyl)-6-(ethyloxy)-7-[(morpholin-2-ylmethyl)oxy]quinazolin-4-



amine


385
N-(3,4-dichlorophenyl)-6-(ethyloxy)-7-{[(4-methylmorpholin-2-



yl)methyl]oxy}quinazolin-4-amine


386
N-(4-bromo-2-methylphenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


387
N-(4-chloro-3-methylphenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


388
N′-cyano-2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)-N-methylmorpholine-4-carboximidamide


389
N-(4-bromo-3-chlorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


390
N-(3,4-dichlorophenyl)-6-[(1-methylethyl)oxy]-7-{[(4-methylmorpholin-2-



yl)methyl]oxy}quinazolin-4-amine


391
N-(3,4-dichlorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-{[2-



(methyloxy)ethyl]oxy}quinazolin-4-amine


392
N-(4-bromo-2-chlorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


393
7-{[(4-acetyl-1,4-oxazepan-2-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-



(methyloxy)quinazolin-4-amine


394
4-[(3,4-dichlorophenyl)amino]-7-{[(4-methylmorpholin-2-



yl)methyl]oxy}quinazolin-6-ol


395
N-(3-bromo-4-chlorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


396
3-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)morpholin-4-yl]-3-oxopropanoic acid


397
methyl 4-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)morpholin-4-yl]-4-oxobutanoate


398
N-(3,4-dichlorophenyl)-7-{[(4-methylmorpholin-3-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


399
N-(3-bromo-2-chlorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


400
N′-cyano-2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)-N-[2-(methyloxy)ethyl]morpholine-4-carboximidamide


401
N′-cyano-2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)-N-ethylmorpholine-4-carboximidamide


402
[(1E)-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)morpholin-4-yl](piperidin-1-yl)methylidene]cyanamide


403
[(1E)-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)morpholin-4-yl](pyrrolidin-1-yl)methylidene]cyanamide


404
[(1E)-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)morpholin-4-yl](4-methylpiperazin-1-yl)methylidene]cyanamide


405
N-(3,4-dichlorophenyl)-7-{[(6-ethyl-4,6-dimethylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


406
N-(4-bromo-3-methylphenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


407
N-(3,4-dichlorophenyl)-7-{[(6,6-dimethylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


408
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4,6,6-trimethylmorpholin-2-



yl)methyl]oxy}quinazolin-4-amine


409
N-(3,4-dichlorophenyl)-7-{[2-(5,5-dimethylmorpholin-2-yl)ethyl]oxy}-6-



(methyloxy)quinazolin-4-amine


410
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[2-(4,5,5-trimethylmorpholin-2-



yl)ethyl]oxy}quinazolin-4-amine


411
1,1-dimethylethyl 2-(2-{[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-



7-yl]oxy}ethyl)-5,5-dimethylmorpholine-4-carboxylate


412
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4,5,5-trimethylmorpholin-2-



yl)methyl]oxy}quinazolin-4-amine


413
N-(4-bromo-2,3-dichlorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


414
N-(4,5-dichloro-2-fluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


415
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[2-(4,6,6-trimethylmorpholin-2-



yl)ethyl]oxy}quinazolin-4-amine


416
N-(4-bromo-2,3-difluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


417
N-(4-bromo-2,5-difluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


418
N-(4-bromo-3,5-difluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


419
N-(3,4-dichloro-2-methylphenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


420
N-(3,4-dichlorophenyl)-7-({[(2R,5S,6S)-5,6-dimethylmorpholin-2-yl]methyl}oxy)-



6-(methyloxy)quinazolin-4-amine


421
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[(2R,5S,6S)-4,5,6-trimethylmorpholin-



2-yl]methyl}oxy)quinazolin-4-amine


422
N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[(2S,5S,6S)-4,5,6-trimethylmorpholin-



2-yl]methyl}oxy)quinazolin-4-amine


423
N-(4-bromo-3-chloro-2-methylphenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-



6-(methyloxy)quinazolin-4-amine


424
N-(4-bromo-5-chloro-2-fluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-



6-(methyloxy)quinazolin-4-amine


425
N-(4-bromo-3-chloro-2-fluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-



6-(methyloxy)quinazolin-4-amine


426
N-(3,4-dichloro-2-fluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


427
N-(3-chloro-2,4-difluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


428
N-(2,3-dichloro-4-methylphenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-



(methyloxy)quinazolin-4-amine


429
6-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-



3,3,4-trimethylmorpholin-2-one


430
N-(4-bromo-2,3-dichlorophenyl)-6-(methyloxy)-7-{[(4,5,5-trimethylmorpholin-2-



yl)methyl]oxy}quinazolin-4-amine


431
N-(4-bromo-5-chloro-2-fluorophenyl)-6-(methyloxy)-7-{[(4,5,5-



trimethylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine


432
N-(4,5-dichloro-2-fluorophenyl)-6-(methyloxy)-7-{[(4,5,5-trimethylmorpholin-2-



yl)methyl]oxy}quinazolin-4-amine


433
N-(3,4-dichloro-2-fluorophenyl)-6-(methyloxy)-7-{[(4,5,5-trimethylmorpholin-2-



yl)methyl]oxy}quinazolin-4-amine


434
N-(4-bromo-3-chloro-2-fluorophenyl)-6-(methyloxy)-7-{[(4,5,5-



trimethylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine


435
N-(3-chloro-2,4-difluorophenyl)-6-(methyloxy)-7-{[(4,5,5-trimethylmorpholin-2-



yl)methyl]oxy}quinazolin-4-amine


436
(6S)-6-({[4-[(4-bromo-3-chloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-



7-yl]oxy}methyl)-4-methylpiperazin-2-one


437
(6S)-6-({[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)-4-methylpiperazin-2-one


438
(6S)-6-({[4-[(4-bromo-3-chloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-



7-yl]oxy}methyl)-1,4-dimethylpiperazin-2-one


439
(6S)-6-({[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-



yl]oxy}methyl)-1,4-dimethylpiperazin-2-one


440
N-(4-bromo-3-chlorophenyl)-7-{[(3a′S,4R,6′S,6a′R)-2,2-



dimethyltetrahydrospiro[1,3-dioxolane-4,3′-furo[3,2-b]furan]-6′-yl]oxy}-6-



(methyloxy)quinazolin-4-amine


441
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-O-methyl-5-C-[(methyloxy)methyl]-L-glucitol


442
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-O-(methylsulfonyl)-L-glucitol


443
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-L-glucitol


444
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-S-methyl-5-thio-D-iditol


445
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-morpholin-4-yl-D-iditol


446
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-(4-methylpiperazin-1-yl)-D-iditol


447
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-pyrrolidin-1-yl-D-iditol


448
2-O-acetyl-1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-D-iditol


449
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-D-iditol


450
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-(methylsulfonyl)-D-iditol


451
2-amino-1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-D-iditol


452
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-(dimethylamino)-D-iditol


453
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-(diethylamino)-D-iditol


454
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-piperidin-1-yl-D-iditol


455
2-(acetylamino)-1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-D-iditol


456
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-O-methyl-5-C-(trifluoromethyl)-L-glucitol


457
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-[(methylsulfonyl)amino]-D-iditol


458
N-(4-bromo-3-chlorophenyl)-6-(methyloxy)-7-[(1-methylpyrrolidin-3-



yl)oxy]quinazolin-4-amine


459
N-(4-bromo-3-chlorophenyl)-6-(methyloxy)-7-[(3R)-tetrahydrofuran-3-



yloxy]quinazolin-4-amine


460
N-(4-bromo-3-chlorophenyl)-6-(methyloxy)-7-{[(3S,4R)-4-



(methyloxy)tetrahydrofuran-3-yl]oxy}quinazolin-4-amine


461
1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-(6-(methyloxy)-4-{[4-(4-



methylpiperazin-1-yl)phenyl]amino}quinazolin-7-yl)-D-iditol


462
1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-[4-{[3-fluoro-4-(4-methylpiperazin-1-



yl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-D-iditol


463
1,4:3,6-dianhydro-2-deoxy-5-O-[4-{[2,3-dichloro-4-(4-methylpiperazin-1-



yl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol


464
1,4:3,6-dianhydro-2-deoxy-5-O-[4-{[3,4-dichloro-2-(4-methylpiperazin-1-



yl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol


465
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-C-(trifluoromethyl)-D-glucitol


466
(3,4-dichlorophenyl)[6-(methyloxy)-7-({[4-(tetrahydrofuran-2-ylmethyl)-1,4-



oxazepan-2-yl]methyl}oxy)quinazolin-4-amine


467
N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta-



[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


468
N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-



penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


469
N-(3-chloro-2,4-difluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta-



[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


470
N-(4,5-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-



penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


471
N-(4-bromo-5-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-



penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


472
N-(4-bromo-2,3-dichlorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-



penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


473
N-(3,4-dichlorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-



5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


474
N-(3,4-dichlorophenyl)-7-[(2-{[(3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-



yl]amino}ethyl)oxy]-6-(methyloxy)quinazolin-4-amine


475
N-(3,4-dichlorophenyl)-7-({2-[(3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-



yl]ethyl}oxy)-6-(methyloxy)quinazolin-4-amine


476
N-(3,4-dichlorophenyl)-7-({[(3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-



yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine


477
N-(3,4-dichlorophenyl)-7-{[(3-exo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]oxy}-6-



(methyloxy)quinazolin-4-amine


478
1,4:3,6-Dianhydro-5-O-[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-



7-yl]-2-O-methyl-D-glucitol


479
1,4:3,6-dianhydro-5-O-{4-[(3-chloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-



7-yl}-2-deoxy-2-fluoro-L-iditol


480
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-O-(methylsulfonyl)-D-glucitol


481
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-D-glucitol


482
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-S-methyl-5-thio-L-iditol


483
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-morpholin-4-yl-L-iditol


484
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-(4-methylpiperazin-1-yl)-L-iditol


485
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-pyrrolidin-1-yl-L-iditol


486
2-O-acetyl-1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-L-iditol


487
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-L-iditol


488
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-(methylsulfonyl)-L-iditol


489
2-amino-1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-L-iditol


490
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-(dimethylamino)-L-iditol


491
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-(diethylamino)-L-iditol


492
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-piperidin-1-yl-L-iditol


493
2-(acetylamino)-1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-L-iditol


494
1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-O-methyl-5-C-(trifluoromethyl)-D-glucitol


495
1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-2-deoxy-2-[(methylsulfonyl)amino]-L-iditol


496
1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-(6-(methyloxy)-4-{[4-(4-



methylpiperazin-1-yl)phenyl]amino}quinazolin-7-yl)-L-iditol


497
1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-[4-{[3-fluoro-4-(4-methylpiperazin-1-



yl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-L-iditol


498
1,4:3,6-dianhydro-2-deoxy-5-O-[4-{[2,3-dichloro-4-(4-methylpiperazin-1-



yl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-2-fluoro-L-iditol


499
1,4:3,6-dianhydro-2-deoxy-5-O-[4-{[3,4-dichloro-2-(4-methylpiperazin-1-



yl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-2-fluoro-L-iditol


500
1,4:3,6-Dianhydro-5-O-[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-



7-yl]-2-O-methyl-D-glucitol


501
1,4:3,6-Dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-



(methyloxy)quinazolin-7-yl]-5-O-methyl-L-glucitol









The Compounds in Table 5a can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 5a can be used to practice the invention.











Entry
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552






 


553






 


554






 


555






 


556






 


557






 


558






 


559






 


560






 


561






 


562






 


563






 


564






 


565






 


566






 


567






 


568






 


569






 


570






 


571






 


572













The Compounds in Table 5b can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 5b can be used to practice the invention.












Entry
Structure
Name







573




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-N6-[3-(diethylamino)propyl]- N2-{[3-(1-methylethyl)isoxazol-5- yl]methyl}pyrimidine-2,4,6- triamine


 


574




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-N6-[2-(diethylamino)ethyl]-N2- {[3-(1-methylethyl)isoxazol-5- yl]methyl}pyrimidine-2,4,6- triamine


 


575




N2-{[3-(1-methylethyl)isoxazol-5- yl]methyl}-N4-[5-(1-methylethyl)- 1H-pyrazol-3-yl]-6-[(3S)-3- methylpiperazin-1-yl]pyrimidine- 2,4-diamine


 


576




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-6-{[2- (dimethylamino)ethyl]oxy}-N2- {[3-(1-methylethyl)isoxazol-5- yl]methyl}pyrimidine-2,4-diamine


 


577




N4-[3-(1-methylethyl)-1H- pyrazol-5-yl]-6-[(1- methylpyrrolidin-3-yl)oxy]-N2- [(3-phenylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


578




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-N2-{[3-(1- methylethyl)isoxazol-5- yl]methyl}-6-[(1- methylpyrrolidin-3- yl)oxy]pyrimidine-2,4-diamine


 


579




N2-{[3-(1-methylethyl)isoxazol-5- yl]methyl}-N4-[3-(1-methylethyl)- 1H-pyrazol-5-yl]-6-[(1- methylpyrrolidin-3- yl)oxy]pyrimidine-2,4-diamine


 


580




N4-[2-(diethylamino)ethyl]-N2- {[3-(1-methylethyl)isoxazol-5- yl]methyl}-N6-[5-(1-methylethyl)- 1H-pyrazol-3-yl]pyrimidine-2,4,6- triamine


 


581




N2-{[3-(1-methylethyl)isoxazol-5- yl]methyl}-N4-[5-(1-methylethyl)- 1H-pyrazol-3-yl]pyrimidine-2,4- diamine


 


582




N4-[5-(1-methylethyl)-1H- pyrazol-3-yl]-6-[(1- methylpiperidin-3-yl)oxy]-N2-[(3- phenylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


583




N2-{[3-(1-methylethyl)isoxazol-5- yl]methyl}-N4-[5-(1-methylethyl)- 1H-pyrazol-3-yl]-6-[(1- methylpiperidin-3- yl)oxy]pyrimidine-2,4-diamine


 


584




N-(5-cyclopropyl-1H-pyrazol-3- yl)-6-methyl-2-{[(3- phenylisoxazol-5- yl)methyl]oxy}pyrimidin-4-amine


 


585




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-6-methyl-N2-[(4-phenyl-1H- imidazol-2-yl)methyl]pyrimidine- 2,4-diamine


 


586




6-{[2-(dimethylamino)ethyl]oxy}- N2-{[3-(1-methylethyl)isoxazol-5- yl]methyl}-N4-[5-(1-methylethyl)- 1H-pyrazol-3-yl]pyrimidine-2,4- diamine


 


587




N2-{[3-(1-methylethyl)isoxazol-5- yl]methyl}-N4-[5-(1-methylethyl)- 1H-pyrazol-3-yl]-6-[(2- morpholin-4- ylethyl)oxy]pyrimidine-2,4- diamine


 


588




N4-[5-(1-methylethyl)-1H- pyrazol-3-yl]-6-[(2-morpholin-4- ylethyl)oxy]-N2-[(3- phenylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


589




N4-[3-(1-methylethyl)-1H- pyrazol-5-yl]-N2-[(3- phenylisoxazol-5-yl)methyl]-6- [(2-piperidin-1- ylethyl)oxy]pyrimidine-2,4- diamine


 


590




N4-[3-(diethylamino)propyl]-N2- {[3-(1-methylethyl)isoxazol-5- yl]methyl}-N6-[5-(1-methylethyl)- 1H-pyrazol-3-yl]pyrimidine-2,4,6- triamine


 


591




N4-[5-(1-methylethyl)-1H- pyrazol-3-yl]-6-[(3S)-3- methylpiperazin-1-yl]-N2-[(3- phenylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


592




N4-[2-(diethylamino)ethyl]-N6-[5- (1-methylethyl)-1H-pyrazol-3-yl]- N2-[(3-phenylisoxazol-5- yl)methyl]pyrimidine-2,4,6- triamine


 


593




N4-[5-(1-methylethyl)-1H- pyrazol-3-yl]-6-[(1- methylpiperidin-4-yl)oxy]-N2-[(3- phenylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


594




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-N2-{[3-(1- methylethyl)isoxazol-5- yl]methyl}-6-[(2-morpholin-4- ylethyl)oxy]pyrimidine-2,4- diamine


 


595




N2-{[3-(1-methylethyl)isoxazol-5- yl]methyl}-N4-[3-(1-methylethyl)- 1H-pyrazol-5-yl]-6-[(2-piperidin- 1-ylethyl)oxy]pyrimidine-2,4- diamine


 


596




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-6-[3-(diethylamino)propyl]- N2-[(3-phenylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


597




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-N2-{[3-(1- methylethyl)isoxazol-5- yl]methyl}-6-[(2-piperidin-1- ylethyl)oxy]pyrimidine-2,4- diamine


 


598




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-N2-{[3-(1- methylethyl)isoxazol-5- yl]methyl}-6-[(1-methylpiperidin- 3-yl)oxy]pyrimidine-2,4-diamine


 


599




N2-{[3-(1-methylethyl)isoxazol-5- yl]methyl}-N4-[3-(1-methylethyl)- 1H-pyrazol-5-yl]-6-[(1- methylpiperidin-4- yl)oxy]pyrimidine-2,4-diamine


 


600




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-6-methyl-N2-[(3- methylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


601




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-N2-[(3-methylisoxazol-5- yl)methyl]-6-morpholin-4- ylpyrimidine-2,4-diamine


 


602




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-N2-[(3-methylisoxazol-5- yl)methyl]-6-(4-methylpiperazin- 1-yl)pyrimidine-2,4-diamine


 


603




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-N2-{[3-(1- methylethyl)isoxazol-5- yl]methyl}-6-[(1-methylpiperidin- 4-yl)oxy]pyrimidine-2,4-diamine


 


604




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-N2-{[3-(4- fluorophenyl)isoxazol-5- yl]methyl}-6-morpholin-4- ylpyrimidine-2,4-diamine


 


605




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-N2-{[3-(4- fluorophenyl)isoxazol-5- yl]methyl}-6-(4-methylpiperazin- 1-yl)pyrimidine-2,4-diamine


 


606




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-N2-{[3-(4- fluorophenyl)isoxazol-5- yl]methyl}-6-[(2-morpholin-4- ylethyl)oxy]pyrimidine-2,4- diamine


 


607




N2-{[3-(4-fluorophenyl)isoxazol- 5-yl]methyl}-N4-[3-(1- methylethyl)-1H-pyrazol-5-yl]-6- morpholin-4-ylpyrimidine-2,4- diamine


 


608




N2-{[3-(4-fluorophenyl)isoxazol- 5-yl]methyl}-N4-[3-(1- methylethyl)-1H-pyrazol-5-yl]-6- (4-methylpiperazin-1- yl)pyrimidine-2,4-diamine


 


609




N2-{[3-(4-fluorophenyl)isoxazol- 5-yl]methyl}-N4-[3-(1- methylethyl)-1H-pyrazol-5-yl]-6- [(2-morpholin-4- ylethyl)oxy]pyrimidine-2,4- diamine


 


610




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-6-methyl-N2-[(3-pyridin-3- ylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


611




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-6-(4-methylpiperazin-1-yl)-N2- [(3-pyridin-2-ylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


612




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-6-morpholin-4-yl-N2-[(3- pyridin-2-ylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


613




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-N2-{[3-(1- methylethyl)isoxazol-5- yl]methyl}-6-piperazin-1- ylpyrimidine-2,4-diamine


 


614




6-(4-acetylpiperazin-1-yl)-N4-(5- cyclopropyl-1H-pyrazol-3-yl)-N2- {[3-(1-methylethyl)isoxazol-5- yl]methyl}pyrimidine-2,4-diamine


 


615




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-N2-{[3-(1- methylethyl)isoxazol-5- yl]methyl}-6-[4- (methylsulfonyl)piperazin-1- yl]pyrimidine-2,4-diamine


 


616




4-{6-[(5-cyclopropyl-1H-pyrazol- 3-yl)amino]-2-({[3-(1- methylethyl)isoxazol-5- yl]methyl}amino)pyrimidin-4- yl}piperazine-1-carbaldehyde


 


617




N4-(3-methyl-1H-pyrazol-5-yl)-6- morpholin-4-yl-N2-[(3- phenylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


618




6-(4-methylpiperazin-1-yl)-N4-(3- methyl-1H-pyrazol-5-yl)-N2-[(3- phenylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


619




N4-(3-methyl-1H-pyrazol-5-yl)-6- [(2-morpholin-4-ylethyl)oxy]-N2- [(3-phenylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


620




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-6-methyl-N2-[(3-pyridin-4- ylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


621




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-N2-{[3-(3,4- difluorophenyl)isoxazol-5- yl]methyl}-6-methylpyrimidine- 2,4-diamine


 


622




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-N2-{[3-(2,4- difluorophenyl)isoxazol-5- yl]methyl}-6-methylpyrimidine- 2,4-diamine


 


623




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-6-methyl-N2-[(3-pyrazin-2- ylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


624




5-chloro-N4-(3-cyclopropyl-1H- pyrazol-5-yl)-6-morpholin-4-yl- N2-[(3-phenylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


625




5-chloro-N4-(3-cyclopropyl-1H- pyrazol-5-yl)-6-(4- methylpiperazin-1-yl)-N2-[(3- phenylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


626




N2-[(3-methylisoxazol-5- yl)methyl]-6-(4-methylpiperazin- 1-yl)-N4-(3-methyl-1H-pyrazol-5- yl)pyrimidine-2,4-diamine


 


627




N2-[(3-methylisoxazol-5- yl)methyl]-N4-(3-methyl-1H- pyrazol-5-yl)-6-morpholin-4- ylpyrimidine-2,4-diamine


 


628




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-6-(4-methylpiperazin-1-yl)-N2- [(3-pyrimidin-4-ylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


629




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-N2-[(3-furan-3-ylisoxazol-5- yl)methyl]-6-(4-methylpiperazin- 1-yl)pyrimidine-2,4-diamine


 


630




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-N6-(8-methyl-8- azabicyclo[3.2.1]oct-3-yl)-N2-[(3- methylisoxazol-5- yl)methyl]pyrimidine-2,4,6- triamine


 


631




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-6-(5-methyl-2,5- diazabicyclo[2.2.1]hept-2-yl)-N2- [(3-methylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


632




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-6-(5-methyl-2,5- diazabicyclo[2.2.1]hept-2-yl)-N2- {[3-(1-methylethyl)isoxazol-5- yl]methyl}pyrimidine-2,4-diamine


 


633




N4-bicyclo[2.2.1]hept-2-yl-N6-(5- cyclopropyl-1H-pyrazol-3-yl)-N2- {[3-(1-methylethyl)isoxazol-5- yl]methyl}pyrimidine-2,4,6- triamine


 


634




N4-bicyclo[2.2.1]hept-2-yl-N6-(5- cyclopropyl-1H-pyrazol-3-yl)-N2- [(3-methylisoxazol-5- yl)methyl]pyrimidine-2,4,6- triamine


 


635




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-N2-[(3-methylisoxazol-5- yl)methyl]-6-[(1R,4R)-5- (phenylmethyl)-2,5- diazabicyclo[2.2.1]hept-2- yl]pyrimidine-2,4-diamine


 


636




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-N2-{[3-(1- methylethyl)isoxazol-5- yl]methyl}-6-[(1R,4R)-5- (phenylmethyl)-2,5- diazabicyclo[2.2.1]hept-2- yl]pyrimidine-2,4-diamine


 


637




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-6-morpholin-4-yl-N2-[(3- pyrimidin-4-ylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


638




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-6-{[2- (dimethylamino)ethyl]oxy}-N2- [(3-pyrimidin-4-ylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


639




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-N2-{[3-(5-fluoropyridin-2- yl)isoxazol-5-yl]methyl}-6- methylpyrimidine-2,4-diamine


 


640




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-6-(4-methylpiperazin-1-yl)-N2- {[3-(2-thienyl)isoxazol-5- yl]methyl}pyrimidine-2,4-diamine


 


641




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-6-{[2- (dimethylamino)ethyl]oxy}-N2- [(3-pyridin-2-ylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


642




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-6-(4-methylpiperazin-1-yl)-N2- [(3-pyrimidin-5-ylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


643




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-6-morpholin-4-yl-N2-[(3- pyrimidin-5-ylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


644




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-6-{[2- (diethylamino)ethyl]oxy}-N2-{[3- (1-methylethyl)isoxazol-5- yl]methyl}pyrimidine-2,4-diamine


 


645




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-N2-{[3-(1- methylethyl)isoxazol-5- yl]methyl}-6-[(2-pyrrolidin-1- ylethyl)oxy]pyrimidine-2,4- diamine


 


646




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-6-{[2- (diethylamino)ethyl]oxy}-N2-[(3- methylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


647




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-N2-[(3-methylisoxazol-5- yl)methyl]-6-[(2-pyrrolidin-1- ylethyl)oxy]pyrimidine-2,4- diamine


 


648




N4-(5-cyclopropyl-1H-pyrazol-3- yl)-6-(4-methylpiperazin-1-yl)-N2- {[3-(1,3-thiazol-2-yl)isoxazol-5- yl]methyl}pyrimidine-2,4-diamine


 


649




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-6-[2-(dimethylamino)ethoxy]- N2-[(3-methylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


650




6-{[2-(dimethylamino)ethyl]oxy}- N2-[(3-methylisoxazol-5- yl)methyl]-N4-(3-methyl-1H- pyrazol-5-yl)pyrimidine-2,4- diamine


 


651




6-{[2-(diethylamino)ethyl]oxy}- N2-[(3-methylisoxazol-5- yl)methyl]-N4-(3-methyl-1H- pyrazol-5-yl)pyrimidine-2,4- diamine


 


652




N2-[(3-methylisoxazol-5- yl)methyl]-N4-(3-methyl-1H- pyrazol-5-yl)-6-[(2-pyrrolidin-1- ylethyl)oxy]pyrimidine-2,4- diamine


 


653




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-6-methyl-N2-[2-(3- phenylisoxazol-5- yl)ethyl]pyrimidine-2,4-diamine


 


654




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-6-methyl-N2-[1-(3- phenylisoxazol-5- yl)ethyl]pyrimidine-2,4-diamine


 


655




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-N2-[(3-ethylisoxazol-5- yl)methyl]-6-(4-methylpiperazin- 1-yl)pyrimidine-2,4-diamine


 


656




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-N2-[(3-ethylisoxazol-5- yl)methyl]-6-morpholin-4- ylpyrimidine-2,4-diamine


 


657




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-6-{[2- (dimethylamino)ethyl]oxy}-N2- [(3-ethylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


658




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-6-{[2- (diethylamino)ethyl]oxy}-N2-[(3- ethylisoxazol-5- yl)methyl]pyrimidine-2,4-diamine


 


659




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-N2-[(3-ethylisoxazol-5- yl)methyl]-6-[(2-pyrrolidin-1- ylethyl)oxy]pyrimidine-2,4- diamine


 


660




N2-{[3-(2-aminopyrimidin-4- yl)isoxazol-5-yl]methyl}-N4-(3- cyclopropyl-1H-pyrazol-5-yl)-6- (4-methylpiperazin-1- yl)pyrimidine-2,4-diamine


 


661




N4-(3-cyclopropyl-1H-pyrazol-5- yl)-6-(4-ethylpiperazin-1-yl)-N2- {[3-(1-methylethyl)isoxazol-5- yl]methyl}pyrimidine-2,4-diamine


 


662




2-(1-{6-[(3-cyclopropyl-1H- pyrazol-5-yl)amino]-2-({[3-(1- methylethyl)isoxazol-5- yl]methyl}amino)pyrimidin-4- yl}piperidin-4-yl)ethanol


 


663




2-(4-{6-[(3-cyclopropyl-1H- pyrazol-5-yl)amino]-2-({[3-(1- methylethyl)isoxazol-5- yl]methyl}amino)pyrimidin-4- yl}piperazin-1-yl)ethanol









The Compounds in Table 6 can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 6 can be used to practice the invention.











Entry
Name
















1
6-(2-butyl-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-benzoxazin-



3(4H)-one


2
6-[1-hydroxy-3-oxo-2-(2-phenylethyl)-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-



benzoxazin-3(4H)-one


3
6-(1-hydroxy-2-{[4-(methyloxy)phenyl]methyl}-3-oxo-2,3-dihydro-1H-isoindol-



1-yl)-2H-1,4-benzoxazin-3(4H)-one


4
6-(1-hydroxy-2-{[3-(methyloxy)phenyl]methyl}-3-oxo-2,3-dihydro-1H-isoindol-



1-yl)-2H-1,4-benzoxazin-3(4H)-one


5
6-{2-[(4-fluorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-



2H-1,4-benzoxazin-3(4H)-one


6
6-(1-hydroxy-3-oxo-2-phenyl-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-benzoxazin-



3(4H)-one


7
6-{2-[(3-bromophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-



2H-1,4-benzoxazin-3(4H)-one


8
6-{2-[(4-bromophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-



2H-1,4-benzoxazin-3(4H)-one


9
6-[1-hydroxy-3-oxo-2-(3-phenylpropyl)-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-



benzoxazin-3(4H)-one


10
6-{2-[(3,4-dichlorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl}-2H-1,4-benzoxazin-3(4H)-one


11
6-{1-hydroxy-2-[(4-methylphenyl)methyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-



2H-1,4-benzoxazin-3(4H)-one


12
6-{2-[(4-chlorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-



2H-1,4-benzoxazin-3(4H)-one


13
6-[1-hydroxy-2-(1-methylethyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-



benzoxazin-3(4H)-one


14
methyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


15
6-{2-[(3,4-dimethylphenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl}-2H-1,4-benzoxazin-3(4H)-one


16
6-(2-{[4-chloro-3-(trifluoromethyl)phenyl]methyl}-1-hydroxy-3-oxo-2,3-



dihydro-1H-isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one


17
6-(2-{[4-(dimethylamino)phenyl]methyl}-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one


18
6-[2-(3-chlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-



benzoxazin-3(4H)-one


19
6-[2-(4-chlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-



benzoxazin-3(4H)-one


20
6-[2-(3,4-dichlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-



1,4-benzoxazin-3(4H)-one


21
6-[1-hydroxy-2-(4-methylphenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-



benzoxazin-3(4H)-one


22
3-(2-{[3,5-bis(methyloxy)phenyl]amino}-1H-benzimidazol-5-yl)-3-(methyloxy)-



2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one


23
3-(2-{[3,5-bis(methyloxy)phenyl]amino}-1H-benzimidazol-5-yl)-2-(1-



methylethyl)-3-(methyloxy)-2,3-dihydro-1H-isoindol-1-one


24
3-(2-{[3,5-bis(methyloxy)phenyl]amino}-1H-benzimidazol-5-yl)-3-hydroxy-2-



phenyl-2,3-dihydro-1H-isoindol-1-one


25
3-(2-{[3,5-bis(methyloxy)phenyl]amino}-1H-benzimidazol-5-yl)-3-hydroxy-2-



(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one


26
methyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1-



methyl-1H-benzimidazol-2-yl}carbamate


27
3-(1H-benzimidazol-5-yl)-3-hydroxy-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-



1-one


28
5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-N-methyl-



1H-benzimidazole-2-carboxamide


29
3-hydroxy-3-(2-methyl-1H-benzimidazol-5-yl)-2-(phenylmethyl)-2,3-dihydro-



1H-isoindol-1-one


30
7-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-3,4-



dihydroquinoxalin-2(1H)-one


31
7-[2-(3-chlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-3,4-



dihydroquinoxalin-2(1H)-one


32
1,1-dimethylethyl 4-{[1-hydroxy-3-oxo-1-(3-oxo-3,4-dihydro-2H-1,4-



benzoxazin-6-yl)-1,3-dihydro-2H-isoindol-2-yl]methyl}piperidine-1-carboxylate


33
6-(1-hydroxy-2-{[2-(methyloxy)phenyl]methyl}-3-oxo-2,3-dihydro-1H-isoindol-



1-yl)-2H-1,4-benzoxazin-3(4H)-one


34
6-{2-[(3-chlorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-



2H-1,4-benzoxazin-3(4H)-one


35
6-{2-[(2-chlorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-



2H-1,4-benzoxazin-3(4H)-one


36
6-{2-[(3-fluorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-



2H-1,4-benzoxazin-3(4H)-one


37
6-{2-[(2-bromophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-



2H-1,4-benzoxazin-3(4H)-one


38
6-{2-[(2-fluorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-



2H-1,4-benzoxazin-3(4H)-one


39
6-[2-(3-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-



benzoxazin-3(4H)-one


40
6-[1-hydroxy-2-(3-iodophenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-



benzoxazin-3(4H)-one


41
6-[2-(3-bromophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-



benzoxazin-3(4H)-one


42
6-[1-hydroxy-2-(3-nitrophenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-



benzoxazin-3(4H)-one


43
6-{1-hydroxy-2-[3-(methyloxy)phenyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-



2H-1,4-benzoxazin-3(4H)-one


44
6-[1-hydroxy-2-(3-methylphenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-



benzoxazin-3(4H)-one


45
3-hydroxy-3-(1H-indol-5-yl)-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one


46
methyl [6-(1-hydroxy-3-oxo-2-phenyl-2,3-dihydro-1H-isoindol-1-yl)-1H-



benzimidazol-2-yl]carbamate


47
6-[2-(2-aminophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-



benzoxazin-3(4H)-one


48
6-{[2-(3-phenyl-1,2,4-oxadiazol-5-yl)phenyl]carbonyl}-2H-1,4-benzoxazin-



3(4H)-one


49
6-{[2-(1H-benzimidazol-2-yl)phenyl]carbonyl}-2H-1,4-benzoxazin-3(4H)-one


50
6-(1-hydroxy-3-oxo-2-{[2-(trifluoromethyl)phenyl]methyl}-2,3-dihydro-1H-



isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one


51
6-{2-[(5-bromo-2-fluorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one


52
6-{1-hydroxy-2-[(3-nitrophenyl)methyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-



2H-1,4-benzoxazin-3(4H)-one


53
6-(1-hydroxy-3-oxo-2-{[3-(trifluoromethyl)phenyl]methyl}-2,3-dihydro-1H-



isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one


54
6-(2-{[2,3-bis(methyloxy)phenyl]methyl}-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one


55
6-{1-hydroxy-2-[(3-iodophenyl)methyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-



2H-1,4-benzoxazin-3(4H)-one


56
6-[1-hydroxy-3-oxo-2-({3-[(trifluoromethyl)oxy]phenyl}methyl)-2,3-dihydro-



1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one


57
6-(1-hydroxy-2-{[2-(methylthio)phenyl]methyl}-3-oxo-2,3-dihydro-1H-isoindol-



1-yl)-2H-1,4-benzoxazin-3(4H)-one


58
6-[2-(3,4-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-



1,4-benzoxazin-3(4H)-one


59
6-{1-hydroxy-2-[3-(1-methylethyl)phenyl]-3-oxo-2,3-dihydro-1H-isoindol-1-



yl}-2H-1,4-benzoxazin-3(4H)-one


60
6-(1-hydroxy-3-oxo-2-{3-[(trifluoromethyl)oxy]phenyl}-2,3-dihydro-1H-



isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one


61
6-{1-hydroxy-3-oxo-2-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1H-isoindol-1-



yl}-2H-1,4-benzoxazin-3(4H)-one


62
3-[1-hydroxy-3-oxo-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-1,3-dihydro-



2H-isoindol-2-yl]benzenesulfonamide


63
6-{2-[5-chloro-2-(methyloxy)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-



1-yl}-2H-1,4-benzoxazin-3(4H)-one


64
6-{2-[4-fluoro-3-(trifluoromethyl)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one


65
3-hydroxy-3-(1H-indol-6-yl)-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one


66
6-[2-(3-fluoro-5-iodophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



2H-1,4-benzoxazin-3(4H)-one


67
6-[2-(3-aminophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-



benzoxazin-3(4H)-one


68
6-[2-(3,5-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-



1,4-benzoxazin-3(4H)-one


69
6-{1-hydroxy-2-[3-(methylsulfonyl)phenyl]-3-oxo-2,3-dihydro-1H-isoindol-1-



yl}-2H-1,4-benzoxazin-3(4H)-one


70
ethyl 3-[1-hydroxy-3-oxo-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-1,3-



dihydro-2H-isoindol-2-yl]benzoate


71
3-[1-hydroxy-3-oxo-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-1,3-dihydro-



2H-isoindol-2-yl]benzonitrile


72
6-[2-(2-chlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-



benzoxazin-3(4H)-one


73
6-[2-(3-amino-5-chlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



2H-1,4-benzoxazin-3(4H)-one


74
6-[2-(5-chloro-2-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



2H-1,4-benzoxazin-3(4H)-one


75
6-[2-(3-chloro-2-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



2H-1,4-benzoxazin-3(4H)-one


76
6-[2-(3-ethylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-



benzoxazin-3(4H)-one


77
6-[2-(3-ethynylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-



benzoxazin-3(4H)-one


78
6-[1-hydroxy-2-(3-hydroxyphenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-



benzoxazin-3(4H)-one


79
6-{1-hydroxy-3-oxo-2-[3-(phenyloxy)phenyl]-2,3-dihydro-1H-isoindol-1-yl}-



2H-1,4-benzoxazin-3(4H)-one


80
6-(1-hydroxy-3-oxo-2-{3-[(phenylmethyl)oxy]phenyl}-2,3-dihydro-1H-isoindol-



1-yl)-2H-1,4-benzoxazin-3(4H)-one


81
3-[1-hydroxy-3-oxo-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-1,3-dihydro-



2H-isoindol-2-yl]benzamide


82
6-{1-hydroxy-2-[3-(hydroxymethyl)phenyl]-3-oxo-2,3-dihydro-1H-isoindol-1-



yl}-2H-1,4-benzoxazin-3(4H)-one


83
6-[2-(2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-



benzoxazin-3(4H)-one


84
3-hydroxy-3-[2-(methylamino)-1H-benzimidazol-5-yl]-2-(phenylmethyl)-2,3-



dihydro-1H-isoindol-1-one


85
6-(2-biphenyl-3-yl-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-



benzoxazin-3(4H)-one


86
6-(2-{3-[(dimethylamino)methyl]phenyl}-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one


87
6-[2-(3,5-dichlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-



1,4-benzoxazin-3(4H)-one


88
6-(1-hydroxy-3-oxo-2-piperidin-4-yl-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-



benzoxazin-3(4H)-one


89
6-[2-(3-{[2-(dimethylamino)ethyl]oxy}phenyl)-1-hydroxy-3-oxo-2,3-dihydro-



1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one


90
6-[1-hydroxy-2-(2-methylphenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-



benzoxazin-3(4H)-one


91
N-methyl-2-[(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)carbonyl]-N-



phenylbenzamide


92
methyl {5-[1-(ethyloxy)-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


93
phenylmethyl 2-[(2-{[(methyloxy)carbonyl]amino}-1H-benzimidazol-5-



yl)carbonyl]benzoate


94
3-hydroxy-3-(1H-indazol-5-yl)-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one


95
3-hydroxy-3-(1H-indazol-6-yl)-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one


96
ethyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-



benzimidazol-2-yl}carbamate


97
2-methylpropyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


98
methyl {5-[1-hydroxy-3-oxo-2-(2-thienylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


99
methyl {5-[1-hydroxy-3-oxo-2-(2-phenylethyl)-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


100
3-[2-amino-1-(1,1-dimethylethyl)-1H-benzimidazol-5-yl]-3-hydroxy-2-



(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one


101
3-(2-amino-1H-benzimidazol-5-yl)-3-hydroxy-2-(phenylmethyl)-2,3-dihydro-



1H-isoindol-1-one


102
methyl [5-(1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-



yl]carbamate


103
3-(methyloxy)butyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


104
methyl (5-{1-hydroxy-3-oxo-2-[(1R)-1-phenylethyl]-2,3-dihydro-1H-isoindol-1-



yl}-1H-benzimidazol-2-yl)carbamate


105
methyl (5-{1-hydroxy-3-oxo-2-[(1S)-1-phenylethyl]-2,3-dihydro-1H-isoindol-1-



yl}-1H-benzimidazol-2-yl)carbamate


106
2-(methyloxy)ethyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


107
methyl {6-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1-



methyl-1H-benzimidazol-2-yl}carbamate


108
prop-2-yn-1-yl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-



1-yl]-1H-benzimidazol-2-yl}carbamate


109
but-2-yn-1-yl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-



1-yl]-1H-benzimidazol-2-yl}carbamate


110
1-methylethyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-



1-yl]-1H-benzimidazol-2-yl}carbamate


111
methyl {5-[2-(2,3-dihydro-1H-inden-2-yl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


112
methyl {5-[1-hydroxy-3-oxo-2-(pyridin-4-ylmethyl)-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


113
methyl {5-[1-hydroxy-3-oxo-2-(pyridin-3-ylmethyl)-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


114
methyl (6-{2-[(3-fluorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


115
methyl {5-[1-hydroxy-2-(3-methylphenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


116
methyl [5-(1-hydroxy-2-{[2-(methyloxy)phenyl]methyl}-3-oxo-2,3-dihydro-1H-



isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate


117
methyl [5-(1-hydroxy-2-{[3-(methyloxy)phenyl]methyl}-3-oxo-2,3-dihydro-1H-



isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate


118
methyl [5-(1-hydroxy-2-{[4-(methyloxy)phenyl]methyl}-3-oxo-2,3-dihydro-1H-



isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate


119
methyl (6-{2-[(4-fluorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


120
methyl (6-{2-[(3-bromophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


121
methyl (5-{1-hydroxy-2-[(3-iodophenyl)methyl]-3-oxo-2,3-dihydro-1H-isoindol-



1-yl}-1H-benzimidazol-2-yl)carbamate


122
methyl (5-{2-[(3-chlorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


123
methyl (5-{2-[(2-fluorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


124
methyl {5-[1-hydroxy-3-oxo-2-(pyridin-2-ylmethyl)-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


125
phenylmethyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-



1-yl]-1H-benzimidazol-2-yl}carbamate


126
2-fluoroethyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


127
propyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


128
methyl (5-{1-hydroxy-2-[4-(methyloxy)phenyl]-3-oxo-2,3-dihydro-1H-isoindol-



1-yl}-1H-benzimidazol-2-yl)carbamate


129
methyl (5-{2-[(2-chlorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


130
methyl (5-{2-[(2-bromophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


131
methyl (5-{1-hydroxy-2-[(3-methylphenyl)methyl]-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


132
methyl (5-{1-hydroxy-2-[(4-methylphenyl)methyl]-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


133
methyl (5-{1-hydroxy-2-[(2-methylphenyl)methyl]-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


134
methyl {5-[2-(3-bromophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


135
methyl {5-[2-(3-chlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


136
methyl {5-[2-(3-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


137
methyl (5-{1-hydroxy-2-[3-(methyloxy)phenyl]-3-oxo-2,3-dihydro-1H-isoindol-



1-yl}-1H-benzimidazol-2-yl)carbamate


138
methyl {5-[2-(4-bromophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


139
methyl {5-[2-(4-chlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


140
methyl {5-[2-(4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


141
methyl {5-[2-(3,5-dimethylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


142
methyl {5-[2-(2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


143
methyl {5-[2-(2-chlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


144
methyl {5-[1-hydroxy-2-(2-methylphenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


145
methyl (5-{1-hydroxy-2-[2-(methyloxy)phenyl]-3-oxo-2,3-dihydro-1H-isoindol-



1-yl}-1H-benzimidazol-2-yl)carbamate


146
methyl {5-[1-hydroxy-2-(4-methylphenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


147
methyl (5-{1-hydroxy-3-oxo-2-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


148
but-2-yn-1-yl (5-{1-hydroxy-3-oxo-2-[(1R)-1-phenylethyl]-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


149
N-ethyl-N′-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}urea


150
phenylmethyl (5-{1-hydroxy-3-oxo-2-[(1R)-1-phenylethyl]-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


151
methyl {6-[2-(3-amino-5-chlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


152
piperidin-4-ylmethyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


153
methyl {5-[2-(cyclopropylmethyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


154
methyl {5-[2-(2,2-dimethylpropyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


155
methyl {5-[2-(3,5-dichlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


156
methyl {5-[2-(3,5-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


157
N-ethyl-N′-(5-{1-hydroxy-3-oxo-2-[(1R)-1-phenylethyl]-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)urea


158
N′-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-



benzimidazol-2-yl}-N,N-dimethylurea


159
methyl {5-[2-(3-{[2-(dimethylamino)ethyl]oxy}phenyl)-1-hydroxy-3-oxo-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


160
3-(4-methylpiperazin-1-yl)propyl {6-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


161
methyl {5-[2-(cyclohexylmethyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


162
methyl {5-[1-hydroxy-2-(2-methylpropyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


163
methyl {5-[1-hydroxy-3-oxo-2-(1,3-thiazol-2-ylmethyl)-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


164
methyl {5-[2-(3,4-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


165
methyl (5-{2-[1-(3,5-difluorophenyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


166
methyl (5-{2-[1-(3-fluorophenyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


167
methyl [5-(2-cyclohexyl-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-1H-



benzimidazol-2-yl]carbamate


168
methyl {5-[2-(2,5-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


169
N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-



benzimidazol-2-yl}-N′-(phenylmethyl)urea


170
piperidin-4-yl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-



1-yl]-1H-benzimidazol-2-yl}carbamate


171
N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-



benzimidazol-2-yl}-N′-methylurea


172
methyl (5-{2-[1-(2-fluorophenyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


173
methyl (5-{1-hydroxy-3-oxo-2-[1-(2-thienyl)ethyl]-2,3-dihydro-1H-isoindol-1-



yl}-1H-benzimidazol-2-yl)carbamate


174
methyl (5-{2-[1-(3-chlorophenyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


175
methyl (5-{1-hydroxy-2-[3-methyl-5-(trifluoromethyl)phenyl]-3-oxo-2,3-



dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


176
N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-



benzimidazol-2-yl}propanamide


177
methyl {5-[2-(3,4-dichlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


178
methyl {5-[2-(3-ethylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


179
methyl {5-[2-(3-ethynylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


180
methyl {5-[2-(4-chloro-3-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


181
methyl [5-(1-hydroxy-3-oxo-2-{1-[3-(trifluoromethyl)phenyl]ethyl}-2,3-dihydro-



1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate


182
methyl (5-{1-hydroxy-3-oxo-2-[(1R)-1-phenylpropyl]-2,3-dihydro-1H-isoindol-



1-yl}-1H-benzimidazol-2-yl)carbamate


183
methyl [5-(1-hydroxy-3-oxo-2-{2-[(trifluoromethyl)oxy]phenyl}-2,3-dihydro-



1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate


184
methyl {5-[2-(2,3-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


185
cyclohexyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


186
tetrahydrofuran-2-ylmethyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-



1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


187
cyclopropylmethyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


188
N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-



benzimidazol-2-yl}morpholine-4-carboxamide


189
methyl {5-[2-(cyclopentylmethyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


190
methyl {5-[2-(2,3-dimethylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


191
methyl {5-[2-(2,3-dihydro-1H-inden-1-yl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


192
methyl (2S)-cyclohexyl[1-hydroxy-1-(2-{[(methyloxy)carbonyl]amino}-1H-



benzimidazol-5-yl)-3-oxo-1,3-dihydro-2H-isoindol-2-yl]ethanoate


193
methyl {5-[2-(2,6-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


194
methyl {5-[2-(3-chloro-4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


195
but-3-en-1-yl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


196
2,2,2-trifluoroethyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


197
methyl {5-[2-(5-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


198
methyl (5-{2-[1-(5-chloro-2-methylphenyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-



1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


199
methyl (5-{1-hydroxy-3-oxo-2-[(1S)-1-phenylpropyl]-2,3-dihydro-1H-isoindol-



1-yl}-1H-benzimidazol-2-yl)carbamate


200
methyl (5-{2-[1-(3-chloro-2-methylphenyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-



1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


201
methyl (5-{1-hydroxy-2-[1-(5-methyl-2-thienyl)ethyl]-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


202
methyl (5-{2-[1-(5-chloro-2-thienyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


203
methyl {5-[1-hydroxy-2-(3-iodophenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


204
methyl (5-{1-hydroxy-2-[3-(1-methylethyl)phenyl]-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


205
methyl {5-[2-(furan-2-ylmethyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


206
methyl {5-[1-hydroxy-3-oxo-2-(3-thienylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


207
methyl {5-[2-(cyclobutylmethyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


208
3,3,3-trifluoro-2-hydroxy-N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-



1H-isoindol-1-yl]-1H-benzimidazol-2-yl}-2-(trifluoromethyl)propanamide


209
methyl (5-{1-hydroxy-2-[1-(4-methyl-2-thienyl)ethyl]-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


210
methyl (5-{2-[1-(4-bromo-2-thienyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


211
methyl {5-[1-hydroxy-2-(3-{[2-(methyloxy)ethyl]oxy}phenyl)-3-oxo-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


212
tetrahydrofuran-3-ylmethyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-



1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


213
N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-



benzimidazol-2-yl}piperidine-1-carboxamide


214
methyl {5-[2-(3-bromo-4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


215
2,3-dihydroxypropyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


216
methyl {5-[1-hydroxy-3-oxo-2-(tetrahydrofuran-2-ylmethyl)-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


217
methyl (5-{2-[3-(aminocarbonyl)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


218
4,4,4-trifluoro-3-hydroxy-N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-



1H-isoindol-1-yl]-1H-benzimidazol-2-yl}-3-(trifluoromethyl)butanamide


219
methyl (5-{1-hydroxy-2-[3-(methylsulfonyl)phenyl]-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


220
methyl (5-{1-hydroxy-3-oxo-2-[3-(phenyloxy)phenyl]-2,3-dihydro-1H-isoindol-



1-yl}-1H-benzimidazol-2-yl)carbamate


221
methyl [5-(1-hydroxy-3-oxo-2-{3-[(phenylmethyl)oxy]phenyl}-2,3-dihydro-1H-



isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate


222
methyl [5-(2-biphenyl-3-yl-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-1H-



benzimidazol-2-yl]carbamate


223
2,2-dimethyl-3-[(phenylmethyl)oxy]propyl {5-[1-hydroxy-3-oxo-2-



(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


224
methyl {5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


225
methyl {5-[2-(3-cyanophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


226
methyl {5-[2-(3-ethynyl-4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


227
methyl {5-[2-(4-fluoro-3-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


228
methyl {6-[2-(3,4-dichloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


229
[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl {5-[1-hydroxy-3-oxo-2-



(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


230
methyl {5-[2-(5-bromo-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


231
methyl (5-{2-[3-(acetylamino)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


232
methyl (5-{1-hydroxy-3-oxo-2-[3-(phenylmethyl)phenyl]-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


233
methyl (5-{2-[1-(4-chloro-2-thienyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


234
methyl (5-{1-hydroxy-3-oxo-2-[3-(phenylcarbonyl)phenyl]-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


235
methyl [5-(2-{3-[(dimethylamino)methyl]phenyl}-1-hydroxy-3-oxo-2,3-dihydro-



1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate


236
methyl (5-{2-[3-(aminosulfonyl)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


237
methyl {5-[2-(3-acetylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


238
methyl {5-[2-(3-ethyl-4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


239
methyl {5-[2-(3-chloro-5-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


240
N-{6-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-



benzimidazol-2-yl}-2-methylpropanamide


241
methyl (5-{2-[1-(3-chloro-2-thienyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


242
methyl [5-(1-hydroxy-3-oxo-2-pyridin-3-yl-2,3-dihydro-1H-isoindol-1-yl)-1H-



benzimidazol-2-yl]carbamate


243
methyl (5-{1-hydroxy-3-oxo-2-[3-(phenylamino)phenyl]-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


244
methyl {5-[2-(5-bromo-2,4-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


245
methyl {5-[2-(5-chloro-2,4-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


246
methyl {5-[2-(3,5-dichloro-4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


247
2,2-dimethyl-3-(methyloxy)propyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


248
3-hydroxy-2,2-dimethylpropyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


249
methyl (5-{2-[1-(5-bromo-2-thienyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


250
methyl {5-[2-(4,5-dichloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


251
methyl {5-[2-(3-bromo-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


252
methyl {5-[2-(3-chloro-2,4-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


253
N-{6-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-



benzimidazol-2-yl}pent-4-ynamide


254
methyl (6-{1-methyl-3-oxo-2-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


255
methyl [5-(1-hydroxy-3-oxo-2-{3-[(1,1,2,2-tetrafluoroethyl)oxy]phenyl}-2,3-



dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate


256
methyl {5-[1-hydroxy-3-oxo-2-(3-piperidin-4-ylphenyl)-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


257
methyl {5-[2-(3-ethenylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


258
methyl (5-{2-[3-(dimethylamino)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


259
2,2-difluoro-N-{6-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-



1-yl]-1H-benzimidazol-2-yl}cyclopropanecarboxamide


260
N-ethyl-N′-{6-[2-(4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}urea


261
methyl {5-[2-(3-aminophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


262
N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-



benzimidazol-2-yl}-4-[(phenylmethyl)oxy]butanamide


263
N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-



benzimidazol-2-yl}-4-piperidin-1-ylbutanamide


264
N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-



benzimidazol-2-yl}-4-(4-methylpiperazin-1-yl)butanamide


265
N-{6-[2-(4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-



benzimidazol-2-yl}butanamide


266
methyl {6-[2-(3-bromophenyl)-5,6-dichloro-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


267
methyl [5-(1-hydroxy-2-{3-[methyl(phenyl)amino]phenyl}-3-oxo-2,3-dihydro-



1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate


268
methyl {5-[1-hydroxy-3-oxo-2-(phenylsulfonyl)-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


269
methyl {5-[(2-{[(phenylamino)carbonyl]amino}phenyl)carbonyl]-1H-



benzimidazol-2-yl}carbamate


270
methyl (5-{[2-({[(phenylmethyl)oxy]carbonyl}amino)phenyl]carbonyl}-1H-



benzimidazol-2-yl)carbamate


271
methyl [5-({2-[(2-phenylhydrazino)carbonyl]phenyl}carbonyl)-1H-



benzimidazol-2-yl]carbamate


272
methyl {5-[(2-{[(phenyloxy)amino]carbonyl}phenyl)carbonyl]-1H-



benzimidazol-2-yl}carbamate


273
but-2-yn-1-yl {5-[2-(4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-



1-yl]-1H-benzimidazol-2-yl}carbamate


274
N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-



benzimidazol-2-yl}-3-piperidin-1-ylpropanamide


275
N-{6-[2-(4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-



benzimidazol-2-yl}propanamide


276
N-(4-fluorophenyl)-2-{[2-(pent-4-ynoylamino)-1H-benzimidazol-6-



yl]carbonyl}benzamide


277
4-(diethylamino)-N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}butanamide


278
N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-



benzimidazol-2-yl}-4-pyrrolidin-1-ylbutanamide


279
3-piperidin-1-ylpropyl {6-[2-(4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


280
3-(4-methylpiperazin-1-yl)propyl {6-[2-(4-fluorophenyl)-1-hydroxy-3-oxo-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


281
methyl {5-[2-(3-bromophenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-



benzimidazol-2-yl}carbamate


282
methyl {5-[2-(3-ethynyl-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


283
2-piperidin-1-ylethyl {5-[2-(4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


284
methyl {5-[2-(3-chloro-2-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


285
methyl {5-[2-(5-chloro-2-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


286
N-{6-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-



benzimidazol-2-yl}-2,2-dimethyl-3-piperidin-1-ylpropanamide


287
N-{5-[2-(4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-



benzimidazol-2-yl}-4-piperidin-1-ylbutanamide


288
N-{5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}-4-piperidin-1-ylbutanamide


289
methyl [6-({2-[(phenylcarbonyl)amino]phenyl}carbonyl)-1H-benzimidazol-2-



yl]carbamate


290
methyl {5-[1-hydroxy-2-(3-morpholin-4-ylphenyl)-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


291
2-(dimethylamino)ethyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


292
2-(diethylamino)ethyl {5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


293
2-piperidin-1-ylethyl {5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


294
3-piperidin-1-ylpropyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


295
2-piperidin-1-ylethyl {6-[2-(3-bromophenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


296
methyl {6-[2-(3-bromophenyl)-4,7-difluoro-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


297
2-[methyl(phenylmethyl)amino]ethyl {5-[2-(3-chloro-2-fluorophenyl)-1-



hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


298
methyl {5-[1-hydroxy-3-oxo-2-(3-pyrrolidin-1-ylphenyl)-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


299
methyl {5-[2-(5-chloro-2,3-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


300
methyl {5-[1-hydroxy-3-oxo-2-(pyrrolidin-2-ylmethyl)-2,3-dihydro-1H-isoindol-



1-yl]-1H-benzimidazol-2-yl}carbamate


301
methyl {5-[1-hydroxy-3-oxo-2-(pyrrolidin-3-ylmethyl)-2,3-dihydro-1H-isoindol-



1-yl]-1H-benzimidazol-2-yl}carbamate


302
(1-methylpiperidin-2-yl)methyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-



oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


303
[(2S)-1-methylpyrrolidin-2-yl]methyl {6-[2-(3-chloro-2-fluorophenyl)-1-



hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


304
octahydro-2H-quinolizin-1-ylmethyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-



3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


305
methyl {5-[2-(5-bromo-2-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


306
5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1,3-dihydro-2H-benzimidazol-2-one


307
methyl {5-[2-(3-bromo-2,5-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


308
2-morpholin-4-ylethyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


309
(1-methylpiperidin-3-yl)methyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-



oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


310
methyl (5-{2-[5-chloro-2-(methyloxy)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


311
methyl [5-(2-{3-[cyclohexyl(methyl)amino]phenyl}-1-hydroxy-3-oxo-2,3-



dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate


312
8-azabicyclo[3.2.1]oct-3-ylmethyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-



oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


313
methyl {6-[1-(3-bromophenyl)-5-oxopyrrolidin-2-yl]-1H-benzimidazol-2-



yl}carbamate


314
(1-methylpiperidin-4-yl)methyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


315
1,1-dimethylethyl 4-({[({5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}amino)carbonyl]oxy}methyl)piperidine-1-



carboxylate


316
(1-methylpiperidin-4-yl)methyl {5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-



oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


317
2-(1-methylpiperidin-4-yl)ethyl {5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-



oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


318
methyl ({6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}amino)(oxo)acetate


319
N-(5-{1-hydroxy-3-oxo-2-[3-(phenyloxy)phenyl]-2,3-dihydro-1H-isoindol-1-yl}-



1H-benzimidazol-2-yl)-4-piperidin-1-ylbutanamide


320
methyl {6-[2-(3-bromophenyl)-1-methyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


321
4-(diethylamino)but-2-yn-1-yl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-



oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


322
methyl {5-[2-(3-chloro-2,6-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


323
2-(2-oxopyrrolidin-1-yl)ethyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-



2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


324
2-(2,5-dioxopyrrolidin-1-yl)ethyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-



oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


325
2,2,3,3-tetrafluorocyclobutyl {5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-



2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


326
1-acetyl-N-{5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}piperidine-4-carboxamide


327
N-{5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}cyclobutanecarboxamide


328
methyl [5-(2-{3-[ethyl(phenyl)amino]phenyl}-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate


329
N-{6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}-2,2-difluorocyclopropanecarboxamide


330
cyclobutyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


331
2,2-difluoroethyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-



1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


332
2-(3-chloro-2-fluorophenyl)-3-hydroxy-3-[2-(pyridin-2-ylamino)-1H-



benzimidazol-5-yl]-2,3-dihydro-1H-isoindol-1-one


333
1-methylethyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-



1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


334
cyclopropylmethyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


335
N-{5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}cyclopropanecarboxamide


336
2-(methyloxy)ethyl {5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


337
tetrahydrofuran-2-ylmethyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-



2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


338
N-{5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}-2-(2-thienyl)acetamide


339
methyl {6-[2-(3-chloro-2-fluorophenyl)-4,7-difluoro-1-hydroxy-3-oxo-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


340
ethyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


341
2-fluoroethyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


342
methyl (5-{1-hydroxy-3-oxo-2-[2-(phenyloxy)phenyl]-2,3-dihydro-1H-isoindol-



1-yl}-1H-benzimidazol-2-yl)carbamate


343
N′-{5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}-N,N-diethylpentanediamide


344
cyclobutylmethyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-



1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


345
2,2,2-trifluoroethyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


346
methyl (5-{2-[3-(1,1-dimethylethyl)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


347
methyl {6-[2-(3-chloro-2-fluorophenyl)-7-fluoro-1-hydroxy-3-oxo-2,3-dihydro-



1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


348
2-(3-chloro-2-fluorophenyl)-3-hydroxy-3-[2-(phenylamino)-1H-benzimidazol-5-



yl]-2,3-dihydro-1H-isoindol-1-one


349
methyl {6-[4,7-dichloro-2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


350
phenylmethyl 2-[(2-{[(ethyloxy)carbonyl]amino}-1,3-benzoxazol-5-



yl)carbonyl]benzoate


351
methyl {5-[2-(5-chloro-3-ethynyl-2-methylphenyl)-1-hydroxy-3-oxo-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


352
methyl {5-[2-(5-ethynyl-2,4-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


353
methyl {5-[2-(3-ethynyl-2,4-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


354
2-(3-chloro-2-fluorophenyl)-3-hydroxy-3-[2-(pyrimidin-2-ylamino)-1H-



benzimidazol-5-yl]-2,3-dihydro-1H-isoindol-1-one


355
methyl {5-[2-(3-ethynyl-2-fluorophenyl)-4,7-difluoro-1-hydroxy-3-oxo-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


356
2-(3-chloro-2-fluorophenyl)-3-hydroxy-3-[2-(1,3-thiazol-2-ylamino)-1H-



benzimidazol-5-yl]-2,3-dihydro-1H-isoindol-1-one


357
ethyl {5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1,3-benzoxazol-2-yl}carbamate


358
methyl {5-[2-(5-chloro-3-iodo-2-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-



1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


359
methyl {5-[2-(3-ethyl-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


360
methyl {5-[2-(5-ethynyl-2-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


361
2-(3-chloro-2-fluorophenyl)-3-hydroxy-3-[2-(pyrazin-2-ylamino)-1H-



benzimidazol-5-yl]-2,3-dihydro-1H-isoindol-1-one


362
methyl {5-[2-(2-fluoro-3-iodophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


363
methyl {6-[2-(5-ethynyl-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


364
2-(3-ethynyl-2-fluorophenyl)-3-hydroxy-3-[2-(pyrimidin-2-ylamino)-1H-



benzimidazol-5-yl]-2,3-dihydro-1H-isoindol-1-one


365
methyl {5-[2-(2,5-dimethylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-



yl]-1H-benzimidazol-2-yl}carbamate


366
methyl {5-[2-(3-ethenyl-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


367
methyl (6-{2-[2-fluoro-3-(methyloxy)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


368
methyl (5-{1-hydroxy-2-[2-methyl-5-(methyloxy)phenyl]-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


369
methyl {5-[2-(3-ethynyl-2-fluorophenyl)-7-fluoro-1-hydroxy-3-oxo-2,3-dihydro-



1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


370
methyl {5-[2-(2-fluoro-3-prop-1-yn-1-ylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-



1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


371
methyl {5-[2-(5-chloro-2-methylphenyl)-7-fluoro-1-hydroxy-3-oxo-2,3-dihydro-



1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


372
methyl {5-[2-(3-ethynyl-2-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


373
3-hydroxy-2-[3-(methyloxy)phenyl]-3-[2-(pyrimidin-2-ylamino)-1H-



benzimidazol-6-yl]-2,3-dihydro-1H-isoindol-1-one


374
3-hydroxy-2-(3-methylphenyl)-3-[2-(pyrimidin-2-ylamino)-1H-benzimidazol-6-



yl]-2,3-dihydro-1H-isoindol-1-one


375
2-(5-chloro-2-methylphenyl)-3-hydroxy-3-[2-(pyrimidin-2-ylamino)-1H-



benzimidazol-6-yl]-2,3-dihydro-1H-isoindol-1-one


376
methyl {6-[2-(5-chloro-2-methylphenyl)-4,7-difluoro-1-hydroxy-3-oxo-2,3-



dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


377
methyl {5-[2-(3-ethynyl-2-fluorophenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-



1H-benzimidazol-2-yl}carbamate


378
2-(3-chloro-2-fluorophenyl)-3-{2-[(6-chloropyridazin-3-yl)amino]-1H-



benzimidazol-5-yl}-3-hydroxy-2,3-dihydro-1H-isoindol-1-one


379
2-(3-chloro-2-fluorophenyl)-4,7-difluoro-3-hydroxy-3-[2-(pyrimidin-2-ylamino)-



1H-benzimidazol-5-yl]-2,3-dihydro-1H-isoindol-1-one


380
methyl {5-[2-(2-fluoro-5-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


381
methyl (5-{2-[2-fluoro-5-(methyloxy)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


382
methyl (5-{1-hydroxy-2-[5-methyl-2-(methyloxy)phenyl]-3-oxo-2,3-dihydro-1H-



isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate


383
methyl {5-[2-(3-ethynyl-5-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


384
2-(3-chloro-2-fluorophenyl)-3-{2-[(5-chloropyrimidin-2-yl)amino]-1H-



benzimidazol-5-yl}-3-hydroxy-2,3-dihydro-1H-isoindol-1-one


385
2-(3-chloro-2-fluorophenyl)-3-hydroxy-3-{2-[(4-methylpyrimidin-2-yl)amino]-



1H-benzimidazol-5-yl}-2,3-dihydro-1H-isoindol-1-one


386
3-(2-{[4,6-bis(methyloxy)pyrimidin-2-yl]amino}-1H-benzimidazol-5-yl)-2-(3-



chloro-2-fluorophenyl)-3-hydroxy-2,3-dihydro-1H-isoindol-1-one


387
2-(3-chloro-2-fluorophenyl)-3-hydroxy-3-(2-{[4-methyl-6-



(methyloxy)pyrimidin-2-yl]amino}-1H-benzimidazol-5-yl)-2,3-dihydro-1H-



isoindol-1-one


388
3-hydroxy-2-(3-methylphenyl)-3-[2-(pyrazin-2-ylamino)-1H-benzimidazol-6-yl]-



2,3-dihydro-1H-isoindol-1-one


389
2-(5-chloro-2-methylphenyl)-3-hydroxy-3-[2-(pyrazin-2-ylamino)-1H-



benzimidazol-6-yl]-2,3-dihydro-1H-isoindol-1-one


390
methyl {6-[2-(2-fluoro-3-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-



isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate


391
3-hydroxy-2-[3-(methyloxy)phenyl]-3-[2-(pyrazin-2-ylamino)-1H-benzimidazol-



5-yl]-2,3-dihydro-1H-isoindol-1-one


392
methyl {6-[(2-{[(2-thienylmethyl)amino]carbonyl}phenyl)carbonyl]-1H-



benzimidazol-2-yl}carbamate


393
methyl {6-[(2-{[(3-methylphenyl)amino]carbonyl}phenyl)carbonyl]-1H-



benzimidazol-2-yl}carbamate


394
methyl {6-[(2-{[(3-bromophenyl)amino]carbonyl}phenyl)carbonyl]-1H-



benzimidazol-2-yl}carbamate


395
methyl {6-[(2-{[(3-chlorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-



benzimidazol-2-yl}carbamate


396
methyl {6-[(2-{[(3-fluorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-



benzimidazol-2-yl}carbamate


397
methyl (6-{[2-({[3-(methyloxy)phenyl]amino}carbonyl)phenyl]carbonyl}-1H-



benzimidazol-2-yl)carbamate


398
methyl (6-{[2-({[3-(trifluoromethyl)phenyl]amino}carbonyl)phenyl]carbonyl}-



1H-benzimidazol-2-yl)carbamate


399
methyl {6-[(2-{[(3-ethylphenyl)amino]carbonyl}phenyl)carbonyl]-1H-



benzimidazol-2-yl}carbamate


400
methyl {6-[(2-{[(3-ethynylphenyl)amino]carbonyl}phenyl)carbonyl]-1H-



benzimidazol-2-yl}carbamate


401
methyl {6-[(2-{[(3-chloro-4-fluorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-



benzimidazol-2-yl}carbamate


402
methyl {6-[(2-{[(5-chloro-2-fluorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-



benzimidazol-2-yl}carbamate


403
methyl {6-[(2-{[(3-iodophenyl)amino]carbonyl}phenyl)carbonyl]-1H-



benzimidazol-2-yl}carbamate


404
methyl (6-{[2-({[3-(1-methylethyl)phenyl]amino}carbonyl)phenyl]carbonyl}-



1H-benzimidazol-2-yl)carbamate


405
methyl {6-[(2-{[(3-thienylmethyl)amino]carbonyl}phenyl)carbonyl]-1H-



benzimidazol-2-yl}carbamate


406
methyl {6-[(2-{[(3-bromo-4-fluorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-



benzimidazol-2-yl}carbamate


407
methyl {6-[(2-{[(3-chloro-2-fluorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-



benzimidazol-2-yl}carbamate


408
methyl {6-[(2-{[(4-fluoro-3-methylphenyl)amino]carbonyl}phenyl)carbonyl]-



1H-benzimidazol-2-yl}carbamate


409
methyl {6-[(2-{[(5-bromo-2-fluorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-



benzimidazol-2-yl}carbamate


410
methyl {6-[(2-{[(5-bromo-2,4-difluorophenyl)amino]carbonyl}phenyl)carbonyl]-



1H-benzimidazol-2-yl}carbamate


411
methyl {6-[(2-{[(5-chloro-2,4-difluorophenyl)amino]carbonyl}phenyl)carbonyl]-



1H-benzimidazol-2-yl}carbamate


412
methyl {6-[(2-{[(3-bromo-2-fluorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-



benzimidazol-2-yl}carbamate


413
methyl {6-[(2-{[(3-ethenylphenyl)amino]carbonyl}phenyl)carbonyl]-1H-



benzimidazol-2-yl}carbamate


414
methyl {6-[(2-{[(3-ethynyl-2-fluorophenyl)amino]carbonyl}phenyl)carbonyl]-



1H-benzimidazol-2-yl}carbamate


415
methyl {6-[(2-{[(5-chloro-2-methylphenyl)amino]carbonyl}phenyl)carbonyl]-



1H-benzimidazol-2-yl}carbamate


416
methyl {6-[(2-{[(5-bromo-2-methylphenyl)amino]carbonyl}phenyl)carbonyl]-



1H-benzimidazol-2-yl}carbamate


417
methyl {6-[(2-{[(2-fluoro-3-iodophenyl)amino]carbonyl}phenyl)carbonyl]-1H-



benzimidazol-2-yl}carbamate


418
methyl {6-[(2-{[(3-ethenyl-2-fluorophenyl)amino]carbonyl}phenyl)carbonyl]-



1H-benzimidazol-2-yl}carbamate


419
methyl {6-[(2-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenyl)carbonyl]-



1H-benzimidazol-2-yl}carbamate









The Compounds in Table 7 can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 7 can be used to practice the invention.











Entry
Name
















1
(3Z)-3-[[5-(methyloxy)-1H-benzimidazol-2-yl](phenyl)methylidene]-5-{[1-



(phenylmethyl)pyrrolidin-3-yl]amino}-1,3-dihydro-2H-indol-2-one


2
(3Z)-5-[(1-ethylpiperidin-3-yl)amino]-3-[[5-(methyloxy)-1H-benzimidazol-2-



yl](phenyl)methylidene]-1,3-dihydro-2H-indol-2-one


3
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[[5-(methyloxy)-1H-benzimidazol-2-



yl](phenyl)methylidene]-1,3-dihydro-2H-indol-2-one


4
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[1H-imidazol-2-yl(phenyl)methylidene]-1,3-



dihydro-2H-indol-2-one


5
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-{[5-(methyloxy)-1H-benzimidazol-2-yl][4-



(methyloxy)phenyl]methylidene}-1,3-dihydro-2H-indol-2-one


6
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[[5-(methyloxy)-1H-benzimidazol-2-yl](4-



methylphenyl)methylidene]-1,3-dihydro-2H-indol-2-one


7
(3Z)-3-[1H-benzimidazol-2-yl(4-nitrophenyl)methylidene]-5-[(1-ethylpiperidin-4-



yl)amino]-1,3-dihydro-2H-indol-2-one


8
(3Z)-3-{1H-benzimidazol-2-yl[4-(methyloxy)phenyl]methylidene}-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


9
(3Z)-3-[1H-benzimidazol-2-yl(phenyl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-



1,3-dihydro-2H-indol-2-one


10
(3Z)-3-[[5-(methyloxy)-1H-benzimidazol-2-yl](phenyl)methylidene]-5-[(2,2,6,6-



tetramethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


11
(3Z)-3-[(4-aminophenyl)(1H-benzimidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-



yl)amino]-1,3-dihydro-2H-indol-2-one


12
(3Z)-3-[1H-benzimidazol-2-yl(4-methylphenyl)methylidene]-5-[(1-ethylpiperidin-4-



yl)amino]-1,3-dihydro-2H-indol-2-one


13
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[1H-imidazol-2-yl(4-



methylphenyl)methylidene]-1,3-dihydro-2H-indol-2-one


14
(3Z)-5-[(1-ethylpiperidin-4-yl)oxy]-3-[[5-(methyloxy)-1H-benzimidazol-2-



yl](phenyl)methylidene]-1,3-dihydro-2H-indol-2-one


15
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-{1H-imidazol-2-yl[4-



(methyloxy)phenyl]methylidene}-1,3-dihydro-2H-indol-2-one


16
(3Z)-3-[1H-benzimidazol-2-yl(4-fluorophenyl)methylidene]-5-[(1-ethylpiperidin-4-



yl)amino]-1,3-dihydro-2H-indol-2-one


17
(3Z)-3-[1H-benzimidazol-2-yl(3,5-difluorophenyl)methylidene]-5-[(1-ethylpiperidin-4-



yl)amino]-1,3-dihydro-2H-indol-2-one


18
(3Z)-3-[1H-benzimidazol-2-yl(3-fluorophenyl)methylidene]-5-[(1-ethylpiperidin-4-



yl)amino]-1,3-dihydro-2H-indol-2-one


19
(3Z)-3-[1H-benzimidazol-2-yl(3-nitrophenyl)methylidene]-5-[(1-ethylpiperidin-4-



yl)amino]-1,3-dihydro-2H-indol-2-one


20
3-((Z)-1H-benzimidazol-2-yl{5-[(1-ethylpiperidin-4-yl)amino]-2-oxo-1,2-dihydro-3H-



indol-3-ylidene}methyl)benzonitrile


21
(3Z)-3-[(3-aminophenyl)(1H-benzimidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-



yl)amino]-1,3-dihydro-2H-indol-2-one


22
(3Z)-3-[1H-benzimidazol-2-yl(phenyl)methylidene]-5-(piperidin-4-ylamino)-1,3-



dihydro-2H-indol-2-one


23
3-((Z)-1H-benzimidazol-2-yl{5-[(1-ethylpiperidin-4-yl)amino]-2-oxo-1,2-dihydro-3H-



indol-3-ylidene}methyl)benzenecarboximidamide


24
(3Z)-3-[1H-benzimidazol-2-yl(phenyl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


25
(3Z)-3-[1H-benzimidazol-2-yl(phenyl)methylidene]-5-[(2,2,6,6-tetramethylpiperidin-4-



yl)amino]-1,3-dihydro-2H-indol-2-one


26
(3Z)-3-{1H-benzimidazol-2-yl[3-(methyloxy)phenyl]methylidene}-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


27
(3Z)-3-[1H-benzimidazol-2-yl(3-chlorophenyl)methylidene]-5-[(1-ethylpiperidin-4-



yl)amino]-1,3-dihydro-2H-indol-2-one


28
2-(2-{2-[(Z)-{5-[(1-ethylpiperidin-4-yl)amino]-2-oxo-1,2-dihydro-3H-indol-3-



ylidene}(phenyl)methyl]-1H-imidazol-4-yl}ethyl)-1H-isoindole-1,3(2H)-dione


29
(3Z)-3-[1H-benzimidazol-2-yl(phenyl)methylidene]-5-({1-[2-



(dimethylamino)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


30
(3Z)-3-[1H-benzimidazol-2-yl(phenyl)methylidene]-5-{[1-(methylsulfonyl)piperidin-



4-yl]amino}-1,3-dihydro-2H-indol-2-one


31
(3Z)-5-(8-azabicyclo[3.2.1]oct-3-ylamino)-3-[1H-benzimidazol-2-



yl(phenyl)methylidene]-1,3-dihydro-2H-indol-2-one


32
(3Z)-3-{1H-benzimidazol-2-yl[3-(methyloxy)phenyl]methylidene}-5-[(1-



ethylpiperidin-4-yl)oxy]-1,3-dihydro-2H-indol-2-one


33
(3Z)-3-[1H-benzimidazol-2-yl(3,5-difluorophenyl)methylidene]-5-[(1-ethylpiperidin-4-



yl)oxy]-1,3-dihydro-2H-indol-2-one


34
(3Z)-3-[1H-benzimidazol-2-yl(phenyl)methylidene]-5-{[1-(phenylmethyl)piperidin-4-



yl]oxy}-1,3-dihydro-2H-indol-2-one


35
(3Z)-3-[1H-benzimidazol-2-yl(3-chlorophenyl)methylidene]-5-[(1-ethylpiperidin-4-



yl)oxy]-1,3-dihydro-2H-indol-2-one


36
(3Z)-3-[1H-benzimidazol-2-yl(3,5-difluorophenyl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}oxy)-1,3-dihydro-2H-indol-2-one


37
(3Z)-3-[1H-benzimidazol-2-yl(3-chlorophenyl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}oxy)-1,3-dihydro-2H-indol-2-one


38
(3Z)-3-[1H-benzimidazol-2-yl(3-chlorophenyl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


39
(3Z)-3-{1H-benzimidazol-2-yl[3-(methyloxy)phenyl]methylidene}-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


40
(3Z)-3-[(3-chlorophenyl)(1H-imidazol-2-yl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


41
(3Z)-3-[(3-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


42
(3Z)-3-[1H-benzimidazol-2-yl(3,5-difluorophenyl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


43
(3Z)-3-[1H-benzimidazol-2-yl(3-chlorophenyl)methylidene]-5-[(1-ethylpiperidin-4-



yl)(methyl)amino]-1,3-dihydro-2H-indol-2-one


44
(3Z)-3-[(3-chlorophenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-



yl)oxy]-1,3-dihydro-2H-indol-2-one


45
(3Z)-3-[1H-benzimidazol-2-yl(4-chlorophenyl)methylidene]-5-[(1-ethylpiperidin-4-



yl)amino]-1,3-dihydro-2H-indol-2-one


46
(3Z)-3-[1H-benzimidazol-2-yl(3-fluorophenyl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


47
(3Z)-3-[1H-benzimidazol-2-yl(4-fluorophenyl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


48
(3Z)-3-[(3-chlorophenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-



yl)amino]-1,3-dihydro-2H-indol-2-one


49
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(3-fluorophenyl)(1H-imidazol-2-



yl)methylidene]-1,3-dihydro-2H-indol-2-one


50
(3Z)-3-[1H-benzimidazol-2-yl(3-fluoro-4-methylphenyl)methylidene]-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


51
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(3-fluorophenyl)(4-methyl-lH-imidazol-2-



yl)methylidene]-1,3-dihydro-2H-indol-2-one


52
(3Z)-3-[1H-benzimidazol-2-yl(4-fluoro-3-methylphenyl)methylidene]-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


53
(3Z)-3-[(3-chloro-4-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


54
(3Z)-3-[(3,4-difluorophenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-



yl)amino]-1,3-dihydro-2H-indol-2-one


55
(3Z)-3-[(5-chloro-1H-benzimidazol-2-yl)(phenyl)methylidene]-5-[(1-ethylpiperidin-4-



yl)amino]-1,3-dihydro-2H-indol-2-one


56
(3Z)-3-[(5-chloro-1H-benzimidazol-2-yl)(3,5-difluorophenyl)methylidene]-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


57
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(3-fluoro-4-methylphenyl)(1H-imidazol-2-



yl)methylidene]-1,3-dihydro-2H-indol-2-one


58
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(4-fluorophenyl)(1H-imidazol-2-



yl)methylidene]-1,3-dihydro-2H-indol-2-one


59
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[1H-imidazol-2-yl(4-



propylphenyl)methylidene]-1,3-dihydro-2H-indol-2-one


60
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-{1H-imidazol-2-yl[4-



(trifluoromethyl)phenyl]methylidene}-1,3-dihydro-2H-indol-2-one


61
(3E)-3-[(3,5-difluorophenyl)(5-fluoro-1H-benzimidazol-2-yl)methylidene]-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


62
(3Z)-3-[(3,5-difluorophenyl)(5-fluoro-1H-benzimidazol-2-yl)methylidene]-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


63
(3Z)-3-[(3-fluoro-4-methylphenyl)(1H-imidazol-2-yl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


64
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(4-methyl-1H-imidazol-2-yl)(4-



methylphenyl)methylidene]-1,3-dihydro-2H-indol-2-one


65
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[[3-fluoro-4-(trifluoromethyl)phenyl](1H-



imidazol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one


66
(3Z)-3-[(4-chlorophenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-



yl)amino]-1,3-dihydro-2H-indol-2-one


67
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(3-fluoro-4-methylphenyl)(4-methyl-1H-



imidazol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one


68
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-{1H-imidazol-2-yl[6-(trifluoromethyl)pyridin-



3-yl]methylidene}-1,3-dihydro-2H-indol-2-one


69
(3Z)-3-[1H-imidazol-2-yl(4-methylphenyl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


70
(3Z)-3-[(3-fluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


71
(3Z)-3-{1H-imidazol-2-yl[4-(trifluoromethyl)phenyl]methylidene}-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


72
(3Z)-3-[(5-chloro-1H-benzimidazol-2-yl)(phenyl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


73
(3Z)-3-[(3,5-difluorophenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-



yl)amino]-1,3-dihydro-2H-indol-2-one


74
(3Z)-3-[(3,5-difluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


75
(3Z)-3-[(3,5-difluorophenyl)(1H-imidazol-2-yl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


76
(3Z)-3-[(3,5-difluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


77
(3Z)-3-[(4-methyl-1H-imidazol-2-yl)(4-methylphenyl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


78
(3Z)-3-[(4-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


79
(3Z)-3-[(3,4-difluorophenyl)(1H-imidazol-2-yl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


80
(3Z)-3-[(3-chloro-4-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


81
(3Z)-3-[(3-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-(piperidin-4-ylamino)-1,3-



dihydro-2H-indol-2-one


82
(3Z)-3-[(3-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-{[1-(2-piperidin-1-



ylethyl)piperidin-4-yl]amino}-1,3-dihydro-2H-indol-2-one


83
(3Z)-3-[(3-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-{[1-(2-morpholin-4-



ylethyl)piperidin-4-yl]amino}-1,3-dihydro-2H-indol-2-one


84
(3Z)-5-({1-[2-(diethylamino)ethyl]piperidin-4-yl}amino)-3-[(3-fluorophenyl)(1H-



imidazol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one


85
(3Z)-3-[(3-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-{[1-(2-pyrrolidin-1-



ylethyl)piperidin-4-yl]amino}-1,3-dihydro-2H-indol-2-one


86
(3Z)-3-[1H-imidazol-2-yl(4-methylphenyl)methylidene]-5-[(1-methylpiperidin-4-



yl)amino]-1,3-dihydro-2H-indol-2-one


87
(3Z)-3-[(3-fluorophenyl)(1H-1,2,4-triazol-5-yl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


88
ethyl 2-{(Z)-(3-fluorophenyl)[5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-2-oxo-



1,2-dihydro-3H-indol-3-ylidene]methyl}-4-methyl-1H-imidazole-5-carboxylate


89
(3Z)-3-[1H-imidazol-2-yl(phenyl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-



yl}amino)-1,3-dihydro-2H-indol-2-one


90
(3Z)-3-{1H-imidazol-2-yl[4-(methyloxy)phenyl]methylidene}-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


91
(3Z)-3-[(4-chlorophenyl)(1H-imidazol-2-yl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


92
(3Z)-3-[[3-fluoro-4-(trifluoromethyl)phenyl](1H-imidazol-2-yl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


93
(3Z)-3-[(3-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-{[1-



(methylsulfonyl)piperidin-4-yl]amino}-1,3-dihydro-2H-indol-2-one


94
(3Z)-3-[1H-imidazol-2-yl(4-propylphenyl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


95
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(3-fluorophenyl)(4-phenyl-1H-imidazol-2-



yl)methylidene]-1,3-dihydro-2H-indol-2-one


96
(3Z)-3-[(3-fluorophenyl)(4-phenyl-1H-imidazol-2-yl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


97
(3Z)-3-[(3-fluoro-4-methylphenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


98
(3Z)-3-{1H-imidazol-2-yl[6-(trifluoromethyl)pyridin-3-yl]methylidene}-5-({1-[2-



(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one


99
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(3-fluorophenyl)(1H-1,2,4-triazol-5-



yl)methylidene]-1,3-dihydro-2H-indol-2-one


100
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[[2-fluoro-4-(trifluoromethyl)phenyl](1H-



imidazol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one


101
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-{(4-methyl-1H-imidazol-2-yl)[4-



(trifluoromethyl)phenyl]methylidene}-1,3-dihydro-2H-indol-2-one


102
(3Z)-3-[(4-chlorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


103
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[[3-fluoro-4-(trifluoromethyl)phenyl](4-



methyl-1H-imidazol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one


104
(3Z)-3-[(3,4-difluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


105
(3Z)-3-[(3-chloro-4-fluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


106
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(4-fluorophenyl)(4-methyl-1H-imidazol-2-



yl)methylidene]-1,3-dihydro-2H-indol-2-one


107
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(2-fluorophenyl)(1H-imidazol-2-



yl)methylidene]-1,3-dihydro-2H-indol-2-one


108
(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[[2-fluoro-4-(trifluoromethyl)phenyl](4-



methyl-1H-imidazol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one


109
(3Z)-3-[(2,3-difluorophenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-



yl)amino]-1,3-dihydro-2H-indol-2-one


110
(3Z)-3-[(2,3-difluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


111
(3Z)-3-[(2,4-difluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


112
(3Z)-3-[(2,4-difluorophenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-



yl)amino]-1,3-dihydro-2H-indol-2-one


113
(3Z)-3-[(2-fluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


114
(3Z)-3-[(3-trifluoromethylphenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


115
(3Z)-3-[(3-trifluoromethylphenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


116
(3Z)-3-[(2,4-dichloro-5-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


117
(3Z)-3-[(2,4-dichloro-5-fluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one


118
(3Z)-3-[(4-chloro-2-fluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-[(1-



ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one









The Compounds in Table 8 can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 8 can be used to practice the invention.











Entry
Name
















1
N-[5-chloro-2-(methyloxy)phenyl]-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


2
N-phenyl-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide


3
N-(2-methylphenyl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide


4
N-(2-chlorophenyl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide


5
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


6
ethyl 2-[({[3-(1H-tetrazol-1-yl)phenyl]oxy}acetyl)amino]-4,5,6,7-



tetrahydro-1-benzothiophene-3-carboxylate


7
N-(3-chloro-2-methylphenyl)-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


8
N-(3-fluorophenyl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide


9
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(2H-tetrazol-5-



yl)phenyl]oxy}acetamide


10
N-(4-chloro-2-fluorophenyl)-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


11
N-(4-bromo-3-methylphenyl)-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


12
N-(4-morpholin-4-ylphenyl)-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


13
N-[4-fluoro-3-(trifluoromethyl)phenyl]-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


14
N-[4-bromo-3-(trifluoromethyl)phenyl]-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


15
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[4-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


16
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}propanamide


17
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(5-methyl-1H-tetrazol-1-



yl)phenyl]oxy}acetamide


18
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[2-methyl-5-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


19
N-(4-chlorophenyl)-N-methyl-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


20
N-[4-chloro-2-(trifluoromethyl)phenyl]-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


21
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(2,5-dioxopyrrolidin-1-



yl)phenyl]oxy}acetamide


22
(2E)—N-[4-chloro-3-(trifluoromethyl)phenyl]-3-[3-(1H-tetrazol-1-



yl)phenyl]prop-2-enamide


23
N-[4-fluoro-3-(trifluoromethyl)phenyl]-2-{[4-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


24
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(2-methyl-2H-tetrazol-5-



yl)phenyl]oxy}acetamide


25
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[2,4-dichloro-5-(1H-



tetrazol-1-yl)phenyl]oxy}acetamide


26
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(1H-tetrazol-1-



yl)phenyl]thio}acetamide


27
N-[4-chloro-3-(trifluoromethyl)phenyl]-N~2~-[3-(1H-tetrazol-1-



yl)phenyl]glycinamide


28
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[2-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


29
methyl 1-{3-[(2-{[4-chloro-3-(trifluoromethyl)phenyl]amino}-2-



oxoethyl)oxy]phenyl}-1H-1,2,3-triazole-4-carboxylate


30
1,1-dimethylethyl {4-[({[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetyl)amino]phenyl}carbamate


31
1,1-dimethylethyl {4-[({[4-(1H-tetrazol-1-



yl)phenyl]oxy}acetyl)amino]phenyl}carbamate


32
N-{4-[(1-ethylpiperidin-4-yl)amino]phenyl}-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


33
N-{4-[(1-ethylpiperidin-3-yl)amino]phenyl}-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


34
N-(4-aminophenyl)-2-{[4-(1H-tetrazol-1-yl)phenyl]oxy}acetamide


35
N-{4-[(1-ethylpiperidin-4-yl)amino]phenyl}-2-{[4-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


36
N-{4-[(1-ethylpiperidin-3-yl)amino]phenyl}-2-{[4-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


37
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(3-pyridin-4-



ylphenyl)oxy]acetamide


38
N-[4-chloro-3-(trifluoromethyl)phenyl]-N~2~-methyl-N~2~-[3-(1H-



tetrazol-1-yl)phenyl]glycinamide


39
N-1,3-benzothiazol-2-yl-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide


40
N-quinolin-8-yl-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide


41
N-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


42
N-isoquinolin-5-yl-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide


43
N-{3-[(phenylmethyl)oxy]phenyl}-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


44
N-[5-methyl-2-(methyloxy)phenyl]-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


45
N-[2,5-bis(methyloxy)phenyl]-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide


46
N-(6-fluoro-1,3-benzothiazol-2-yl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide


47
methyl 3-[({[3-(1H-tetrazol-1-yl)phenyl]oxy}acetyl)amino]benzoate


48
5-chloro-2-[({[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetyl)amino]benzamide


49
N-[5-chloro-2,4-bis(methyloxy)phenyl]-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


50
N-[2-(phenyloxy)phenyl]-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


51
N-[3-(aminosulfonyl)phenyl]-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


52
N-[2-(methyloxy)-5-(trifluoromethyl)phenyl]-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


53
N-(4-{[(4-methylphenyl)sulfonyl]amino}phenyl)-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


54
N-(5-phenyl-1H-pyrazol-3-yl)-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


55
N-1,3-benzothiazol-2-yl-2-{[4-(1H-tetrazol-1-yl)phenyl]oxy}acetamide


56
N-quinolin-8-yl-2-{[4-(1H-tetrazol-1-yl)phenyl]oxy}acetamide


57
1,1-dimethylethyl 2-{3-[(2-{[4-chloro-3-



(trifluoromethyl)phenyl]amino}-2-oxoethyl)oxy]phenyl}-1H-pyrrole-



1-carboxylate


58
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(1H-pyrrol-2-



yl)phenyl]oxy}acetamide


59
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(3-pyrimidin-5-



ylphenyl)oxy]acetamide


60
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(1H-1,2,3-triazol-1-



yl)phenyl]oxy}acetamide


61
4-chloro-N-(2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}ethyl)-3-



(trifluoromethyl)aniline


62
N-[4-chloro-3-(trifluoromethyl)phenyl]-N-(2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}ethyl)formamide


63
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(3-pyridin-3-



ylphenyl)oxy]acetamide


64
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(3-furan-3-



ylphenyl)oxy]acetamide


65
(2E)—N-[4-fluoro-3-(trifluoromethyl)phenyl]-3-[3-(1H-tetrazol-1-



yl)phenyl]prop-2-enamide


66
N-[4-fluoro-3-(trifluoromethyl)phenyl]-3-[3-(1H-tetrazol-1-



yl)phenyl]propanamide


67
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[6-(1H-tetrazol-1-



yl)pyrimidin-4-yl]oxy}acetamide


68
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(3,5-dimethylisoxazol-4-



yl)phenyl]oxy}acetamide


69
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(3-quinolin-7-



ylphenyl)oxy]acetamide


70
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(3-furan-2-



ylphenyl)oxy]acetamide


71
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[3-(1H-tetrazol-1-



yl)phenyl]hydrazinecarboxamide


72
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(3-dibenzo[b,d]furan-4-



ylphenyl)oxy]acetamide


73
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(4-pyrimidin-5-



ylphenyl)oxy]acetamide


74
N-methyl-N-[4-(methyloxy)phenyl]-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


75
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-{[3-(1H-tetrazol-1-



yl)phenyl]methyl}urea


76
N-[4-chloro-3-(trifluoromethyl)phenyl]-N-methyl-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


77
N-[4-fluoro-3-(trifluoromethyl)phenyl]-N~2~-[3-(1H-tetrazol-1-



yl)phenyl]glycinamide


78
N-[4-fluoro-3-(trifluoromethyl)phenyl]-2-{[3-(pyridin-2-



ylamino)phenyl]oxy}acetamide


79
N-[2-fluoro-5-(trifluoromethyl)phenyl]-2-[3-(1H-tetrazol-1-



yl)phenyl]hydrazinecarboxamide


80
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(4-pyridin-3-



ylphenyl)oxy]acetamide


81
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[(3-pyrimidin-5-



ylphenyl)methyl]urea


82
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[(4-pyrimidin-5-



ylphenyl)methyl]urea


83
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[(4-pyridin-3-



ylphenyl)methyl]urea


84
[3-(1H-tetrazol-1-yl)phenyl]methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


85
N-[4-fluoro-3-(trifluoromethyl)phenyl]-2-[(4-pyrimidin-5-



ylphenyl)oxy]acetamide


86
N~2~-[4-chloro-3-(trifluoromethyl)phenyl]-N-[3-(1H-tetrazol-1-



yl)phenyl]glycinamide


87
2-{[4-chloro-3-(trifluoromethyl)phenyl]oxy}-N-[3-(1H-tetrazol-1-



yl)phenyl]acetamide


88
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-methyl-4-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


89
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[4-(1H-1,2,3-triazol-1-



yl)phenyl]oxy}acetamide


90
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-fluoro-4-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


91
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[2-fluoro-4-(1H-tetrazol-1-



yl)phenyl]oxy}acetamide


92
N-({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)-3-(1H-



tetrazol-1-yl)benzenesulfonamide


93
N-({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)-N-methyl-3-



(1H-tetrazol-1-yl)benzenesulfonamide


94
N-[4-fluoro-3-(trifluoromethyl)phenyl]-2-[(4-pyridin-3-



ylphenyl)oxy]acetamide


95
2-({4-[2,4-bis(methyloxy)pyrimidin-5-yl]phenyl}oxy)-N-[4-fluoro-3-



(trifluoromethyl)phenyl]acetamide


96
2-({4-[2,4-bis(methyloxy)pyrimidin-5-yl]phenyl}oxy)-N-[4-chloro-3-



(trifluoromethyl)phenyl]acetamide


97
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(4-pyridin-4-



ylphenyl)oxy]acetamide


98
N-[4-chloro-3-(trifluoromethyl)phenyl]-N~2~-[3-(methyloxy)-4-(1H-



tetrazol-1-yl)phenyl]glycinamide


99
N-[4-chloro-3-(trifluoromethyl)phenyl]-N~2~-[4-(methyloxy)-3-(1H-



tetrazol-1-yl)phenyl]glycinamide


100
N-[4-chloro-3-(trifluoromethyl)phenyl]-N~2~-[4-(1H-tetrazol-1-



yl)phenyl]glycinamide


101
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(2,3,5,6-tetrafluoro-4-



pyrimidin-5-ylphenyl)hydrazinecarboxamide


102
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-{[4-(1H-tetrazol-1-



yl)phenyl]methyl}urea


103
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(4-pyrimidin-5-



ylphenyl)hydrazinecarboxamide


104
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[(3-pyridin-3-



ylphenyl)methyl]urea


105
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-methyl-2-{[3-(1H-tetrazol-1-



yl)phenyl]oxy}propanamide


106
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[4-(1H-tetrazol-1-



yl)phenyl]oxy}propanamide


107
N-({4-[2,4-bis(methyloxy)pyrimidin-5-yl]phenyl}methyl)-N′-[4-



chloro-3-(trifluoromethyl)phenyl]urea


108
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-({3-[2-



(methyloxy)pyrimidin-5-yl]phenyl}methyl)urea


109
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-({3-[6-(methyloxy)pyridin-



3-yl]phenyl}methyl)urea


110
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-({4-[2-



(methyloxy)pyrimidin-5-yl]phenyl}methyl)urea


111
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-({4-[6-(methyloxy)pyridin-



3-yl]phenyl}methyl)urea


112
1,1-dimethylethyl 2-{4-[(2-{[4-chloro-3-



(trifluoromethyl)phenyl]amino}-2-oxoethyl)oxy]phenyl}-1H-indole-1-



carboxylate


113
N-({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)-4-(1H-



tetrazol-1-yl)benzenesulfonamide


114
N-[4-chloro-3-(trifluoromethyl)phenyl]-N~2~-[3-(2H-tetrazol-5-



yl)phenyl]glycinamide


115
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[2,6-difluoro-4-(1H-



tetrazol-1-yl)phenyl]oxy}acetamide


116
(3-pyridin-3-ylphenyl)methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


117
(3-pyrimidin-5-ylphenyl)methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


118
(3-pyridin-4-ylphenyl)methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


119
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[4-(1H-tetrazol-1-



yl)phenyl]hydrazinecarboxamide


120
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(4-pyridin-3-



ylphenyl)hydrazinecarboxamide


121
(4-pyridin-3-ylphenyl)methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


122
(4-pyridin-4-ylphenyl)methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


123
(4-pyrimidin-5-ylphenyl)methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


124
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[(4-pyridin-4-



ylphenyl)methyl]urea


125
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(3-pyridin-3-



ylphenyl)hydrazinecarboxamide


126
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(3-pyrimidin-5-



ylphenyl)hydrazinecarboxamide


127
N-[5-chloro-2,4-bis(methyloxy)phenyl]-N′-[(4-pyrimidin-5-



ylphenyl)methyl]urea


128
N-[5-chloro-2,4-bis(methyloxy)phenyl]-N′-[(4-pyridin-3-



ylphenyl)methyl]urea


129
(4-pyrimidin-5-ylphenyl)methyl [5-chloro-2,4-



bis(methyloxy)phenyl]carbamate


130
(4-pyridin-3-ylphenyl)methyl [5-chloro-2,4-



bis(methyloxy)phenyl]carbamate


131
1-(4-pyridin-3-ylphenyl)ethyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


132
1-(4-pyrimidin-5-ylphenyl)ethyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


133
N-[5-chloro-2,4-bis(methyloxy)phenyl]-N′-[(3-pyridin-3-



ylphenyl)methyl]urea


134
N-[5-chloro-2,4-bis(methyloxy)phenyl]-N′-[(3-pyrimidin-5-



ylphenyl)methyl]urea


135
(3-pyridin-3-ylphenyl)methyl [5-chloro-2,4-bis(methyloxy)phenyl]carbamate


136
(3-pyrimidin-5-ylphenyl)methyl [5-chloro-2,4-bis(methyloxy)phenyl]carbamate


137
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-methyl-2-(3-pyrimidin-5-



ylphenyl)hydrazinecarboxamide


138
N-[4-fluoro-3-(trifluoromethyl)phenyl]-N′-[(4-pyridin-3-



ylphenyl)methyl]urea


139
N-{[3-(6-aminopyridin-3-yl)phenyl]methyl}-N′-[4-chloro-3-



(trifluoromethyl)phenyl]urea


140
N-{[4-(6-aminopyridin-3-yl)phenyl]methyl}-N′-[4-chloro-3-



(trifluoromethyl)phenyl]urea


141
N-{[3-(2-aminopyrimidin-5-yl)phenyl]methyl}-N′-[4-chloro-3-



(trifluoromethyl)phenyl]urea


142
N-{[4-(2-aminopyrimidin-5-yl)phenyl]methyl}-N′-[4-chloro-3-



(trifluoromethyl)phenyl]urea


143
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[1-(4-pyridin-3-



ylphenyl)ethyl]urea


144
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[1-(4-pyrimidin-5-



ylphenyl)ethyl]urea


145
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[4-(1H-indol-2-



yl)phenyl]oxy}acetamide


146
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(isoquinolin-7-yloxy)acetamide


147
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(4-pyridin-4-



ylphenyl)hydrazinecarboxamide


148
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(3-pyridin-4-



ylphenyl)hydrazinecarboxamide


149
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[(3-pyridin-4-ylphenyl)methyl]urea


150
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[(3-quinoxalin-6-



ylphenyl)methyl]urea


151
methyl 3-amino-6-(3-{[({[4-chloro-3-



(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazine-



2-carboxylate


152
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[(4-quinoxalin-6-



ylphenyl)methyl]urea


153
N-{[3-(2-amino-5-methylpyridin-3-yl)phenyl]methyl}-N′-[4-chloro-3-



(trifluoromethyl)phenyl]urea


154
methyl 3-amino-6-(4-{[({[4-chloro-3-



(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazine-



2-carboxylate


155
[3-(1H-tetrazol-1-yl)phenyl]methyl [3-chloro-4-



(methyloxy)phenyl]carbamate


156
N-[3-chloro-4-(methyloxy)phenyl]-N′-{[3-(1H-tetrazol-1-



yl)phenyl]methyl}urea


157
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[4-(5-hydroxy-1H-tetrazol-



1-yl)phenyl]oxy}acetamide


158
N-{[3-(2-amino-5-chloropyridin-3-yl)phenyl]methyl}-N′-[4-chloro-3-



(trifluoromethyl)phenyl]urea


159
N-{[4-(2-amino-5-chloropyridin-3-yl)phenyl]methyl}-N′-[4-chloro-3-



(trifluoromethyl)phenyl]urea


160
N-{[3-(6-chloropyridin-3-yl)phenyl]methyl}-N′-[4-chloro-3-



(trifluoromethyl)phenyl]urea


161
N-{[4-(6-chloropyridin-3-yl)phenyl]methyl}-N′-[4-chloro-3-



(trifluoromethyl)phenyl]urea


162
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-{[4-(pyrimidin-2-



yloxy)phenyl]methyl}urea


163
N-({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)-3-(1H-



tetrazol-1-yl)benzamide


164
3-amino-6-(3-{[({[4-chloro-3-



(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-[2-



(dimethylamino)ethyl]pyrazine-2-carboxamide


165
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-{[3-(6-fluoropyridin-3-



yl)phenyl]methyl}urea


166
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-({3-[2-(methyloxy)pyridin-



3-yl]phenyl}methyl)urea


167
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-{[4-(6-fluoropyridin-3-



yl)phenyl]methyl}urea


168
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-({4-[2-(methyloxy)pyridin-



3-yl]phenyl}methyl)urea


169
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-{[4-(6-methylpyridin-3-



yl)phenyl]methyl}urea


170
N-{[4-(2-amino-5-fluoropyridin-3-yl)phenyl]methyl}-N′-[4-chloro-3-



(trifluoromethyl)phenyl]urea


171
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-{[3-(6-methylpyridin-3-



yl)phenyl]methyl}urea


172
N-{[4-(2-aminopyridin-3-yl)phenyl]methyl}-N′-[4-chloro-3-



(trifluoromethyl)phenyl]urea


173
N-{[3-(2-aminopyridin-3-yl)phenyl]methyl}-N′-[4-chloro-3-



(trifluoromethyl)phenyl]urea


174
[3-(6-methylpyridin-3-yl)phenyl]methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


175
[3-(2-amino-5-fluoropyridin-3-yl)phenyl]methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


176
[3-(2-aminopyridin-3-yl)phenyl]methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


177
(3-pyrazin-2-ylphenyl)methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


178
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-({3-[6-



(hydroxymethyl)pyridin-3-yl]phenyl}methyl)urea


179
N-{[3-(6-acetylpyridin-3-yl)phenyl]methyl}-N′-[4-chloro-3-



(trifluoromethyl)phenyl]urea


180
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-{[3-(6-cyanopyridin-3-



yl)phenyl]methyl}urea


181
1,1-dimethylethyl (3S)-3-({[3-amino-6-(3-{[({[4-chloro-3-



(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazin-



2-yl]carbonyl}amino)piperidine-1-carboxylate


182
3-amino-6-(3-{[({[4-chloro-3-



(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-



[(3S)-piperidin-3-yl]pyrazine-2-carboxamide


183
1,1-dimethylethyl (3S)-3-({[3-amino-6-(4-{[({[4-chloro-3-



(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazin-



2-yl]carbonyl}amino)piperidine-1-carboxylate


184
3-amino-6-(4-{[({[4-chloro-3-



(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-



[(3S)-piperidin-3-yl]pyrazine-2-carboxamide


185
[3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


186
N-{[3-(2-amino-5-fluoropyridin-3-yl)phenyl]methyl}-N′-[4-chloro-3-



(trifluoromethyl)phenyl]urea


187
[6-(1H-tetrazol-1-yl)pyridin-2-yl]methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


188
[3-(1H-benzimidazol-2-yl)phenyl]methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


189
[3-(6-amino-2-methylpyridin-3-yl)phenyl]methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


190
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-({3-[5-(methylthio)pyridin-



3-yl]phenyl}methyl)urea


191
[4-(6-methylpyridin-3-yl)phenyl]methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


192
[4-(2-amino-5-fluoropyridin-3-yl)phenyl]methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


193
[4-(2-aminopyridin-3-yl)phenyl]methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


194
(4-pyrazin-2-ylphenyl)methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


195
[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


196
[4-(6-amino-2-methylpyridin-3-yl)phenyl]methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


197
[3-(1H-tetrazol-1-yl)phenyl]methyl 1,3-benzothiazol-2-ylcarbamate


198
[3-(1H-tetrazol-1-yl)phenyl]methyl (5-bromopyridin-2-yl)carbamate


199
(3-pyridin-3-ylphenyl)methyl (3,5-dimethylphenyl)carbamate


200
(3-pyridin-3-ylphenyl)methyl [5-chloro-2-



(methyloxy)phenyl]carbamate


201
[4-(1H-tetrazol-1-yl)phenyl]methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


202
(3-pyrimidin-5-ylphenyl)methyl [5-chloro-2-



(methyloxy)phenyl]carbamate


203
(4-pyrimidin-5-ylphenyl)methyl (3,4-dimethylphenyl)carbamate


204
(3-pyridin-3-ylphenyl)methyl (3,4-dimethylphenyl)carbamate


205
1,1-dimethylethyl 3-({[3-amino-6-(3-{[({[4-chloro-3-



(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazin-



2-yl]carbonyl}amino)piperidine-1-carboxylate


206
1,1-dimethylethyl 3-({[3-amino-6-(4-{[({[4-chloro-3-



(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazin-



2-yl]carbonyl}amino)piperidine-1-carboxylate


207
3-amino-6-(3-{[({[4-chloro-3-



(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-



piperidin-3-ylpyrazine-2-carboxamide


208
3-amino-6-(4-{[({[4-chloro-3-



(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-



piperidin-3-ylpyrazine-2-carboxamide


209
1,1-dimethylethyl 4-{[3-amino-6-(3-{[({[4-chloro-3-



(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazin-



2-yl]carbonyl}piperazine-1-carboxylate


210
1,1-dimethylethyl 4-{[3-amino-6-(4-{[({[4-chloro-3-



(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazin-



2-yl]carbonyl}piperazine-1-carboxylate


211
N-({3-[5-amino-6-(piperazin-1-ylcarbonyl)pyrazin-2-



yl]phenyl}methyl)-N′-[4-chloro-3-(trifluoromethyl)phenyl]urea


212
N-({4-[5-amino-6-(piperazin-1-ylcarbonyl)pyrazin-2-



yl]phenyl}methyl)-N′-[4-chloro-3-(trifluoromethyl)phenyl]urea


213
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-{[3-(1H-pyrazol-4-



yl)phenyl]methyl}urea


214
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-{[4-(1H-pyrazol-4-



yl)phenyl]methyl}urea


215
[3-(2-piperazin-1-ylpyrimidin-5-yl)phenyl]methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


216
[4-(2-piperazin-1-ylpyrimidin-5-yl)phenyl]methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


217
N-{[3-(2-chloropyridin-3-yl)phenyl]methyl}-N′-[4-chloro-3-



(trifluoromethyl)phenyl]urea


218
N-{[4-(2-chloropyridin-3-yl)phenyl]methyl}-N′-[4-chloro-3-



(trifluoromethyl)phenyl]urea


219
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-{[3-(2-fluoropyridin-3-



yl)phenyl]methyl}urea


220
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-{[4-(2-fluoropyridin-3-



yl)phenyl]methyl}urea


221
[3-(1H-tetrazol-1-yl)phenyl]methyl [3-



(trifluoromethyl)phenyl]carbamate


222
[3-(1H-tetrazol-1-yl)phenyl]methyl [6-(trifluoromethyl)pyridin-2-yl]carbamate


223
[3-(1H-tetrazol-1-yl)phenyl]methyl [4-(trifluoromethyl)pyridin-2-yl]carbamate


224
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-({3-[5-(methylthio)pyridin-



2-yl]phenyl}methyl)urea


225
[3-(2,6-dimethylpyridin-3-yl)phenyl]methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


226
{3-[5-(methyloxy)pyridin-3-yl]phenyl}methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


227
2,3′-bipyridin-6-ylmethyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


228
(6-pyrimidin-5-ylpyridin-2-yl)methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


229
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[(3-isoquinolin-4-



ylphenyl)methyl]urea


230
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[(4-isoquinolin-4-



ylphenyl)methyl]urea


231
[6-(1H-tetrazol-1-yl)pyridin-2-yl]methyl [4-(trifluoromethyl)pyridin-2-



yl]carbamate


232
[3-(1H-pyrazol-4-yl)phenyl]methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate


233
[4-(1H-pyrazol-4-yl)phenyl]methyl [4-chloro-3-



(trifluoromethyl)phenyl]carbamate









The Compounds in Table 9 can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 9 can be used to practice the invention.











Entry
Name
















1
4-((E)-2-{3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-



yl}ethenyl)phenol


2
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(4-{3-[5-(4-ethylpiperazin-1-yl)-1H-



benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea


3
N-(3-ethylphenyl)-N′-(4-{3-[5-(4-ethylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-



pyrazol-5-yl}phenyl)urea


4
N-(4-{3-[5-(4-ethylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-



yl}phenyl)-N′-[3-(trifluoromethyl)phenyl]urea


5
N-(3-acetylphenyl)-N′-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-



1H-pyrazol-5-yl}phenyl)urea


6
N-(3,4-dichlorophenyl)-N′-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-



yl]-1H-pyrazol-5-yl}phenyl)urea


7
N-(3-bromophenyl)-N′-(4-{3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-



1H-pyrazol-5-yl}phenyl)urea


8
N-[4-fluoro-3-(trifluoromethyl)phenyl]-N′-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-



benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea


9
N-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-



yl}phenyl)-N′-[4-(phenyloxy)phenyl]urea


10
N-(3-chlorophenyl)-N′-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-



1H-pyrazol-5-yl}phenyl)urea


11
N-[3,5-bis(methyloxy)phenyl]-N′-(4-{3-[6-(4-methylpiperazin-1-yl)-1H-



benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea


12
N-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-



yl}phenyl)-N′-{4-[(trifluoromethyl)oxy]phenyl}urea


13
N-(4-{3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-



yl}phenyl)-N′-[4-(trifluoromethyl)phenyl]urea


14
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-



benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea


15
N-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-



yl}phenyl)-N′-[3-(trifluoromethyl)phenyl]urea


16
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(4-{3-[4-(4-methylpiperazin-1-



yl)phenyl]-1H-pyrazol-5-yl}phenyl)urea


17
N-(3,4-dimethylphenyl)-N′-(4-{5-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazol-



3-yl}phenyl)urea


18
N-(4-chlorophenyl)-N′-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-



1H-pyrazol-5-yl}phenyl)urea


19
N-(3,5-difluorophenyl)-N′-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-



yl]-1H-pyrazol-5-yl}phenyl)urea


20
N-[3-(methyloxy)phenyl]-N′-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-



2-yl]-1H-pyrazol-5-yl}phenyl)urea


21
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(4-{3-[4-(4-ethylpiperazin-1-yl)phenyl]-



1H-pyrazol-5-yl}phenyl)urea


22
N-(3-fluorophenyl)-N′-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-



1H-pyrazol-5-yl}phenyl)urea


23
N-(4-fluorophenyl)-N′-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-



1H-pyrazol-5-yl}phenyl)urea


24
N-(3-cyanophenyl)-N′-(4-{3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-



1H-pyrazol-5-yl}phenyl)urea


25
N-(3,4-difluorophenyl)-N′-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-



yl]-1H-pyrazol-5-yl}phenyl)urea


26
N-[3,4-bis(methyloxy)phenyl]-N′-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-



benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea


27
N-[5-chloro-2-(methyloxy)phenyl]-N′-(4-{5-[4-(4-methylpiperazin-1-yl)phenyl]-



1H-pyrazol-3-yl}phenyl)urea


28
N-(4-{5-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazol-3-yl}phenyl)-N′-[4-



(phenyloxy)phenyl]urea


29
N-(2,4-difluorophenyl)-N′-(4-{3-[6-(4-ethylpiperazin-1-yl)-1H-benzimidazol-2-yl]-



1H-pyrazol-5-yl}phenyl)urea


30
N-{4-[3-(1H-benzimidazol-2-yl)-1H-pyrazol-5-yl]phenyl}-N′-[4-chloro-3-



(trifluoromethyl)phenyl]urea


31
N-{4-[3-(1H-benzimidazol-2-yl)-1H-pyrazol-5-yl]phenyl}-N′-[2-fluoro-5-



(trifluoromethyl)phenyl]urea


32
N-(2,4-difluorophenyl)-N′-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-



yl]-1H-pyrazol-5-yl}phenyl)urea


33
N-{4-[3-(1H-benzimidazol-2-yl)-1H-pyrazol-5-yl]phenyl}-N′-phenylurea


34
N-[3,5-bis(trifluoromethyl)phenyl]-N′-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-



benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea


35
N-(2-fluorophenyl)-N′-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-



1H-pyrazol-5-yl}phenyl)urea


36
4-((E)-2-{5-[(E)-2-phenylethenyl]-1H-pyrazol-3-yl}ethenyl)phenol


37
2-(methyloxy)-4-((E)-2-{5-[(E)-2-phenylethenyl]-1H-pyrazol-3-yl}ethenyl)phenol


38
N-(5-fluoro-2-methylphenyl)-N′-(4-{3-[6-(4-methylpiperazin-1-yl)-1H-



benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea


39
N-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-



yl}phenyl)-N′-phenylurea


40
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(4-{3-[3-(4-methylpiperazin-1-



yl)phenyl]-1H-pyrazol-5-yl}phenyl)urea


41
N-(2,4-difluorophenyl)-N′-(4-{3-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazol-5-



yl}phenyl)urea


42
N-(2,3-dihydro-1,4-benzodioxin-6-yl)-N′-(4-{5-[4-(4-methylpiperazin-1-



yl)phenyl]-1H-pyrazol-3-yl}phenyl)urea


43
N-[2,4-bis(methyloxy)phenyl]-N′-(4-{5-[4-(4-methylpiperazin-1-yl)phenyl]-1H-



pyrazol-3-yl}phenyl)urea


44
4-((E)-2-{3-[(E)-2-(4-fluorophenyl)ethenyl]-1H-pyrazol-5-yl}ethenyl)-2-



(methyloxy)phenol


45
4-{(E)-2-[3-(1-benzofuran-2-yl)-1H-pyrazol-5-yl]ethenyl}phenol


46
N-(4-{3-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazol-5-yl}phenyl)-N′-(2-



phenylethyl)ethanediamide


47
4-{(E)-2-[3-(1H-benzimidazol-2-yl)-1H-pyrazol-5-yl]ethenyl}phenol


48
4-((E)-2-{3-[(E)-2-(4-chlorophenyl)ethenyl]-1H-pyrazol-5-yl}ethenyl)-2-



(methyloxy)phenol


49
4-{(E)-2-[3-(1-benzothien-2-yl)-1H-pyrazol-5-yl]ethenyl}phenol


50
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[4-(3-phenyl-1H-pyrazol-5-



yl)phenyl]urea


51
4-((E)-2-{3-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazol-5-yl}ethenyl)phenol


52
1,1-dimethylethyl {4-[3-(1H-benzimidazol-2-yl)-1H-pyrazol-5-



yl]phenyl}carbamate


53
N-(5-fluoro-2-methylphenyl)-N′-(4-{5-[4-(4-methylpiperazin-1-yl)phenyl]-1H-



pyrazol-3-yl}phenyl)urea


54
4-[(E)-2-(3-phenyl-1H-pyrazol-5-yl)ethenyl]phenol


55
2-(methyloxy)-4-[(E)-2-(5-phenyl-1H-pyrazol-3-yl)ethenyl]phenol


56
4-[(E)-2-(5-naphthalen-2-yl-1H-pyrazol-3-yl)ethenyl]phenol


57
4-{(E)-2-[5-(2-fluorophenyl)-1H-pyrazol-3-yl]ethenyl}phenol


58
4-((E)-2-{3-[3-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazol-5-yl}ethenyl)phenol


59
4-((E)-2-{3-[(E)-2-(2,4-difluorophenyl)ethenyl]-1H-pyrazol-5-yl}ethenyl)-2-



(methyloxy)phenol


60
4-{(E)-2-[5-(4-fluorophenyl)-1H-pyrazol-3-yl]ethenyl}phenol


61
4-{(E)-2-[3-(4-chlorophenyl)-1H-pyrazol-5-yl]ethenyl}phenol


62
4-[(E)-2-(5-pyridin-2-yl-1H-pyrazol-3-yl)ethenyl]phenol


63
4-{(E)-2-[3-(5-chloro-1-benzofuran-2-yl)-1H-pyrazol-5-yl]ethenyl}phenol


64
N-(1,1-dimethylethyl)-N′-(4-{3-[5-(4-ethylpiperazin-1-yl)-1H-benzimidazol-2-yl]-



1H-pyrazol-5-yl}phenyl)urea


65
4-[(E)-2-(3-pyridin-4-yl-1H-pyrazol-5-yl)ethenyl]phenol


66
4-{(E)-2-[3-(3-chlorophenyl)-1H-pyrazol-5-yl]ethenyl}phenol


67
4-((E)-2-{5-[2-(methyloxy)phenyl]-1H-pyrazol-3-yl}ethenyl)phenol


68
4-{(E)-2-[3-(2-chlorophenyl)-1H-pyrazol-5-yl]ethenyl}phenol


69
4-[(E)-2-(3-pyridin-3-yl-1H-pyrazol-5-yl)ethenyl]phenol


70
4-((E)-2-{5-[3-(methyloxy)phenyl]-1H-pyrazol-3-yl}ethenyl)phenol


71
1,1-dimethylethyl (4-{3-[(E)-2-phenylethenyl]-1H-pyrazol-5-yl}phenyl)carbamate


72
4-{(E)-2-[3-(3,4-dichlorophenyl)-1H-pyrazol-5-yl]ethenyl}phenol


73
2-{5-[(E)-2-phenylethenyl]-1H-pyrazol-3-yl}-1-benzofuran-6-ol


74
4-{(E)-2-[5-(3-fluorophenyl)-1H-pyrazol-3-yl]ethenyl}phenol


75
2-(5-phenyl-1H-pyrazol-3-yl)-1H-benzimidazole


76
N-phenyl-N′-[4-(3-phenyl-1H-pyrazol-5-yl)phenyl]urea


77
4-[3-(1H-benzimidazol-2-yl)-1H-pyrazol-5-yl]aniline


78
4-[(E)-2-(5-biphenyl-3-yl-1H-pyrazol-3-yl)ethenyl]phenol


79
4-((E)-2-{5-[5-(4-methylpiperazin-1-yl)-1H-



benzimidazol-2-yl]-1H-pyrazol-3-yl}ethenyl)phenol









General Administration
In one aspect, the invention provides pharmaceutical compositions comprising an inhibitor of PI3K according to the invention and a pharmaceutically acceptable carrier, excipient, or diluent. In certain other specific embodiments, administration may specifically be by the oral route. Administration of the compounds of the invention, or their pharmaceutically acceptable salts, in pure form or in an appropriate pharmaceutical composition, can be carried out via any of the accepted modes of administration or agents for serving similar utilities. Thus, administration can be, for example, orally, nasally, parenterally (intravenous, intramuscular, or subcutaneous), topically, transdermally, intravaginally, intravesically, intracistemally, or rectally, in the form of solid, semi-solid, lyophilized powder, or liquid dosage forms, such as for example, tablets, suppositories, pills, soft elastic and hard gelatin capsules, powders, solutions, suspensions, or aerosols, or the like, specifically in unit dosage forms suitable for simple administration of precise dosages. When treating brain cancers, including glioblastomas, the administration may specifically be by placing a gliadel, a dissolvable material that contains the chemotherapy drug (in particular BCNU), directly into brain tumors during an operation.
The compositions will include a compound of Formula I or II as the/an active agent and can include a conventional pharmaceutical carrier or excipient and in addition may include other medicinal agents and pharmaceutical agents that are generally administered to a patient being treated for cancer.
Adjuvants include preserving, wetting, suspending, sweetening, flavoring, perfuming, emulsifying, and dispensing agents. Prevention of the action of microorganisms can be ensured by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, and the like. It may also be desirable to include isotonic agents, for example sugars, sodium chloride, and the like. Prolonged absorption of the injectable pharmaceutical form can be brought about by the use of agents delaying absorption, for example, aluminum monostearate and gelatin.
If desired, a pharmaceutical composition of the invention may also contain minor amounts of auxiliary substances such as wetting or emulsifying agents, pH buffering agents, antioxidants, and the like, such as, for example, citric acid, sorbitan monolaurate, triethanolamine oleate, butylalted hydroxytoluene, etc.
The choice of formulation depends on various factors such as the mode of drug administration (e.g., for oral administration, formulations in the form of tablets, pills or capsules) and the bioavailability of the drug substance. Recently, pharmaceutical formulations have been developed especially for drugs that show poor bioavailability based upon the principle that bioavailability can be increased by increasing the surface area i.e., decreasing particle size. For example, U.S. Pat. No. 4,107,288 describes a pharmaceutical formulation having particles in the size range from 10 to 1,000 nm in which the active material is supported on a crosslinked matrix of macromolecules. U.S. Pat. No. 5,145,684 describes the production of a pharmaceutical formulation in which the drug substance is pulverized to nanoparticles (average particle size of 400 nm) in the presence of a surface modifier and then dispersed in a liquid medium to give a pharmaceutical formulation that exhibits remarkably high bioavailability.
Compositions suitable for parenteral injection may comprise physiologically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, and sterile powders for reconstitution into sterile injectable solutions or dispersions. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (propyleneglycol, polyethyleneglycol, glycerol, and the like), suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants.
One specific route of administration is oral, using a convenient daily dosage regimen that can be adjusted according to the degree of severity of the disease-state to be treated.
Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is admixed with at least one inert customary excipient (or carrier) such as sodium citrate or dicalcium phosphate or (a) fillers or extenders, as for example, starches, lactose, sucrose, glucose, mannitol, and silicic acid, (b) binders, as for example, cellulose derivatives, starch, alignates, gelatin, polyvinylpyrrolidone, sucrose, and gum acacia, (c) humectants, as for example, glycerol, (d) disintegrating agents, as for example, agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, croscarmellose sodium, complex silicates, and sodium carbonate, (e) solution retarders, as for example paraffin, (f) absorption accelerators, as for example, quaternary ammonium compounds, (g) wetting agents, as for example, cetyl alcohol, and glycerol monostearate, magnesium stearate and the like (h) adsorbents, as for example, kaolin and bentonite, and (i) lubricants, as for example, talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, or mixtures thereof. In the case of capsules, tablets, and pills, the dosage forms may also comprise buffering agents.
Solid dosage forms as described above can be prepared with coatings and shells, such as enteric coatings and others well known in the art. They may contain pacifying agents, and can also be of such composition that they release the active compound or compounds in a certain part of the intestinal tract in a delayed manner. Examples of embedded compositions that can be used are polymeric substances and waxes. The active compounds can also be in microencapsulated form, if appropriate, with one or more of the above-mentioned excipients.
Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs. Such dosage forms are prepared, for example, by dissolving, dispersing, etc., a compound(s) of the invention, or a pharmaceutically acceptable salt or solvate thereof, and optional pharmaceutical adjuvants in a carrier, such as, for example, water, saline, aqueous dextrose, glycerol, ethanol and the like; solubilizing agents and emulsifiers, as for example, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propyleneglycol, 1,3-butyleneglycol, dimethylformamide; oils, in particular, cottonseed oil, groundnut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol, tetrahydrofurfuryl alcohol, polyethyleneglycols and fatty acid esters of sorbitan; or mixtures of these substances, and the like, to thereby form a solution or suspension.
Suspensions, in addition to the active compounds, may contain suspending agents, as for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, or mixtures of these substances, and the like.
Compositions for rectal administrations are, for example, suppositories that can be prepared by mixing the compounds of the present invention with for example suitable non-irritating excipients or carriers such as cocoa butter, polyethyleneglycol or a suppository wax, which are solid at ordinary temperatures but liquid at body temperature and therefore, melt while in a suitable body cavity and release the active component therein.
Dosage forms for topical administration of a compound of this invention include ointments, powders, sprays, and inhalants. The active component is admixed under sterile conditions with a physiologically acceptable carrier and any preservatives, buffers, or propellants as may be required. Ophthalmic formulations, eye ointments, powders, and solutions are also contemplated as being within the scope of this invention.
Compressed gases may be used to disperse a compound of this invention in aerosol form. Inert gases suitable for this purpose are nitrogen, carbon dioxide, etc.
Generally, depending on the intended mode of administration, the pharmaceutically acceptable compositions will contain about 1% to about 99% by weight of a compound(s) of the invention, or a pharmaceutically acceptable salt or solvate thereof, and 99% to 1% by weight of a suitable pharmaceutical excipient. In one example, the composition will be between about 5% and about 75% by weight of a compound(s) of the invention, or a pharmaceutically acceptable salt or solvate thereof, with the rest being suitable pharmaceutical excipients.
Actual methods of preparing such dosage forms are known, or will be apparent, to those skilled in this art; for example, see Remington's Pharmaceutical Sciences, 18th Ed., (Mack Publishing Company, Easton, Pa., 1990). The composition to be administered will, in any event, contain a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt or solvate thereof, for treatment of a disease-state in accordance with the teachings of this invention.
The compounds of the invention, or their pharmaceutically acceptable salts, are administered in a therapeutically effective amount which will vary depending upon a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of the compound, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular disease-states, and the host undergoing therapy. The compounds of the present invention can be administered to a patient at dosage levels in the range of about 0.1 to about 1,000 mg per day. For a normal human adult having a body weight of about 70 kilograms, a dosage in the range of about 0.01 to about 100 mg per kilogram of body weight per day is an example. The specific dosage used, however, can vary. For example, the dosage can depend on a number of factors including the requirements of the patient, the severity of the condition being treated, and the pharmacological activity of the compound being used. The determination of optimum dosages for a particular patient is well known to one of ordinary skill in the art.
If formulated as a fixed dose, such combination products employ the compounds of this invention within the dosage range described above and the other pharmaceutically active agent(s) within its approved dosage range. Compounds of the instant invention may alternatively be used sequentially with known pharmaceutically acceptable agent(s) when a combination formulation is inappropriate.
Representative pharmaceutical formulations containing a compound of Formula I or II are described below in the Pharmaceutical Composition Examples.
UTILITY
Certain compounds of Formula I have been tested using the assay described in Biological Example 1 and have been determined to be PI3K inhibitors. As such compounds of Formula I are useful for treating diseases, particularly cancer in which PI3K activity contributes to the pathology and/or symptomatology of the disease. For example, cancer in which PI3K activity contributes to its pathology and/or symptomatology include breast cancer, colon cancer, rectal cancer, endometrial cancer, gastric carcinoma, glioblastoma, hepatocellular carcinoma, small cell lung cancer, non-small cell lung cancer, melanoma, ovarian cancer, pancreatic cancer, prostate carcinoma, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), and thyroid carcinoma, and the like.
Suitable in vitro assays for measuring PI3K activity and the inhibition thereof by compounds are known. Typically, the assay will measure PI3K-induced ATP consumption. For further details of an in vitro assay for measuring PI3K activity see Biological Examples, Example 1 infra. Cellular activity can be determined using assays as described in Biological Examples 2, 3, and 4 infra. Suitable in vivo models of cancer are known to those of ordinary skill in the art. For further details of in vivo assays see Biological Examples 5-10, infra. Examples describing the administration of a Compound of Formula I in combination with anticancer agents are described in Biological Examples 11-14, infra. Following the examples disclosed herein, as well as that disclosed in the art, a person of ordinary skill in the art can determine what combinations of a Compound of Formula I and anti-cancer agents would be effective for treating cancer.
Preparations of the Intermediates and Compounds of the Invention
Compounds of this invention can be made by the synthetic procedures described in WO 2007/044729, the disclosure of which is incorporated by reference herein.
The starting materials and reagents used in preparing these compounds are either available from commercial suppliers such as Aldrich Chemical Co. (Milwaukee, Wis.), or Bachem (Torrance, Calif.), or are prepared by methods known to those skilled in the art following procedures set forth in references such as Fieser and Fieser's Reagents for Organic Synthesis, Volumes 1-17 (John Wiley and Sons, 1991); Rodd's Chemistry of Carbon Compounds, Volumes 1-5 and Supplementals (Elsevier Science Publishers, 1989); Organic Reactions, Volumes 1-40 (John Wiley and Sons, 1991), March's Advanced Organic Chemistry, (John Wiley and Sons, 4th Edition) and Larock's Comprehensive Organic Transformations (VCH Publishers Inc., 1989). These schemes are merely illustrative of some methods by which the compounds of this invention can be synthesized, and various modifications to these schemes can be made and will be suggested to one skilled in the art having referred to this disclosure. The starting materials and the intermediates of the reaction may be isolated and purified if desired using conventional techniques, including but not limited to filtration, distillation, crystallization, chromatography and the like. Such materials may be characterized using conventional means, including physical constants and spectral data.
Unless specified to the contrary, the reactions described herein take place at atmospheric pressure and over a temperature range from about −78° C. to about 150° C., in another embodiment from about 0° C. to about 125° C. and most specifically at about room (or ambient) temperature, e.g., about 20° C. Unless otherwise stated (as in the case of a hydrogenation), all reactions are performed under an atmosphere of nitrogen.
Prodrugs can be prepared by techniques known to one skilled in the art. These techniques generally modify appropriate functional groups in a given compound. These modified functional groups regenerate original functional groups by routine manipulation or in vivo. Amides and esters of the compounds of the present invention may be prepared according to conventional methods. A thorough discussion of prodrugs is provided in T. Higuchi and V. Stella, “Pro-drugs as Novel Delivery Systems,” Vol 14 of the A.C.S. Symposium Series, and in Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987, both of which are incorporated herein by reference for all purposes.
The compounds of the invention, or their pharmaceutically acceptable salts, may have asymmetric carbon atoms or quaternized nitrogen atoms in their structure. Compounds of Formula I that may be prepared through the syntheses described herein may exist as single stereoisomers, racemates, and as mixtures of enantiomers and diastereomers. The compounds may also exist as geometric isomers. All such single stereoisomers, racemates and mixtures thereof, and geometric isomers are intended to be within the scope of this invention. Some of the compounds of the invention may exist as tautomers. For example, where a ketone or aldehyde is present, the molecule may exist in the enol form; where an amide is present, the molecule may exist as the imidic acid; and where an enamine is present, the molecule may exist as an imine. All such tautomers are within the scope of the invention.
In particular, in this application B can be 2-hydroxy-pyridinyl, also described as its structure:




Both 2-hydroxy-pyridinyl and the above structure 14 include, and are equivalent to, pyridin-2(1H)-one and its structure 15:





Regardless of which structure or which terminology is used, each tautomer is included within the scope of the Invention.

The present invention also includes N-oxide derivatives and protected derivatives of compounds of Formula I. For example, when compounds of Formula I contain an oxidizable nitrogen atom, the nitrogen atom can be converted to an N-oxide by methods well known in the art. When compounds of Formula I contain groups such as hydroxy, carboxy, thiol or any group containing a nitrogen atom(s), these groups can be protected with a suitable “protecting group” or “protective group”. A comprehensive list of suitable protective groups can be found in T. W. Greene, Protective Groups in Organic Synthesis, John Wiley & Sons, Inc. 1991, the disclosure of which is incorporated herein by reference in its entirety. The protected derivatives of compounds of Formula I can be prepared by methods well known in the art.
Methods for the preparation and/or separation and isolation of single stereoisomers from racemic mixtures or non-racemic mixtures of stereoisomers are well known in the art. For example, optically active (R)- and (S)-isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. Enantiomers (R- and S-isomers) may be resolved by methods known to one of ordinary skill in the art, for example by: formation of diastereoisomeric salts or complexes which may be separated, for example, by crystallization; via formation of diastereoisomeric derivatives which may be separated, for example, by crystallization, selective reaction of one enantiomer with an enantiomer-specific reagent, for example enzymatic oxidation or reduction, followed by separation of the modified and unmodified enantiomers; or gas-liquid or liquid chromatography in a chiral environment, for example on a chiral support, such as silica with a bound chiral ligand or in the presence of a chiral solvent. It will be appreciated that where a desired enantiomer is converted into another chemical entity by one of the separation procedures described above, a further step may be required to liberate the desired enantiomeric form. Alternatively, specific enantiomer may be synthesized by asymmetric synthesis using optically active reagents, substrates, catalysts or solvents or by converting on enantiomer to the other by asymmetric transformation. For a mixture of enantiomers, enriched in a particular enantiomer, the major component enantiomer may be further enriched (with concomitant loss in yield) by recrystallization.
In addition, the compounds of the present invention can exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. In general, the solvated forms are considered equivalent to the unsolvated forms for the purposes of the present invention.
In Compounds of Formula I




the hydrogen on the —NHS(O)2— group is highly acidic. Thus, intermediates leading to Compounds of Formula I, as well as Compounds of Formula I themselves, can be recovered as uncharged or zwitterionic molecules, or cationic salts such a sodium or potassium, depending on the substitutions on the B ring and on reaction conditions. In the examples that follow, unless otherwise specified, the final form of the compound was assumed to be the uncharged molecule in the absence of analytical techniques that would have determined otherwise.

Compounds of Formula I can be prepared using methods known to one of ordinary skill in the art. In another embodiment, fusion of appropriate reagents at 180° C. in the presence of a base such as K2CO3 and metallic copper is known to provide intermediates of formula 1 (see S. H. Dandegaonker and C. K. Mesta, J. Med. Chem. 1965, 8, 884).
Alternatively, the intermediate of formula 3 can be prepared according to the scheme below where each LG1 is a leaving group (in one embodiment halo, in another embodiment chloro) and all other groups are as defined in the Detailed Description of the Invention.




In scheme 1, an intermediate of formula 3 can be prepared by briefly heating commercially available 2,3-dichloroquinoxaline and an intermediate of formula 2 (which are commercially available or can be prepared by one of ordinary skill in the art), a base such as K2CO3, in a solvent, such as DMF or DMSO. Upon completion (about 2 hours), the reaction mixture is then poured into water and followed by 2 N HCl. The product is then extracted into a solvent such as ethyl acetate and washed with water and brine. The organic layers are combined and dried over a drying agent such as sodium sulfate, filtered, and concentrated under vacuum.
The intermediate of formula 3 is then treated with an intermediate of formula 4 in a solvent such as DMF or p-xylene at reflux temperature. Upon completion of the reaction (about 16 hours or less), the reaction is allowed to cool, extracted into DCM, washed with 2 N HCl and brine, dried over a drying agent such as sodium sulfate or magnesium sulfate, filtered, and concentrated to give a compound of Formula I.
Alternatively, other methods to prepare quinoxaline derivatives are known to one skilled in the art and include, but are not limited to S. V. Litvinenko, V. I. Savich, D. D. Bobrovnik, Chem. Heterocycl. Compd. (Engl. Transl), 1994, 30, 340 and W. C. Lumma, R. D. Hartman, J. Med. Chem. 1981, 24, 93.
The following compounds were prepared in a manner similar to that described above.
Example 1
N-(3-{[2,5-bis(methoxy)phenyl]amino}quinoxalin-2-yl)-3-nitrobenzenesulfonamide
Example 2
N-(3-{[2,5-bis(methoxy)phenyl]amino}quinoxalin-2-yl)-4-chlorobenzenesulfonamide
Example 3
N-(3-chloroquinoxalin-2-yl)-3-nitrobenzenesulfonamide
Example 4
4-chloro-N-(3-chloroquinoxalin-2-yl)benzenesulfonamide
Example 5
4-chloro-N-(3-(2,5-dimethoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide
1H NMR (400 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.78 (s, 1H), 8.40-8.60 (m, 3H), 7.98 (t, 2H), 7.62 (d, 1H), 7.41 (m, 2H), 6.98 (d, 1H), 6.59 (d, 1H), 3.78 (s, 3H), 3.76 (s, 3H); MS (EI) m/z for C22H19N5O6S: 482.1 (MH+).
Example 6
N-(3-(2,5-dimethoxyphenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide
1H NMR (400 MHz, CDCl3) δ 12.68 (br s, 1H), 9.18 (s, 1H), 8.55 (s, 1H), 8.08 (d, 2H), 7.98 (d, 1H), 7.78 (d, 2H), 7.62 (dd, 1H), 7.40 (m, 2H), 7.00 (d, 1H), 6.60 (dd, 1H), 3.78 (s, 6H); MS (EI) m/z for C22H19ClN4O4S: 471.1 (MH+).
Example 7
N-(3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-4-methylphenyl)-2-(dimethylamino)acetamide
1H NMR (400 MHz, DMSO-d6) δ 12.0 (br s, 1H), 10.6 (s, 1H), 10.0 (br s, 1H), 9.52 (s, 1H), 8.91 (d, 1H), 8.25 (d, 1H), 7.69 (dd, 1H), 7.47 (m, 1H), 7.39 (d, 1H), 7.16 (m, 3H), 6.01 (dd, 1H); MS (EI) m/z for C26H27ClN6O4S: 555 (MH+).
Compounds of Formula I where B is phenyl substituted with R3a where R3a is alkylamino or dialkylamino or B is heteroaryl substituted with R3 where R3 is amino, alkylamino, or dialkylamino, and all other groups are as defined in the Summary of the Invention can be prepared according to Scheme 2.




LG is a leaving group such as chloro. 5 is reacted with NHRaRb or HO—C1-C6-alkylene-NHRaRb where Ra and Rb are independently hydrogen or alkyl. The reaction is carried out in the presence of a base, such as KHCO3, in a solvent such as DMF.

Compounds of Formula I where B is phenyl substituted with R1a where R3a is aminoalkyloxy, alkylaminoalkyloxy, or dialkylaminoalkyloxy or B is heteroaryl substituted with R3 where R3 is aminoalkyloxy, alkylaminoalkyloxy, or dialkylaminoalkyloxy, and all other groups are as defined in the Summary of the Invention can be prepared according to Scheme 3.




The reaction is carried out in the presence of a base such as NaH in a solvent such as DMF.

Compounds of Formula I where B is phenyl substituted with R3a or B is heteroaryl substituted with R3 where R3a and R3 are

    
    
        i. —N(R7)C(O)—C1-C6-alkylene-N(R7a)(R7b) where R7, R7a, and R7b are as defined in the Summary of the Invention;
        ii. —NR9C(O)R9a where R9 is as defined in the Summary of the Invention;
        iii. —NR11C(O)NR11aR11b where R11a, R11a, and R11b are as defined in the Summary of the Invention;
        iv. —NR13C(O)OR13a where R13 and R13a are as defined in the Summary of the Invention;
        v. —N(R18)C(O)—C1-C6-alkylene-N(R18b)C(O)R18a where R18, R18a, and R18b are as defined in the Summary of the Invention;
        vi. —N(R20)C(O)—C1-C6-alkylene-C(O)R20a where R20 and R20a as defined in the Summary of the Invention;
        vii. —NR21S(O)2—C1-C6-alkylene-N(R21b)R21a where R21, R21a, and R21b are as defined in the Summary of the Invention;
        viii. —N(R22)C(O)—C0-C6-alkylene-N(R22b)—N(R22c)(R22a), where R22, R22a and R22b are as defined in the Summary of the Invention;
        ix. —NR24C(O)—C1-C6-alkylene-OR24a where R24 and R24a are as defined in the Summary of the Invention;

and where the alkylene in R3 and R3a are independently optionally substituted as described in the Summary of the Invention can be prepared according to Scheme 4 by reacting with an intermediate of formula 9(a), 9(b), 9(c), 9(d), 9(e), 9(f), or 9(g):

        9(a) HOC(O)—C1-C6-alkylene-N(R7a)(R7b) where Ra is R7a or a N-protecting group, such as Boc or Fmoc;
        9(b) HOC(O)R9a;
        9(c) HOC(O)NR11aR11b;
        9(d) HOC(O)OR13a;
        9(e) HOC(O)—C1-C6-alkylene-N(R18b)C(O)R18a;
        9(f) HOC(O)—C1-C6-alkylene-C(O)R20a;
        9(g) LG-S(O)2—C1-C6-alkylene-N(R21b)Ra where Ra is R21a or a N-protecting group, such as Boc or Fmoc.
    
    






    R100 in Scheme 4 is —C(O)R9a, —C(O)NR11aR11b, —C(O)OR13a, —C(O)—C1-C6-alkylene-N(R18b)C(O)R18a, —C(O)—C1-C6-alkylene-C(O)R20a, or —S(O)2—C1-C6-alkylene-N(R21b)Ra. The reaction is carried out under standard amide coupling conditions known to one of ordinary skill in the art. In particular, the reaction is carried out in the presence of a coupling agent such as HATU, a base such as DIEA, and in a solvent such as DMF. Where applicable, the N-protecting group is then removed using procedures known to one of ordinary skill in the art, such as treating with acid where PG is Boc.


Proceeding as described for Scheme 4, compounds of the invention where B is phenyl substituted with R3a or B is heteroaryl substituted with R3 where R3a and R3 are

    
    
        a) —C(O)NR8R8a;
        b) —C(O)N(R10)—C1-C6-alkylene-N(R10a)R10b;
        c) —C(O)R12 where R12 is an N-substituted heterocycloalkyl;
        d) —C(O)N(R14)N(R14a)(R14b);
        e) —C(O)N(R16)—C1-C6-alkylene-C(O)OR16a; or
        f) —C(O)N(R19)—C1-C6-alkylene-C(O)R19a; or

can be prepared by exchanging the starting materials as necessary. In particular, the intermediate of formula 11:

    
    






is used instead of 8.

Compounds of Formula I where B is phenyl substituted with R3a or B is heteroaryl substituted with R3 where R3a and R3 are —NHC(O)CH2NR7aR7b where R7a and R7b are as defined in the Summary of the Invention can be prepared according to Scheme 5.




LG is a leaving group such as bromo or chloro. 12 is reacted with NH(R7b)R7a in the presence of a base, such as DIEA, in a solvent such as ACN.

Compounds of Formula I can be prepared according to Scheme 6.




LG in Scheme 6 is a leaving group such as chloro. The reaction can be carried out by irradiating in a solvent such as DMA. Alternatively, the reaction can be carried out in the presence of acetic acid in a solvent such as DMA and by heating.

Example 8
6-chloro-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)pyridine-3-sulfonamide




6-chloropyridine-3-sulfonamide
6-chloropyridine-3-sulfonyl chloride (4.1 g, 19.3 mmol) was stirred in ammonium hydroxide (30 mL) at room temperature for 2 hr. The reaction mixture was diluted with EtOAc (150 mL) and any insoluble material filtered. The filtrate was transferred to a separatory funnel and the phases were separated. The aqueous phase was further extracted with EtOAc (1×15 mL). The combined EtOAc extractions were washed with H2O (1×50 mL) and saturated NaCl (1×50 mL), dried over Na2SO4, and concentrated in vacuo to give 6-chloropyridine-3-sulfonamide (2.58 g, 69%). MS (EI) m/z for C5H5Cl2N2O2S: 190.9 (MH−).
6-chloro-N-(3-chloroquinoxalin-2-yl)pyridine-3-sulfonamide
2,3-dichloroquinoxaline (1.09 g, 5.48 mmol), 6-chloropyridine-3-sulfonamide (1.05 g, 5.45 mmol), K2CO3 (753 mg, 5.45 mmol) and dry DMSO (30 mL) were combined and heated to 150° C. with vigorous stirring for 3-4 hr. The reaction mixture was allowed to cool to room temperature, then poured into 1% AcOH in ice water (300 mL) with vigorous stirring. The resulting solids were filtered, washed with H2O and dried under high vacuum to give 6-chloro-N-(3-chloroquinoxalin-2-yl)pyridine-3-sulfonamide (1.87 g, 96%). MS (EI) m/z for C13H8Cl2N4O2S: 354.99 (MH+).
6-chloro-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)pyridine-3-sulfonamide
6-Chloro-N-(3-chloroquinoxalin-2-yl)pyridine-3-sulfonamide (775 mg, 2.2 mmol), 3,5-dimethoxyaniline (355 mg, 2.3 mmol) and toluene (12 mL) were combined and heated to 125° C. with stirring overnight. The reaction was allowed to cool to room temperature and diluted with Et2O with vigorous stirring. The resulting solids were filtered, washed with Et2O and dried to give 6-chloro-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)pyridine-3-sulfonamide (920 mg, 89%). 1H NMR (400 MHz, DMSO-d6) δ 12.20 (br s, 1H), 9.12 (d, 1H), 9.01 (br s, 1H), 8.53 (dd, 1H), 7.91 (br d, 1H), 7.77 (d, 1H), 7.60 (dd, 1H), 7.40 (m, 4H), 6.26 (m, 1H), 3.78 (s, 6H). MS (EI) m/z for C21H18ClN5O4S: 472.0 (MH+).
Example 9
N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-6-(2-(dimethylamino)-ethylamino)pyridine-3-sulfonamide




6-chloro-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-pyridine-3-sulfonamide (100 mg, 0.21 mmol), prepared using procedures similar to those used in Example 8, KHCO3 (40 mg, 0.40 mmol), N1,N1-dimethylethane-1,2-diamine (225 μL, 2.0 mmol) and dry DMF (1.0 mL) were combined and heated to 130° C. with stirring overnight. The reaction mixture was concentrated in vacuo and purified by preparative HPLC to give N-(3-(3,5-dimethoxyphenylamino)-quinoxalin-2-yl)-6-(2-(dimethylamino)ethylamino)pyridine-3-sulfonamide (21.0 mg, 19%). 1H NMR (400 MHz, DMSO-d6) δ 8.76 (br s, 1H), 8.63 (d, 1H), 8.07 (dd, 1H), 7.40 (m, 1H), 7.34 (m, 1H), 7.28 (d, 2H), 7.14 (m, 4H), 6.47 (d, 1H), 6.12 (m, 1H), 3.75 (s, 6H), 3.35 (m, 2H), 3.14 (m, 2H), 2.74 (s, 6H). MS (EI) m/z for C25H29N7O4S: 524.1 (MH+).
Example 10
N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-6-(dimethylamino)pyridine-3-sulfonamide was prepared using procedures similar to those used in Example 9. 1H NMR (400 MHz, DMSO-d6) δ 12.00 (br s, 1H), 8.92 (br s, 1H), 8.74 (d, 1H), 8.10 (dd, 1H), 7.38 (br s, 1H), 7.54 (m, 1H), 7.33 (m, 4H), 6.70 (d, 1H), 6.22 (s, 1H), 3.77 (s, 6H), 3.08 (s, 6H). MS (EI) m/z for C23H24N6O4S: 481.1 (MH+).
Example 11
N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-6-(2-(dimethylamino)-ethoxy)pyridine-3-sulfonamide




N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)pyridine-3-sulfonamide (100 mg, 0.21 mmol), prepared using procedures similar to those described above in Example 1,2-(dimethylamino)ethanol (50 μL, 0.50 mmol) and dry DMF were combined and 60% NaH in oil (80 mg, 2.0 mmol) was added. The mixture was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and purified by preparative HPLC to give N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-6-(2-(dimethylamino)ethoxy)pyridine-3-sulfonamide (23 mg, 21%). 1H NMR (400 MHz, DMSO-d6) δ 8.78 (d, 1H), 8.73 (s, 1H), 8.38 (dd, 1H), 7.40 (dd, 1H), 7.31 (m, 3H), 7.14 (m, 2H), 6.85 (d, 1H), 6.12 (m, 1H), 4.56 (m, 2H), 3.76 (s, 6H), 3.43 (m, 2H), 2.77 (s, 6H). MS (EI) m/z for C25H28N6O5S: 525.1 (MH+).
Example 12
N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-6-oxo-1,6-dihydropyridine-3-sulfonamide




N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)pyridine-3-sulfonamide (220 mg, 0.47 mmol), prepared using procedures similar to those described above in Example 8, DMSO (5 mL), and 3N NaOH (5 mL) are combined and heated to 100° C. overnight with stirring. Upon cooling to room temperature, the reaction mixture was diluted with H2O and the pH was adjusted to 7.0 with 1N HCl. The resulting solid was filtered, washed with H2O, and air-dried. The solid was then sonicated in EtOAc, filtered, washed with EtOAc, and dried under high vacuum to give N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-6-oxo-1,6-dihydropyridine-3-sulfonamide (190 mg, 90%). 1H NMR (400 MHz, DMSO-d6) δ 12.23 (br s, 1H), 12.10 (br s, 1H), 8.97 (s, 1H), 8.23 (s, 1H), 7.95 (m, 2H), 7.59 (m, 1H), 7.37 (m, 4H), 6.43 (d, 1H), 6.25 (s, 1H), 3.77 (s, 6H). MS (EI) m/z for C21H19N5O5S: 454.0 (MH+).
Example 13
N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)-6-oxo-1,6-dihydropyridine-3-sulfonamide
The title compound was prepared according to the above Example 12. 1H NMR (400 MHz, DMSO-d6) δ 12.22 (br s, 1H), 12.10 (br s, 1H), 9.16 (s, 1H), 8.60 (s, 1H), 8.14 (d, 1H), 7.94 (m, 1H), 7.85 (dd, 1H), 7.62 (m, 1H), 7.40 (m, 3H) 6.69 (dd, 1H), 6.43 (d, 1H), 3.81 (s, 3H). MS (EI) m/z for C20H16ClN5O4S: 456.0 (MH−).
Example 14
3-amino-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide




N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide
A flask was charged with N-(3-chloroquinoxalin-2-yl)-3-nitrobenzenesulfonamide (5 g, 13.7 mmol), prepared using procedures similar to those in Example 1, 3,5-dimethoxyaniline (4.2 g, 27.4 mmol), and 80 mL of xylene. The reaction mixture was stirred under an N2 atmosphere at 150° C. for 3 hours, after which time, solvent was removed on a rotary evaporator, and 10 mL of Dichloromethane and 50 mL of methanol were added. The slurry was heated to reflux and filtered while hot, resulting in 4.6 g (69.7%) of N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide MS (EI) m/z for C22H19N5O6S: 482.2 (MH+).
Example 15
3-amino-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide




A flask was charged with N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-3-nitro-benzenesulfonamide (3.4 g, 7.06 mmol), prepared using procedures similar to those in Example 14, tin chloride solvate (6.4 g, 28.2 mmol), and 30 mL of DMA. A few drops of water were added and the reaction mixture was stirred at 80° C. for 3 hours, after which time, solvent was removed on a rotary evaporator, and 50 mL of water and 10 mL of Methanol were added. The slurry was filtered, and the filtrate was washed with MeOH, water, and diethyl ether (20 mL of each), resulting in 3.25 g 3-amino-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. 1H NMR (400 MHz, DMSO) δ 12.2 (br s, 1H), 8.85 (s, 1H), 7.90 (br s, 1H), 7.50-7.60 (m, 1H), 7.3-7.4 (m, 4H), 7.2 (m, 3H), 6.74 (m, 1H), 6.24 (m, 1H), 5.56 (br s, 2H), 3.76 (s, 6H). MS (EI) m/z for C22H21N5O4S: 452.0 (MH+).
The following compounds were made using procedures similar to those used in Example 15.
Example 16
Proceeding as above, 3-amino-N-(3-(2,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide was prepared. 1H NMR (400 MHz, DMSO) δ 12.4 (br s, 1H), 9.20 (s, 1H), 8.56 (d, 1H), 7.95 (d, 1H), 7.62 (m, 1H), 7.38 (m, 2H), 7.24 (q, 2H), 7.14 (d, 1H), 6.98 (d, 1H), 6.8 (m, 1H), 6.60 (m, 1H), 5.6 (br s, 2H), 3.78 (d, 6H). MS (EI) m/z for C22H21N5O4S: 452.3 (MH+).
Example 17
Proceeding as above, 3-amino-N-(3-(2-chloro-5-hydroxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide was prepared. MS (EI) m/z for C20H16ClN5O3S 1.0×C2H1O2F3: 442.2, 444.2 (MH+).
Example 18
Proceeding as above, 3-amino-N-(3-(6-methoxyquinolin-8-ylamino)quinoxalin-2-yl)benzenesulfonamide was prepared. MS (EI) m/z for C24H20N6O3S: 473.0 (MH+).
Example 19
3-amino-N-(3-(3-fluoro-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z for C21H18FN5O3S: 439.99 (MH+).
Example 20
3-amino-N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z for C21H18ClN5O3S: 457.02 (MH+).
Example 21
3-amino-N-(3-(5-methoxy-2-methyl-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z for C22H21N5O3S: 436.32 (MH+).
Example 22a and Example 22b
3-amino-N-(3-(3-methoxy-5-nitro-phenylamino)quinoxalin-2-yl)benzenesulfonamide and 3-amino-N-(3-(3-amino-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide




To a mixture of N-(3-{[3-(methyloxy)-5-nitrophenyl]amino}quinoxalin-2-yl)-3-nitrobenzenesulfonamide (400 mg), THF (2 mL) and EtOH (2 mL) was added formic acid (938 μL), potassium formate (203 mg). After the mixture was flushed with N2, 10% wt Pd/C (50 mg) was added. The resulting mixture was heated at 60° C. with stirring. LC/MS analysis indicated that the reaction mixture contained the complete reduced di-amino compound as the major product and the partially reduced mono-amino compound as a minor product. A portion of the crude mixture was purified by HPLC to give the two products. Product A: 3-amino-N-(3-(3-methoxy-5-nitro-phenylamino)quinoxalin-2-yl)benzenesulfonamide. 1H NMR (400 MHz, DMSO) δ 12.2 (br s, 1H), 9.51 (s, 1H), 8.77 (s, 1H), 8.21 (s, 1H), 7.92 (s, 1H), 7.48 (m, 1H), 7.43-7.38 (m, 3H), 7.24-7.16 (m, 3H), 6.75 (d, 1H), 5.57 (br s, 2H), 3.90 (s, 3H). MS (EI) for C21H18N6O5S: 467.00 (MH+). Product B: 3-amino-N-(3-(3-amino-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. 1H NMR (400 MHz, DMSO) δ 12.0 (br. s, 1H), 8.53 (s, 1H), 7.84 (s, 1H), 7.56 (d, 1H), 7.37-7.30 (m, 2H), 7.21-7.17 (m, 3H), 6.87 (s, 1H), 6.81 (s, 1H), 6.74 (br s, 2H), 5.91 (s, 1H), 5.56 (br s, 3H), 3.69 (s, 3H). MS (EI) for C21H20N6O3S: 437.2 (MH+).
Example 23a and Example 23b
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3-(hydroxyamino)-benzenesulfonamide and 3-amino-N-(3-{[3,5-(dimethoxy)phenyl]amino}quinoxalin-2-yl)benzenesulfonamide




To a solution N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide (1.3 g) in 20 mL of THF and 10 mL of MeOH was added 10% wt Pd/C (100 mg). The mixture was stirred under a H2 balloon overnight. A portion of the reaction mixture was taken out and filtered, then purified by HPLC to afford two products. Product A: N-(3-{[3,5-bis(methyloxy)phenyl]amino}quinoxalin-2-yl)-3-(hydroxyamino)benzenesulfonamide. MS (EI) for C22H21N5O5S: 468.1 (MH+). Product B: 3-amino-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. 1H NMR (400 MHz, DMSO) δ 12.2 (br s, 1H), 8.85 (s, 1H), 7.90 (br s, 1H), 7.50-7.60 (m, 1H), 7.3-7.4 (m, 4H), 7.2 (m, 3H), 6.74 (m, 1H), 6.24 (m, 1H), 5.56 (br s, 2H), 3.76 (s, 6H). MS (EI) for C22H21N5O4S: 452.0 (MH+).
Example 24
(S)-2-amino-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)propanamide hydrochloride




(S)-tert-butyl 1-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenylamino)-1-oxopropan-2-ylcarbamate
3-amino-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide (1.1 mmol, 500 mg), prepared using procedures similar to those described above in Example 15, (L)-Boc-Ala-OH (1.5 mmol, 284 mg), dichloromethane (15 mL), DMF (10 mL), DIEA (2 mmol, 330 μL), and HATU (2 mmol, 760 mg) stirred at room temperature over night. The crude mixture was column purified using 1/1 ethyl acetate/hexanes on silica to gave 160 mg.
(S)-2-amino-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)propanamide hydrochloride
4 N HCl is dioxane (10 mL) was added to a solution of (S)-tert-butyl 1-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenylamino)-1-oxopropan-2-ylcarbamate (160 mg) and DCM (15 mL). The mixture was stirred at room temperature for 3 hours. The solvent decanted and ether added to the solid, ether decanted to gave 80 mg product as HCl salt. 1H NMR (400 MHz, CD3OD) δ 8.50-8.49 (t, 1H), 7.89-7.87 (m, 1H), 7.74-7.72 (m, 1H), 7.61-7.5 (m, 3H), 7.40-7.36 (m, 2H), 7.21-7.20 (d, 2H), 6.23-6.21 (t, 1H), 4.09-4.03 (q, 1H), 3.78 (s, 6H), 1.60-1.58 (d, 3H); MS (EI) m/z for C25H26N6O5S.HCl: 523.1 (MH+).
The following compounds were prepared as the free amine and/or HCl salt using procedures similar to those in Example 24. Where the deprotection step is not necessary, Step B in the above scheme was not preformed.
Example 25
N-(2-chloro-5-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)acetamide
The title compound was prepared according to the Examples above. 1H NMR (400 MHz, DMSO-d6) δ 10.50 (s, 1H), 9.14 (s, 1H), 9.03 (m, 2H), 8.63 (d, 1H), 8.44 (d, 1H), 7.98 (m, 1H), 7.91 (dd, 1H), 7.80 (d, 1H), 7.67 (m, 1H), 7.44 (m, 3H), 6.71 (dd, 1H), 4.06 (m, 2H), 3.83 (s, 3H), 2.64 (t, 3H). MS (EI) m/z for C24H22Cl2N6O4S: 561.0 (MH+).
Example 26
(S)-2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)propanamide hydrochloride
1H NMR (400 MHz, CD3OD) δ 8.72-8.71 (d, 1H), 8.48-8.46 (t, 1H), 7.86-7.84 (m, 1H), 7.80-7.78 (m, 1H), 7.63-7.59 (m, 2H), 7.58-7.55 (t, 1H), 7.41-7.38 (m, 2H), 7.24-7.22 (d, 1H), 6.60-6.58 (dd, 1H), 4.10-4.04 (q, 1H), 3.83 (s, 3H), 1.61-1.60 (d, 3H); MS (EI) m/z for C24H23ClN6O4S.HCl: 527.2 (MH+).
Example 27
(S)-2-amino-N-(3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)butanamide hydrochloride
1H NMR (400 MHz, CD3OD) δ 8.74-8.73 (d, 1H), 8.80-8.47 (t, 1H), 7.87-7.85 (m, 1H), 7.80-7.78 (m, 1H), 7.67-7.61 (m, 2H), 7.59-7.55 (t, 1H), 7.42-7.39 (m, 2H), 7.26-7.24 (d, 1H), 6.62-6.59 (dd, 1H), 3.96-3.93 (t, 1H), 3.84 (s, 3H), 2.02-1.94 (m, 2H, 1.09-1.06 (t, 3H); MS (EI) m/z for C25H25ClN6O4S.HCl: 541.3 (MH+).
Example 28
(S)—N-(3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)pyrrolidine-2-carboxamide hydrochloride
1H NMR (400 MHz, CD3OD) δ 8.78-8.77 (d, 1H), 8.47-8.46 (t, 1H), 7.87-7.85 (m, 1H), 7.80-7.75 (m, 1H), 7.69-7.65 (m, 2H), 7.59-7.55 (t, 1H), 7.45-7.41 (m, 2H), 7.31-7.28 (d, 1H), 6.65-6.63 (dd, 1H), 4.42-4.38 (m, 1H), 3.86 (s, 3H), 3.48-3.42 (m, 2H), 2.55-2.49 (m, 1H), 2.18-2.08 (m, 3H); MS (EI) m/z for C26H25ClN6O4S.HCl: 553.3 (MH+).
Example 29
(S)—N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)pyrrolidine-2-carboxamide hydrochloride. 1H NMR (400 MHz, CD3OD) δ 10.62 (br s, 1H), 8.50-8.49 (t, 1H), 7.90-7.87 (m, 1H), 7.76-7.73 (m, 1H), 7.63-7.58 (m, 3H), 7.43-7.35 (m, 2H), 7.14 (s, 2H), 6.27-6.26 (t, 1H), 4.43-4.38 (m, 1H), 3.78 (s, 6H), 3.48-3.41 (m, 1H), 3.40-3.36 (m, 1H(, 2.54-2.48 (m, 1H), 2.19-2.05 (m, 3H); MS (EI) m/z for C27H28N6O5S.HCl: 549.3 (MH+).
Example 30
(R)-2-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-hydroxypropanamide hydrochloride
1H NMR (400 MHz, CD3OD) δ 8.49-8.48 (t, 1H), 7.89-7.87 (m, 1H), 7.75-7.72 (m, 1H), 7.65-7.62 (m, 2H), 7.62-7.55 (t, 1H), 7.44-7.38 (m, 2H), 7.23-7.22 (d, 2H), 6.27-6.26 (t, 1H), 4.07-4.05 (m, 1H), 3.99-3.93 (m, 2H), 3.80 (s, 6H); MS (EI) m/z for C25H26N6O6S.HCl: 539.1 (MH+).
Example 31
N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)piperidine-3-carboxamide hydrochloride. 1H NMR (400 MHz, CD3OD) δ 8.79-8.78 (d, 1H), 8.45 (m, 1H), 7.83-7.81 (d, 1H), 7.76-7.74 (m, 1H), 7.636 (m, 2H), 7.54-7.50 (t, 1H), 7.41 (m, 2H), 7.30-7.28 (d, 1H), 6.65-6.62 (dd, 1H), 3.86 (s, 3H), 3.40-3.32 (m, 2H), 3.20-3.13 (m, 3H), 2.93 (m, 1H), 2.15-2.11 (m, 1H), 1.98-1.93 (m, 2H), 1.83 (m, 1H); MS (EI) m/z for C27H27ClN6O4S.HCl: 567.3 (MH+).
Example 32
(S)-2-amino-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)butanamide hydrochloride
MS (EI) m/z for C26H28N6O5S.HCl: 537.1 (MH+).
Example 33
(R)—N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)pyrrolidine-2-carboxamide hydrochloride
MS (EI) m/z for C27H28N6O5S.HCl: 549.1 (MH+).
Example 34
(R)—N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)pyrrolidine-2-carboxamide hydrochloride
MS (EI) m/z for C26H25ClN6O4S.HCl: 553 (MH+).
Example 35
(R)-2-amino-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)propanamide
1H NMR (400 MHz, DMSO-d6) δ 10.2 (br s, 1H), 8.82 (s, 1H), 8.27 (m, 1H), 7.75 (m, 2H), 7.33 (m, 5H), 7.13 (m, 2H), 6.14 (t, 1H), 3.77 (s, 6H), 1.39 (d, 3H); MS (EI) m/z for C25H26N6O5S: 523 (MH+).
Example 36
N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)acetamide
1H NMR (400 MHz, DMSO-d6) δ 10.6 (s, 1H), 9.48 (s, 1H), 8.95 (br s, 1H), 8.75 (br s, 1H), 8.19 (br s, 1H), 7.77 (dd, 1H), 7.69 (dd, 1H), 7.41 (m, 4H), 7.17 (m, 2H), 6.60 (dd, 1H), 3.91 (s, 2H), 3.82 (s, 6H), 2.62 (s, 3H); MS (EI) m/z for C24H23ClN6O4S: 527 (MH+).
Example 37
(R)-2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)propanamide
1H NMR (400 MHz, DMSO-d6) δ 10.5 (s, 1H), 9.47 (s, 1H), 8.95 (d, 1H), 8.22 (d, 2H), 8.14 (br s, 2H), 7.76 (m, 2H), 7.40 (m, 4H), 7.17 (m, 2H), 6.60 (m, 1H), 3.97 (q, 1H), 3.96 (s, 3H), 1.45 (d, 3H); MS (EI) m/z for C24H23ClN6O4S: 527 (MH+).
Example 38
2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methylpropanamide
1H NMR (400 MHz, DMSO-d6) δ 10.1 (s, 1H), 9.46 (s, 1H), 8.95 (d, 1H), 8.50 (br s, 1H), 8.27 (m, 1H), 7.81 (m, 2H), 7.47 (m, 1H), 7.37 (m, 3H), 7.17 (m, 2H), 6.61 (dd, 1H), 3.83 (s, 3H), 1.60 (s, 6H); MS (EI) m/z for C25H25ClN6O4S: 541 (MH+).
Example 39
2-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methylpropanamide
1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.89 (s, 1H), 8.32 (br s, 4H), 7.92 (m, 3H), 7.59 (m, 2H), 7.37 (m, 4H), 6.24 (s, 1H), 3.76 (s, 6H), 1.61 (s, 6H); MS (EI) m/z for C26H28N6O5S: 537 (MH+).
Example 40
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-4-methylphenyl)-2-(dimethylamino)acetamide
1H NMR (400 MHz, DMSO-d6) δ 10.58 (s, 1H), 9.80 (br s, 1H), 8.85 (s, 1H), 8.25 (s, 1H), 7.67 (dd, 1H), 7.30 (m, 7H), 6.16 (m, 1H), 4.02 (br s, 2H), 3.77 (s, 6H), 2.81 (s, 6H), 2.54 (s, 3H); MS (EI) m/z for C27H30N6O5S: 551 (MH+).
Example 41
N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-((2-(dimethylamino)ethyl)(methyl)amino)acetamide
1H NMR (400 MHz, DMSO-d6) δ 10.0 (s, 1H), 9.48 (s, 1H), 8.96 (d, 1H), 8.16 (m, 1H), 7.76 (m, 2H), 7.39 (m, 4H), 7.17 (m, 2H), 6.61 (dd, 1H), 3.82 (s, 3H), 3.40 (br s, 2H), 2.94 (br s, 2H), 2.71 (br t, 2H), 2.60 (s, 6H), 2.33 (s, 3H); MS (EI) m/z for C28H32ClN7O4S: 598 (MH+).
Example 42
2-amino-N-(3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
1H NMR (400 MHz, DMSO-d6) δ 10.5 (s, 1H), 9.48 (s, 1H), 8.94 (s, 1H), 8.15 (s, 1H), 8.06 (br s, 3H), 7.74 (m, 2H), 7.39 (m, 4H), 7.18 (m, 2H), 6.61 (dd, 1H), 3.83 (s, 3H), 3.77 (s, 2H); MS (EI) m/z for C23H21ClN6O4S: 513 (MH+).
Example 43
N-(3-(N-(3-(2-acetyl-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide
1H NMR (400 MHz, DMSO-d6) δ 12.4 (s, 1H), 10.5 (s, 1H), 9.27 (s, 1H), 8.25 (s, 1H), 8.01 (d, 1H), 7.82 (d, 1H), 7.71 (d, 1H), 7.42 (m, 3H), 7.21 (m, 2H), 6.63 (dd, 1H), 3.91 (m, 5H), 2.75 (s, 6H), 2.61 (s, 3H); MS (EI) m/z for C27H28N6O5S: 549 (MH+).
Example 44
N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)formamide
1H NMR (400 MHz, DMSO-d6) δ 12.6 (s, 1H), 10.5 (s, 1H), 9.16 (s, 1H), 8.53 (br s, 1H), 8.35 (m, 2H), 8.02 (s, 1H), 7.56 (m, 7H), 6.70 (dd, 1H), 3.83 (s, 3H); MS (EI) m/z for C22H18ClN5O4S: 484 (MH+).
Example 45
2-amino-N-(5-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-2-methylphenyl)acetamide
1H NMR (400 MHz, DMSO-d6) δ 12.4 (s, 1H), 10.1 (br s, 1H), 8.82 (s, 1H), 8.20 (m, 3H), 7.82 (m, 1H), 7.30 (m, 6H), 6.20 (s, 1H), 3.85 (s, 2H), 3.77 (s, 6H), 2.26 (s, 3H); MS (EI) m/z for C25H26N6O5S: 523 (MH+).
Example 46
N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methyl-2-(methylamino)propanamide
1H NMR (400 MHz, DMSO-d6) δ 10.09 (s, 1H), 9.46 (s, 1H), 8.95 (m, 3H), 8.28 (s, 1H), 7.81 (m, 2H), 7.41 (m, 4H), 7.17 (m, 2H), 6.60 (dd, 1H), 3.82 (s, 3H), 2.53 (s, 3H), 1.60 (s, 6H); MS (EI) m/z for C26H27ClN6O4S: 555 (MH+).
Example 47
(S)—N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)propanamide
1H NMR (400 MHz, DMSO-d6) δ 10.61 (s, 1H), 9.47 (s, 1H), 8.95 (s, 1H), 8.82 (br s, 2H), 8.27 (m, 1H), 7.74 (m, 2H), 7.42 (m, 4H), 7.17 (m, 2H), 6.60 (dd, 1H), 3.90 (m, 1H), 3.82 (s, 3H), 2.59 (s, 3H), 1.49 (d, 3H); MS (EI) m/z for C25H25ClN6O4S: 541 (MH+).
Example 48
3-amino-N-(5-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-2-methylphenyl)propanamide
1H NMR (400 MHz, DMSO-d6) δ 12.25 (s, 1H), 9.77 (s, 1H), 8.82 (s, 1H), 7.84 (m, 5H), 7.50 (d, 1H), 7.37 (m, 5H), 6.22 (m, 1H), 3.74 (s, 6H), 3.08 (m, 2H), 2.77 (m, 2H), 2.27 (s, 3H); MS (EI) m/z for C26H28N6O5S: 537 (MH+).
Example 49
1-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)cyclopropanecarboxamide
1H NMR (400 MHz, DMSO-d6) δ 9.54 (br s, 1H), 9.42 (s, 1H), 8.91 (s, 1H), 8.21 (s, 1H), 8.20 (br s, 2H), 7.81 (m, 2H), 7.48 (m, 4H), 7.22 (m, 2H), 6.61 (dd, 1H), 3.82 (s, 3H), 1.63 (m, 2H), 1.26 (m, 2H); MS (EI) m/z for C25H23ClN6O4S: 539 (MH+).
Example 50
(S)-2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-6-(dimethylamino)hexanamide
1H NMR (400 MHz, DMSO-d6) δ 9.47 (br s, 1H), 8.95 (d, 1H), 8.26 (m, 1H), 7.73 (m, 2H), 7.30 (m, 4H), 7.26 (m, 4H), 7.16 (m, 2H), 6.59 (dd, 1H), 3.82 (s, 3H), 3.34 (m, 1H), 2.20 (m, 2H), 2.09 (s, 6H), 1.50 (m, 6H); MS (EI) m/z for C29H34ClN7O4S: 610 (MH+).
Example 51
1-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)cyclopentanecarboxamide
1H NMR (400 MHz, DMSO-d5) δ 10.12 (br s, 1H), 9.46 (s, 1H), 8.95 (d, 1H), 8.26 (m, 1H), 8.16 (m, 3H), 7.84 (m, 2H), 7.35 (m, 6H), 6.60 (dd, 1H), 3.82 (s, 3H), 2.34 (m, 2H), 1.91 (m, 6H); MS (EI) m/z for C27H27ClN6O4S: 567 (MH+).
Example 52
N-(5-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-2-methylphenyl)-2-(dimethylamino)acetamide
1H NMR (400 MHz, DMSO-d6) δ 12.0 (br s, 1H), 9.98 (s, 1H), 9.43 (s, 1H), 8.91 (m, 1H), 8.08 (s, 1H), 7.84 (dd, 1H), 7.32 (m, 6H), 6.61 (dd, 1H), 4.07 (s, 2H), 3.82 (s, 3H), 2.82 (s, 6H), 2.21 (s, 3H); MS (EI) m/z for C26H27ClN6O4S: 555 (MH+).
Example 53
1-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)cyclobutanecarboxamide
1H NMR (400 MHz, DMSO-d6) δ 10.34 (br s, 1H), 8.81 (s, 1H), 8.49 (br s, 3H), 8.34 (s, 1H), 7.83 (m, 2H), 7.43 (m, 3H), 7.31 (m, 2H), 7.16 (m, 2H), 6.16 (s, 1H), 3.77 (s, 6H), 2.83 (m, 2H), 2.25 (m, 3H), 2.05 (m, 1H); MS (EI) m/z for C27H28N6O5S: 549 (MH+).
Example 54
N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-3-(3-(2-(dimethylamino)ethyl)ureido)benzenesulfonamide
1H NMR (400 MHz, DMSO-d6) δ 8.91 (br s, 1H), 8.81 (s, 1H), 8.08 (s, 1H), 7.60 (s, 1H), 7.38 (m, 9H), 6.28 (m, 1H), 6.15 (s, 1H), 3.78 (s, 6H), 3.40 (m, 2H), 3.08 (m, 2H), 2.74 (s, 6H); MS (EI) m/z for C27H31N7O5S: 566 (MH+).
Example 55
1-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)cyclopentanecarboxamide
1H NMR (400 MHz, DMSO-d6) δ 12.40 (br s, 1H), 10.58 (s, 1H), 8.46 (m, 4H), 7.80 (m, 3H), 7.59 (m, 2H), 7.34 (m, 4H), 6.25 (m, 1H), 3.76 (s, 6H), 2.35 (m, 2H), 1.90 (m, 8H); MS (EI) m/z for C28H30N6O5S: 563 (MH+).
Example 56
1-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)cyclopropanecarboxamide
1H NMR (400 MHz, DMSO-d6) δ 9.54 (br s, 1H), 8.84 (s, 1H), 8.29 (s, 1H), 7.75 (m, 2H), 7.39 (m, 6H), 7.17 (m, 2H), 6.16 (m, 1H), 3.78 (s, 6H), 1.52 (m, 2H), 1.17 (m, 2H); MS (EI) m/z for C26H26N6O5S: 535 (MH+).
Example 57
2-(dimethylamino)ethyl 3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenylcarbamate
1H NMR (400 MHz, DMSO-d6) δ 9.78 (br s, 1H), 8.79 (s, 1H), 8.19 (s, 1H), 7.66 (d, 1H), 7.31 (m, 9H), 6.14 (m, 1H), 4.17 (t, 2H), 3.78 (s, 6H), 2.54 (t, 2H), 2.21 (s, 6H): MS (EI) m/z for C27H30N6O6S: 567 (MH+).
Example 58
4-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)tetrahydro-2H-pyran-4-carboxamide
1H NMR (400 MHz, DMSO-d6) δ 12.2 (br s, 1H), 10.6 (s, 1H), 8.74 (m, 5H), 7.93 (m, 2H), 7.47 (m, 6H), 6.24 (m, 1H), 3.77 (m, 10H), 2.45 (m, 2H), 1.81 (m, 2H); MS (EI) m/z for C28H30N6O6S: 579 (MH+).
Example 59
N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-N-3-(2-(dimethylamino)ethyl)benzene-1,3-disulfonamide
1H NMR (400 MHz, DMSO-d6) δ 9.35 (m, 2H), 8.92 (m, 1H), 8.64 (s, 1H), 8.30 (m, 1H), 8.11 (s, 1H), 7.86 (m, 1H), 7.68 (m, 1H), 7.49 (s, 1H), 7.42 (m, 2H), 7.21 (m, 2H), 6.61 (m, 1H), 3.82 (s, 3H), 3.05 (m, 4H), 2.74 (s, 6H); MS (EI) m/z for C25H27ClN6O5S2: 591 (MH+).
Example 60
N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-N3-(3-(dimethylamino)propyl)benzene-1,3-disulfonamide
1H NMR (400 MHz, DMSO-d6) δ 9.38 (m, 2H), 8.90 (m, 1H), 8.60 (s, 1H), 8.32 (m, 1H), 8.12 (s, 1H), 7.88 (m, 1H), 7.72 (m, 1H), 7.59 (s, 1H), 7.40 (m, 2H), 7.20 (m, 2H), 6.67 (m, 1H), 3.82 (s, 3H), 2.97 (m, 2H), 2.78 (m, 2H), 2.71 (s, 6H), 1.70 (m, 2H); MS (EI) m/z for C26H29ClN6O5S2: 605 (MH+).
Example 61
N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-4-methylphenyl)-2-(methylamino)acetamide
MS (EI) m/z for C25H25ClN6O4S: 541.0 (MH+).
Example 62
(S)-2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-4-methylphenyl)propanamide
MS (EI) m/z for C25H25ClN6O4S: 541.2 (MH+).
Example 63
(R)-2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-4-methylphenyl)propanamide
MS (EI) m/z for C25H25ClN6O4S: 541.0 (MH+).
Example 64
(S)—N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)propanamide
MS (EI) m/z for C26H28N6O5S: 537.1 (MH+).
Example 65
(R)—N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)propanamide
MS (EI) m/z for C25H25ClN6O4S: 541.1 (MH+).
Example 66
(R)—N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)propanamide
MS (EI) m/z for C26H28N6O5S: 537.3 (MH+).
Example 67
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)piperidine-2-carboxamide
MS (EI) m/z for C28H30N6O5S: 563.1 (MH+).
Example 68
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-(dimethylamino)ethylamino)acetamide
MS (EI) m/z for C28H33N7O5S: 580.1 (MH+).
Example 69
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-(methylamino)piperidin-1-yl)acetamide
MS (EI) m/z for C30H35N7O6S: 606.1 (MH+).
Example 70
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-(dimethylamino)piperidin-1-yl)acetamide
MS (EI) m/z for C31H37N7O5S: 620.1 (MH+).
Example 71
N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide
1H NMR (400 MHz, DMSO) δ 12.4 (br s, 1H), 10.9 (s, 1H), 9.8 (s, 1H), 8.9 (s, 1H), 8.3 (br s, 1H), 7.9 (d, 2H), 7.8 (d, 1H), 7.6 (t, 2H), 7.4 (q, 2H), 7.3 (s, 1H), 6.25 (s, 1H), 4.15 (s, 2H), 3.8 (s, 6H), 2.9 (s, 6H). MS (EI) m/z for C26H28N6O5S 2.0×C2H1O2F3: 537.1 (MH+).
Example 72
N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(ethylamino)acetamide
1H NMR (400 MHz, DMSO) δ 10.8 (s, 1H), 9.20 (s, 1H), 8.84 (br s, 2H), 8.64 (br s, 1H), 8.30 (s, 1H), 7.9-8.0 (br s, 1H), 7.80 (t, 2H), 7.55-7.68 (m, 2H), 7.4 (d, 3H), 6.70 (m, 1H), 3.97 (br s, 2H), 3.83 (s, 3H), 3.04 (br s, 2H), 1.3 (t, 3H). MS (EI) m/z for C25H25ClN6O4S 2.0×C2H1O2F3: 541.3, 543.2 (MH+).
Example 73
2-(azetidin-1-yl)-N-(3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
1H NMR (400 MHz, DMSO) δ 10.8 (s, 1H), 10.2 (s, 1H), 9.2 (s, 1H), 8.7 (s, 1H), 8.3 (s, 1H), 7.9-8.0 (br s, 1H), 7.80 (d, 1H), 7.72 (d, 1H), 7.65 (br s, 1H), 7.56 (t, 1H), 7.40 (d, 3H), 6.70 (m, 1H), 4.28 (s, 2H), 4.15 (m, 4H), 3.82 (s, 3H), 2.32 (br s, 1H). MS (EI) m/z for C26H25ClN6O4S 2.0×C2H1O2F3: 553.3, 555.2 (MH+).
Example 74
N-(3-(N-(3-(2-bromo-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)acetamide
The title compound was prepared according to the Examples above. 1H NMR (400 MHz, DMSO) δ 10.6 (s, 1H), 9.5 (s, 1H), 8.95 (d, 1H), 8.18 (t, 1H), 7.78 (m, 1H), 7.70 (m, 1H), 7.54 (d, 1H), 7.46 (m, 1H), 7.38 (t, 1H), 7.32 (d, 1H), 7.12-7.22 (m, 2H), 6.56 (m, 1H), 3.90 (s, 2H), 3.82 (s, 3H), 2.62 (s, 3H). MS (EI) m/z for C24H23BrN6O4S: 572.77, 570.90 (MH+).
Example 75
2-(dimethylamino)-N-(3-(N-(3-(6-methoxy-quinolin-8-ylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
The title compound was prepared according to the Examples above. 1H NMR (400 MHz, DMSO) δ 10.9 (s, 1H), 10.6 (s, 1H), 9.13 (s, 1H), 8.80 (d, 1H), 8.26-8.30 (m, 2H), 7.85 (d, 1H), 7.70 (d, 1H), 7.60 (q, 1H), 7.54 (m, 1H), 7.44 (t, 2H), 7.20 (t, 2H), 6.80 (d, 1H), 4.00 (s, 2H), 3.94 (s, 3H), 2.78 (s, 6H). MS (EI) m/z for C28H27N7O4S: 558.3 (MH+).
Example 76
N-(3-(N-(3-(2-bromo-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide
1H NMR (400 MHz, DMSO) δ 10.6 (s, 1H), 9.4 (s, 1H), 8.9 (s, 1H), 8.25 (s, 1H), 7.78 (d, 1H), 7.70 (d, 1H), 7.54 (d, 1H), 7.48 (d, 1H), 7.40 (t, 2H), 6.56 (d, 1H), 4.02 (s, 2H), 3.82 (s, 3H), 2.80 (s, 6H). MS (EI) m/z for C25H25BrN6O4S: 586.79, 584.91 (MH+).
Example 77
N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-fluoroethylamino)acetamide
1H NMR (400 MHz, DMSO) δ 10.6 (s, 1H), 9.4 (s, 1H), 8.9 (d, 1H), 8.20 (s, 1H), 7.78 (d, 1H), 7.70 (d, 1H), 7.48 (m, 1H), 7.36-7.44 (m, 3H), 7.20 (q, 3H), 6.6 (m, 1H), 4.78 (t, 1H), 4.66 (t, 1H), 3.94 (s, 2H), 3.82 (s, 3H), 3.4 (t, 1H), 3.3 (t, 1H). MS (EI) m/z for C25H24ClFN6O4S: 559.2, 561.2 (MH+).
Example 78
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)formamide
1H NMR (400 MHz, DMSO) δ 12.4 (br s, 1H), 10.5 (s, 1H), 8.90 (s, 1H), 8.3 (s, 1H), 7.9 (br s, 1H), 7.85 (d, 1H), 7.75 (d, 1H), 7.5-7.6 (m, 2H), 7.3-7.4 (m, 4H), 6.2 (s, 1H), 3.8 (s, 3H). MS (EI) m/z for C23H21N5O5S: 480.1 (MH+).
Example 79
N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-(dimethylamino)azetidin-1-yl)acetamide
1H NMR (400 MHz, DMSO) δ 10.2 (br s, 1H), 9.5 (s, 1H), 8.95 (d, 1H), 8.2 (s, 1H), 7.75 (d, 1H), 7.65 (d, 1H), 7.45 (d, 1H), 7.40 (d, 1H), 7.30-7.35 (t, 1H), 7.1-7.2 (q, 2H), 6.60 (m, 1H), 3.82 (s, 3H). MS (EI) m/z for C28H30ClN7O4S: 480.1 (MH+).
Example 80
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(pyrrolidin-1-yl)acetamide
MS (EI) m/z for C28H30N6O5S: 563.18 (MH+).
Example 81
N-(3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(ethyl(methyl)amino)acetamide
1H NMR (400 MHz, DMSO) δ 12.0 (s, 1H), 10.6 (s, 1H), 9.65 (s, 1H), 9.5 (s, 1H), 8.95 (s, 1H), 8.25 (s, 1H), 7.8 (d, 1H), 7.70 (d, 1H), 7.45-7.50 (d, 1H), 7.3-7.4 (m, 3H), 7.2 (t, 2H), 6.60 (d, 1H), 4.02 (br s, 2H), 3.82 (s, 3H), 3.14 (br s, 2H), 2.80 (s, 3H) 1.2 (t, 3H). MS (EI) m/z for C26H27ClN6O4S: 555.2, 557.3 (MH+).
Example 82
N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-(piperidin-1-yl)azetidin-1-yl)acetamide
MS (EI) m/z for C31H34ClN7O4S 2.0×C2H1O2F3: 636.3, 638.3 (MH+).
Example 83
N-(3-(N-(3-(3-fluoro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)acetamide
MS (EI) m/z for C24H23FN6O4S: 511.04 (MH+).
Example 84
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1-methylpiperidine-4-carboxamide
MS (EI) m/z for C29H32N6O5S 1.0×C2H4O2: 577.2 (MH+).
Example 85
N-(3-(N-(3-(3-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)acetamide
1H NMR (400 MHz, DMSO) δ 10.6 (s, 1H), 8.82 (s, 1H), 8.22 (t, 1H), 7.86 (t, 1H), 7.76 (m, 1H), 7.66 (m, 1H), 7.46 (m, 1H), 7.41 (m, 1H), 7.38 (t, 1H), 7.28 (m 1H), 7.24 (t, 1H), 7.12 (m, 2H), 6.56 (d, 1H), 3.88 (s, 2H), 3.80 (s, 3H), 2.60 (s, 3H). MS (EI) m/z for C24H24N6O4S: 492.99 (MH+).
Example 86
N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2,2,2-trifluoroethylamino)acetamide
1H NMR (400 MHz, DMSO) δ 10.4 (s, 1H), 9.2 (s, 1H), 8.65 (s, 1H), 8.4 (s, 1H), 8.00 (m, 1H), 7.80 (d, 1H), 7.75 (d, 1H), 7.65 (q, 1H), 7.55 (t, 1H), 7.40-7.5 (m, 3H), 6.7 (m, 1H), 3.82 (s, 3H), 3.62 (br s, 2H), 3.55 (br d, 2H). MS (EI) m/z for C25H22ClF3N6O4S 1.0×C2H1O2F3: 595.0, 597.0 (MH+).
Example 87
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-(piperidin-1-yl)propanamide
MS (EI) m/z for C30H34N6O5S: 591.2 (MH+).
Example 88
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-4-(dimethylamino)butanamide
MS (EI) m/z for C28H32N6O5S 1.0×C2H4O2: 565.2 (MH+).
Example 89
2-(dimethylamino)-N-(3-(N-(3-(3-fluoro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
1H NMR (400 MHz, DMSO) δ 10.9 (s, 1H), 9.8 (br s, 1H), 9.1 (s, 1H), 8.34 (s, 1H), 7.90 (d, 1H), 7.76 (d, 1H), 7.52-7.68 (m, 4H), 7.40 (m, 2H), 6.54 (m, 1H), 4.16 (s, 2H), 3.82 (s, 3H), 2.86 (s, 6H). MS (EI) m/z for C25H25FN6O4S: 525.05 (MH+).
Example 90
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(piperidin-1-yl)acetamide
MS (EI) m/z for C29H32N6O5S: 577.37 (MH+).
Example 91
2-(dimethylamino)-N-(3-(N-(3-(3-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
1H NMR (400 MHz, DMSO) δ 10.5 (s, 1H), 8.8 (s, 1H), 8.25 (s, 1H), 7.83 (t, 1H), 7.76 (d, 1H), 7.64 (d, 1H), 7.3-7.48 (m, 4H), 7.22 (t, 1H), 7.12 (t, 2H), 6.56 (m, 1H), 3.96 (s, 2H), 3.78 (s, 3H), 2.76 (s, 6H). MS (EI) m/z for C25H26N6O4S: 507.1 (MH+).
Example 92
N-(3-(N-(3-(2-chloro-5-hydroxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide
1H NMR (400 MHz, DMSO) δ 10.8 (s, 1H), 9.9 (s, 1H), 9.8 (s, 1H), 9.1 (s, 1H), 8.55 (s, 1H), 8.34 (s, 1H), 7.9-8.0 (br s, 1H), 7.82 (d, 1H), 7.76 (d, 1H), 7.52-7.66 (m, 2H), 7.42 (t, 1H), 7.26 (d, 1H), 6.50 (m, 1H), 4.16 (s, 2H), 2.86 (s, 6H). MS (EI) m/z for C24H23ClN6O4S: 527.1, 529.0 (MH+).
Example 93
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-morpholinoacetamide
MS (EI) m/z for C28H30N6O6S: 579.1 (MH+).
Example 94
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z for C24H23N5O5S: 494.0 (MH+).
Example 97
2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-4-methylphenyl)-2-methylpropanamide
MS (EI) m/z for C26H27ClN6O4S: 556.12 (MH+).
Example 98
N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide
MS (EI) m/z for C25H25ClN6O4S: 542.05 (MH+).
Example 99
2-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z for C24H24N6O5S: 509.59 (MH+).
Example 100
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)benzoic acid




To a solution of N-(3-{[2-chloro-5-(methoxy)-phenyl]amino}quinoxalin-2-yl)-3-cyanobenzenesulfonamide (6.02 g, 12.95 mmol), prepared using procedures similar to those in Example 115 or Example 423, in methanol (20 mL) and 1,4-dioxane (20 mL) was added 6.0 N aqueous sodium hydroxide (40 mL) at room temperature. The solution was stirred at 90° C. for 3.5 h. The reaction was cooled to room temperature and neutralized slowly by adding 2.0 N hydrochloric acid until the pH of the solution became in the 2-3 range at 0° C. The solution was diluted with ethyl acetate (300 mL). The organic layer was washed with saturated aqueous sodium chloride (50 mL) and dried over magnesium sulfate. Filtration and concentration at reduced pressure afforded 3-{[(3-{[2-chloro-5-(methoxy)-phenyl]amino}quinoxalin-2-yl)amino]sulfonyl}benzoic acid (5.921 g, 94%). MS (EI) m/z for C22H17ClN4O5S: 485.0 (MH+).
The following compounds were prepared using procedures similar to those used in Example 100.
Example 101
Proceeding as above, 3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)benzoic acid was prepared. MS (EI) m/z for C23H20N4O6S: 481.0 (MH+).
Example 102
3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-methyl-1-(piperidin-1-yl)propan-2-yl)benzamide
MS (EI) m/z for C31H35ClN6O4S: 623.06 (MH+).
Example 103
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-methyl-1-oxo-1-(piperidin-1-yl)propan-2-yl)benzamide
MS (EI) m/z for C31H33ClN6O5S: 637.65 (MH+).
Example 104
3-{[(3-{[2-chloro-5-(methoxy)phenyl]amino}quinoxalin-2-yl)amino]sulfonyl}-N-[2-(dimethylamino)ethyl]benzamide




To a solution of 3-{[(3-{[2-chloro-5-(methoxy)phenyl]amino}quinoxalin-2-yl)amino]sulfonyl}benzoic acid (0.20 g, 0.42 mmol), prepared using procedures similar to Example 100, in dimethylformamide (4 mL) were added 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, 0.32 g, 0.83 mmol) and N-ethyldiisopropylamine (DIEA, 0.13 g, 1.04 mmol) at room temperature. The reaction was stirred for 15 min before N,N-dimethylethane-1,2-diamine (73 mg, 0.83 mmol) was added. The reaction mixture was allowed to stir overnight. The reaction was diluted with ethyl acetate (200 mL) and washed with water (50 mL), saturated aqueous sodium bicarbonate (40 mL), 1.0 N aqueous hydrochloric acid (30 mL), and saturated aqueous sodium chloride (25 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated at reduced pressure to afford 3-{[(3-{[2-chloro-5-(methoxy)phenyl]amino}quinoxalin-2-yl)amino]sulfonyl}-N-[2-(dimethylamino)ethyl]benzamide (0.20 g, 87%) as yellow solid. MS (EI) m/z for C26H27ClN6O4S: 555.1 (MH+).
The following compounds were prepared using procedures similar to those in Example 104.
Example 105
5-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(dimethylamino)ethyl)-2-methoxybenzamide
1H NMR (400 MHz, DMSO-d6) δ 9.45 (s, 1H), 8.95 (d, 1H), 8.57 (d, 1H), 8.28 (t, 1H), 8.14 (dd, 1H), 7.46 (dd, 1H), 7.39 (m, 2H), 7.17 (m, 4H), 6.60 (dd, 1H), 3.89 (s, 3H), 3.82 (s, 3H), 3.38 (m, 2H), 2.43 (m, 2H), 2.21 (s, 6H). MS (EI) m/z for C27H29ClN6O5S: 585.3 (MH+).
Example 106
5-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(dimethylamino)ethyl)-2-fluorobenzamide
1H NMR (400 MHz, DMSO-d6) δ 9.40 (br s, 1H), 9.16 (s, 1H), 8.73 (m, 1H), 8.67 (d, 1H), 8.36 (dd, 1H), 8.26 (m, 1H), 7.94 (br s, 1H), 7.66 (m, 1H), 7.59 (t, 1H), 7.43 (m, 3H), 6.71 (dd, 1H), 3.83 (s, 3H), 3.62 (m, 2H), 3.27 (m, 2H), 2.85 (d, 6H). MS (EI) m/z for C26H26ClFN6O4S: 573.1 (MH+).
Example 107
3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(dimethylamino)ethyl)benzamide
MS (EI) m/z for C27H30N6O5S: 551.1 (MH+).
Example 108
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(dimethylamino)ethyl)-N-methylbenzamide
MS (EI) m/z for C27H29ClN6O4S: 569.1 (MH+).
Example 109
3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(dimethylamino)ethyl)-N-methylbenzamide
MS (EI) m/z for C28H32N6O5S: 565.1 (MH+).
Example 110
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)benzamide
MS (EI) m/z for C22H18ClN5O4S: 484.0 (MH+).
Example 111
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-morpholinoethyl)benzamide
MS (EI) m/z for C28H29ClN6O5S: 597.0 (MH+).
Example 112
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-methylbenzamide
MS (EI) m/z for C23H20ClN5O4S: 498.0 (MH+).
Example 113
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-morpholinobenzamide
MS (EI) m/z for C26H25ClN6O5S: 569.0 (MH+).
Example 114
N-(3-{[2-chloro-5-(methoxy)phenyl]amino}quinoxalin-2-yl)-3-{5-[(dimethylamino)methyl]-1,3,4-oxadiazol-2-yl}benzenesulfonamide




To a solution of 3-{[(3-{[2-chloro-5-(methoxy)phenyl]amino}quinoxalin-2-yl)amino]sulfonyl}benzoic acid (0.25 g, 0.52 mmol), prepared as described above in Example 100, in dimethylformamide (2.6 mL) were added 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, 0.25 g, 0.67 mmol) and N-ethyldiisopropylamine (DIEA, 0.11 g, 0.88 mmol) at room temperature. The reaction was stirred for 15 min before 2-(dimethylamino)acetohydrazide (78 mg, 0.67 mmol) was added. The reaction mixture was allowed to stir overnight. The reaction was diluted with ethyl acetate (200 mL) and washed with water (30 mL), saturated aqueous sodium bicarbonate (30 mL), 1.0 N aqueous hydrochloric acid (20 mL), and saturated aqueous sodium chloride (25 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated at reduced pressure to afford 180 mg of a coupled intermediate which was then heated in phosphorus oxychloride (5 mL) at 100° C. for 4 h. The reaction was cooled to room temperature and treated with ice water (50 mL) and extracted with dichloromethane (3×50 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated at reduced pressure to afford a crude product which was subjected to reverse phase HPLC to afford N-(3-{[2-chloro-5-(methoxy)-phenyl]amino}quinoxalin-2-yl)-3-{5-[(dimethylamino)methyl]-1,3,4-oxadiazol-2-yl}-benzenesulfonamide (16 mg, 5%) as yellow solid. MS (EI) m/z for C26H24ClN7O4S: 566.0 (MH+).
Example 115
N-(3-(3-methoxy-5-nitro-phenylamino)-quinoxalin-2-yl)-3-nitrobenzenesulfonamide




N-(3-chloroquinoxalin-2-yl)-3-nitrobenzenesulfonamide
2,3-Dichloroquinoxaline (26.1 g, 131.1 mmol), m-Nitrobenzene sulfonamide (26.5 g, 131.1 mmol) and potassium carbonate (18.1 g, 131.1) were dissolved in anhydrous DMSO (500 mL). The reaction was heated to 150° C. for 2 h. The reaction mixture was poured into water (400 mL), followed by addition of 2M HCl (60 mL). The product was extracted with EtOAc (3×500 mL). The organic layers were combined and washed water (2×500 mL) and brine (2×500 mL). The product was then dried with sodium sulfate to give N-(3-chloroquinoxalin-2-yl)-3-nitrobenzenesulfonamide. MS (EI) m/z for C14H9ClN4O4S: 364.94, 366.97 (MH+)
N-(3-(3-methoxy-5-nitrophenylamino)quinoxalin-2-yl)-3-nitro-benzenesulfonamide
N-(3-chloroquinoxalin-2-yl)-3-nitrobenzenesulfonamide (700 mg, 1.92 mmol), 3-methoxy-5-nitroaniline (645 mg, 3.84 mmol) and p-xylene (7 mL) were combined and heated to 140° C., then stirred for 16 hours at 130° C. The reaction was allowed to cool, placed in a sep. funnel, diluted with DCM, and washed with 2M HCl and brine and concentrated in vacuo. The resulting solid was washed with Et2O to give N-(3-(3-methoxy-5-nitro-phenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide (400 mg, 42%). MS (EI) m/z for C21H16N6O7S: 496.94 (MH+).
The following compounds were prepared using procedures similar to those in Example 115.
Example 116
N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)-3-cyanobenzenesulfonamide
MS (EI) m/z for C22H16ClN5O3S: 465.9 (MH+).
Example 117
3-cyano-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z for C23H19N5O4S: 462.3 (MH+).
Example 118
N-(3-(2,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3-fluorobenzenesulfonamide
MS (EI) m/z for C22H19FN4O4S: 456.0 (MH+).
Example 119
3-bromo-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z for C22H19BrN4O4S: 516.9 (MH+).
Example 120
3-bromo-N-(3-(2,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z for C22H19BrN4O4S: 516.9 (MH+).
Example 121
N-(3-(3-methoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z for C21H18N4O3S: 407.0 (MH+).
Example 122
N-(3-(4-fluoro-3-methoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z for C21H17FN4O3S: 425.0 (MH+).
Example 123
N-(3-(2,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide
MS (EI) m/z for C23H22N4O5S: 467.0 (MH+).
Example 124
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide
MS (EI) m/z for C23H22N4O5S: 467.0 (MH+).
Example 125
N-(3-(4-chloro-3-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z for C21H17ClN4O3S: 440.9 (MH+).
Example 126
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)thiophene-2-sulfonamide
MS (EI) m/z for C20H18N4O4S2: 443.0 (MH+).
Example 127
N-(3-(6-methoxyquinolin-8-ylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide
MS (EI) m/z for C24H18N6O5S: 502.95 (MH+).
Example 128
3-nitro-N-(3-(pyridin-4-ylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z for C19H14N6O4S: 423.2 (MH+).
Example 129
N-(3-(2-chloropyridin-4-ylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide
MS (EI) m/z for C19H13ClN6O4S: 456.93, 458.90 (MH+).
Example 130
N-(3-(4,6-dimethoxypyrimidin-2-ylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide
MS (EI) m/z for C20H17N7O6S: 484.03 (MH+).
Example 131
N-(3-(4-hydroxy-6-methoxypyrimidin-2-ylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide
MS (EI) m/z for C19H15N7O6S: 469.97 (MH+).
Example 132
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-2-fluorobenzenesulfonamide
MS (EI) m/z for C22H19FN4O4S: 455.3 (MH+).
Example 133
N-(3-(2-bromo-5-methoxy-phenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide
MS (EI) m/z for C21H16BrN5O5S: 531.82, 532.84 (MH+).
Example 134
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-methylbenzenesulfonamide
MS (EI) m/z for C23H22N4O4S: 451.0 (MH+).
Example 136
N-(3-(2,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-methylbenzenesulfonamide
MS (EI) m/z for C23H22N4O4S: 451.0 (MH+).
Example 137
N-(3-(3-fluoro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide
MS (EI) m/z for C21H16FN5O5S: 470.0 (MH+).
Example 138
4-bromo-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z for C22H19BrN4O4S: 516.9, 514.9 (MH+).
Example 139
N-(3-(3-methoxyphenylamino)quinoxalin-2-yl)-3-nitro-benzenesulfonamide
MS (EI) m/z for C21H17N5O5S: 451.93 (MH+).
Example 140
N-(3-(2-chloro-5-hydroxy-phenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide.
MS (EI) m/z for C20H14ClN5O5S: 472.15, 474.13 (MH+).
Example 141
3-acetyl-N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z for C23H19ClN4O4S: 483.08 (MH+).
Example 142
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z for C22H20N4O4S: 437.49 (MH+).
Example 143
N-(3-(5-methoxy-2-methyl-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z for C22H20N4O3S: 421.46 (MH+).
Example 144
N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z for C21H17ClN4O3S: 440.59 (MH+).
Example 145
N-(3-(2,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z for C22H20N4O4S: 437.53 (MH+).
Example 146
4-chloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z for C22H19ClN4O4S: 470.54 (MH+).
Example 147
N-(3-(5-methoxy-2-methyl-phenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide
MS (EI) m/z for C22H19N5O5S: 466.32 (MH+).
Example 148
N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide
MS (EI) m/z for C21H16ClN5O5S: 485.86 (MH+).
Example 149
N-(3-(4-chloro-2,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z for C22H19ClN4O4S: 470.99 (MH+).
Example 150
N-(3-{[3,5-bis(methoxy)phenyl]amino}quinoxalin-2-yl)-3-(2H-tetrazol-5-yl)benzenesulfonamide




To a stirred solution of 3-cyano-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide (0.20 g, 0.44 mmol), prepared using procedures similar to those described in Example 115, in dimethylformamide (1.2 mL) at 50° C. were added sodium azide (0.11 g, 1.76 mmol) and ammonium chloride (94 mg, 1.76 mmol). The crude mixture was heated at 100° C. overnight. The reaction was cooled to room temperature treated with ice water (20 mL) followed by concentrated hydrochloric acid (10 mL). The solid obtained was filtered under reduced pressure and washed with hexane (20 mL), diethyl ether (20 mL), and ethyl acetate (5 mL) to afford N-(3-{[3,5-bis(methoxy)phenyl]amino}quinoxalin-2-yl)-3-(2H-tetrazol-5-yl)benzenesulfonamide (55 mg, 25%) as light yellow solid. MS (EI) m/z for C23H20N8O4S: 505.0 (MH+).
Example 151
N-(3-(2,6-dichloropyridin-4-ylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide
A mixture of N-(3-chloroquinoxalin-2-yl)-3-nitrobenzenesulfonamide (1 g), 2,6-dichloropyridin-4-amine (760 mg) and p-xylene (10 mL) was heated at 135° C. with stirring overnight. Upon cooling to room temperature, the mixture was dissolved in dichloromethane, washed with 2 N HCl (2×) and brine, concentrated in vacuo to give a crude product of N-{3-[(2,6-dichloropyridin-4-yl)amino]quinoxalin-2-yl}-3-nitrobenzenesulfonamide. A small portion of this crude product was purified by HPLC to give N-{3-[(2,6-dichloropyridin-4-yl)amino]quinoxalin-2-yl}-3-nitro-benzenesulfonamide. 1H NMR (400 MHz, DMSO) δ 9.71 (s, 1H), 8.90 (s, 1H), 8.50 (d, 2H), 8.8.41 (d, 1H), 8.30 (s, 2H), 7.88-7.78 (m, 27.65 (d, 1H), 7.47-7.37 (m, 2H); MS (EI) m/z for C19H12C12N6O4S: 491.1, 493.1 (MH+).
Example 152
N-(3-(2-chloro-6-methoxypyridin-4-ylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide
To a crude product of N-{3-[(2,6-dichloropyridin-4-yl)amino]quinoxalin-2-yl}-3-nitrobenzenesulfonamide (1.24 g) prepared using procedures similar to those for Example 151, was added anhydrous DMSO (10 mL), followed by sodium methoxide (273 mg). The resulting mixture was heated at 100° C. for 3 days. The mixture was diluted with EtOAc and water, and the pH was adjusted to about 4 by adding acetic acid. The product was extracted with EtOAc (3×). The combined extracts were washed with brine to give the crude product. A portion of the crude product was purified by prep HPLC to give N-(3-{[2-chloro-6-(methyloxy)pyridin-4-yl]amino}quinoxalin-2-yl)-3-nitrobenzenesulfonamide. 1H NMR (400 MHz, DMSO) δ 9.44 (s, 1H), 8.90 (s, 1H), 8.50 (d, 1H), 8.42 (d, 1H), 7.88-7.84 (m, 2H), 7.77 (s, 1H), 7.74 (s, 1H), 7.64 (d, 1H), 7.45-7.38 (m, 2H), 3.82 (s, 3H); MS (EI) m/z for C20H15ClN6O5S: 496.94 (MH+).
Example 153
2-(dimethylamino)-N-(3-(N-(3-(3-(2-(dimethylamino)acetamido)-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide




3-amino-N-(3-(3-amino-5-methoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide
N-(3-(3-Methoxy-5-nitrophenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide (400 mg, 0.81 mmol), prepared as described above in Example 115, was dissolved in 1:1 THF:EtOH (4 mL), to which was added formic acid (938 μl, 2.42 mmol) and potassium formate (203 mg, 2.42 mmol). The system was flushed with nitrogen, and then 10% wt Pd/C (50 mg) was added. The reaction was then heated to 60° C. Once the reaction was determined complete by LC-MS, it was allowed to cool, and DMF was added for solubility. The solution was then filtered through a nylon fit to remove the catalyst. The filtrate was diluted water and the pH adjusted to 7 and extracted with DCM (2×) and EtOAc (2×). All organic layers were combined and evaporated to dryness to give 3-amino-N-(3-(3-amino-5-methoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide (330 mg, 93%). MS (EI) m/z for C21H20N6O3S: 437.06 (MH+)
2-(dimethylamino)-N-(3-(N-(3-(3-(2-(dimethylamino)-acetamido)-5-methoxyphenylamino)quinoxalin-2-yl)-sulfamoyl)phenyl)acetamide
3-Amino-N-(3-(3-amino-5-methoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide (330 mg, 0.76 mmol), DMF (4 mL), N,N-Dimethylglycine (312 mg, 3.02 mmol), HATU (1.15 g, 3.02 mmol), and 1.29 (mL) (7.56 mmol) DIEA (1.29 mL, 7.56 mmol) were combined and heated to 90° C., followed by heating at 50° C. for over 16 hours. The reaction was allowed to cool, placed into a sep. funnel diluted with water and aqueous LiCl and extracted with EtOAc. The final compound was then purified by prep. HPLC to give 2-(dimethylamino)-N-(3-(N-(3-(3-(2-(dimethylamino)acetamido)-5-methoxy-phenylamino)-quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. 1H NMR (400 MHz, CD3OD) δ 8.45 (t, 1H), 7.93 (t, 1H), 7.85-7.88 (m, 1H), 7.70-7.74 (m, 1H), 7.65-7.68 (m, 1H), 7.58-7.62 (m, 1H), 7.58 (t, 1H), 7.34-7.42 (m, 3H), 7.0 (t, 1H), 4.05 (d, 2H), 3.8 (s, 3H), 2.9-3.0 (d, 12H). MS (EI) m/z for C29H34N8O5S: 607.2 (MH+).
The following title compounds were prepared using procedures similar to those in Example 153.
Example 154
N-(3-(2,5-dimethoxyphenylamino)-7-methylquinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z for C23H22N4O4S: 451.0 (MH+).
Example 155a and Example 155b
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3-(methylamino)benzenesulfonamide and N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3-(dimethylamino)benzenesulfonamide




To a solution of 3-amino-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide (414 mg) in DMF (4.5 mL) was added iodomethane (114 μl). The reaction mixture was heated at 35-50° C. until the formation of both mono-methylated and di-methylated products was detected by LC/MS. The mixture was diluted with EtOAc, washed with water, 10% LiCl (2×) and brine. After removal of solvent in vacuo, the crude mixture was purified by flash silica column chromatography eluting with 15% EtOAc in hexanes, affording the mono-methylated and di-methylated products. Product A: N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-3-(methylamino)-benzenesulfonamide (35 mg). 1H NMR (400 MHz, DMSO) δ 12.2 (s, 1H), 8.93 (s, 1H), 7.85 (d, 1H), 7.58 (d, 1H), 7.40-7.20 (m, 7H), 6.76 (m, 1H), 6.24 (m, 1H), 6.16 (br s, 1H), 3.77 (s, 6H), 2.71 (s, 3H). MS (EI) for C23H23N5O4S: 466.05 (MH+). Product B: N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-3-(dimethylamino)benzenesulfonamide (33 mg). 1H NMR (400 MHz, DMSO) δ 1220 (s, 1H), 8.98 (s, 1H), 7.98 (d, 1H), 7.56 (d, 1H), 7.42-7.32 (m, 7H), 6.74 (m, 1H), 6.24 (m, 1H), 3.77 (s, 6H), 2.97 (s, 6H). MS (EI) for C24H25N5O4S: 480.04 (MH+).
Example 156
N-(3-{[(2-{[3,5-bis(methoxy)phenyl]amino}pyrido[2,3-b]pyrazin-3-yl)amino]sulfonyl}phenyl)-N-2-[2-(dimethylamino)ethyl]-N-2-methylglycinamide




To a THF suspension (1.3 mL) of 3-amino-N-(3-{[3,5-(dimethoxy)-phenyl]amino}-quinoxalin-2-yl)benzenesulfonamide (126 mg, 0.28 mmol), prepared using procedures similar to those described for Example 15, was added 0.143 mL of 2M aqueous Na2CO3. To this yellow suspension is added dropwise 33 μL (0.42 mmol) of chlororacetyl chloride. The reaction mixture turns clear after a few minutes and is allowed to stir at 23° C. for 1 h. To the reaction is added a DMSO (1 mL) solution containing 180 μL (1.4 mmol) of N,N′,N′ trimethylethelyenediamine. The reaction is then warmed to 60° C. and stirred for 18 h. The product is isolated by preparative RP-HPLC (NH4OAc/ACN) gradient, the appropriate fractions were pooled and lyophilize to give a solid yellow as the acetic acid salt: 59 mg (51%). 1H-NMR (400 MHz, CDCL3): δ 10.1 (br s, 1H), 8.37 (br s, 2H), 8.18 (d, 1H), 7.97 (d, 1H), 7.60 (br d, 1H), 7.27 (s, 2H), 7.20 (br s, 3H), 6.15 (s, 1H), 3.82 (m, 2H), 3.65 (s, 6H), 3.20 (br m, 2H), 2.82 (br s, 8H), 2.42 (s, 3H), 2.02 (s, 3H). MS (EI) m/z for C28H34N8O5S: 595.84 (MH+).
The following title compounds were prepared using similar procedures to those in Example 156.
Example 157
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-((3-(dimethylamino)propyl)(methyl)amino)acetamide
MS (EI) m/z for C30H37N7O5S: 608.1 (MH+).
Example 158
2-(1,4′-bipiperidin-1′-yl)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z for C34H41N7O5S: 660.1 (MH+).
Example 159
tert-butyl 2-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenylcarbamoyl)piperidine-1-carboxylate
MS (EI) m/z for C33H38N6O7S: 663.1 (MH+).
Example 160
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(1-(dimethylamino)propan-2-yl)benzamide
MS (EI) m/z for C27H29ClN6O4S: 569.0 (MH+).
Example 161
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3-ureidobenzenesulfonamide
MS (EI) m/z for C23H22N6O5S: 495.40 (MH+).
Example 162
2-(dimethylamino)-N-(3-(N-(3-(5-methoxy-2-methylphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z for C26H28N6O4S: 521.69 (MH+).
Example 163
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-methylpiperazin-1-yl)acetamide
MS (EI) m/z for C29H33N7O5S: 592.61 (MH+).
Example 164
2-acetamido-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z for C26H26N6O6S: 550.59 (MH+).
Example 165
tert-butyl 2-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenylamino)-2-oxoethylcarbamate
MS (EI) m/z for C29H32N6O7S: 609.32 (MH+).
Example 166
N-(2-(3,5-dimethoxy-phenylamino)pyrido[2,3-b]pyrazin-3-yl)-3-nitrobenzenesulfonamide




To a xylene suspension (15 mL) of N-(2-chloropyrido[2,3-b]pyrazin-3-yl)-3-nitrobenzenesulfonamide (1 g, 2.7 mmol) (prepared using procedures similar to those in Asier, et al J. Org Chem 2005, 70(7), 2878 and Leeson, et al J. Med. Chem. 1991, 34, 1243) was added 420 mg (2.7 mmol) of 3,5 dimethoxyaniline. After refluxing the reaction for 1 h, the reaction is cooled, the precipitate is collected by filtration and dried under vacuum to give 830 mg of the product as a  ̃6:1 mixture of isomers with the major being N-(2-(3,5-dimethoxy-phenylamino)pyrido[2,3-b]pyrazin-3-yl)-3-nitrobenzenesulfonamide which was assigned by known chemical reactivity. Analytical HPLC, ret. time=3.3 min (14%), 3.05 min (86%), (conditions: Phenomenex Gemini C18 50×4.6 column, gradient 5% to 95% MeCN/H2O, in the presence of 0.1% TFA, 5 min run at 3.5 ml/min flow rate, λ=254 nm). 1H-NMR (400 MHz, DMSO-d6): major isomer δ 9.14 (br s, 1H), 8.69 (dd, 1H), 8.60 (dd, 1H), 8.33 (dt, 2H), 7.77 (t, 1H), 7.49 (dd, 1H), 7.37 d, 2H), 7.05 (s, 1H), 6.26 (t, 1H), 3.77 (s, 6H); MS (EI) m/z for C21H18N6O6S: 483.08 (MH+).
Example 167
3-amino-N-(2-(3,5-dimethoxy-phenylamino)pyrido[2,3-b]pyrazin-3-yl)benzenesulfonamide
To a 1:1 THF/EtOH suspension (1 mL) of N-(3-(3,5-dimethoxyphenylamino)-pyrido[3,2-b]pyrazin-2-yl)-3-nitrobenzenesulfonamide (190 mg, 0.21 mmol) (prepared using procedures similar to those in Examples 166) was added 47 μL (1.26 mmol) of formic acid plus 99 mg (1.17 mmol) of potassium formate and 50 mg of 10% palladium on charcoal. After refluxing the reaction for 1 h, hot filtration through celite (washing with a small portion of DMF), dilution with 30 mL of water, the pH was adjusted to 5.5 with 5% NaHCO3, the product is isolated as a precipitate 140 mg (80%) of white powder. Analytical HPLC, ret. time=2.6 min (90%), 3.05 min (10%), 100% pure (conditions: YMC C18 5×4.6 column, gradient 10% to 90% MeCN/H2O, in the presence of 0.1% TFA, 9 min run at 1 ml/min flow rate, λ=254 nm). 1H-NMR (400 MHz, CDCL3): δ 8.48 (br s, 1H), 8.34 (dd, 1H), 7.92 (dd, 1H), 7.41 (dd, 1H), 7.15 (m, 3H), 7.13 (d, 2H), 6.86 (dd, 1H), 6.28 (t, 1H), 3.83 (s, 6H); MS (EI) m/z for C21H20N6O4S: 453.03 (MH+).
Example 168
3-amino-N-(3-{[3,5-bis(methoxy)phenyl]amino}pyrido[2,3-b]pyrazin-2-yl)benzenesulfonamide




To a 1:1 THF/EtOH suspension (1 mL) of 3-nitro-N-(3-{[3,5-bis(methoxy)-phenyl]amino}pyrido[2,3-b]pyrazin-2-yl)benzenesulfonamide (100 mg, 0.21 mmol) (prepared using procedures similar to those used in Example 166) was added 46 μL (0.63 mmol) of formic acid plus 100 mg (0.63 mmol) of potassium formate and 100 mg of 10% palladium on charcoal. After refluxing the reaction for 1 h, hot filtration through celite, and concentration, the product is isolated by preparative RP-HPLC (NH4OAc/ACN) gradient. The appropriate fractions were pooled and lyophilize to give solid yellow product: 3.2 mg (4%). 1H-NMR (400 MHz, CDCl3): δ 8.62 (d, 1H), 8.52 (s, 1H), 7.62 (d, 1H), 7.3 (m, 4H), 7.18 (d, 2H), 6.88 (d, 1H), 6.27 (t, 1H), 3.96 (br s, 2H), 3.83 (s, 6H). MS (EI) m/z for C21H20N6O4S: 453.22 (MH+).
Example 169
N-(3-{[2-chloro-5-(methoxy)phenyl]amino}quinoxalin-2-yl)-3-(1-{[2-(dimethylamino)-ethyl]amino}ethyl)benzenesulfonamide trifluoracetic acid salt




To a dichloroethane solution (0.6 mL) of 3-acetyl-N-(3-{[2-chloro-5-(methoxy)-phenyl]amino}quinoxalin-2-yl)benzenesulfonamide (150 mg, 0.31 mmol), prepared using procedures similar to those in Example 115, and 51 μL (0.37 mmol) of N,N-dimethylethylenediamine was added 19 μL of acetic acid followed by 132 mg (0.62 mmol) of sodium cyanoborohydride. The reaction mixture was refluxed for 18 h under a nitrogen atmosphere. After concentration (in vacuo), the product is isolated by preparative RP-HPLC (0.1% TFA/ACN) gradient, followed by lyophilization of appropriate fractions to give solid yellow solid: 189 mg (90%). 1H-NMR (400 MHz, d3-MeOD): δ 8.74 (s, 1H), 8.18 (s, 1H), 8.12 (d, 1H), 7.71 (m, 3H), 7.48 (m, 4H), 7.28 (d, 1H), 6.63 (d, 1H), 4.38 (q, 1H), 3.80 (s, 3H), 3.30 (m, 3H), 3.12 (m, 1H), 2.84 (s, 3H), 1.60 (d, 3H). MS (EI) m/z for C27H31ClN6O3S: 555.56 (MH+).
Example 170
N,N-{[(3-{[(3-{[2-chloro-5-(methoxy)phenyl]amino}quinoxalin-2-yl)amino]sulfonyl}-4-methylphenyl)amino](dimethylamino)methylidene}-N-methylmethanaminium




To a dimethylformamide solution (1 mL) of 3-amino-N-(3-{[2-chloro-5-(methoxy)-phenyl]amino}quinoxalin-2-yl)2-methylbenzenesulfonamide (200 mg, 0.40 mmol), prepared using procedures similar to those described in Example 115, is added 312 μL (1.8 mmol) of DIEA and 122 mg (0.6 mmol) of HATU. After stirring for 18 h at 60° C., the product was precipitated from a 1:1 mixture of hexane/ethyl acetate, filtered and dried to afford 60 mg (26%). 1H NMR (400 MHz, DMSO-d6): δ 9.26 (b rs, 1H), 8.96 (br s, 1H), 7.80 (s, 1H), 7.51 (br s, 1H), 7.45 (d, 1H), 7.18 (brm, 4H), 6.91 (br s, 1H), 6.60 (br d, 1H), 3.82 (s, 3H), 3.36 (s, 3H), 2.85 (s, 6H), 2.58 (s, 3H). MS (EI) m/z for C27H31ClN7O3S+: 569.32 (MH+).
Example 171
2-Bromo-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide




In a 50 mL round-bottom flask was added 2-bromoacetic acid (1.87 g, 13.5 mmol), N,N-diisopropylcarbodiimide (860 mg, 6.8 mmol) and 10 mL DCM. To this mixture was added 3-amino-N-(3-(3,5-dimethoxyphenylamino) quinoxalin-2-yl)benzenesulfonamide (2.03 g, 4.5 mmol), prepared using procedures similar to those in Example 168. The reaction was stirred overnight at room temperature. Complete consumption of the starting aniline was confirmed by LCMS. The solvent was evaporated off to yield the crude product (2-bromo-N-(3-(N-(3-(3,5-dimethoxyphenylamino) quinoxalin-2-yl)sulfamoyl)phenyl)acetamide). This was used directly in the next step without further purification.
General Alkylation Procedure 1




Into a 2-dram vial was placed 2-bromo-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl) sulfamoyl)phenyl)acetamide (86 mg, 0.15 mmol), prepared using procedures similar to those in Example 171,along with 2 mL of acetonitrile. Eight equivalents (1.2 mmol) of the desired amine, aniline, hydrazine or alkoxyamine were added followed by the addition of Hunig's Base (41 μL, 0.25 mmol). The reaction then was stirred at 50° C. for one hour (overnight for aniline reagents). Preparative reverse-phase HPLC was used to isolate the desired product directly from the crude reaction mixture. A Waters Fractionlynx preparative reverse-phase HPLC—equipped with a Waters SunFire Prep C18, OCD 5 μM, 30×70 mm column and running a 5-100% gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile—was used to carry out the purification.
The following title compounds were prepared according to General Library Alkylation Procedure 1.
Example 172
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)acetamide
1H-NMR (400 MHz, d6-DMSO): 8.81 (s, 1H), 8.23 (t, 1H), 7.75 (d, 1H), 7.66 (d, 1H), 7.41-7.38 (m, 1H), 7.35 (m, 1H), 7.32 (d, 2H), 7.29-7.27 (m, 1H), 7.14-7.11 (m, 2H), 6.14 (t, 1H), 3.80 (s, 1H), 3.78 (s, 6H), 2.58 (s, 3H), 1.91 (s, 2H); MS (EI) m/z C25H26N605S: 523.6 (MH+).
Example 173
2-(cyclopropylmethylamino)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
1H-NMR (400 MHz, d6-DMSO): 10.58 (s, 1H), 8.81 (s, 1H), 8.20 (t, 1H), 7.76 (d, 1H), 7.67 (d, 1H), 7.42-7.36 (m, 2H), 7.32 (d, 2H), 7.27 (s, 1H), 7.14-7.12 (m, 2H), 6.15 (t, 1H), 3.93 (s, 2H), 3.78 (s, 6H), 2.89 (s, 1H), 2.88 (s, 1H), 1.05-1.00 (m, 1H), 0.59 (d, 1H), 0.57 (d, 1H), 0.35 (d, 1H), 0.34 (d, 1H); MS (EI) m/z C28H30N6O5S: 563.6 (MH+).
Example 174
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-hydroxy-propylamino)acetamide
1H-NMR (400 MHz, d6-DMSO): 10.49 ppm (s, 1H), 8.81 ppm (s, 1H), 8.23 ppm (t, 1H), 8.13 ppm (s, 1H), 7.76 ppm (d, 1H), 7.765-7.763 (dd, 1H), 7.41-7.37 ppm (m, 2H), 7.33-7.32 ppm (d, 1H), 7.30-7.28 ppm (m, 1H), 7.16-7.09 ppm (m, 2H), 6.55 ppm (s, 1H), 6.14 ppm (t, 1H), 5.49 ppm (d, 2H), 5.25 ppm (s, 1H), 3.85 ppm (s, 1H), 3.78 ppm (s, 6H) 3.67-3.59 ppm (m, 1H), 3.00-2.89 ppm (dd, 1H), 2.79-2.76 ppm (m, 1H), 1.10 ppm (d, 1H), 1.01-0.99 ppm (d, 1H); MS (EI) m/z C27H30N6O6S: 566.6 (MH+).
Example 175
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-fluorobenzylamino)acetamide
1H-NMR (400 MHz, d6-DMSO): 10.42 ppm (s, 1H), 8.82 ppm (s, 1H), 8.23 ppm (s, 1H), 8.14 ppm (s, 1H), 7.75 ppm (d, 1H), 7.65 ppm (d, 1H), 7.49-7.32 ppm (m, 6H), 7.25-7.20 ppm (m, 1H), 7.14-7.12 ppm (m, 2H), 6.55 ppm (s, 1H), 6.15 ppm (t, 1H), 4.14 ppm (s, 2H), 3.78 ppm (s, 6H), 3.74 ppm (s, 2H); MS (EI) m/z C31H29FN6O5S: 616.7 (MH+).
Example 176
2-(benzylamino)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C31H30N6O5S: 599 (MH+).
Example 177
2-(diethylamino)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C28H32N6O5S: 565 (MH+).
Example 178
2-(4-(3,4-dichlorophenyl)piperazin-1-yl)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C34H33Cl2N7O5S: 722 (MH+).
Example 179
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2,2-dimethylhydrazinyl)acetamide
MS (EI) m/z C26H29N7O5S: 552 (MH+).
Example 180
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(p-tolylamino)acetamide
MS (EI) m/z C31H30N6O5S: 599 (MH+).
Example 181
2-(benzyloxyamino)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C31H30N6O6S: 615 (MH+).
Example 182
2-(2-chlorophenylamino)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C30H27ClN6O5S: 619 (MH+).
Example 183
N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(isopropylamino)acetamide
MS (EI) m/z C27H30N6O5S: 551 (MH+).
Example 184
2-(4-cyclopentylpiperazin-1-yl)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C33H39N7O5S: 646 (MH+).
Example 185
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-propylpiperidin-1-yl)acetamide
MS (EI) m/z C32H38N6O5S: 619 (MH+).
Example 186
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(isobutoxyamino)acetamide
MS (EI) m/z C28H32N6O6S: 581 (MH+).
Example 187
2-(3-tert-butylphenylamino)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C34H36N6O5S: 641 (MH+).
Example 188
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-phenylpropan-2-ylamino)acetamide
MS (EI) m/z C33H34N6O5S: 627 (MH+).
Example 189
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-fluoro-4-hydroxyphenylamino)acetamide
MS (EI) m/z C30H27FN6O6S: 619 (MH+).
Example 190
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-(methylthio)benzylamino)acetamide
MS (EI) m/z C32H32N6O5S2: 645 (MH+).
Example 191
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(5-fluoro-2-methylbenzylamino)acetamide
MS (EI) C32H31FN6O5S: 631 (MH+).
Example 192
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-phenylpyrrolidin-1-yl)acetamide
MS (EI) m/z C34H34N6O5S: 639 (MH+).
Example 193
2-(2-benzylpyrrolidin-1-yl)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C35H36N6O5S: 653 (MH+).
Example 194
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-phenylmorpholino)acetamide
MS (EI) m/z C34H34N6O6S: 655 (MH+).
Example 195
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-(pyridin-4-yl)piperidin-1-yl)acetamide
MS (EI) m/z C34H35N7O5S: 654 (MH+).
Example 196
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(o-tolylamino)acetamide
MS (EI) m/z C31H30N6O5S: 599 (MH+).
Example 197
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2,4-dimethylbenzylamino)acetamide
MS (EI) m/z C33H34N6O5S: 627 (MH+).
Example 198
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methyl(pyridin-3-ylmethyl)amino)acetamide
MS (EI) m/z C31H31N7O5S: 614 (MH+).
Example 199
2-(3-chloro-4-methylbenzylamino)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C32H31ClN6O5S: 647 (MH+).
Example 200
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-((2-(dimethylamino)-ethyl)(methyl)amino)acetamide
MS (EI) m/z C29H35N7O5S: 594 (MH+).
Example 201
2-(4-acetylpiperazin-1-yl)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C30H33N7O6S: 620 (MH+).
Example 202
N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methyl(1-methylpyrrolidin-3-yl)amino)acetamide
MS (EI) m/z C30H35N7O5S: 606 (MH+).
Example 203
N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-methyl-1,4-diazepan-1-yl)acetamide
MS (EI) m/z C30H35N7O5S: 606 (MH+).
Example 204
2-(4-allylpiperazin-1-yl)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C31H35N7O5S: 618 (MH+).
Example 205
N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-isopropylpiperazin-1-yl)acetamide
MS (EI) m/z C31H37N7O5S: 620 (MH+).
Example 206
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-(dimethylamino)pyrrolidin-1-yl)acetamide
MS (EI) m/z C30H35N7O5S: 606 (MH+).
Example 207
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-(dimethylamino)azetidin-1-yl)acetamide
MS (EI) m/z C29H33N7O5S: 592 (MH+).
Example 208
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-oxopiperidin-1-yl)acetamide
MS (EI) m/z C29H30N6O6S: 591 (MH+).
Example 209
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-((2-methoxyethyl)(methyl)amino)acetamide
MS (EI) m/z C28H32N6O6S: 581 (MH+).
Example 210
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-methylbenzyloxyamino)acetamide
MS (EI) m/z C32H32N6O6S: 629 (MH+).
Example 211
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-methoxybenzyloxyamino)acetamide
MS (EI) m/z C32H32N6O7S: 645 (MH+).
Example 212
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(propylamino)acetamide
MS (EI) m/z C27H30N6O5S: 551 (MH+).
Example 213
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(ethyl(methyl)amino)acetamide
MS (EI) m/z C27H30N6O5S: 551 (MH+).
Example 214
2-(allyl(methyl)amino)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C28H30N6O5S: 563 (MH+).
Example 215
2-(tert-butylamino)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C28H32N6O5S: 565 (MH+).
Example 216
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(isobutylamino)acetamide
MS (EI) m/z C28H32N6O5S: 565 (MH+).
Example 217
2-(butylamino)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C28H32N6O5S: 565 (MH+).
Example 218
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(isopropyl(methyl)amino)acetamide
MS (EI) m/z C28H32N6O5S: 565 (MH+).
Example 219
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-formylpiperazin-1-yl)acetamide
MS (EI) m/z C29H31N7O6S: 606 (MH+).
Example 220
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-ethylpiperazin-1-yl)acetamide
MS (EI) m/z C30H35N7O5S: 606 (MH+).
Example 221
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-formyl-1,4-diazepan-1-yl)acetamide
MS (EI) m/z C30H33N7O6S: 620 (MH+).
Example 222
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(ethyl(2-hydroxyethyl)amino)acetamide
MS (EI) m/z C28H32N6O6S: 581 (MH+).
Example 223
(S)—N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-hydroxypyrrolidin-1-yl)acetamide
MS (EI) m/z C28H30N6O6S: 579 (MH+).
Example 224
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2,6-dimethylmorpholino)acetamide
MS (EI) m/z C30H34N6O6S: 607 (MH+).
Example 225
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxatin-2-yl)sulfamoyl)phenyl)-2-(2-methylbenzylamino)acetamide
MS (EI) m/z C32H32N6O5S: 613 (MH+).
Example 226
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-methoxy-ethylamino)acetamide
MS (EI) m/z C27H30N6O6S: 567 (MH+).
Example 227
N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(thiazolidin-3-yl)acetamide
MS (EI) m/z C27H28N6O5S2: 581 (MH+).
Example 228
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-(hydroxymethyl)piperidin-1-yl)acetamide
MS (EI) m/z C30H34N6O6S: 607 (MH+).
Example 229
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-phenylpropylamino)acetamide
MS (EI) m/z C33H34N6O5S: 627 (MH+).
Example 230
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(isobutyl(methyl)amino)acetamide
MS (EI) m/z C29H34N6O5S: 579 (MH+).
Example 231
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(phenylamino)acetamide
MS (EI) m/z C30H28N6O5S: 585 (MH+).
Example 232
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-propylphenylamino)acetamide
MS (EI) m/z C33H34N6O5S: 627 (MH+).
Example 233
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-isopropylphenylamino)acetamide
MS (EI) m/z C33H34N6O5S: 627 (MH+).
Example 234
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-fluoro-4-methylphenylamino)acetamide
MS (EI) m/z C31H29FN6O5S: 617 (MH+).
Example 235
2-(4-chlorophenylamino)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C30H27ClN6O5S: 619 (MH+).
Example 236
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-methoxyphenylamino)acetamide
MS (EI) m/z C31H30N6O6S: 615 (MH+).
Example 237
2-(3-chlorophenylamino)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C30H27ClN6O5S: 619 (MH+).
Example 238
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2,3-dimethylphenylamino)acetamide
MS (EI) m/z C32H32N6O5S: 613 (MH+).
Example 239
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-fluorophenylamino)acetamide
MS (EI) m/z C30H27FN6O5S: 603 (MH+).
Example 240
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-fluorophenylamino)acetamide
MS (EI) m/z C30H27FN6O5S: 603 (MH+).
Example 241
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(thiophen-2-ylmethylamino)acetamide
MS (EI) m/z C29H28N6O5S2: 605 (MH+).
Example 242
2-(cyclohexyl(ethyl)amino)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C32H38N6O5S: 619 (MH+).
Example 243
2-((cyclopropylmethyl)(propyl)amino)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C31H36N6O5S: 605 (MH+).
Example 244
2-(allyl(cyclopentyl)amino)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C32H36N6O5S: 617 (MH+).
Example 245
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(ethyl(isopropyl)amino)acetamide
MS (EI) m/z C29H34N6O5S: 579 (MH+).
Example 246
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(ethyl(phenyl)amino)acetamide
MS (EI) m/z C32H32N6O5S: 613 (MH+).
Example 247
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-methylpyrrolidin-1-yl)acetamide
MS (EI) m/z C29H32N6O5S: 577 (MH+).
Example 248
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-methylpiperidin-1-yl)acetamide
MS (EI) m/z C30H34N6O5S: 591 (MH+).
Example 249
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(pyridin-2-ylmethylamino)acetamide
MS (EI) m/z C30H29N7O5S: 600 (MH+).
Example 250
2-(benzyl(methyl)amino)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C32H32N6O5S: 613 (MH+).
Example 251
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(1-phenylethylamino)acetamide
MS (EI) m/z C32H32N6O5S: 613 (MH+).
Example 252
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-methylpiperidin-1-yl)acetamide
MS (EI) m/z C30H34N6O5S: 591 (MH+).
Example 253
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-methylpiperidin-1-yl)acetamide
MS (EI) m/z C30H34N6O5S: 591 (MH+).
Example 254
2-(3,4-dihydroisoquinolin-2(1H)-yl)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C33H32N6O5S: 625 (MH+).
Example 255
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2,6-dimethylpiperidin-1-yl)acetamide
MS (EI) m/z C31H36N6O5S: 605 (MH+).
Example 256
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-hydroxybenzylamino)acetamide
MS (EI) m/z C31H30N6O6S: 615 (MH+)
General Library Acylation Procedure 1




Into a 2-dram vial were added 3-amino-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide (54 mg, 0.12 mmol), prepared using procedures similar to those described in Example 15, DMA (2 mL) and the desired carboxylic acid (0.17 mmol). DIEA (70 μL, 0.4 mmol) followed by HATU (53 mg, 0.14 mmol) were added to the vial and the reaction mixture stirred at 50° C. overnight. Preparative reverse-phase HPLC was used to isolate the desired product directly from the crude reaction mixture. A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C18, OCD 5 μM, 30×70 mm column and running a 5-100% gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification.
The following title compounds were prepared according to General Library Acylation Procedure 1.
Example 257
N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)morpholine-4-carboxamide
MS (EI) m/z for C26H25ClN6O5S: 567 (MH−).
Example 258
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide
MS (EI) m/z for C26H28N6O5S: 535.1 (MH−).
Example 259
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)propionamide
1H-NMR (400 MHz, d6-DMSO): 12.37 (s, 1H), 10.20 (s, 1H), 8.88 (s, 1H), 8.37 (s, 1H), 7.93 (s, 1H), 7.77 (t, 2H), 7.59 (t, 1H), 7.51 (t, 1H), 7.41-7.34 (m, 4H), 6.24 (t, 1H), 3.76 (s, 6H), 2.36-2.31 (dd, 2H), 1.10 (s, 1H), 1.08 (s, 1H), 1.06 (s, 1H); MS (EI) m/z C25H25N505S: 508.6 (MH+).
Example 260
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)Phenyl)pyridazine-4-carboxamide
1H-NMR (400 MHz, d6-DMSO): 11.01 (s, 1H), 9.66 (dd, 1H), 9.52 (dd, 1H), 8.90 (s, 1H), 8.55 (s, 1H), 8.13 (dd, 1H), 7.99 (d, 1H), 7.93 (d, 1H), 7.65-7.58 (m, 2H), 7.42-7.35 (m, 4H), 6.24 (t, 1H), 3.75 (s, 6H); MS (EI) m/z C27H23N705S: 558.6 (MH+).
Example 261
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methylnicotinamide
1H-NMR (400 MHz, d6-DMSO): 10.78 ppm (s, 1H), 8.90 ppm (s, 1H), 8.58-8.57 ppm (dd, 2H), 7.90-7.86 (m, 4H), 7.60-7.56 ppm (m, 2H), 7.42-7.34 (m, 5H), 6.23 ppm (t, 1H), 3.74 ppm (s, 6H), 2.57 ppm (s, 3H); MS (EI) m/z C29H26N5O5S: 570.6 (MH+).
Example 262
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(o-tolyloxy)acetamide
1H-NMR (400 MHz, d6-DMSO): 12.37 ppm (s, 1H), 10.41 ppm (s, 1H), 8.90 ppm (s, 1H), 8.41 ppm (s, 1H), 7.93 ppm (s, 1H), 7.90-7.8 (m, 2H), 7.59-7.53 ppm (m, 2H), 7.42-7.33 ppm (m, 4H), 7.17-7.12 ppm (m, 2H), 6.89-6.85 ppm (m, 2H), 6.24 ppm (t, 1H), 4.74 ppm (s, 2H), 3.76 ppm (s, 6H), 2.33 ppm (s, 2H); MS (EI) m/z C31H29N5O6S: 599.7 (MH+).
Example 263
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-methoxy-4-methylbenzamide
MS (EI) m/z C31H29N5O6S: 600 (MH+).
Example 264
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-methoxy-4-methylbenzamide
MS (EI) m/z C28H24N6O5S: 557 (MH+).
Example 265
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)thiazole-4-carboxamide
MS (EI) m/z C26H22N6O5S2: 563 (MH+).
Example 266
2-bromo-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)thiophene-3-carboxamide
MS (EI) m/z C27H22BrN5O5S2 640 (MH+).
Example 267
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)pivalamide
MS (EI) m/z C27H29N5O5S: 536 (MH+).
Example 268
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)pent-4-enamide
MS (EI) m/z C27H27N5O5S: 534 (MH+).
Example 269
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)benzamide
MS (EI) m/z C29H25N5O5S: 556 (MH+).
Example 270
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)butyramide
MS (EI) m/z C26H27N5O5S: 522 (MH+).
Example 271
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methoxyacetamide
MS (EI) m/z C25H25N5O6S: 524 (MH+).
Example 272
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)cyclobutanecarboxamide
MS (EI) m/z C27H27N5O5S: 534 (MH+).
Example 273
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methylcyclopropanecarboxamide
MS (EI) m/z C27H27N5O5S: 534 (MH+).
Example 274
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1-methylcyclopropanecarboxamide
MS (EI) m/z C27H27N5O5S: 534 (MH+).
Example 275
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-methylbutanamide
MS (EI) m/z C27H29N5O5S: 536 (MH+).
Example 276
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-ethoxyacetamide
MS (EI) m/z C26H27N5O6S: 538 (MH+).
Example 277
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-methoxypropanamide
MS (EI) m/z C26H27N5O6S: 538 (MH+).
Example 278
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-hydroxyacetamide
MS (EI) m/z C24H23N5O6S: 510 (MH+).
Example 279
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)isobutyramide
MS (EI) m/z C26H27N5O5S: 522 (MH+).
Example 280
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1-hydroxycyclopropanecarboxamide
MS (EI) m/z C26H25N5O6S: 536 (MH+).
Example 281
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)furan-3-carboxamide
MS (EI) m/z C27H23N5O6S: 546 (MH+).
Example 282
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)tetrahydrofuran-3-carboxamide
MS (EI) m/z C27H27N5O6S: 550 (MH+).
Example 283
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)tetrahydrofuran-2-carboxamide
MS (EI) m/z C27H27N5O6S: 550 (MH+).
Example 284
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)furan-2-carboxamide
MS (EI) m/z C27H23N5O6S: 546 (MH+).
Example 285
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)isonicotinamide
MS (EI) m/z C28H24N6O5S: 557 (MH+).
Example 286
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1H-pyrrole-2-carboxamide
MS (EI) m/z C27H24N6O5S: 545 (MH+).
Example 287
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)pyrazine-2-carboxamide
MS (EI) m/z C27H23N7O5S: 558 (MH+).
Example 288
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1-methyl-1H-pyrrole-2-carboxamide
MS (EI) m/z C28H26N6O5S: 559 (MH+).
Example 289
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-5-methylisoxazole-3-carboxamide
MS (EI) m/z C27H24N6O6S: 561 (MH+).
Example 290
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)thiophene-2-carboxamide
MS (EI) m/z C27H23N5O5S2: 562 (MH+).
Example 291
(S)—N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1-methylpyrrolidine-2-carboxamide
MS (EI) m/z C28H30N6O5S: 563 (MH+).
Example 292
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methylbenzamide
MS (EI) m/z C30H27N5O5S: 570 (MH+).
Example 293
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-phenylacetamide
MS (EI) m/z C30H27N5O5S: 570 (MH+).
Example 294
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-methylpicolinamide
MS (EI) m/z C29H26N6O5S: 571 (MH+).
Example 295
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(pyridin-3-yl)acetamide
MS (EI) m/z C29H26N6O5S: 571 (MH+).
Example 296
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-6-hydroxypicolinamide
MS (EI) m/z C28H24N6O6S: 573 (MH+).
Example 297
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-fluorobenzamide
MS (EI) m/z C29H24FN5O5S: 574 (MH+).
Example 298
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-4-fluorobenzamide
MS (EI) m/z C29H24FN5O5S: 574 (MH+).
Example 299
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-fluorobenzamide
MS (EI) m/z C29H24FN5O5S: 574 (MH+).
Example 300
2-cyclohexyl-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C30H33N5O5S: 576 (MH+).
Example 301
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-oxocyclopentyl)acetamide
MS (EI) m/z C29H29N5O6S: 576 (MH+).
Example 302
4-cyclopropyl-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-4-oxobutanamide
MS (EI) m/z C29H29N5O6S: 576 (MH+).
Example 303
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-oxocyclohexanecarboxamide
MS (EI) m/z C29H29N5O6S: 576 (MH+).
Example 304
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-(pyridin-3-yl)propanamide
MS (EI) m/z C30H28N6O5S: 585 (MH+).
Example 305
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methoxybenzamide
MS (EI) m/z C30H27N5O6S: 586 (MH+).
Example 306
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-methoxybenzamide
MS (EI) m/z C30H27N5O6S: 586 (MH+).
Example 307
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-phenoxyacetamide
MS (EI) m/z C30H27N5O6S: 586 (MH+).
Example 308
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-4-methoxybenzamide
MS (EI) m/z C30H27N5O6S: 586 (MH+).
Example 309
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-fluorophenyl)acetamide
MS (EI) m/z C30H26FN5O5S: 588 (MH+).
Example 310
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-fluorophenyl)acetamide
MS (EI) m/z C30H26FN5O5S: 588 (MH+).
Example 311
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-fluorophenyl)acetamide
MS (EI) m/z C30H26FN5O5S: 588 (MH+).
Example 312
2-chloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)benzamide
MS (EI) m/z C29H24ClN5O5S: 590 (MH+).
Example 313
4-chloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)benzamide
MS (EI) m/z C29H24ClN5O5S: 590 (MH+).
Example 314
3-chloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)benzamide
MS (EI) m/z C29H24ClN5O5S: 590 (MH+).
Example 315
(1R,2R)—N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-phenylcyclopropanecarboxamide
MS (EI) m/z C32H29N5O5S: 596 (MH+).
Example 316
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1-phenylcyclopropanecarboxamide
MS (EI) m/z C32H29N5O5S: 596 (MH+).
Example 317
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(1H-imidazol-4-yl)acetamide
MS (EI) m/z C27H25N7O5S: 560 (MH+).
Example 318
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-4-methoxy-2-methylbenzamide
MS (EI) m/z C31H29N5O6S: 600 (MH+).
Example 319
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-fluorophenoxy)acetamide
MS (EI) m/z C30H26FN5O6S: 604 (MH+).
Example 320
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-5-fluoro-2-methoxybenzamide
MS (EI) m/z C30H26FN5O6S: 604 (MH+).
Example 321
2-(4-chlorophenyl)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C30H26ClN5O5S: 604 (MH+).
Example 322
2-(2-chlorophenyl)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C30H26ClN5O5S: 604 (MH+).
Example 323
2-(3-chlorophenyl)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C30H26ClN5O5S: 604 (MH+).
Example 324
1-acetyl-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)piperidine-4-carboxamide
MS (EI) m/z C30H32N6O6S: 605 (MH+).
Example 325
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(pyridin-4-yl)acetamide
MS (EI) m/z C29H26N6O5S: 571 (MH+).
Example 326
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(pyridin-2-yl)acetamide
MS (EI) m/z C29H26N6O5S: 571 (MH+).
Example 327
2,4-dichloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)benzamide
MS (EI) m/z C29H23Cl2N5O5S: 624 (MH+).
Example 328
3,4-dichloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)benzamide
MS (EI) m/z C29H23Cl2N5O5S: 624 (MH+).
Example 329
2,5-dichloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)benzamide
MS (EI) m/z C29H23Cl2N5O5S: 624 (MH+).
Example 330
3,5-dichloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)benzamide
MS (EI) m/z C29H23Cl2N5O5S: 624 (MH+).
Example 331
2,3-dichloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)benzamide
MS (EI) m/z C29H23Cl2N5O5S: 624 (MH+).
Example 332
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)pentanamide
MS (EI) m/z C27H29N5O5S: 536 (MH+).
Example 333
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methylbutanamide
MS (EI) m/z C27H29N5O5S: 536 (MH+).
Example 334
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1H-imidazole-2-carboxamide
MS (EI) m/z C26H23N7O5S: 546 (MH+).
Example 335
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1H-imidazole-4-carboxamide
MS (EI) m/z C26H23N7O5S: 546 (MH+).
Example 336
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)isoxazole-5-carboxamide
MS (EI) m/z C26H22N6O6S: 547 (MH+).
Example 337
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3,3-dimethylbutanamide
MS (EI) m/z C28H31N5O5S: 550 (MH+).
Example 338
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methylpentanamide
MS (EI) m/z C28H31N5O5S: 550 (MH+).
Example 339
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2,2-dimethylbutanamide
MS (EI) m/z C28H31N5O5S: 550 (MH+).
Example 340
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-4-methylpentanamide
MS (EI) m/z C28H31N5O5S: 550 (MH+).
Example 341
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)pyrimidine-5-carboxamide
MS (EI) m/z C27H23N7O5S: 558 (MH+).
Example 342
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-methylfuran-2-carboxamide
MS (EI) m/z C28H25N5O6S: 560 (MH+).
Example 343
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)thiophene-3-carboxamide
MS (EI) m/z C27H23N5O5S2: 562 (MH+).
Example 344
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-oxocyclopentanecarboxamide
MS (EI) m/z C28H27N5O6S: 562 (MH+).
Example 345
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-methoxyethoxy)acetamide
MS (EI) m/z C27H29N5O7S: 568 (MH+).
Example 346
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-4-methylbenzamide
MS (EI) m/z C30H27N5O5S: 570 (MH+).
Example 347
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-methylisoxazol-4-yl)acetamide
MS (EI) m/z C28H26N6O6S: 575 (MH+).
Example 348
3-cyclopentyl-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)propanamide
MS (EI) m/z C30H33N5O5S: 576 (MH+).
Example 349
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-o-tolylacetamide
MS (EI) m/z C31H29N5O5S: 584 (MH+).
Example 350
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methoxynicotinamide
MS (EI) m/z C29H26N6O6S: 587 (MH+).
Example 351
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-4-fluoro-3-methylbenzamide
MS (EI) m/z C30H26FN5O5S: 588 (MH+).
Example 352
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-fluoro-2-methylbenzamide
MS (EI) m/z C30H26FN5O5S: 588 (MH+).
Example 353
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-fluoro-4-methylbenzamide
MS (EI) m/z C30H26FN5O5S: 588 (MH+).
Example 354
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-fluoro-5-methylbenzamide
MS (EI) m/z C30H26FN5O5S: 588 (MH+).
Example 355
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-5-fluoro-2-methylbenzamide
MS (EI) m/z C30H26FN5O5S: 588 (MH+).
Example 356
6-chloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)nicotinamide
MS (EI) m/z C28H23ClN6O5S: 591 (MH+).
Example 357
2-chloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)nicotinamide
MS (EI) m/z C28H23ClN6O5S: 591 (MH+).
Example 358
2-chloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)isonicotinamide
MS (EI) m/z C28H23ClN6O5S: 591 (MH+).
Example 359
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-4-(dimethylamino)benzamide
MS (EI) m/z C31H30N6O5S: 599 (MH+).
Example 360
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-(dimethylamino)benzamide
MS (EI) m/z C31H30N6O5S: 599 (MH+).
Example 361
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)benzo[d][1,3]-dioxole-5-carboxamide
MS (EI) m/z C30H25N5O7S: 600 (MH+).
Example 362
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(m-tolyloxy)acetamide
MS (EI) m/z C31H29N5O6S: 600 (MH+).
Example 363
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-methoxyphenyl)acetamide
MS (EI) m/z C31H29N5O6S: 600 (MH+).
Example 364
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-methoxyphenyl)acetamide
MS (EI) m/z C31H29N5O6S: 600 (MH+).
Example 365
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-methoxyphenyl)acetamide
MS (EI) m/z C31H29N5O6S: 600 (MH+).
Example 366
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methoxy-4-methylbenzamide
MS (EI) m/z C31H29N5O6S: 600 (MH+).
Example 367
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-fluoro-4-methoxybenzamide
MS (EI) m/z C30H26FN5O6S: 604 (MH+).
Example 368
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-fluoro-6-methoxybenzamide
MS (EI) m/z C30H26FN5O6S: 604 (MH+).
Example 369
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-(4-methoxyphenyl)propanamide
MS (EI) m/z C32H31N5O6S: 614 (MH+).
Example 370
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-(2-methoxyphenyl)propanamide
MS (EI) m/z C32H31N5O6S: 614 (MH+).
Example 371
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-(3-methoxyphenyl)propanamide
MS (EI) m/z C32H31N5O6S: 614 (MH+).
Example 372
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide




Into a 20 mL vial was added 3-amino-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide (0.24 mmol, 1 equiv), prepared using procedures similar to those described in Example 15, DMA (5 mL) and 1-(tert-butoxycarbonyl)azetidine-3-carboxylic acid (0.336 mmol, 1.4 equiv). Hunig's Base (0.792 mmol, 3.3 equiv) and HATU (0.288 mmol, 1.2 equiv) were added to the vial and the reaction mixture was then stirred at room temperature overnight. Completion of the reaction was indicated by LCMS. The solvent was removed by rotary evaporation. The crude mixture was carried forward without further purification. The residue was suspended in 5 mL ethyl acetate and chilled in an ice bath. A solution of 4 N HCl in dioxane (3 mL, 5 equiv) was added with stirring. The reaction mixture was then stirred at room temperature overnight. The solid materials were collected by filtration, washed with ethylacetate then purified further by preparative reverse-phase HPLC (ammonium acetate/ACN). A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C18, OCD 5 μM, 30×70 mm column and running a 5-100% gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification. N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide was obtained (26 mg, 20%). 1H-NMR (400 MHz, d6-DMSO): 10.26 (s, 1H), 8.81 (s, 1H), 8.25 (t, 8.14 (s, 1H), 7.74 (d, 1H), 7.69 (d, 1H), 7.41-7.39 (m, 1H), 7.36 (d, 1H), 7.32 (d, 2H), 7.30-7.28 (dd, 1H), 7.14-7.11 (m, 2H), 6.14 (t, 1H), 4.09 (d, 4H), 3.78 (s, 6H); MS (EI) m/z C26H26N6O5S: 535.6 (MH+).
Example 373
N-(3-(4-fluorophenylamino)quinoxalin-2-yl)benzenesulfonamide




A flask was charged with 2,3-dichloroquinoxaline (3.5 g, 18 mmol), 85 mL of dimethylsulfoxide, benzene sulfonamide (2.8 g, 18 mmol), and cesium carbonate (5.8 g, 18 mmol). The reaction mixture was stirred under an N2 atmosphere for 15 h at 150° C., after which time, it was transferred to a separatory funnel and 100 mL of water were added. Concentrated HCl was then added in order to acidify the reaction mixture to pH<2. The aqueous layer was subsequently washed three times with 90 mL ethyl acetate. The ethyl acetate layers were then washed two times with 150 mL water, three times with 100 mL brine and then dried over sodium sulfate. The ethyl acetate was removed on a rotary-evaporator. A slurry was formed by adding ethyl acetate and dichloromethane to the dried crude product, filtration yielded N-(3-chloroquinoxalin-2-yl)-benzenesulfonamide which was used without further purification. MS (EI) m/z C14H10ClN3O2S: 319.9 (MH+).
A CEM microwave reaction vessel was charged with N-(3-chloroquinoxalin-2-yl)benzenesulfonamide (52 mg, 0.16 mmol), prepared using procedures similar to those described in the above step, 4-fluoroaniline (36 mg, 0.32 mmol), and 0.8 mL of dimethylacetamide. The vessel was sealed and the reaction mixture was heated under microwave radiation for 25 m at 120° C. in a CEM Discover microwave instrument. Methanol (1 mL) was added to the reaction mixture and after 20 minutes the product precipitated out of the solution. Filtration yielded N-(3-(4-fluorophenylamino)quinoxalin-2-yl)benzenesulfonamide (39 mg, 62%). 1H-NMR (400 MHz, do-DMSO): δ 12.30 (s, 1H), 9.11 (s, 1H), 8.16-8.10 (d, 2H), 8.02-7.90 (m, 3H), 7.68-7.58 (m, 3H), 7.55-7.51 (m, 1H), 7.41-7.32 (m, 2H), 7.25-7.16 (m, 2H); MS (EI) m/z C20H15FN4O2S: 395.0 (MH+).
Example 374
N-(3-(N-(3-chloroquinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide








Scheme A

A flask was charged with 3-aminobenzene sulfonamide (3.3 g, 19 mmol), and 20 mL of 1:1 acetone:H2O. The solution was stirred at room temperature until the aminobenzene sulfonamide had dissolved. The flask was then cooled in an ice bath and dimethylamino-acetyl chloride HCl (4.6 g, 29 mmol) was added. To the resulting slurry sodium bicarbonate (4.8 g, 57 mmol) was added over a 15 m period. After 30 min the reaction was removed from the ice bath and allowed to stir at room temperature for 15 h. The reaction mixture was then filtered and washed with methanol and acetonitrile. The filtrate was dried on a rotary evaporator to yield 2-(dimethylamino)-N-(3-sulfamoyl-phenyl)acetamide, which was submitted to the next step without further purification. MS (EI) m/z C10H15N3O3S: 258.0 (MH+).
Scheme B
A flask was charged with dichloroquinozaline (1.0 g, 5.8 mmol), 10 mL of dimethylacetamide, 2-(dimethylamino)-N-(3-sulfamoylphenyl)acetamide (0.70 g, 2.7 mmol), and cesium carbonate (1.8 g, 5.5 mmol). The reaction mixture was stirred for 3 h at 140° C. and then filtered. The solvent was evaporated from the filtrate on a rotary-evaporator to yield (N-(3-(N-(3-chloroquinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide) which was submitted to the next step without further purification. MS (EI) m/z C18H18ClN5O3S: 420.0 (MH+).
General Amination Procedure 1a




A CEM microwave reaction vessel was charged with N-(3-(N-(3-chloroquinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide (30 mg, 0.071 mmol), prepared using procedures similar to those described in Example 374, the desired aniline (16 mg, 0.14 mmol, 2 eq), and 0.5 mL of dimethylacetamide. The vessel was sealed and the reaction mixture was heated under microwave radiation for 70 min at 140° C. in a CEM Discover microwave instrument. The solvent was then removed by rotary-evaporation. Purification of the final product was accomplished by preparatory reverse-phase HPLC with the eluents 25 mM aqueous NH4OAc/ACN to the desired product.
The following compounds were prepared according to the above General Amination Procedure 1a.
Example 375
2-(dimethylamino)-N-(3-(N-(3-(3-fluorophenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
1H-NMR (400 MHz, CDCl3): 9.40 ppm (s, 1H), 8.43 ppm (s, 1H), 8.22 ppm (s, 1H), 8.07-8.02 ppm (d, 1H), 7.97-7.93 ppm (d, 1H), 7.76-7.71 (m, 2H), 7.53-7.48 ppm (t, 1H), 7.45-7.36 ppm (m, 4H), 7.35-7.28 ppm (m, 2H), 6.84-6.77 ppm (t, 1H), 3.10 ppm (s, 2H), 2.38 ppm (s, 6H); MS (EI) m/z C24H23FN6O3S: 495 (MH+).
Example 376
2-(dimethylamino)-N-(3-(N-(3-(4-fluorophenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C24H23FN6O3S: 495 (MH+).
Example 377
N-(3-(N-(3-(4-chloro-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide
MS (EI) m/z C24H23ClN6O3S: 511 (MH+).
General Amination Procedure 1b




A CEM microwave reaction vessel was charged with N-(3-(N-(3-chloroquinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide (62 mg, 0.147 mmol), prepared using procedures similar to those in Example 374, the desired aniline (0.567 mmol, 4 eq), and 1.0 mL of toluene. The vessel was sealed and the reaction mixture was heated under microwave radiation for 60 min at 180° C. in a CEM Discover microwave instrument. The solvent was removed on a rotary-evaporator. Purification of the final product was done by preparatory HPLC with NH4OAc/ACN as eluent to yield the desired product.
The following compounds were prepared according to the above General Amination Procedure 1b.
Example 378
N-(3-(N-(3-(3-chloro-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide
MS (EI) m/z C24H23ClN6O3S: 511 (MH+).
Example 379
2-(dimethylamino)-N-(3-(N-(3-(4-fluoro-3-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
2-(dimethylamino)-N-(3-(N-(3-(4-fluoro-3-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl). 1H-NMR (400 MHz, CDCl3): δ 9.47 (s, 1H), 8.36 (s, 1H), 8.29 (s, 1H), 7.91-7.87 (d, 1H), 7.80-7.73 (m, 2H), 7.66-7.63 (d, 1H), 7.53-7.47 (t, 1H), 7.43-7.30 (m, 4H), 7.10-7.04 (t, 1H), 6.55-5.95 (br s, 1H), 3.96 (s, 3H), 3.12 (s, 2H), 2.39 (s, 6H), 2.08 (s, 3H(AcOH); MS (EI) m/z C25H25FN6O4S: 525 (MH+).
Example 380
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-isopropoxybenzenesulfonamide




N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-isopropoxybenzenesulfonamide
A solution of 2,3-dichloroquinoxaline (2.0 mL, 0.38 M) was combined with K2CO3 (105 mg, 0.76 mmol) in a glass vial. A solution of 4-isopropoxybenzene sulfonamide (1.75 mL, 0.43 M) was added and the solution was stirred overnight at 125° C. After cooling, acetic acid (45 mL, 0.79 mmol) and 3,5-dimethoxyaniline (230 mg, 1.5 mmol) were added. The reaction mixture was stirred again at 125° C. overnight. Upon cooling, the reaction mixture was diluted with 8 mL of methanol and then 8 mL of water. The precipitate was collected by filtration and recrystallized from N,N-dimethylacetamide/water to give N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-isopropoxy-benzenesulfonamide (45 mg, 12%). 1H-NMR (400 MHz, d6-DMSO): 12.16 (bs, 1H), 8.93 (s, 1H), 8.03 (d, 2H), 7.92 (bs, 1H), 7.56 (d, 1H), 7.36 (m, 4H), 7.07 (d, 2H), 6.24 (s, 1H), 4.72 (m, 1H), 3.76 (s, 6H), 1.27 (d, 6H); MS (EI) m/z C25H26N4O5S: 495 (MH+).
Examples 381-411 were synthesized proceeding as above in Example 423. In the cases where the product did not precipitate, the mixture was purified by reverse phase HPLC.
Example 381
3-chloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-methylbenzenesulfonamide
1H-NMR (400 MHz, d6-DMSO): 12.31 (bs, 1H), 8.96 (s, 1H), 8.18 (s, 1H), 7.98 (d, 1H), 7.92 (bs, 1H), 7.58 (d, 2H), 7.43-7.33 (m, 4H), 6.24 (t, 1H), 3.76 (s, 6H), 2.39 (s, 3H); MS (EI) m/z C23H21ClN4O4S: 485 (MH+).
Example 382
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)naphthalene-1-sulfonamide
MS (EI) m/z C26H22N4O4S: 487 (MH+).
Example 383
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-fluorobenzenesulfonamide
MS (EI) m/z C22H19FN4O4S: 455 (MH+).
Example 384
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3-fluorobenzenesulfonamide
MS (EI) m/z C22H19FN4O4S: 455 (MH+).
Example 385
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide
MS (EI) m/z C23H19F3N4O4S: 505 (MH+).
Example 386
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide
MS (EI) m/z C23H19F3N4O4S: 505 (MH+).
Example 387
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-(trifluoromethoxy)benzenesulfonamide
MS (EI) m/z C23H19F3N4O5S: 521 (MH+).
Example 388
N-(4-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide
MS (EI) m/z C24H23N5O5S: 494 (MH+).
Example 389
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-fluoro-2-methylbenzenesulfonamide
MS (EI) m/z C23H21FN4O4S: 469 (MH+).
Example 390
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-2-methylbenzenesulfonamide
MS (EI) m/z C23H22N4O4S: 451 (MH+).
Example 391
2-chloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z C22H19ClN4O4S: 471 (MH+).
Example 392
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3,5-difluorobenzenesulfonamide
MS (EI) m/z C22H18F2N4O4S: 473 (MH+).
Example 393
3,5-dichloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z C22H18Cl2N4O4S: 505 (MH+).
Example 394
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3-fluoro-4-methylbenzenesulfonamide
MS (EI) m/z C23H21FN4O4S: 469 (MH+).
Example 395
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-2-(trifluoromethyl)benzenesulfonamide
MS (EI) m/z C23H19F3N4O4S: 505 (MH+).
Example 396
4-cyano-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z C23H19N5O4S: 462 (MH+).
Example 397
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-1-phenylmethanesulfonamide
MS (EI) m/z C23H22N4O4S: 451 (MH+).
Example 398
4,5-dichloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)thiophene-2-sulfonamide
MS (EI) m/z C20H16Cl2N4O4S2: 511 (MH+).
Example 399
1-(3-chlorophenyl)-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)methanesulfonamide
MS (EI) m/z C23H21ClN4O4S: 485 (MH+).
Example 400
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-2,5-dimethylthiophene-3-sulfonamide
MS (EI) m/z C22H22N4O4S2: 471 (MH+).
Example 401
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3,5-bis(trifluoromethyl)benzenesulfonamide
MS (EI) m/z C24H18F6N4O4S: 573 (MH+).
Example 402
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-fluoro-3-(trifluoromethyl)benzenesulfonamide
MS (EI) m/z C23H18F4N4O4S: 523 (MH+).
Example 403
5-chloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-1,3-dimethyl-1H-pyrazole-4-sulfonamide
MS (EI) m/z C21H21ClN6O4S: 489 (MH+).
Example 404
5-chloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-2-methoxybenzenesulfonamide
MS (EI) m/z C23H21ClN4O5S: 501 (MH+).
Example 405
5-bromo-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-2-methoxybenzenesulfonamide
MS (EI) m/z C23H21BrN4O5S: 545 (MH+).
Example 406
2,5-dichloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)thiophene-3-sulfonamide
MS (EI) m/z C20H16Cl2N4O4S2: 511 (MH+).
Example 407
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3,5-dimethylisoxazole-4-sulfonamide
MS (EI) m/z C21H21N5O5S: 456 (MH+).
Example 408
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-2,5-dimethoxybenzenesulfonamide
MS (EI) m/z C24H24N4O6S: 497 (MH+).
Example 409
3-chloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-fluorobenzenesulfonamide
MS (EI) m/z C22H18ClFN4O4S: 489 (MH+).
Example 410
4-(difluoromethoxy)-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z C23H20F2N4O5S: 503 (MIT).
Example 411
N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3-(methylsulfonyl)benzenesulfonamide
MS (EI) m/z C23H22N4O6S2: 515 (MH+).
General Acylation Procedure 2




N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-sulfamoyl)phenyl)azetidine-3-carboxamide (125 mg, 0.23 mmol), prepared using procedures similar to those described in Example 372, was dissolved into 5 mL DCE in a 10 mL round-bottom flask. DIEA (1.17 mmol, 5.0 equiv.) was then added with stirring followed by acid chloride (0.47 mmol, 2.0 equiv.). The reaction was then stirred at room temperature for 1 hour or until complete as indicated by LCMS. The solvent was subsequently removed under reduced pressure on a rotary evaporator. The crude material was then redissolved in methanol. Purification of the final product was accomplished by preparatory reverse-phase HPLC with the eluents 25 mM aqueous NH4OAc/CAN. A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C18, OCD 5 μM, 30×70 mm column and running a 5-100% gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification.
The following compounds were prepared according to General Acylation Procedure 2.
Example 412
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1-propionylazetidine-3-carboxamide
1H-NMR (400 MHz, d6-DMSO): 12.40 (s, 1H), 10.45 (s, 1H), 8.88 (s, 1H), 8.40 (s, 1H), 7.93 (s, 1H), 7.82 (d, 1H), 7.77 (d, 1H), 7.60-7.45 (m, 2H), 7.41-7.30 (m, 4H), 6.24 (s, 1H), 4.26 (t, 1H), 4.22-4.17 (m, 1H), 3.99 (t, 1H), 3.95-3.89 (m, 1H), 3.76 (s, 6H), 3.59-3.45 (m, 1H), 2.05 (dd, 2H), 0.95 (t, 3H); MS (EI) m/z C29H30N6O6S: 591 (MH+).
Example 413
1-acetyl-N-(3-{[(3-{[3,5-bis(methoxy)-phenyl]amino}quinoxalin-2-yl)amino]sulfonyl}phenyl)azetidine-3-carboxamide
MS (EI) m/z C28H28N6O6S: 577 (MH+).
Example 414
1-(cyclopropanecarbonyl)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide
MS (EI) m/z C30H30N6O6S: 603 (MH+).
General Reductive Amination Procedure 1




To a solution of N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide (110 mg, 0.19 mmol), prepared using procedures similar to those described in Example 372, in 3 mL of DCE and 200 μL of DMF, aldehyde (0.77 mmol, 4.0 eq.)was added slowly followed by tetramethylammonium triacetoxyborohydride (1.16 mmol, 6.0 eq). The reaction was stirred at room temperature overnight. LC/MS indicated the reaction was completed. The solvent was subsequently removed under reduced pressure on a rotary evaporator. The crude material was then redissolved in methanol. Purification of the final product was accomplished by preparatory reverse-phase HPLC with the eluents 25 mM aqueous NH4OAc/CAN. A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C18, OCD 5 μM, 30×70 mm column and running a 5-100% gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification.
The following title compounds were prepared according to General Reductive Amination Procedure 1.
Example 415
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1-ethylazetidine-3-carboxamide
1H-NMR (400 MHz, d6-DMSO): 10.29 (s, 1H), 8.82 (s, 1H), 8.25 (t, 1H), 7.75-7.68 (m, 2H), 7.43-7.38 (m, 1H), 7.375-7.340 (m, 1H), 7.338-7.310 (d, 2H), 7.305-7.262 (m, 1H), 7.15-7.08 (m, 2H), 6.56 (s, 1H), 6.15 (t, 1H), 4.15-4.08 (m, 2H), 4.06-3.95 (m, 2H), 3.78 (s, 6H), 3.65-3.56 (m, 1H), 3.12-3.04 (m, 2H), 1.03 (t, 3H); MS (EI) m/z C28H30N6O5S: 563 (MH+).
Example 416
1-(cyclopropylmethyl)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide
MS (EI) m/z C30H32N6O5S: 589 (MH+).
Example 417
1-benzyl-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide
MS (EI) m/z C33H32N6O5S: 625 (MH+).
Example 418
N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1-(furan-2-ylmethyl)azetidine-3-carboxamide
MS (EI) m/z C31H30N6O6S: 615 (MH+).
Example 419
1-((1H-imidazol-5-yl)methyl)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide
MS (EI) m/z C30H30N8O5S: 615 (MH+).
General Amide Formation Procedure 1a




Into a small 1 dram vial was added 3-(N-(3-(2-chloro-5-methoxy-phenylamino)-quinoxalin-2-yl)sulfamoyl)benzoic acid (61 mg, 0.13 mmol, 1.1 equiv), prepared using procedures described for Example 100. The acid was dissolved in DMA (1 mL) and DIEA (42 μL, 0.24 mmol, 2 equiv) was added then added to the solution. The amine reagent (1 mL of 0.12 M solution in DMA) was added to solution with stirring followed by HATU (64 mg, 0.17 mmol, 1.4 equiv). The reaction was stirred overnight at room temperature. Upon completion as indicated by LCMS analysis, 2 mL of methanol was added to the solution. Preparative reverse-phase HPLC was used to isolate the desired product. A Waters Fractionlynx preparative reverse-phase HPLC—equipped with a Waters SunFire Prep C18, OCD 5 μM, 30×70 mm column and running a 5-100% gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile—was used to carry out the purification.
The following compounds were prepared according to General Amide Formation Procedure 1.
Example 420
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-(dimethylamino)propyl)benzamide
3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-(dimethylamino)propyl)benzamide: 1H NMR (400 MHz, d6-DMSO): 9.44 (s, 1H), 8.94 (s, 1H), 8.79 (t, 1H), 8.54 (s, 1H), 8.24 (d, 1H), 7.87 (d, 1H), 7.48 (m, 3H), 7.33 (d, 1H), 7.18 (m, 2H), 6.60 (dd, 1H), 3.82 (1H), 3.04 (m, 3H), 2.51 (m, 5H), 1.91 (s, 1H), 1.86 (m, 3H); MS (EI) m/z for C27H29ClN6O4S: 569 (MH+).
Example 421
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(1-methylazetidin-3-yl)benzamide
3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(1-methylazetidin-3-yl)benzamide: 1H NMR (400 MHz, d6-DMSO): 9.43 (s, 1H), 9.23 (d, 1H), 8.94 (d, 1H), 8.58 (s, 1H), 8.29 (d, 1H), 7.89 (d, 1H), 7.56 (t, 1H), 7.47 (d, 1H), 7.44 (d, 1H), 7.33 (d, 1H), 7.18 (m, 2H), 6.60 (dd, 1H), 4.81 (m, 1H), 4.33 (m, 2H), 4.19 (m, 2H), 3.82 (s, 1H), 2.51 (s, 3H); MS (EI) m/z for C26H25ClN6O4S: 553 (MH+).
Example 422
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(pyridin-4-ylmethyl)benzamide
MS (EI) m/z C28H23ClN6O4S: 575 (MH+).
Example 423
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-(dimethylamino)propyl)benzamide
MS (EI) m/z C28H26ClN7O4S: 592 (MH+).
Example 424
N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-(2,2-dimethylhydrazinecarbonyl)benzenesulfonamide
MS (EI) m/z C24H23ClN6O4S: 527 (MH+).
Example 425
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-methoxyethyl)benzamide
MS (EI) m/z C25H24ClN5O5S: 542 (MH+).
Example 426
N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-(4-methylpiperazine-1-carbonyl)benzenesulfonamide
MS (EI) m/z C27H27ClN6O4S: 567 (MH+).
Example 427
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(pyrrolidin-1-yl)ethyl)benzamide
MS (EI) m/z C28H29ClN6O4S: 581 (MH+).
Example 428
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(pyridin-4-yl)ethyl)benzamide
MS (EI) m/z C29H25ClN6O4S: 589 (MH+).
Example 429
N-(2-(1H-imidazol-4-yl)ethyl)-3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)benzamide
MS (EI) m/z C27H24ClN7O4S: 578 (MH+).
Example 430
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(piperidin-1-yl)benzamide
MS (EI) m/z C27H27ClN6O4S: 567 (MH+).
Example 431
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-hydroxyethyl)benzamide
MS (EI) m/z C24H22ClN5O5S: 528 (MH+).
Example 432
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-ethoxypropyl)benzamide
MS (EI) m/z C27H28ClN5O5S: 570 (MH+).
Example 433
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-(pyrrolidin-1-yl)propyl)benzamide
MS (EI) m/z C29H31ClN6O4S: 595 (MH+).
Example 434
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-(diethylamino)propyl)benzamide
MS (EI) m/z C29H33ClN6O4S: 597 (MH+).
Example 435
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-(2-oxopyrrolidin-1-yl)propyl)benzamide
MS (EI) m/z C29H29ClN6O5S: 609 (MH+).
Example 436
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(pyridin-2-ylmethyl)benzamide
MS (EI) m/z C28H23ClN6O4S: 575 (MH+).
Example 437
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-cyanoethyl)-N-methylbenzamide
MS (EI) m/z C26H23ClN6O4S: 551 (MH+).
Example 438
3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-cyanoethyl)-N-ethylbenzamide
MS (EI) m/z C27H25ClN6O4S: 565 (MH+).
Example 439
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(ethylthio)ethyl)benzamide
MS (EI) m/z C26H26ClN5O4S2: 572 (MH+).
Example 440
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-propoxypropyl)benzamide
MS (EI) m/z C28H30ClN5O5S: 584 (MH+).
Example 441
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(5-(diethylamino)pentan-2-yl)benzamide
MS (EI) m/z C31H37ClN6O4S: 625 (MH+).
Example 442
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-methoxypropyl)benzamide
MS (EI) m/z C26H26ClN5O5S: 556 (MH+).
Example 443
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-morpholinopropyl)benzamide
MS (EI) m/z C29H31ClN6O5S: 611 (MH+).
Example 444
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(pyridin-3-ylmethyl)benzamide MS (EI) m/z C28H23ClN6O4S: 575 (MH+)
Example 445
3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-cyanoethyl)benzamide
MS (EI) m/z C25H21ClN6O4S: 537 (MH+).
Example 446
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(1-methoxypropan-2-yl)benzamide
MS (EI) m/z C26H26ClN5O5S: 556 (MH+).
Example 447
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(methylthio)ethyl)benzamide
MS (EI) m/z C25H24ClN5O4S2: 558 (MH+).
Example 448
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-(dimethylamino)propyl)-N-methylbenzamide
MS (EI) m/z C28H31ClN6O4S: 583 (MH+).
Example 449
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-isopropoxypropyl)benzamide
MS (EI) m/z C28H30ClN5O5S: 584 (MH+).
Example 450
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(dimethylamino)ethyl)-N-ethylbenzamide
MS (EI) m/z C28H31ClN6O4S: 583 (MH+).
Example 451
N-(3-butoxypropyl)-3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)benzamide
MS (EI) m/z C29H32ClN5O5S: 598 (MH+).
Example 452
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(diethylamino)ethyl)benzamide
MS (EI) m/z C28H31ClN6O4S: 583 (MH+).
Example 453
methyl 3-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)benzamido)propanoate. MS (EI) m/z C26H24ClN5O6S: 570 (MH+)
Example 454
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-methyl-N-propylbenzamide
MS (EI) m/z C26H26ClN5O4S: 540 (MH+).
Example 455
ethyl 3-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)benzamido)propanoate
MS (EI) m/z C27H26ClN5O6S: 584 (MH+).
Example 456
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(piperidin-1-yl)ethyl)benzamide
MS (EI) m/z C29H31ClN6O4S: 595 (MH+).
Example 457
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-((1-ethylpyrrolidin-2-yl)methyl)benzamide
MS (EI) m/z C29H31ClN6O4S: 595 (MH+).
Example 458
N-(2-(bis(2-hydroxyethyl)amino)ethyl)-3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)benzamide
MS (EI) m/z C28H3ClN6O6S: 615 (MH+).
Example 459
N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-(3-(diethylamino)pyrrolidine-1-carbonyl)benzenesulfonamide
MS (EI) m/z C30H33ClN6O4S: 609 (MH+).
Example 460
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide
MS (EI) m/z C28H29ClN6O4S: 581 (MH+).
Example 461
N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-(3-(dimethylamino)pyrrolidine-1-carbonyl)benzenesulfonamide
MS (EI) m/z C28H29ClN6O4S: 581 (MH+).
Example 462
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-methyl-1-morpholinopropan-2-yl)benzamide
MS (EI) m/z C30H33ClN6O5S: 625 (MH+).
Example 463
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(1H-pyrrol-1-yl)benzamide
MS (EI) m/z C26H21ClN6O4S: 549 (MH+).
Example 464
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-oxopyrazolidin-4-yl)benzamide
MS (EI) m/z C25H22ClN7O5S: 568 (MH+).
Example 465
N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-(2-((dimethylamino)methyl)piperidine-1-carbonyl)benzenesulfonamide
MS (EI) m/z C30H33ClN6O4S: 609 (MH+).
Example 466
N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-(2-(piperidin-1-ylmethyl)piperidine-1-carbonyl)benzenesulfonamide
MS (EI) m/z C33H37ClN6O4S: 649 (MH+).
Example 467
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(1-ethylpiperidin-3-yl)benzamide
MS (EI) m/z C29H31ClN6O4S: 595 (MH+).
General Amide Formation Procedure 1b
The procedure outlined in General Amide Formation Procedure 1a was used to incorporate a number of amines that contained a second amine group protected as the tert-butylcarbamate (i.e. where R′, within NHR′R′′, contained a Boc-protected amine group). The deprotection was carried out after HPLC purification of the Boc-protected precursor.
Into a small 1 dram vial was added 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)benzoic acid (61 mg, 0.13 mmol, 1.1 equiv). The acid was dissolved in 1 mL of DMA and DIEA (42 μL, 0.24 mmol, 2 equiv) was added then added to the solution. The mono-Boc-protected diamine reagent (1 mL of 0.12 M solution in DMA, 1 equiv) was added to solution with stirring followed by HATU (64 mg, 0.17 mmol, 1.4 equiv). The reaction was stirred overnight at room temperature. Upon completion as indicated by LCMS analysis, 2 mL of methanol was added to the solution. Preparative reverse-phase HPLC was used to isolate the desired product directly from this crude reaction solution. A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C18, OCD 5 μM, 30×70 mm column and running a 5-100% gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification. The product fractions were combined and concentrated to dryness under reduced pressure by rotary evaporation. A solution of 4 N HCl in dioxane (2 mL) was added. The solution was then stirred at room temperature until no starting material was detected. The deprotected product precipitated out of solution as an HCL salt and was collected by filtration, washed with ether and dried under vacuum.
The following compounds were prepared according to the above General Amide Formation Procedure 1b.
Example 468
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(piperidin-3-yl)benzamide
3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(piperidin-3-yl)benzamide: 1H NMR (400 MHz, d6-DMSO): 12.82 (s, 1H), 9.12 (s, 1H), 9.04 (s, 1H), 8.85 (d, 1H), 8.65 (s, 1H), 8.55 (s, 1H), 8.18 (m, 1H), 7.98 (s, 1H), 7.69 (m, 2H), 7.43 (m, 2H), 6.69 (dd, 1H), 4.21 (s, 1H), 3.83 (s, 3H), 3.69 (m, 1H), 3.48 (m, 1H), 3.18 (s, 1H), 2.84 (q, 2H), 1.91 (s, 2H); MS (EI) m/z for C27H27ClN6O4S: 567 (MH+).
Example 469
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(piperidin-2-ylmethyl)benzamide
3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(piperidin-2-ylmethyl)benzamide: NMR (400 MHz, d6-DMSO): 12.78 (s, 1H), 9.16 (s, 1H), 9.09 (s, 1H), 8.79 (s, 1H), 8.59 (d, 2H), 8.22 (t, 2H), 7.99 (s, 1H), 7.74 (t, 1H), 7.66 (s, 1H), 7.42 (m, 2H), 6.69 (dd, 1H), 3.82 (s, 3H), 3.69 (dd, 1H), 3.57 (m, 1H), 3.50 (m, 3H), 3.22 (s, 2H), 2.82 (d, 1H), 1.68 (m, 5H); MS (EI) m/z for C28H29ClN6O4S: 581 (MH+).
Example 470
3-(3-aminopyrrolidine-1-carbonyl)-N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z C26H25ClN6O4S: 553 (MH+).
Example 471
3-(3-aminoazetidine-1-carbonyl)-N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z C25H23ClN6O4S: 539 (MH+).
Example 472
3-(3-aminopiperidine-1-carbonyl)-N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z C27H27ClN6O4S: 567 (MH+).
Example 473
3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(pyrrolidin-3-yl)benzamide
MS (EI) m/z C26H25ClN6O4S: 553 (MH+).
Example 474
N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-(3-(methylamino)pyrrolidine-1-carbonyl)benzenesulfonamide
MS (EI) m/z C27H27ClN6O4S: 567 (MH+).
Example 475
N-(2-aminoethyl)-3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)benzamide
MS (EI) m/z C24H23ClN6O4S: 527 (MH+).
Example 476
3-(4-amino-3-oxopyrazolidine-1-carbonyl)-N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide
MS (EI) m/z C25H22ClN7O5S: 568 (MH+).
Example 477
3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-((1-methylpiperidin-2-yl)methyl)benzamide
3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(piperidin-2-ylmethyl)benzamide (299 mg, 0.51 mmol, 1 equiv), prepared using procedures similar to those described for Example 514, was dissolved in 2.3 mL of DMA. Formic acid (388 μL, 10.28 mmol, 20 equiv) was added to solution with stirring followed by the addition of formaldehyde (508 μL of 37% aq. solution). The reaction was then stirred at room temperature overnight. Analysis of an aliquot of the reaction mixture by LCMS indicated the complete consumption of starting material. The reaction was diluted with methanol (2 mL). Preparative reverse-phase HPLC was used to isolate the desired product directly from the crude reaction mixture. A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C18, OCD 5 μM, 30×70 mm column and running a 5-100% gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification. 1H NMR (400 MHz, d6-DMSO): 9.44 (s, 1H), 8.94 (s, 1H), 8.79 (t, 1H), 8.57 (s, 1H), 8.27 (d, 1H), 7.90 (d, 1H) 7.54 (t, 1H), 7.46 (d, 1H), 7.39 (d, 1H), 7.33 (d, 1H), 7.18 (m, 2H), 6.60 (dd, 1H), 3.82 (s, 3H), 3.59 (m, 2H), 3.00 (s, 1H), 2.90 (s, 3H), 1.62 (m, 7H); MS (EI) m/z for C29H31ClN6O4S: 595 (MH+).
Example 478
3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(1-methylpiperidin-3-yl)benzamide
The title compound was prepared using similar procedures to those used in Example 522. 1H NMR (400 MHz, d6-DMSO): 9.43 (s, 1H), 8.93 (s, 1H), 8.59 (s, 1H), 8.24 (d, 1H), 7.87 (d, 1H), 7.47 (m, 2H), 7.40 (d, 1H), 7.33 (d, 1H), 7.19 (m, 2H), 6.60 (dd, 1H), 4.21 (s, 1H), 3.82 (s, 1H), 2.76 (s, 1H), 2.50 (m, 7H), 1.91 (m, 2H), 1.63 (m, 2H); MS (EI) m/z for C28H29ClN6O4S: 581 (MH+).
BIOLOGICAL EXAMPLES
Biological Example 1
PI3Kalpha Luciferase-Coupled Chemiluminescence Assay Protocol
PI3Kα activity is measured as the percent of ATP consumed following the kinase reaction using luciferase-luciferin-coupled chemiluminescence. Reactions were conducted in 384-well white, medium binding microtiter plates (Greiner). Kinase reactions were initiated by combining test compounds, ATP, substrate (PIP2), and kinase in a 20 μL volume in a buffer solution. The standard PI3Kalpha assay buffer is composed 50 mM Tris, pH 7.5, 1 mM EGTA, 10 mM MgCl2, 1 mM DTT and 0.03% CHAPS. The standard assay concentrations for enzyme, ATP, and substrate are 0.5-1.1 nM, 1 μM, and 7.5 μM, respectively. The reaction mixture was incubated at ambient temperature for approximately 2 h. Following the kinase reaction, a 100 μL aliquot of luciferase-luciferin mix (Promega Kinase-Glo) was added and the chemiluminescence signal measured using a Victor2 plate reader (Perkin Elmer). Total ATP consumption was limited to 40-60% and IC50 values of control compounds correlate well with literature references.
Certain compounds of the invention demonstrated the ability to bind to PI3K when tested in this assay. The following embodiments are directed to the compounds themselves as well as their use in a method of treating. For example, in one embodiment of the invention, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 8 μM or less. In another embodiment, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 4 μM or less. In another embodiment, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 3 μM or less. In another embodiment, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 2 μM or less. In another embodiment, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 1.5 μM or less. In another embodiment, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 1.5 μM or less. In another embodiment, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 0.750 μM or less. In another embodiment, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 0.5 μM or less. In another embodiment, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 0.3 μM or less. In another embodiment, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 0.2 μM or less. In another embodiment, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 0.1 μM or less. In another embodiment, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 0.075 μM or less. In another embodiment, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 0.050 μM or less.
Biological Example 2
Phospho AKT Assay
PC-3 cells were seeded on 6-well plates at 150,000 cells/well. Cells were cultured for 3 days, then treated with compounds in serum-free medium for 3 hr. EGF (100 ng/ml) was added for the last 10 min. Cells were lysed in TENN buffer. Phospho T308 Akt and total Akt were quantfied by ELISA performed according to the Biosource assay protocol. The readings of phospho Akt were normalized to total Akt readings.
Biological Example 3
Phospho S6 Assay
PC-3 cells were seeded on 96-well plates at 8,000 cells/well. For each experiment, cells were seeded and treated in duplicated plates: one plate for phospho S6 CellELISA, and one plate for total S6 CellELISA. Cells were cultured on the plates for 3 days, then treated with compounds in serum-free medium for 3 hr in triplicate. Cells were fixed with 4% formaldehyde, quenched with 0.6% H2O2, blocked with 5% BSA, incubated with either phospho S6 antibody or total S6 antibody overnight, incubated with goat-anti-rabbit-IgG-HRP for 1 hr, and developed in chemiluminescent substrate.
Biological Example 4
PIP3 Assay
MCF-7 cells grown in 10-cm dishes were starved for 3 hours in DMEM, and then treated with compounds for 20 minutes. In the last 2 minutes of the incubation with the compounds, EGF (100 ng/ml) was added to stimulate the production of PIP3. The medium was aspirated and the cells were scraped with 10% trichloroacetic acid. The lipids were extracted from the pellet after the cell lysates were centrifuged. PIP3 in the cellular lipid extraction was quantified with the AlphaScreen [Registered TM of PerkinElmer] assay in which Grp1-PH is used as the PIP3 specific probe. The amount of cellular PIP3 was calculated from the standard curve of diC8 PI (3,4,5) P3.
Biological Example 5-10
In Vivo Models
Compound A is a Compound of Formula I. Compound B is N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta-[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine.
Female and male athymic nude mice (NCr) 5-8 weeks of age and weighing approximately 20-25 g were used in the following model. Prior to initiation of a study, the animals were allowed to acclimate for a minimum of 48 h. During these studies, animals were provided food and water ad libitum and housed in a room conditioned at 70-75° F. and 60% relative humidity. A12 h light and 12 h dark cycle was maintained with automatic timers. All animals were examined daily for compound-induced or tumor-related deaths.
PC-3 human prostate adenocarcinoma cells were cultured in vitro in DMEM (Mediatech) supplemented with 20% Fetal Bovine Serum (Hyclone), Penicillin-Streptomycin and non-essential amino acids at 37° C. in a humidified 5% CO2 atmosphere. On day 0, cells were harvested by trypsinization and 3×106 cells (passage 13, 99% viability) in 0.1 mL of ice-cold Hank's balanced salt solution were implanted subcutaneously into the hindflank of 5-8 week old male nude mice. A transponder was implanted in each mouse for identification, and animals were monitored daily for clinical symptoms and survival. Body weights were recorded daily. Experiments were conducted with Compound A as a single agent as well as Compound A in combination with Taxol and Compound A in combination with Rapamycin. This model can be used to assess the desirability of treating with Compound A in combination with other anti-cancer agents.
U-87 MG human glioblastoma cells were cultured in vitro in DMEM (Mediatech) supplemented with 10% Fetal Bovine Serum (Hyclone), Penicillin-Streptomycin and non-essential amino acids at 37° C. in a humidified 5% CO2 atmosphere. On day 0, cells were harvested by trypsinization and 2×106 cells (passage 5, 96% viability) in 0.1 mL of ice-cold Hank's balanced salt solution were implanted intradermally into the hindflank of 5-8 week old female nude mice. A transponder was implanted in each mouse for identification, and animals were monitored daily for clinical symptoms and survival. Body weights were recorded daily. Experiments were conducted with Compound A as a single agent and the results are not included. This model can be used to assess the desirability of treating with Compound A in combination with other anti-cancer agents.
A549 human lung carcinoma cells were cultured in vitro in DMEM (Mediatech) supplemented with 10% Fetal Bovine Serum (Hyclone), Penicillin-Streptomycin and non-essential amino acids at 37° C. in a humidified 5% CO2 atmosphere. On day 0, cells were harvested by trypsinization and 10×106 cells (passage 12, 99% viability) in 0.1 mL of ice-cold Hank's balanced salt solution were implanted intradermally into the hindflank of 5-8 week old female nude mice. A transponder was implanted in each mouse for identification, and animals were monitored daily for clinical symptoms and survival. Body weights were recorded daily. Experiments were conducted with Compound A as a single agent as well as Compound A in combination with Compound B. This model can be used to assess the desirability of treating with Compound A in combination with other anti-cancer agents.
MDA-MB-468 human breast adenocarcinoma cells, passage number <6, were maintained and propagated in log-phase growth in Dulbecco's Modification of Eagles's Medium (DMEM; Mediatech) containing L-Glutamine supplemented with 10% Fetal Bovine Serum (Hyclone), Penicillin-Streptomycin and non-essential amino acids at 37° C. in a humidified, 5% CO2 atmosphere. On day 0, cells were harvested by trypsinization, and 10×106 cells (passage 10, 98% viability) in 50% cold Hanks balanced salt solution/50% Matrigel (100 μL total volume per mouse) were implanted subcutaneously into the mammary fat pads of female nude mice. Experiments were conducted with Compound A as a single agent as well as Compound A in combination with erlotinib. This model can be used to assess the desirability of treating with Compound A in combination with other anti-cancer agents.
Calu-6 human lung anaplastic carcinoma cells were cultured in vitro in DMEM (Mediatech) supplemented with 10% Fetal Bovine Serum (Hyclone), Penicillin-Streptomycin and non-essential amino acids at 37° C. in a humidified, 5% CO2 atmosphere. On day 0, cells were harvested by trypsinization, and 5×106 cells (passage #8, 96% viability) in 0.1 mL ice-cold Hank's balanced salt solution were implanted intradermally in the hind-flank of 5-8 week old female athymic nude mice. A transponder was implanted in each mouse for identification, and animals were monitored daily for clinical symptoms and survival. Body weights were recorded daily. Experiments were conducted with Compound A as a single agent as well as Compound A in combination with carboplatin. This model can be used to assess the desirability of treating with Compound A in combination with other anti-cancer agents.
MCF7 human mammary adenocarcinoma cells were cultured in vitro in DMEM (Cellgro) supplemented with 10% Fetal Bovine Serum (Cellgro), Penicillin-Streptomycin and non-essential amino acids at 37° C. in a humidified 5% CO2 atmosphere. On day 0, cells were harvested by trypsinization, and 5×106 cells (passage 10 and 95.4% viability for Study 1, passage 9 and 90% viability for Study 2) in 100 μL of a solution made of 50% cold Hanks balanced salt solution with 50% growth factor reduced matrigel (R&D Systems for Study 1 and Becton Dickinson for Study 2) implanted subcutaneously into the hindflank of female nude mice.
For subcutaneous or intradermal tumors, the mean tumor weight of each animal in the respective control and treatment groups was determined twice weekly during the study. Tumor weight (TW) was determined by measuring perpendicular diameters with a caliper, using the following formula:

tumor weight (mg)=[tumor volume=length (mm)×width2 (mm2)]/2

These data were recorded and plotted on a tumor weight vs. days post-implantation line graph and presented graphically as an indication of tumor growth rates. Percent inhibition of tumor growth (TGI) is determined with the following formula:





  
    (
    
      1
      -
      
        (
        
          
            (
            
              
                X
                f
              
              -
              
                X
                0
              
            
            )
          
          
            (
            
              
                Y
                f
              
              -
              
                X
                0
              
            
            )
          
        
        )
      
    
    )
  
  *
  100




    
    
        where X0=average TW of all tumors on group day
        Xf=TW of treated group on Day f
        Yf=TW of vehicle control group on Day f

If tumors regress below their starting sizes, then the percent tumor regression is determined with the following formula:

    
    






  
    (
    
      
        (
        
          
            X
            0
          
          -
          
            X
            f
          
        
        )
      
      
        X
        0
      
    
    )
  
  *
  100




Tumor size is calculated individually for each tumor to obtain a mean±SEM value for each experimental group. Statistical significance is determined using the 2-tailed Student's t-test (significance defined as P<0.05).

Biological Examples 11-16
Compound A is a Compound of Formula I and is an inhibitor of class I PI3-kinases. Compound B is N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta-[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine.
Prostate Cancer Xenograft Model—A Compound of Formula I in Combination with Taxol
Compound A was tested alone and in combination with taxol in a prostate carcinoma tumor model. PC-3 is a human prostate carcinoma cell line that harbors a homozygous deletion mutation in PTEN, which results in constitutive activation of the PI3K pathway. In single-dose pharmacodynamic experiments, oral administration of Compound A results in a dose-dependent decrease in the phosphorylation of AKT, p70S6K, and S6 in PC-3 tumors grown ectopically in mice. Repeat-dose administration of a Compound A also inhibits the growth of these tumors, but does not induce regressions.
Oral administration of Compound A at 100 mg/kg qd or 300 mg/kg biweekly (biw) resulted in substantial tumor growth inhibition in mice. See FIG. 1. Comparable tumor growth inhibition was achieved with 7.5 mg/kg taxol administered i.v. twice weekly. While tumor growth was inhibited substantially with Compound A alone, the combination of either dose of Compound A with taxol was superior to either agent alone and induced significant regression of the tumors. Body weight loss and dose skipping was minimal in all groups, and was not exacerbated in the combination group indicating that the combination was well tolerated. These results support the use of a Compound of Formula I in combination with taxol in tumors with constitutively activated PI3K signaling.
Prostate Cancer Xenograft Model—A Compound of Formula I in Combination with Rapamycin
Compound A was tested alone and in combination with rapamycin in a prostate carcinoma tumor model (PC-3 cell line). Oral administration of Compound A at 100 mg/kg qd resulted in substantial tumor growth inhibition. See FIG. 2. Comparable tumor growth inhibition was achieved with 5 mg/kg rapamycin administered i.p. daily. While tumor growth was inhibited substantially with Compound A alone, the combination of Compound A with rapamycin was superior to either agent alone and induced significant regression of the tumors. Body weight loss and dose skipping was minimal with each agent alone, but body weight loss was exacerbated in the combination group necessitating dose skipping. The fact that tumor regression was observed despite dose skipping suggests that using an intermittent dosing schedule would maintain efficacy and improve tolerability. These results support the use of a Compound of Formula I in combination with rapamycin in tumors with constitutively activated PI3K signaling.
Non-Small Cell Lung Cancer Xenograft Model—A Compound of Formula I in Combination with Carboplatin
Compound A was tested both as a single agent and in combination with carboplatin in a NSCLC tumor model.
Calu-6 is a human NSCLC cell line that harbors a heterozygous activating mutation in K-Ras (Q61K). Oral administration of a Compound A at 100 mg/kg qd or 300 mg/kg every fourth day (q4d) to mice bearing Calu-6 tumors resulted in substantial tumor growth inhibition. See FIG. 3. Both dose schedules resulted in similar inhibition of tumor growth. Significant tumor growth inhibition was also observed with 50 mg/kg carboplatin administered i.v. q4d, but was not as pronounced as with Compound A. While tumor growth was inhibited substantially with Compound A alone, the combination of the two agents was superior to either agent alone and resulted in almost complete inhibition of tumor growth. Body weight loss and dose skipping was minimal in all groups, and was not exacerbated in the combination group indicating that the combination was well tolerated. These results support the use of a Compound of Formula I both as a single agent and in combination with platins in tumors with activating mutations in K-Ras.
Non-Small Cell Lung Cancer Xenograft Model—A Compound of Formula I in Combination with Compound B
Compound A was tested both as a single agent and in combination with Compound B. The A549 human non-small cell lung carcinoma cell line harbors a homozygous stop mutation in the gene encoding LKB1, and an activating G12S mutation in K-Ras, promoting activation of both PI3K and mTOR. A549 cells also express wild-type EGFR.
As a single agent, Compound B, an inhibitor of EGFR, was orally administered once-daily at 30 mg/kg and Compound A was orally administered either at 30 mg/kg qd or 100 mg/kg q2d. Combination therapies consisted of Compound B with Compound A at 30 mg/kg or 100 mg/kg. Administration of each agent in the combination groups was separated by 6 h. Single agent administration of Compound B for 18 days caused a significant tumor growth inhibition of 80%. See FIG. 4a. A significant tumor growth inhibition of 96% was observed with Compound A at 100 mg/kg q2d, whereas Compound A at 30 mg/kg qd lead to a lower but still significant TGI of 76%. The combination of Compound B 30 mg/kg qd with Compound A 30 mg/kg qd or with Compound A 100 mg/kg q2d resulted in significant efficacy associated with 15% and 39% regression, respectively, which was significantly higher than either of the single agent treatments alone.
As a single agent Compound B dosed at 30 mg/kg qd was generally well tolerated, with a body weight loss of 1.5-6.9% and no dose omission. Administration of Compound A dosed at 30 mg/kg qd was well tolerated with 4 doses skipped at the beginning of the study, which were not compound-related. Compound A dosed at 100 mg/kg q2d was also well tolerated with 1 dose skipped at the beginning of the study, which was not compound-related. The combination of Compound B at 30 mg/kg qd with Compound A at 30 mg/kg qd was fairly well tolerated with body weight loss of 1 to 8% and 2 doses skipped). However, the combination of Compound B at 30 mg/kg qd with Compound A at 100 mg/kg q2d was associated with body weight loss of 2 to 11% and 13 doses skipped within the first 10 days; however, body weights at the end of the study were not significantly different from the vehicle-treated control group. Single agent administration of Compound B and Compound A were well tolerated with minimal dose skipping. When administered in combination, minor body weight loss was observed that necessitated dose skipping primarily in the 100 mg/kg q2d group.
Breast Cancer Xenograft Model—A Compound of Formula I in Combination with Compound B
Compound A was tested both as a single agent and in combination with Compound B, an EGFR inhibitor, in a breast tumor model. The MCF7 human breast carcinoma cell line harbors a heterozygous, activating mutation in PI3K (PI3KCA/E545K) and expresses wild-type EGFR.
Compound B was administered orally once-daily (qd) at 30 mg/kg, and Compound A was administered once-daily at 30 mg/kg or once every other day (q2d) at 100 mg/kg. Combination therapies consisted of Compound B together with Compound A at 30 mg/kg qd or 100 mg/kg q2d. Single agent administration of Compound B at 30 mg/kg qd for 14 days caused a tumor growth inhibition of 38%-61%. See FIGS. 4b-1 and 4b-2. A significant tumor growth inhibition of 83%-91% was observed with Compound A at 100 mg/kg q2d, whereas Compound A at 30 mg/kg qd lead to a lower but still significant TGI of 57%. The combination of Compound B at 30 mg/kg qd with Compound A at 100 mg/kg q2d resulted in a significant efficacy associated with 16-22% regression, which was significantly higher than either of the single agent treatments alone. Combining Compound B at 30 mg/kg qd with Compound A at 30 mg/kg qd lead to a lower but still significant tumor growth inhibition of 66%, but did not add any benefit to the anti-tumor efficacy of the single treatments.
As a single agent Compound B dosed at 30 mg/kg qd was generally well tolerated, with a non significant final body weight loss of 4.5 to 6.1% and 7 to 13 dose omissions. Administration of Compound A at 30 mg/kg qd and 100 mg/kg q2d was well tolerated with minimal dose skipping and body weight loss. The combination of Compound B at 30 mg/kg qd with Compound A at 30 mg/kg qd lead to a body weight loss of 4 to 13% throughout the study and 14 doses skipped mostly within the first 9 days. The combination of Compound B at 30 mg/kg qd with Compound A at 100 mg/kg q2d was associated with a body weight loss of 3.7 to 13% throughout the study and 20 to 32 dose omissions.
Breast Cancer Xenograft Model—A Compound of Formula I in Combination with Erlotinib
Compound A was tested both as a single agent and in combination with erlotinib, in an erolitinib-resistant tumor model with elevated PI3K signaling.
MDA-MB-468 is a human breast carcinoma cell line that has an increase in the copy number of the EGFR gene and a homozygous deletion of PTEN. In vitro treatment of these cells with EGFR inhibitors such as erlotinib inhibits EGFR activity but fails to downregulate the PI3K pathway. Oral administration of erlotinib at 100 mg/kg qd to mice bearing MDA-MB-468 tumors resulted in significant but incomplete tumor growth inhibition. See FIG. 5. Oral administration of Compound A at 100 mg/kg qd resulted in a similar level of tumor growth inhibition. While tumor growth was inhibited substantially with Compound A alone, the combination of the two agents was superior to either agent alone and resulted in a regression of the tumors.
Mice administered Compound A at 100 mg/kg qd exhibited a modest ( ̃3%) loss in body weight comparable to vehicle controls. Mice administered erlotinib exhibited an apparent decrease in their rate of body weight gain relative to vehicle controls. Coadministration with erlotinib resulted in a substantial loss in body weight in mice treated with Compound A (19% body weight loss from start of dosing). Consistent with these data, only minimal dose-skipping was required when Compound A was administered as monotherapy (1-3 doses skipped), but substantial dose-skipping was required for Compound A when erlotinib was coadministered. The fact that tumor regression was observed despite dose skipping suggests that use of an intermittent dosing schedule could maintain efficacy and improve tolerability. These results support the use of a Compound of Formula I in combination with erlotinib in tumors expressing EGF receptors and harboring PTEN deletions.
The foregoing invention has been described in some detail by way of illustration and example, for purposes of clarity and understanding. It will be obvious to one of skill in the art that changes and modifications may be practiced within the scope of the appended claims. Therefore, it is to be understood that the above description is intended to be illustrative and not restrictive. The scope of the invention should, therefore, be determined not with reference to the above description, but should instead be determined with reference to the following appended claims, along with the full scope of equivalents to which such claims are entitled. All patents, patent applications and publications cited in this application are hereby incorporated by reference in their entirety for all purposes to the same extent as if each individual patent, patent application or publication were so individually denoted.

## Claims

1. A method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a compound that is:



or a single isomer or tautomer thereof where the compound is optionally as a pharmaceutically acceptable salt in combination with one or more chemotherapeutic agents.

2. The method of claim 1 where the cancer is selected from breast cancer, colon cancer, rectal cancer, endometrial cancer, gastrointestinal carcinoid tumors, gastrointestinal stromal tumors, glioblastoma, hepatocellular carcinoma, small cell lung cancer, non-small cell lung cancer, melanoma, ovarian cancer, cervical cancer, pancreatic cancer, prostate carcinoma, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, and thyroid carcinoma.

3. The method of claim 1 where the treatment is one chemotherapeutic agent and the chemotherapeutic agent is a platin.

4. The method of claim 1 where the treatment is one chemotherapeutic agent and the chemotherapeutic agent is a taxane.

5. The method of claim 1 where the treatment is one chemotherapeutic agent and the chemotherapeutic agent is rapamycin or a rapamycin analogue.

6. The method of claim 1 where the treatment is one or two chemotherapeutic agents independently selected from rapamycin, a rapamycin analogue, an alkylating agent, a taxane, a platin, an EGFR inhibitor, and an ErbB2 inhibitor.

7. The method of claim 6 where the treatment is one or two chemotherapeutic agents independently selected from rapamycin, paclitaxel, carboplatin, lapatinib, and erlotinib.

8. The method of claim 1, where the treatment is one chemotherapeutic agent where the chemotherapeutic agent is erlotinib.

9. The method of claim 1, where the treatment is one chemotherapeutic agent where the chemotherapeutic agent is lapatinib.

10. The method of claim 1, where the treatment is one chemotherapeutic agent where the chemotherapeutic agent is carboplatin.

11. The method of claim 1, where the treatment is one chemotherapeutic agent where the chemotherapeutic agent is paclitaxel.

12. The method of claim 1, where the treatment is one chemotherapeutic agent where the chemotherapeutic agent is rapamycin.

13. The method of claim 1, where the treatment is one or two agents independently selected from rapamycin, temozolomide, paclitaxel, docetaxel, carboplatin, erlotinib, and lapatinib.