Patent Publication Number: US-2021188860-A1

Title: 3-((Hetero-)Aryl)-8-Amino-2-Oxo-1,3-Diaza-Spiro-[4.5]-Decane Derivatives

Description:
This application is a continuation of U.S. patent application Ser. No. 17/010,089, filed Sep. 2, 2020, pending, which is a continuation of U.S. patent application Ser. No. 16/450,331, filed Jun. 24, 2019, now U.S. Pat. No. 10,807,988, which is a continuation of U.S. patent application Ser. No. 16/207,854, filed Dec. 3, 2018, abandoned, which is a continuation of U.S. patent application Ser. No. 15/923,948, filed Mar. 16, 2018, abandoned; which is a continuation of U.S. patent application Ser. No. 15/405,485, filed Jan. 13, 2017, abandoned; which claims foreign priority benefit under 35 U.S.C. § 119 of European Patent Application No. 16 151 012.8, filed Jan. 13, 2016, the disclosures of which are incorporated herein by reference. 
    
    
     The invention relates to 3-((hetero-)aryl)-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives, their preparation and use in medicine, particularly in various neurological disorders, including but not limited to pain, neurodegenerative disorders, neuroinflammatory disorders, neuropsychiatric disorders, substance abuse/dependence. 
     Opioid receptors are a group of Gi/o protein-coupled receptors which are widely distributed in the human body. The opioid receptors are currently subdivided into four major classes, i.e. the three classical opioid receptors mu-opioid (MOP) receptor, kappa-opioid (KOP) receptor, and delta-opioid (DOP) receptor as well as the opioid receptor-like (ORL-1) receptor, which was more recently discovered based on its high homology with said classical opioid receptors. After identification of the endogenous ligand of the ORL-1 receptor, known as nociceptin/orphanin FQ, a highly basic 17 amino acid peptide isolated from tissue extracts in 1995, the ORL-1 receptor was renamed “nociceptin opioid peptide receptor” and abbreviated as “NOP-receptor”. 
     The classical opioid receptors (MOP, KOP and DOP) as well as the NOP receptor are widely distributed/expressed in the human body, including in the brain, the spinal cord, on peripheral sensory neurons and the intestinal tract, wherein the distribution pattern differs between the different receptor classes. 
     Nociceptin acts at the molecular and cellular level in very much the same way as opioids. However, its pharmacological effects sometimes differ from, and even oppose those of opioids. NOP-receptor activation translates into a complex pharmacology of pain modulation, which, depending on route of administration, pain model and species involved, leads to either pronociceptive or antinociceptive activity. Furthermore, the NOP receptor system is upregulated under conditions of chronic pain. Systemic administration of selective NOP receptor agonists was found to exert a potent and efficacious analgesia in non-human primate models of acute and inflammatory pain in the absence of side effects. The activation of NOP receptors has been demonstrated to be devoid of reinforcing effects but to inhibit opioid-mediated reward in rodents and non-human primates (Review: Schroeder et al, Br J Pharmacol 2014; 171 (16): 3777-3800, and references therein). 
     Besides the involvement of the NOP receptor in nociception, results from preclinical experiments suggest that NOP receptor agonists might be useful inter alia in the treatment of neuropsychiatric disorders (Witkin et al, Pharmacology &amp; Therapeutics, 141 (2014) 283-299; Jenck et al., Proc. Natl. Acad. Sci. USA 94, 1997, 14854-14858). Remarkably, the DOP receptor is also implicated to modulate not only pain but also neuropsychiatric disorders (Mabrouk et al, 2014; Pradhan et al., 2011). 
     Strong opioids acting at the MOP receptor site are widely used to treat moderate to severe acute and chronic pain. However, the therapeutic window of strong opioids is limited by severe side effects such as nausea and vomiting, constipation, dizziness, somnolence, respiratory depression, physical dependence and abuse. Furthermore, it is known that MOP receptor agonists show only reduced effectiveness under conditions of chronic and neuropathic pain. 
     It is known that some of the above mentioned side-effects of strong opioids are mediated by activation of classic opioid-receptors within the central nervous system. Furthermore, peripheral opioid receptors, when activated, can inhibit transmission of nociceptive signals shown in both, clinical and animal studies (Gupta et al., 2001; Kalso et al., 2002; Stein et al., 2003; Zollner et al., 2008). 
     Thus, to avoid CNS-mediated adverse effects after systemic administration, one approach has been to provide peripherally restricted opioid receptor ligands that do not easily cross the blood-brain barrier and therefore distribute poorly to the central nervous system (see for instance WO 2015/192039). Such peripherally acting compounds might combine effective analgesia with limited side-effects. 
     Another approach has been to provide compounds which interact with both the NOP receptor and the MOP receptor. Such compounds have for instance been described in WO 2004/043967, WO 2012/013343 and WO 2009/118168. 
     A further approach has been to provide multi-opioid receptor analgesics that modulate more than one of the opioid receptor subtypes to provide additive or synergistic analgesia and/or reduced side effects like abuse liability or tolerance. 
     On the one hand, it would be desirable to provide analgesics that selectively act on the NOP receptor system but less pronounced on the classic opioid receptor system, especially MOP receptor system, whereas it would be desirable to distinguish between central nervous activity and peripheral nervous activity. On the other hand, it would be desirable to provide analgesics that act on the NOP receptor system and also to a balanced degree on the MOP receptor system, whereas it would be desirable to distinguish between central nervous activity and peripheral nervous activity. 
     There is a need for medicaments which are effective in the treatment of pain and which have advantages compared to the compounds of the prior art. Where possible, such medicaments should contain such a small dose of active ingredient that satisfactory pain therapy can be ensured without the occurrence of intolerable treatment-emergent adverse events. 
     It is an object of the invention to provide pharmacologically active compounds, preferably analgesics that have advantages compared to the prior art. 
     This object has been achieved by the subject-matter of the patent claims. 
     A first aspect of the invention relates to 3-((hetero-)aryl)-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives according to general formula (I) 
     
       
         
         
             
             
         
       
     
     wherein
 
R 1  and R 2  independently of one another mean
 
     —H; 
     —C 1 -C 6 -alkyl, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —OH, —OCH 3 , —CN and —CO 2 CH 3 ;
 
a 3-12-membered cycloalkyl moiety, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —OH, —OCH 3 , —CN and —CO 2 CH 3 ; wherein said 3-12-membered cycloalkyl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted; or
 
a 3-12-membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —OH, —OCH 3 , —CN and —CO 2 CH 3 ; wherein said 3-12-membered heterocycloalkyl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted;
 
or
 
R 1  and R 2  together with the nitrogen atom to which they are attached form a ring and mean —(CH 2 ) 3-6 —; —(CH 2 ) 2 —O—(CH 2 ) 2 —; or —(CH 2 ) 2 —NR A —(CH 2 ) 2 —, wherein R A  means —H or —C 1 -C 6 -alkyl, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br and —I;
 
preferably with the proviso that R 1  and R 2  do not simultaneously mean —H;
 
R 3  means
 
—C 1 -C 6 -alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted;
 
a 3-12-membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered cycloalkyl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted;
 
a 3-12-membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered heterocycloalkyl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted;
 
a 6-14-membered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said 6-14-membered aryl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or
 
a 5-14-membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5-14-membered heteroaryl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted;
 
R 4  means
 
     —H; 
     —C 1 -C 6 -alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said —C 1 -C 6 -alkyl is optionally connected through —C(═O)—, —C(═O)O—, or —S(═O) 2 —;
 
a 3-12-membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered cycloalkyl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein said 3-12-membered cycloalkyl moiety is optionally connected through —C(═O)—, —C(═O)O—, —C(═O)O—CH 2 —, or —S(═O) 2 —;
 
a 3-12-membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered heterocycloalkyl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein said 3-12-membered heterocycloalkyl moiety is optionally connected through —C(═O)—, —C(═O)O—, —C(═O)O—CH 2 —, or —S(═O) 2 —;
 
a 6-14-membered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said 6-14-membered aryl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein said 6-14-membered aryl moiety is optionally connected through —C(═O)—, —C(═O)O—, —C(═O)O—CH 2 —, or —S(═O) 2 —; or
 
a 5-14-membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5-14-membered heteroaryl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein said 5-14-membered heteroaryl moiety is optionally connected through —C(═O)—, —C(═O)O—, —C(═O)O—CH 2 —, or —S(═O) 2 —;
 
R 5  means
 
a 6-14-membered aryl moiety, unsubstituted, mono- or polysubstituted; or
 
a 5-14-membered heteroaryl moiety, unsubstituted, mono- or polysubstituted;
 
R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , and R 20  independently of one another mean —H, —F, —Cl, —Br, —I, —OH, or —C 1 -C 6 -alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted;
 
wherein “mono- or polysubstituted” means that one or more hydrogen atoms are replaced by a substituent independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —R 21 , —C(═O)R 21 , —C(═O)OR 21 , —C(═O)NR 21 R 22 , —C(═O)NH—(CH 2 CH 2 —O) 1-30 —CH 3 , —O—(CH 2 CH 2 —O) 1-30 —H, —O—(CH 2 CH 2 —O) 1-30 —CH 3 , ═O, —OR 21 , —OC(═O)R 21 , —OC(═O)OR 21 , —OC(═O)NR 21 R 22 , —NO 2 , —NR 21 R 22 , —NR 21 —(CH 2 ) 1-6 —C(═O)R 22 , —NR 21 —(CH 2 ) 1-6 —C(═O)OR 22 , —NR 23 —(CH 2 ) 1-6 —C(═O)NR 21 R 22 , —NR 21 C(═O)R 22 , —NR 21 C(═O)—OR 22 , —NR 23 C(═O)NR 21 R 22 , —NR 21 S(═O) 2 R 22 , —SR 21 , —S(═O)R 21 , —S(═O) 2 R 21 , —S(═O) 2 OR 21 , and —S(═O) 2 NR 21 R 22 ;
 
wherein
 
R 21 , R 22  and R 23  independently of one another mean
 
     —H; 
     —C 1 -C 6 -alkyl, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, —NH 2 , —C 2 H, —C(═O)O—C 1 -C 6 -alkyl, —C(═O)NH 2 , —C(═O)NHC 1 -C 6 -alkyl, —C(═O)N(C 1 -C 6 -alkyl) 2 , —O—C 1 -C 6 -alkyl and —S(═O) 2 —C 1 -C 6 -alkyl;
 
a 3-12-membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered cycloalkyl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, —NH 2 , —C 1 -C 6 -alkyl and —O—C 1 -C 6 -alkyl;
 
a 3-12-membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered heterocycloalkyl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, —NH 2 , —C 1 -C 6 -alkyl and —O—C 1 -C 6 -alkyl;
 
a 6-14-membered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said 6-14-membered aryl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, —NH 2 , —C 1 -C 6 -alkyl and —O—C 1 -C 6 -alkyl;
 
a 5-14-membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5-14-membered heteroaryl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, —NH 2 , —C 1 -C 6 -alkyl and —O—C 1 -C 6 -alkyl;
 
or R 21  and R 22  within —C(═O)NR 21 R 22 , —OC(═O)NR 21 R 22 , —NR 21 R 22 , —NR 23 —(CH 2 ) 1-6 —C(═O)NR 21 R 22 , —NR 23 C(═O)NR 21 R 22 , or —S(═O) 2 NR 21 R 22  together with the nitrogen atom to which they are attached form a ring and mean —(CH 2 ) 3-6 —; —(CH 2 ) 2 —O—(CH 2 ) 2 —; —(CH 2 ) 2 —S(═O) 2 —(CH 2 ) 2 — or —(CH 2 ) 2 —NR B —(CH 2 ) 2 —, wherein R B  means —H, —C 1 -C 6 -alkyl, —C(═O)—C 1 -C 6 -alkyl, or —S(═O) 2 —C 1 -C 6 -alkyl, wherein said —C 1 -C 6 -alkyl is linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br —I, —OH, —CO 2 H, —C(═O)O—C 1 -C 6 -alkyl and —C(═O)NH 2 ; and wherein said ring is unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, —NH 2 , —C 1 -C 6 -alkyl and —O—C 1 -C 6 -alkyl;
 
or a physiologically acceptable salt thereof.
 
     “(Hetero-)aryl” means “heteroaryl or aryl”. Preferably, aryl includes but is not limited to phenyl and naphthyl. Preferably, heteroaryl includes but is not limited to -1,2-benzodioxole, -pyrazinyl, -pyridazinyl, -pyridinyl, -pyrimidinyl, -thienyl, -imidazolyl, -benzimidazolyl, -thiazolyl, -1,3,4-thiadiazolyl, -benzothiazolyl, -oxazolyl, -benzoxazolyl, -pyrazolyl, -quinolinyl, -isoquinolinyl, -quinazolinyl, -indolyl, -indolinyl, -benzo[c][1,2,5]oxadiazolyl, -imidazo[1,2-a]pyrazinyl, or -1H-pyrrolo[2,3-b]pyridinyl. Preferably, cycloalkyl includes but is not limited to -cyclopropyl, -cyclobutyl, -cyclopentyl and -cyclohexyl. Preferably, heterocycloalkyl includes but is not limited to -aziridinyl, -azetidinyl, -pyrrolidinyl, -piperidinyl, -piperazinyl, -morpholinyl, -sulfamorpholinyl, -oxiridinyl, -oxetanyl, -tetrahydropyranyl, and -pyranyl. 
     When a moiety is connected through an asymmetric group such as —C(═O)O— or —C(═O)O—CH 2 —, said asymmetric group may be arranged in either direction. For example, when R 4  is connected to the core structure through —C(═O)O—, the arrangement may be either R 4 —C(═O)O-core or core-C(═O)O—R 4 . 
     In preferred embodiments of the compound according to the invention, R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , and R 20  independently of one another mean —H, —F, —OH, or —C 1 -C 6 -alkyl; preferably —H. 
     In a preferred embodiment of the compound according to the invention, R 1  means —H; and R 2  means —C 1 -C 6 -alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted. Preferably, R 1  means —H and R 2  means —CH 3 . 
     In another preferred embodiment of the compound according to the invention, R 1  means —CH 3 ; and R 2  means —C 1 -C 6 -alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted. Preferably, R 1  means —CH 3  and R 2  means —CH 3 . 
     In still another preferred embodiment of the compound according to the invention, R 1  and R 2  together with the nitrogen atom to which they are attached form a ring and mean —(CH 2 ) 3-6 —. Preferably, R 1  and R 2  together with the nitrogen atom to which they are attached form a ring and mean —(CH 2 ) 3 —. 
     In yet another preferred embodiment,
         R 1  means —H or —CH 3 ; and   R 2  means a 3-12-membered cycloalkyl moiety, saturated or unsaturated, unsubstituted; wherein said 3-12-membered cycloalkyl moiety is connected through —CH 2 —, unsubstituted; preferably —CH 2 -cycloalkyl, —CH 2 -cyclobutyl or —CH 2 -cyclopentyl; or R 2  means a 3-12-membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted; wherein said 3-12-membered heterocycloalkyl moiety is connected through —CH 2 —, unsubstituted; preferably —CH 2 -oxetanyl or —CH 2 -tetrahydrofuranyl.       

     In a preferred embodiment of the compound according to the invention, R 3  means —C 1 -C 6 -alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted. Preferably, R 3  means —C 1 -C 6 -alkyl, linear or branched, saturated or unsaturated, unsubstituted or monosubstituted with —OCH 3 . 
     In another preferred embodiment of the compound according to the invention, R 3  means a 6-14-membered aryl moiety, unsubstituted, mono- or polysubstituted, optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted. In a preferred embodiment, R 3  means -phenyl unsubstituted, mono- or polysubstituted. More preferably, R 3  means -phenyl unsubstituted, mono- or disubstituted with —F, —Cl, —CH 3 , —CF 3 , —OH, —OCH 3 , —OCF 3  or —OCH 2 OCH 3 , preferably —F. In another preferred embodiment, R 3  means -benzyl unsubstituted, mono- or polysubstituted. More preferably, R 3  means -benzyl unsubstituted, mono- or disubstituted with —F, —Cl, —CH 3 , —CF 3 , —OH, —OCH 3 , —OCF 3  or —OCH 2 OCH 3 , preferably —F. 
     In still another preferred embodiment of the compound according to the invention, R 3  means a 5-14-membered heteroaryl moiety, unsubstituted, mono- or polysubstituted. Preferably, R 3  means -thienyl or -pyridinyl, in each case unsubstituted, mono- or polysubstituted. More preferably, R 3  means -thienyl, -pyridinyl, -imidazolyl or benzimidazolyl, in each case unsubstituted or monosubstituted with —F, —Cl or —CH 3 . 
     In a preferred embodiment of the compound according to the invention, R 4  means —H. 
     In another preferred embodiment of the compound according to the invention, R 4  means —C 1 -C 6 -alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted. Preferably, R 4  means —C 1 -C 6 -alkyl, linear or branched, saturated or unsaturated, unsubstituted or monosubstituted with a substituent selected from the group consisting of —F, —Cl, —Br, —I, —CN, —CF 3 , —OH, —O—C 1 -C 4 -alkyl, —OCF 3 , —O—(CH 2 CH 2 —O) 1-30 —H, —O—(CH 2 CH 2 —O) 1-30 —CH 3 , —OC(═O)C 1 -C 4 -alkyl, —C(═O)C 1 -C 4 -alkyl, —C(═O)OH, —C(═O)OC 1 -C 4 -alkyl, —C(═O)NH 2 , —C(═O)NHC 1 -C 4 -alkyl, —C(═O)NHC 1 -C 4 -alkylene-CN, —C(═O)NHC 1 -C 4 -alkylene-O—C 1 -C 4 -alkyl, —C(═O)N(C 1 -C 4 -alkyl) 2 ; —S(═O)C 1 -C 4 -alkyl, and —S(═O) 2 C 1 -C 4 -alkyl; or with —C(═O)NR 21 R 22  wherein R 21  and R 22  together with the nitrogen atom to which they are attached form a ring and mean —(CH 2 ) 3-6 —, —(CH 2 ) 2 —O—(CH 2 ) 2 —, or —(CH 2 ) 2 —NR B —(CH 2 ) 2 —, wherein R B  means —H or —C 1 -C 6 -alkyl; or with —C(═O)NH-3-12-membered cycloalkyl, saturated or unsaturated, unsubstituted or monosubstituted with —F, —Cl, —Br, —I, —CN, or —OH; or with —C(═O)NH-3-12-membered heterocycloalkyl, saturated or unsaturated, unsubstituted or monosubstituted with —F, —Cl, —Br, —I, —CN, or —OH. More preferably, R 4  means —C 1 -C 6 -alkyl, linear or branched, saturated or unsaturated, unsubstituted or monosubstituted with —O—C 1 -C 4 -alkyl or —C(═O)N(C 1 -C 4 -alkyl) 2 . 
     In still another preferred embodiment of the compound according to the invention, R 4  means a 3-12-membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein the 3-12-membered cycloalkyl moiety is connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted. Preferably, R 4  means a 3-12-membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered cycloalkyl moiety is connected through —CH 2 — or —CH 2 CH 2 —. More preferably, R 4  means a 3-12-membered cycloalkyl moiety, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, —C 1 -C 4 -alkyl, —O—C 1 -C 4 -alkyl, —C(═O)OH, —C(═O)OC 1 -C 4 -alkyl, —C(═O)NH 2 , —C(═O)NHC 1 -C 4 -alkyl, —C(═O)N(C 1 -C 4 -alkyl) 2 , —S(═O)C 1 -C 4 -alkyl and —S(═O) 2 C 1 -C 4 -alkyl; wherein said 3-12-membered cycloalkyl moiety is connected through —CH 2 — or —CH 2 CH 2 —. 
     In a preferred embodiment of the compound according to the invention, R 4  means a 3-12-membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered heterocycloalkyl moiety is connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted. Preferably, R 4  means a 3-12-membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered heterocycloalkyl moiety is connected through —CH 2 — or —CH 2 CH 2 —. More preferably, R 4  means -oxetanyl, -tetrahydrofuranyl or -tetrahydropyranyl, in each case unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, —C 1 -C 4 -alkyl, —O—C 1 -C 4 -alkyl, —C(═O)OH, —C(═O)OC 1 -C 4 -alkyl, —C(═O)NH 2 , —C(═O)NHC 1 -C 4 -alkyl, —C(═O)N(C 1 -C 4 -alkyl) 2 , —S(═O)C 1 -C 4 -alkyl and —S(═O) 2 C 1 -C 4 -alkyl; wherein said -oxetanyl, -tetrahydrofuranyl or -tetrahydropyranyl is connected through —CH 2 — or —CH 2 CH 2 —. 
     In yet another preferred embodiment of the compound according to the invention, R 4  means a 6-14-membered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said 6-14-membered aryl moiety is connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted. Preferably, R 4  means -phenyl, unsubstituted, mono- or polysubstituted; wherein said -phenyl is connected through —CH 2 — or —CH 2 CH 2 —. More preferably, R 4  means -phenyl, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, —C 1 -C 4 -alkyl, —O—C 1 -C 4 -alkyl, —C(═O)OH, —C(═O)OC 1 -C 4 -alkyl, —C(═O)NH 2 , —C(═O)NHC 1 -C 4 -alkyl, —C(═O)N(C 1 -C 4 -alkyl) 2 , —S(═O)C 1 -C 4 -alkyl and —S(═O) 2 C 1 -C 4 -alkyl; wherein said -phenyl is connected through —CH 2 — or —CH 2 CH 2 —. 
     In a further preferred embodiment of the compound according to the invention, R 4  means a 5-14-membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5-14-membered heteroaryl moiety is connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted. Preferably, R 4  means a 5-14-membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said -phenyl is connected through —CH 2 — or —CH 2 CH 2 —. More preferably, R 4  means -pyridinyl, -pyrimidinyl, -pyrazinyl, or -pyrazolinyl, in each case unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, —C 1 -C 4 -alkyl, —O—C 1 -C 4 -alkyl, —C(═O)OH, —C(═O)OC 1 -C 4 -alkyl, —C(═O)NH 2 , —C(═O)NHC 1 -C 4 -alkyl, —C(═O)N(C 1 -C 4 -alkyl) 2 , —S(═O)C 1 -C 4 -alkyl and —S(═O) 2 C 1 -C 4 -alkyl; wherein said -pyridinyl, -pyrimidinyl, -pyrazinyl, or -pyrazolinyl is connected through —CH 2 — or —CH 2 CH 2 —. 
     In a preferred embodiment of the compound according to the invention, R means -phenyl, unsubstituted, mono- or polysubstituted. Preferably, R 5  means -phenyl unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F; —Cl; —Br; —I; —CN; —OH; —C 1 -C 4 -alkyl; —CF 3 ; -3-12-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; preferably -cyclopropyl, saturated, unsubstituted; -3-12-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; preferably -pyrrolidinyl, -piperidinyl, -morpholinyl, -piperazinyl, -thiomorpholinyl, or -thiomorpholinyl dioxide, in each case saturated, unsubstituted or monosubstituted with —C 1 -C 4 -alkyl; -6-14-membered aryl, unsubstituted, mono- or polysubstituted; preferably -phenyl, unsubstituted; —O—C 1 -C 4 -alkyl; —S—C 1 -C 4 -alkyl; —C(═O)OH; —C(═O)O—C 1 -C 4 -alkyl; —C(═O)NH 2 ; —C(═O)NHC 1 -C 4 -alkyl; —C(═O)N(C 1 -C 4 -alkyl) 2 ; —C(═O)N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl-OH); —C(═O)NH—(CH 2 ) 1-3 -3-12-membered cycloalkyl, saturated or unsaturated, unsubstituted or monosubstituted with —OH; preferably —C(═O)NH—(CH 2 ) 1-3 -cyclobutyl, saturated or unsaturated, unsubstituted or monosubstituted with —OH; —C(═O)-3-12-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; preferably —C(═O)-morpholinyl, saturated, unsubstituted; —S(═O)C 1 -C 4 -alkyl; —S(═O) 2 C 1 -C 4 -alkyl; and —S(═O) 2 N(C 1 -C 4 -alkyl) 2 . 
     In another preferred embodiment of the compound according to the invention, R 5  means -1,2-benzodioxole, -pyrazinyl, -pyridazinyl, -pyridinyl, -pyrimidinyl, -thienyl, -imidazolyl, -benzimidazolyl, -thiazolyl, -1,3,4-thiadiazolyl, -benzothiazolyl, -oxazolyl, -benzoxazolyl, -pyrazolyl, -quinolinyl, -isoquinolinyl, -quinazolinyl, -indolyl, -indolinyl, -benzo[c][1,2,5]oxadiazolyl, -imidazo[1,2-a]pyrazinyl, or -1H-pyrrolo[2,3-b]pyridinyl, in each case unsubstituted, mono- or polysubstituted; preferably -pyrazinyl, -pyridazinyl, -pyridinyl, -pyrimidinyl, or -thienyl, in each case unsubstituted, mono- or polysubstituted. Preferably, R 5  means -pyrazinyl, -pyridazinyl, -pyridinyl, -pyrimidinyl, or -thienyl, in each case unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F; —Cl; —Br; —I; —CN; —OH; —C 1 -C 4 -alkyl; —CF 3 ; -3-12-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; preferably -cyclopropyl, saturated, unsubstituted; -3-12-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; preferably -pyrrolidinyl, -piperidinyl, -morpholinyl, -piperazinyl, -thiomorpholinyl, or -thiomorpholinyl dioxide, in each case saturated, unsubstituted or monosubstituted with —C 1 -C 4 -alkyl; -6-14-membered aryl, unsubstituted, mono- or polysubstituted; preferably -phenyl, unsubstituted; —O—C 1 -C 4 -alkyl; —S—C 1 -C 4 -alkyl; —C(═O)OH; —C(═O)O—C 1 -C 4 -alkyl; —C(═O)NH 2 ; —C(═O)NHC 1 -C 4 -alkyl; —C(═O)N(C 1 -C 4 -alkyl) 2 ; —C(═O)N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl-OH); —C(═O)NH—(CH 2 ) 1-3 -3-12-membered cycloalkyl, saturated or unsaturated, unsubstituted or monosubstituted with —OH; preferably —C(═O)NH—(CH 2 ) 1-3 -cyclobutyl, saturated or unsaturated, unsubstituted or monosubstituted with —OH; —C(═O)-3-12-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; 
     preferably —C(═O)-morpholinyl, saturated, unsubstituted; —S(═O)C 1 -C 4 -alkyl; —S(═O) 2 C 1 -C 4 -alkyl; and —S(═O) 2 N(C 1 -C 4 -alkyl) 2 . 
     In still another preferred embodiment of the compound according to the invention, R 5  means a bicyclic 9-10-membered heteroaryl moiety, unsubstituted, mono- or polysubstituted. Preferably, R 5  means imidazo[1,2-a]pyrazine, unsubstituted or monosubstituted with —C 1 -C 4 -alkyl. 
     Preferably, R 5  means -phenyl, -1,2-benzodioxole, -pyrazinyl, -pyridazinyl, -pyridinyl, -pyrimidinyl, -thienyl, -imidazolyl, -benzimidazolyl, -thiazolyl, -1,3,4-thiadiazolyl, -benzothiazolyl, -oxazolyl, -benzoxazolyl, -pyrazolyl, -quinolinyl, -isoquinolinyl, -quinazolinyl, -indolyl, -indolinyl, -benzo[c][1,2,5]oxadiazolyl, -imidazo[1,2-a]pyrazinyl, or -1H-pyrrolo[2,3-b]pyridinyl, in each case unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of 
     —F; —Cl; —Br; —I; 
     —CN; —C 1 -C 4 -alkyl; —CF 3 ; —C 1 -C 4 -alkyl-C(═O)NH 2 ; —C 1 -C 4 -alkyl-S(═O) 2 —C 1 -C 4 -alkyl;
 
—C(═O)—C 1 -C 4 -alkyl; —C(═O)OH; —C(═O)O—C 1 -C 4 -alkyl; —C(═O)NH 2 ; —C(═O)NHC 1 -C 4 -alkyl; —C(═O)N(C 1 -C 4 -alkyl) 2 ; —C(═O)NH(C 1 -C 4 -alkyl-OH); —C(═O)N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl-OH); —C(═O)NH—(CH 2 CH 2 O) 1-30 —CH 3 ;
 
—NH 2 ; —NHC 1 -C 4 -alkyl; —N(C 1 -C 4 -alkyl) 2 ; —NHC 1 -C 4 -alkyl-OH; —NCH 3 C 1 -C 4 -alkyl-OH; —NH—C 1 -C 4 -alkyl-C(═O)NH 2 ; —NCH 3 —C 1 -C 4 -alkyl-C(═O)NH 2 ; —NHC(═O)—C 1 -C 4 -alkyl; —NCH 3 C(═O)—C 1 -C 4 -alkyl;
 
—OH; —O—C 1 -C 4 -alkyl; —OCF 3 ; —O—C 1 -C 4 -alkyl-CO 2 H; —O—C 1 -C 4 -alkyl-C(═O)O—C 1 -C 4 -alkyl; —O—C 1 -C 4 -alkyl-CONH 2 ;
 
—S—C 1 -C 4 -alkyl; —S(═O)C 1 -C 4 -alkyl; —S(═O) 2 C 1 -C 4 -alkyl; and —S(═O) 2 N(C 1 -C 4 -alkyl) 2 ;
 
-3-12-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered cycloalkyl is optionally connected through —CH 2 —, —NH—, —NCH 3 —, —NH—(CH 2 ) 1-3 —, —NCH 3 (CH 2 ) 1-3 —, —(C═O)—, —NHC(═O)—, —NCH 3 C(═O)—, —C(═O)NH—(CH 2 ) 1-3 —, —C(═O)NCH 3 —(CH 2 ) 1-3 —;
 
-3-12-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered heterocycloalkyl is optionally connected through —CH 2 —, —NH—, —NCH 3 —, —NH—(CH 2 ) 1-3 —, —NCH 3 (CH 2 ) 1-3 —, —(C═O)—, —NHC(═O)—, —NCH 3 C(═O)—, —C(═O)NH—(CH 2 ) 1-3 —, —C(═O)NCH 3 —(CH 2 ) 1-3 —;
 
-6-14-membered aryl, unsubstituted, mono- or polysubstituted; wherein said 6-14-membered aryl is optionally connected through —CH 2 —, —NH—, —NCH 3 —, —NH—(CH 2 ) 1-3 —, —NCH 3 (CH 2 ) 1-3 —, —(C═O)—, —NHC(═O)—, —NCH 3 C(═O)—, —C(═O)NH—(CH 2 ) 1-3 —, —C(═O)NCH 3 —(CH 2 ) 1-3 —; or
 
-5-14-membered heteroaryl, unsubstituted, mono- or polysubstituted; wherein said 5-14-membered heteroaryl is optionally connected through —CH 2 —, —NH—, —NCH 3 —, —NH—(CH 2 ) 1-3 —, —NCH 3 (CH 2 ) 1-3 —, —(C═O)—, —NHC(═O)—, —NCH 3 C(═O)—, —C(═O)NH—(CH 2 ) 1-3 —, —C(═O)NCH 3 —(CH 2 ) 1-3 —.
 
     In preferred embodiments, the compound according to the invention has a structure according to any of general formulas (II-A) to (VIII-C): 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     wherein in each case
 
R 1 , R 2 , R 3 , R 4 , and R 5  are defined as above,
 
R C  means —H, —OH, —F, —CN or —C 1 -C 4 -alkyl; preferably —H or —OH;
 
R D  means —H or —F;
 
or a physiologically acceptable salt thereof.
 
     Preferably, in the compounds according to general formula (I) or any of the compounds according to general formulas (II-A) to (VIII-C), R 5  is selected from the group consisting of: 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     In a particularly preferred embodiment of the compound according to the invention 
     R 1  means —H or —CH 3 ;
 
R 2  means —C 1 -C 6 -alkyl, linear or branched, saturated, unsubstituted; cyclopropyl connected through —CH 2 —; or tetrahydropyranyl connected through —CH 2 —;
 
R 3  means -phenyl, benzyl, -thienyl or -pyridinyl, in each case unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —CN, —CH 3 , —CH 2 CH 3 , —CH 2 F, —CHF 2 , —CF 3 , —OCF 3 , —OH, —OCH 3 , —C(═O)NH 2 , C(═O)NHCH 3 , —C(═O)N(CH 3 ) 2 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , —NHC(═O)CH 3 , —CH 2 OH, SOCH 3  and SO 2 CH 3 ; or
 
R 4  means
 
     —H; 
     —C 1 -C 6 -alkyl, linear or branched, saturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, —O—C 1 -C 4 -alkyl, —C(═O)NH—C 1 -C 6 -alkyl, —C(═O)N(C 1 -C 6 -alkyl) 2  or —C(═O)NRR′ wherein R and R′ together with the nitrogen atom to which they are attached form a ring and mean —(CH 2 ) 3-5 —;
 
3-6-membered cycloalkyl, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, and —O—C 1 -C 4 -alkyl, wherein said 3-6-membered cycloalkyl is connected through —C 1 -C 6 -alkylene;
 
3-6-membered heterocycloalkyl, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, and —O—C 1 -C 4 -alkyl, wherein said 3-6-membered heterocycloalkyl is connected through —C 1 -C 6 -alkylene;
 
-phenyl, unsubstituted or monosubstituted with —OCH 3 ; wherein said -phenyl is connected through —C 1 -C 6 -alkylene-; or
 
-pyridyl, unsubstituted, mono- or polysubstituted; wherein said -pyridyl is connected through —C 1 -C 6 -alkylene-;
 
R 5  means
 
-phenyl, -1,2-benzodioxole, -pyrazinyl, -pyridazinyl, -pyridinyl, -pyrimidinyl, -thienyl, -imidazolyl, -benzimidazolyl, -thiazolyl, -1,3,4-thiadiazolyl, -benzothiazolyl, -oxazolyl, -benzoxazolyl, -pyrazolyl, -quinolinyl, -isoquinolinyl, -quinazolinyl, -indolyl, -indolinyl, -benzo[c][1,2,5]oxadiazolyl, -imidazo[1,2-a]pyrazinyl, or -1H-pyrrolo[2,3-b]pyridinyl, in each case unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of
         —F; —Cl; —Br; —I;   —CN; —C 1 -C 4 -alkyl; —C 1 -C 4 -alkyl-OH; —CF 3 ; —C 1 -C 4 -alkyl-CF 3 ; —C 1 -C 4 -alkyl-C(═O)NH 2 ; —C 1 -C 4 -alkyl-C(═O)NHC 1 -C 6 -alkyl; —C 1 -C 4 -alkyl-C(═O)N(C 1 -C 6 -alkyl) 2 ; —C 1 -C 4 -alkyl-S(═O) 2 —C 1 -C 4 -alkyl;   —C(═O)—C 1 -C 4 -alkyl; —C(═O)OH; —C(═O)O—C 1 -C 4 -alkyl; —C(═O)NH 2 ; —C(═O)NHC 1 -C 4 -alkyl; —C(═O)N(C 1 -C 4 -alkyl) 2 ; —C(═O)NH(C 1 -C 4 -alkyl-OH); —C(═O)N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl-OH); —C(═O)NH—(CH 2 CH 2 O) 1-30 —CH 3 ;   —NH 2 ; —NHC 1 -C 4 -alkyl; —N(C 1 -C 4 -alkyl) 2 ; —NHC 1 -C 4 -alkyl-OH; —NCH 3 C 1 -C 4 -alkyl-OH; —NH—C 1 -C 4 -alkyl-C(═O)NH 2 ; —NCH 3 —C 1 -C 4 -alkyl-C(═O)NH 2 ; —NHC(═O)—C 1 -C 4 -alkyl; —NCH 3 C(═O)—C 1 -C 4 -alkyl;   —OH; —O—C 1 -C 4 -alkyl; —OCF 3 ; —O—C 1 -C 4 -alkyl-CO 2 H; —O—C 1 -C 4 -alkyl-C(═O)O—C 1 -C 4 -alkyl; —O—C 1 -C 4 -alkyl-CONH 2 ;   —S—C 1 -C 4 -alkyl; —S(═O)C 1 -C 4 -alkyl; —S(═O) 2 C 1 -C 4 -alkyl; and —S(═O) 2 N(C 1 -C 4 -alkyl) 2 ;   -3-12-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered cycloalkyl is optionally connected through —CH 2 —, —O—, —NH—, —NCH 3 —, —NH—(CH 2 ) 1-3 —, —NCH 3 (CH 2 ) 1-3 —, —(C═O)—, —NHC(═O)—, —NCH 3 C(═O)—, —C(═O)NH—(CH 2 ) 1-3 —, —C(═O)NCH 3 —(CH 2 ) 1-3 —;   -3-12-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered heterocycloalkyl is optionally connected through —CH 2 —, —O—, —NH—, —NCH 3 —, —NH—(CH 2 ) 1-3 —, —NCH 3 (CH 2 ) 1-3 —, —(C═O)—, —NHC(═O)—, —NCH 3 C(═O)—, —C(═O)NH—(CH 2 ) 1-3 —, —C(═O)NCH 3 —(CH 2 ) 1-3 —;   -6-14-membered aryl, unsubstituted, mono- or polysubstituted; wherein said 6-14-membered aryl is optionally connected through —CH 2 —, —O—, —NH—, —NCH 3 —, —NH—(CH 2 ) 1-3 —, —NCH 3 (CH 2 ) 1-3 —, —(C═O)—, —NHC(═O)—, —NCH 3 C(═O)—, —C(═O)NH—(CH 2 ) 1-3 —, —C(═O)NCH 3 —(CH 2 ) 1-3 —; or   -5-14-membered heteroaryl, unsubstituted, mono- or polysubstituted; wherein said 5-14-membered heteroaryl is optionally connected through —CH 2 —, —O—, —NH—, —NCH 3 —, —NH—(CH 2 ) 1-3 —, —NCH 3 (CH 2 ) 1-3 —, —(C═O)—, —NHC(═O)—, —NCH 3 C(═O)—, —C(═O)NH—(CH 2 ) 1-3 —, —C(═O)NCH 3 —(CH 2 ) 1-3 —; and
 
R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , and R 20  mean —H.
       

     In a particularly preferred embodiment of the compound according to the invention 
     R 1  means —H or —CH 3 ; and/or
 
R 2  means —C 1 -C 6 -alkyl, linear or branched, saturated, unsubstituted; preferably, R 2  means —CH 3  or —CH 2 CH 3 ; more preferably, R 1  and R 2  both mean —CH 3 ; and/or
 
R 3  means -phenyl, -thienyl or -pyridinyl, in each case unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —CN, —CH 3 , —CH 2 CH 3 , —CH 2 F, —CHF 2 , —CF 3 , —OCF 3 , —OH, —OCH 3 , —C(═O)NH 2 , C(═O)NHCH 3 ,
 
—C(═O)N(CH 3 ) 2 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , —NHC(═O)CH 3 , —CH 2 OH, SOCH 3  and SO 2 CH 3 ; preferably, R 3  means -phenyl, -thienyl or -pyridinyl, in each case unsubstituted or substituted with —F; more preferably, R 3  means phenyl, unsubstituted; and/or
 
R 4  means
 
     —H; 
     —C 1 -C 6 -alkyl, linear or branched, saturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, and —O—C 1 -C 4 -alkyl; or
 
3-6-membered cycloalkyl, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, and —O—C 1 -C 4 -alkyl, wherein said 3-6-membered cycloalkyl is connected through —C 1 -C 6 -alkylene; preferably, R 4  means 3-6-membered cycloalkyl, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, and —O—C 1 -C 4 -alkyl, wherein said 3-6-membered cycloalkyl is connected through —CH 2 — or —CH 2 CH 2 —; more preferably, R 4  means -cyclobutyl, unsubstituted or monosubstituted with —OH, wherein said -cyclobutyl is connected through —CH 2 —; and/or
 
R 5  means -phenyl, -pyrazinyl, -pyridazinyl, -pyridinyl, -pyrimidinyl, -thienyl, or imidazo[1,2-a]pyrazine, in each case unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F; —Cl; —Br; —I; —CN; —OH; —C 1 -C 4 -alkyl; —CF 3 ; -3-12-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; preferably cyclopropyl, saturated, unsubstituted; -3-12-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; preferably -pyrrolidinyl, -morpholinyl, -piperazinyl, -thiomorpholinyl, or -thiomorpholinyl dioxide, in each case saturated, unsubstituted or monosubstituted with —C 1 -C 4 -alkyl; -6-14-membered aryl, unsubstituted, mono- or polysubstituted; preferably -phenyl, unsubstituted; —O—C 1 -C 4 -alkyl; —S—C 1 -C 4 -alkyl; —C(═O)OH; —C(═O)O—C 1 -C 4 -alkyl; —C(═O)NH 2 ; —C(═O)NHC 1 -C 4 -alkyl; —C(═O)N(C 1 -C 4 -alkyl) 2 ; —C(═O)N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl-OH); —C(═O)NH—(CH 2 ) 1-3 -3-12-membered cycloalkyl, saturated or unsaturated, unsubstituted or monosubstituted with —OH; preferably —C(═O)NH—(CH 2 ) 1-3 -cyclobutyl, saturated or unsaturated, unsubstituted or monosubstituted with —OH; —C(═O)-3-12-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; preferably —C(═O)-morpholinyl, saturated, unsubstituted; —S(═O)C 1 -C 4 -alkyl; —S(═O) 2 C 1 -C 4 -alkyl; and —S(═O) 2 N(C 1 -C 4 -alkyl) 2 ; and/or
 
R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , and R 20  mean —H.
 
     Preferably, the compound according to the invention is selected from the group consisting of 
                                    SC_3001   cis-5-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3002   cis-5-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrazine-2-carbonitrile       SC_3003   cis-5-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-4-methoxy-pyrimidine-2-carbonitrile       SC_3004   cis-5-[8-Dimethylamino-1-(2-methoxy-ethyl)-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3005   cis-5-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carboxylic acid amide       SC_3006   cis-5-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-2-methylsulfonyl-pyrimidine-4-carbonitrile       SC_3007   cis-5-[1-(2-Methoxy-ethyl)-8-methylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3008   cis-2-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-5-methylsulfonyl-benzonitrile       SC_3009   cis-2-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-benzamide       SC_3010   cis-3-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-benzamide       SC_3011   cis-5-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carboxylic acid amide       SC_3012   cis-5-[1-(Cyclobutyl-methyl)-8-methylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-4-methoxy-pyrimidine-2-carbonitrile       SC_3013   cis-5-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3014   cis-2-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-5-carbonitrile       SC_3015   cis-5-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-3-(2-methoxy-pyrimidin-           5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3016   cis-2-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-5-carboxylic acid amide       SC_3017   cis-4-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-N-methyl-benzamide       SC_3018   cis-5-(8-Dimethylamino-2-oxo-8-phenyl-1-propyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidine-2-carbonitrile       SC_3019   cis-5-[8-Dimethylamino-1-(3-methoxy-propyl)-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3020   cis-5-[1-(Cyclopropyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3021   cis-4-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-benzamide       SC_3022   cis-1-(Cyclobutyl-methyl)-8-dimethylamino-8-phenyl-3-[2-(trifluoromethyl)-           pyrimidin-5-yl]-1,3-diazaspiro[4.51decan-2-one       SC_3023   cis-8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-3-(2-hydroxy-pyrimidin-           5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3024   cis-5-[8-Dimethylamino-1-(2-methyl-propyl)-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3025   cis-5-[8-Dimethylamino-1-(2-hydroxy-ethyl)-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3026   cis-5-[1-(Cyclobutyl-methyl)-8-methylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-4-methyl-pyridine-2-carbonitrile       SC_3027   cis-1-(Cyclobutyl-methyl)-3-(5-methoxy-pyrazin-2-yl)-8-methylamino-8-phenyl-           1,3-diazaspiro[4.5]decan-2-one       SC_3028   cis-4-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-N,N-dimethyl-benzamide       SC_3029   cis-4-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-N-ethyl-N-(2-hydroxy-ethyl)-benzamide       SC_3030   cis-2-[1-(Cyclobutyl-methyl)-8-methylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-5-methylsulfonyl-benzonitrile       SC_3031   cis-1-(Cyclobutyl-methyl)-8-methylamino-3-[2-methylsulfonyl-4-           (trifluoromethyl)-phenyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3032   cis-4-[1-(Cyclobutyl-methyl)-8-methylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-N,N-dimethyl-3-(trifluoromethyl)-benzenesulfonic           acid amide       SC_3033   cis-4-[1-(Cyclobutyl-methyl)-8-(ethyl-methyl-amino)-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-benzonitrile       SC_3034   cis-1-(Cyclobutyl-methyl)-8-(ethyl-methyl-amino)-8-phenyl-3-[2-           (trifluoromethyl)-pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3035   cis-5-[1-(Cyclobutyl-methyl)-8-(ethyl-methyl-amino)-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3036   cis-5-[8-Dimethylamino-1-](1-methyl-cyclobutyl)-methyl]-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3037   cis-2-[3-(2-Cyano-pyrimidin-5-yl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-1-yl]-N,N-dimethyl-acetamide       SC_3038   cis-1-(Cyclobutyl-methyl)-8-methylamino-8-phenyl-3-[2-(trifluoromethyl)-           pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3039   cis-5-[8-Dimethylamino-8-(3-fluorophenyl)-1-(4-methoxy-butyl)-2-oxo-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3040   cis-5-[8-Dimethylamino-1-(3-methoxy-propyl)-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-4-methoxy-pyrimidine-2-carbonitrile       SC_3041   cis-5-[1-[(1-Cyano-cyclobutyl)-methyl]-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3042   cis-N-(Cyclobutyl-methyl)-5-[1-(cyclobutyl-methyl)-8-dimethylamino-8-(3-           fluorophenyl)-2-oxo-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carboxylic acid           amide       SC_3043   cis-5-[1-(3-Methoxy-propyl)-8-methylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3044   cis-5-[8-Dimethylamino-8-(3-fluorophenyl)-1-methyl-2-oxo-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3045   cis-4-Methoxy-5-[1-(3-methoxy-propyl)-8-methylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3046   cis-4-[8-Dimethylamino-1-(2-methoxy-ethyl)-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3047   cis-5-[8-Dimethylamino-1-(2-methoxy-ethyl)-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-4-methoxy-pyrimidine-2-carbonitrile       SC_3048   cis-4-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3049   cis-1-(Cyclobutyl-methyl)-8-dimethylamino-3-(6-methylsulfanyl-pyrimidin-4-yl)-           8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3050   cis-2-[3-(2-Cyano-pyrimidin-4-yl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-1-yl]-N,N-dimethyl-acetamide       SC_3051   cis-6-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-4-carbonitrile       SC_3052   cis-2-(8-Dimethylamino-2-oxo-3,8-diphenyl-1,3-diazaspiro[4.5]decan-1-yl)-N,N-           dimethyl-acetamide       SC_3053   cis-1-(Cyclobutyl-methyl)-8-dimethylamino-3,8-diphenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3054   cis-2-[8-Dimethylamino-1-(2-methoxy-ethyl)-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-5-carbonitrile       SC_3055   cis-8-Dimethylamino-1-(2-methoxy-ethyl)-3,8-diphenyl-1,3-diazaspiro[4.5]decan-           2-one       SC_3056   cis-5-[8-Dimethylamino-1-(2-methoxy-ethyl)-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-4-methyl-pyridine-2-carbonitrile       SC_3057   cis-N,N-Dimethyl-2-(8-methylamino-2-oxo-3,8-diphenyl-1,3-diazaspiro[4.5]decan-           1-yl)-acetamide       SC_3058   cis-5-[1-[(1-Cyano-cyclobutyl)-methyl]-8-methylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3059   cis-5-[1-[(1-Cyano-cyclobutyl)-methyl]-8-(ethyl-methyl-amino)-2-oxo-8-phenyl-           1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3060   cis-4-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-benzonitrile       SC_3061   cis-3-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-benzonitrile       SC_3063   cis-5-[1-[(1-Cyano-cyclobutyl)-methyl]-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyridine-2-carbonitrile       SC_3064   cis-2-[3-(2-Cyano-pyrimidin-5-yl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-1-yl]-N-propyl-acetamide       SC_3065   cis-5-[1-(Cyclobutyl-methyl)-8-(ethyl-methyl-amino)-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-4-methoxy-pyrimidine-2-carbonitrile       SC_3066   cis-4-[1-(Cyclobutyl-methyl)-8-methylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-3-methoxy-benzonitrile       SC_3067   cis-5-[8-Dimethylamino-1-(3-methoxy-propyl)-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-6-methoxy-pyridine-2-carbonitrile       SC_3068   cis-4-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-benzamide       SC_3069   cis-5-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyridine-2-carbonitrile       SC_3070   cis-5-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-N-[(1-hydroxy-cyclobutyl)-methyl]-pyridine-2-           carboxylic acid amide       SC_3071   cis-2-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-benzonitrile       SC_3072   cis-3-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-benzonitrile       SC_3073   cis-1-(Cyclobutyl-methyl)-8-dimethylamino-8-phenyl-3-[2-(trifluoromethyl)-           pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3074   cis-5-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-4-methyl-pyridine-2-carboxylic acid methyl ester       SC_3075   cis-1-(Cyclobutyl-methyl)-8-dimethylamino-3-(5-methoxy-pyrazin-2-yl)-8-phenyl-           1,3-diazaspiro[4.5]decan-2-one       SC_3076   cis-1-(Cyclobutyl-methyl)-8-dimethylamino-3-(2-methoxy-pyrimidin-5-yl)-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3077   cis-4-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-benzonitrile       SC_3078   cis-5-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-4-methyl-pyridine-2-carbonitrile       SC_3079   cis-1-(Cyclobutyl-methyl)-8-dimethylamino-3-(5-fluoro-pyrimidin-2-yl)-8-phenyl-           1,3-diazaspiro[4.5]decan-2-one       SC_3080   cis-4-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-3-methoxy-benzonitrile       SC_3081   cis-4-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-benzoic acid methyl ester       SC_3082   cis-1-(Cyclobutyl-methyl)-8-dimethylamino-8-phenyl-3-(2-pyrrolidin-1-yl-           pyrimidin-4-yl)-1,3-diazaspiro[4.5]decan-2-one       SC_3083   cis-1-(Cyclobutyl-methyl)-8-dimethylamino-8-phenyl-3-(5-pyridin-2-yl-thiophen-           2-yl)-1,3-diazaspiro[4.5]decan-2-one       SC_3084   cis-1-(Cyclobutyl-methyl)-8-dimethylamino-3-[2-methylsulfonyl-4-           (trifluoromethyl)-phenyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3085   cis-1-(Cyclobutyl-methyl)-8-dimethylamino-8-phenyl-3-[6-(trifluoromethyl)-           pyridin-3-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3086   cis-1-(Cyclobutyl-methyl)-3-(2,4-dimethoxy-phenyl)-8-dimethylamino-8-phenyl-           1,3-diazaspiro[4.5]decan-2-one       SC_3087   cis-2-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-4-methylsulfonyl-benzonitrile       SC_3088   cis-5-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-2-fluoro-benzonitrile       SC_3089   cis-4-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-N,N-dimethyl-3-(trifluoromethyl)-benzenesulfonic acid           amide       SC_3090   cis-2-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-benzonitrile       SC_3091   cis-1-(Cyclobutyl-methyl)-8-dimethylamino-3-(2-methyl-imidazo[1,2-a]pyrazin-6-           yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3092   cis-1-(Cyclobutyl-methyl)-8-dimethylamino-3-(4-methylsulfonyl-phenyl)-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3093   cis-2-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-5-methoxy-benzonitrile       SC_3094   cis-1-(Cyclobutyl-methyl)-8-dimethylamino-3,8-diphenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3096   cis-1-(Cyclobutyl-methyl)-8-dimethylamino-8-phenyl-3-pyrazin-2-yl-1,3-           diazaspiro[4.5]decan-2-one       SC_3097   cis-8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-3-(2-morpholin-4-yl-           pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3098   cis-8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-3-[2-(4-methyl-piperazin-           1-yl)-pyrimidin-5-yl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3099   cis-1-[(1-Hydroxy-cyclobutyl)-methyl]-8-methylamino-3-(2-morpholin-4-yl-           pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3100   cis-8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-8-phenyl-3-(2-piperazin-           1-yl-pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one hydrochloride       SC_3101   cis-1-[(1-Hydroxy-cyclobutyl1)-methyl]-8-methylamino-3-[2-(4-methyl-piperazin-           1-yl)-pyrimidin-5-yl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3102   cis-1-[(1-Hydroxy-cyclobutyl)-methyl]-8-methylamino-8-phenyl-3-(2-piperazin-1-           yl-pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one dihydrochloride       SC_3103   cis-1-(Cyclobutyl-methyl)-8-dimethylamino-3-[4-methyl-6-(trifluoromethyl)-           pyridin-3-yl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3104   cis-1-(Cyclobutyl-methyl)-8-methylamino-3-[4-methyl-6-(trifluoromethyl)-pyridin-           3-yl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3105   cis-1-(Cyclopropyl-methyl)-8-dimethylamino-3-(4-methylsulfonyl-phenyl)-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3106   cis-1-(Cyclopropyl-methyl)-8-methylamino-3-(4-methylsulfonyl-phenyl)-8-phenyl-           1,3-diazaspiro[4.5]decan-2-one       SC_3107   cis-1-(Cyclopropyl-methyl)-8-dimethylamino-3-(2-fluoro-4-methylsulfonyl-           phenyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3108   cis-2-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-benzamide; formic acid       SC_3109   cis-2-[8-Dimethylamino-1-[2-(1-methoxy-cyclobutyl)-ethyl]-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-benzamide       SC_3110   cis-8-Dimethylamino-1-[2-(1-methoxy-cyclobutyl)-ethyl]-3-(2-methyl-pyrimidin-           5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3111   cis-5-[1-[(1-Hydroxy-cyclobutyl)-methyl]-8-methylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile       SC_3112   cis-2-[1-[(1-Hydroxy-cyclobutyl)-methyl]-8-methylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-benzonitrile       SC_3113   cis-4-[1-[(1-Hydroxy-cyclobutyl)-methyl]-8-methylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-3-methoxy-benzonitrile       SC_3114   cis-4-[8-Ethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-3-methoxy-benzonitrile       SC_3115   cis-2-[8-Ethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-benzonitrile       SC_3116   cis-5-[1-[(1-Hydroxy-cyclobutyl)-methyl]-8-methylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-4-methoxy-pyrimidine-2-carbonitrile       SC_3117   cis-2-[8-Dimethylamino-1-(oxetan-3-yl-methyl)-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-benzamide       SC_3118   cis-4-Methoxy-5-(8-methylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidine-2-carbonitrile       SC_3119   cis-2-(8-Methylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-benzamide       SC_3120   cis-8-Dimethylamino-3-[2-(3-oxo-piperazin-1-yl)-pyrimidin-5-yl]-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3121   cis-3-(2-Cyclopropyl-pyrimidin-5-yl)-8-dimethylamino-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3122   cis-8-Dimethylamino-3-[4-methyl-6-(trifluoromethyl)-pyridin-3-yl]-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3123   cis-8-Dimethylamino-3-(2-methylsulfonyl-phenyl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3124   cis-8-Dimethylamino-8-phenyl-3-(2-piperazin-1-yl-pyrimidin-5-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3125   trans-2-(8-Ethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-benzamide       SC_3126   cis--2-(8-Ethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-benzamide       SC_3127   cis-2-(8-Ethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-benzamide       SC_3128   cis-2-(8-Ethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-benzamide       SC_3129   cis-3-[5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidin-2-yl]-benzonitrile       SC_3130   cis-8-Dimethylamino-3-[2-(4-methylsulfonyl-piperazin-1-yl)-pyrimidin-5-yl]-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3131   cis-3-[5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidin-2-yl]-benzamide       SC_3132   cis-8-[(Cyclopropyl-methyl)-methyl-amino]-8-phenyl-3-[2-(trifluoromethyl)-           pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3133   cis-8-Dimethylamino-3-[2-(4-methyl-piperazine-1-carbonyl)-pyrimidin-5-yl]-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3134   trans-4-(8-Ethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-3-methoxy-           benzonitrile       SC_3135   cis-4-(8-Ethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-3-methoxy-           benzonitrile       SC_3136   cis-3-[2-(4-Acetyl-piperazin-1-yl)-pyrimidin-5-yl]-8-dimethylamino-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3137   cis-8-Dimethylamino-8-phenyl-3-(2-pyridin-4-yl-pyrimidin-5-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3138   cis-8-Dimethylamino-8-phenyl-3-(2-pyridin-3-yl-pyrimidin-5-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3139   cis-5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-N-(2-           hydroxy-ethyl)-pyrimidine-2-carboxylic acid amide       SC_3140   cis-5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)           pyrimidine-2-carboxylic acid amide       SC_3141   cis-8-Dimethylamino-3-[2-morpholin-4-yl-4-(trifluoromethyl)-pyrimidin-5-yl]-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3142   cis-4-[5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidin-2-yl]-benzonitrile       SC_3143   cis-5-(8-Ethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-4-methoxy-           pyrimidine-2-carbonitrile       SC_3144   trans-5-(8-Ethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-4-methoxy-           pyrimidine-2-carbonitrile       SC_3145   cis-8-Dimethylamino-3-[2-(morpholine-4-carbonyl)-pyrimidin-5-yl]-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3146   cis-2-[4-[5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidin-2-yl]-piperazin-1-yl]-acetic acid methyl ester       SC_3147   cis-8-Dimethylamino-3-[2-(methylsulfonyl-methyl)-phenyl]-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3148   cis-8-Dimethylamino-3-(4-methyl-2-morpholin-4-yl-pyrimidin-5-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3149   cis-8-Dimethylamino-3-[2-(1,1-dioxo-[1,4]thiazinan-4-yl)-pyrimidin-5-yl]-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3150   cis-8-Dimethylamino-3-(4-fluoro-pyridin-3-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-           2-one       SC_3151   cis-5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-N-(2-           hydroxy-ethyl)-N-methyl-pyrimidine-2-carboxylic acid amide       SC_3152   cis-5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-2-           morpholin-4-yl-isonicotinonitrile       SC_3153   cis-4-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-benzamide       SC_3154   cis-8-Dimethylamino-3-(2-fluoro-4-methylsulfonyl-phenyl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3155   cis-4-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-3-fluoro-           benzonitrile       SC_3156   cis-4-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-3,5-           difluoro-benzonitrile       SC_3157   cis-8-Dimethylamino-3-(2-methoxy-pyrimidin-5-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3158   cis-3-[2-(Benzylamino)-pyrimidin-5-yl]-8-dimethylamino-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3159   cis-8-Dimethylamino-3-[2-(4-fluorophenyl)-pyrimidin-5-yl]-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3160   trans-8-Benzyl-8-dimethylamino-3-(2-morpholin-4-yl-pyrimidin-5-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3161   cis-8-Benzyl-8-dimethylamino-3-(2-morpholin-4-yl-pyrimidin-5-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3162   cis-8-Dimethylamino-8-phenyl-3-(2-pyridin-2-yl-pyrimidin-5-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3163   cis-4-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-3,5-           difluoro-benzamide       SC_3164   cis-4-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-3-fluoro-           benzamide       SC_3165   cis-8-Benzyl-8-dimethylamino-3-[2-(trifluoromethyl)-pyrimidin-5-yl]-1,3-           diazaspiro[4.5]decan-2-one       SC_3166   trans-8-Benzyl-8-dimethylamino-3-[2-(trifluoromethyl)-pyrimidin-5-yl]-1,3-           diazaspiro[4.5]decan-2-one       SC_3167   cis-8-Dimethylamino-8-thiophen-2-yl-3-[2-(trifluoromethyl)-pyrimidin-5-yl]-1,3-           diazaspiro[4.5]decan-2-one       SC_3168   trans-8-Dimethylamino-8-thiophen-2-yl-3-[2-(trifluoromethyl)-pyrimidin-5-yl]-           1,3-diazaspiro[4.5]decan-2-one       SC_3169   cis-2-[2-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)           phenoxy]-acetic acid       SC_3170   cis-8-Dimethylamino-8-phenyl-3-(2-piperidin-1-yl-pyrimidin-5-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3171   cis-8-Dimethylamino-8-phenyl-3-(2-pyrrolidin-1-yl-pyrimidin-5-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3172   cis-8-Dimethylamino-8-phenyl-3-(2-pyrimidin-5-yl-pyrimidin-5-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3173   cis-8-Dimethylamino-8-phenyl-3-[2-(piperazine-1-carbonyl)-pyrimidin-5-yl]-1,3-           diazaspiro[4.5]decan-2-one       SC_3174   trans-8-Benzyl-8-dimethylamino-3-[4-methyl-6-(trifluoromethyl)-pyridin-3-yl]-           1,3-diazaspiro[4.5]decan-2-one       SC_3175   cis-5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-2-           morpholin-4-yl-pyridine-4-carboxylic acid amide       SC_3176   cis-8-Dimethylamino-3-[2-(3,5-dimethyl-isoxazol-4-yl)-pyrimidin-5-yl]-8-phenyl-           1,3-diazaspiro[4.5]decan-2-one       SC_3177   cis-3-[2-(Benzothiazol-6-yl)-pyrimidin-5-yl]-8-dimethylamino-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3178   cis-8-Dimethylamino-3-[2-fluoro-4-(trifluoromethyl)-phenyl]-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3179   cis-8-Dimethylamino-3-(6-morpholin-4-yl-pyridin-3-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3180   cis-8-Dimethylamino-8-phenyl-3-(2-phenyl-thiazol-4-yl)-1,3-diazaspiro[4.5[decan-           2-one       SC_3181   cis-8-Dimethylamino-8-phenyl-3-[2-(tetrahydro-pyran-4-ylamino)-pyrimidin-5-yl]-           1,3-diazaspiro[4.5]decan-2-one       SC_3182   cis-8-Dimethylamino-3-[2-(4-hydroxy-piperidin-1-yl)-pyrimidin-5-yl]-8-phenyl-           1,3-diazaspiro[4.5]decan-2-one       SC_3183   cis-8-Dimethylamino-8-phenyl-3-(4-phenyl-thiazol-2-yl)-1,3-diazaspiro[4.5]decan-           2-one       SC_3184   cis-8-Dimethylamino-8-phenyl-3-[2-(1H-pyrrolo[2,3-b]pyridin-1-yl)-pyrimidin-5-           yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3185   cis-8-Dimethylamino-8-phenyl-3-[2-(3,4,5-trifluoro-phenyl)-pyrimidin-5-yl]-1,3-           diazaspiro[4.5]decan-2-one       SC_3186   cis-8-Dimethylamino-3-o-tolyl-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3187   cis-8-Dimethylamino-3-m-tolyl-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3188   cis-8-Dimethylamino-8-phenyl-3-p-tolyl-1,3-diazaspiro[4.5]decan-2-one       SC_3189   cis-8-Dimethylamino-8-phenyl-3-[4-(trifluoromethyl)-phenyl]-1,3-           diazaspiro[4.5]decan-2-one       SC_3190   cis-8-Dimethylamino-8-phenyl-3-[3-(trifluoromethyloxy)-phenyl]-1,3-           diazaspiro[4.5]decan-2-one       SC_3191   cis-8-Dimethylamino-8-phenyl-3-[4-(trifluoromethyloxy)-phenyl]-1,3-           diazaspiro[4.5]decan-2-one       SC_3192   cis-2-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-benzoic           acid methyl ester       SC_3193   cis-3-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-benzoic           acid methyl ester       SC_3194   cis-4-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-benzoic           acid methyl ester       SC_3195   cis-3-(1,3-Benzodioxol-5-yl)-8-dimethylamino-8-phenyl-1,3-diazaspiro[4.5]decan-           2-one       SC_3196   cis-8-Dimethylamino-8-phenyl-3-quinolin-5-yl-1,3-diazaspiro[4.5]decan-2-one       SC_3197   cis-3-(2,3-Dihydro-1H-indol-6-yl)-8-dimethylamino-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3198   cis-5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-4-methyl-           pyridine-2-carboxylic acid methyl ester       SC_3199   cis-8-Dimethylamino-3-(6-methoxy-4-methyl-pyridin-3-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3200   cis-8-Dimethylamino-3-[2-methyl-5-(trifluoromethyl)-2H-pyrazol-3-yl]-8-phenyl-           1,3-diazaspiro[4.5]decan-2-one       SC_3201   cis-8-Dimethylamino-3-(3-methoxy-pyridin-2-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3202   cis-8-Dimethylamino-8-phenyl-3-[5-(trifluoromethyl)-pyridin-2-yl]-1,3-           diazaspiro[4.5]decan-2-one       SC_3203   cis-5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           nicotinonitrile       SC_3204   cis-8-Dimethylamino-3-(3-methyl-pyridin-2-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3205   cis-8-Dimethylamino-3-(6-methoxy-pyridin-3-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3206   cis-8-Dimethylamino-8-phenyl-3-[3-(trifluoromethyl)phenyl]-1,3-           diazaspiro[4.5]decan-2-one       SC_3207   cis-3-(1,3-Benzodioxol-4-yl)-8-dimethylamino-8-phenyl-1,3-diazaspiro[4.5]decan-           2-one       SC_3208   cis-8-Dimethylamino-3-[2-(2-oxo-1,3-dihydro-indol-4-yl)-pyrimidin-5-yl]-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3209   cis-8-Dimethylamino-3-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-pyrimidin-5-yl]-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3210   cis-8-Dimethylamino-3-[2-(3-hydroxy-piperidin-1-yl)-pyrimidin-5-yl]-8-phenyl-           1,3-diazaspiro[4.5]decan-2-one       SC_3211   cis-8-Dimethylamino-3-[2-(3-hydroxy-piperidin-1-yl)-pyrimidin-5-yl]-8-phenyl-           1,3-diazaspiro[4.5]decan-2-one       SC_3212   cis-8-Dimethylamino-3-[2-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-pyrimidin-5-yl]-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3213   cis-2-[4-[5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidin-2-yl]-piperazin-1-yl]-acetic acid       SC_3214   cis-8-Dimethylamino-3-[2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-pyrimidin-5-           yl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3215   cis-8-Benzyl-8-dimethylamino-3-[4-methyl-6-(trifluoromethyl)-pyridin-3-yl]-1,3-           diazaspiro[4.5]decan-2-one       SC_3216   trans-8-Dimethylamino-3-[4-methyl-6-(trifluoromethyl)-pyridin-3-yl]-8-thiophen-           2-yl-1,3-diazaspiro[4.5]decan-2-one       SC_3217   cis-8-Dimethylamino-3-[4-methyl-6-(trifluoromethyl)-pyridin-3-yl]-8-thiophen-2-           yl-1,3-diazaspiro[4.5]decan-2-one       SC_3218   cis-8-Dimethylamino-3-[2-(1,1-dioxo-[1,4]thiazinan-4-yl)-4-(trifluoromethyl)-           pyrimidin-5-yl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3219   cis-8-Dimethylamino-8-(1-methyl-1H-benzoimidazol-2-yl)-3-[2-(trifluoromethyl)-           pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3220   cis-8-Dimethylamino-8-(1-methyl-1H-benzoimidazol-2-yl)-3-[4-methyl-6-           (trifluoromethyl)-pyridin-3-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3221   cis-8-Dimethylamino-3-[2-(2-hydroxy-ethylamino)-pyrimidin-5-yl]-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3222   cis-3-[2-(Benzyl-methyl-amino)-pyrimidin-5-yl]-8-dimethylamino-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3223   cis-5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-N-[2-[2-           [2-(2-methoxy-ethoxy)-ethoxy]-ethoxy]-ethyl]-pyrimidine-2-carboxylic acid amide       SC_3224   cis-8-Dimethylamino-3-[2-(1H-indazol-1-yl)-pyrimidin-5-yl]-8-phenyl-1,3           diazaspiro[4.5]decan-2-one       SC_3225   cis-8-Dimethylamino-3-[2-[(2-hydroxy-ethyl)-methyl-amino]-pyrimidin-5-yl]-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3226   cis-3-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-benzamide       SC_3227   cis-8-Dimethylamino-3-[3-fluoro-5-(trifluoromethyl)-pyridin-2-yl]-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3228   cis-8-Dimethylamino-3-(5-methyl-pyrazin-2-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3229   cis-8-Dimethylamino-3-(5-fluoro-pyrimidin-4-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3230   cis-8-Dimethylamino-3-(5-fluoro-pyrimidin-2-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3231   cis-8-Dimethylamino-8-phenyl-3-pyrazin-2-yl-1,3-diazaspiro[4.5]decan-2-one       SC_3232   cis-3-([2,1,3]Benzoxadiazol-5-yl)-8-dimethylamino-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3233   cis-2-[2-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           phenoxy]-acetamide       SC_3234   cis-8-Dimethylamino-8-phenyl-3-(5-pyridin-4-yl-thiophen-2-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3235   cis-2-[2-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           phenoxy]-acetic acid methyl ester       SC_3236   cis-8-Dimethylamino-3-(2-morpholin-4-yl-pyrimidin-4-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3237   cis-3-[2-(3,4-Difluoro-phenyl)-pyrimidin-5-yl]-8-dimethylamino-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3238   cis-2-[5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidin-2-yl]-benzonitrile       SC_3239   cis-3-(2-Amino-pyrimidin-5-yl)-8-dimethylamino-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3240   cis-N-[5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidin-2-yl]-cyclopropanecarboxylic acid amide       SC_3241   cis-2-[4-[5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidin-2-yl]-piperazin-1-yl]-acetamide       SC_3242   cis-8-Dimethylamino-8-phenyl-3-(6-piperazin-1-yl-pyridin-3-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3243   cis-8-Dimethylamino-3-[6-(4-methyl-piperazin-1-yl)-pyridin-3-yl]-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3244   cis-8-Dimethylamino-3-[2-(1,1-dioxo-[1,4]thiazinan-4-yl)-4-methyl-pyrimidin-5-           yl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3245   cis-8-Dimethylamino-8-phenyl-3-[2-(trifluoromethyl)-pyrimidin-5-yl]-1,3-           diazaspiro[4.5]decan-2-one       SC_3246   cis-2-[8-Dimethylamino-1-(3-methoxy-propyl)-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-5-carbonitrile       SC_3247   cis-8-Dimethylamino-3-[2-(4-methyl-piperazin-1-yl)-pyrimidin-5-yl]-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3248   cis-8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-8-phenyl-3-[2-           (trifluoromethyl)-pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3249   cis-2-[1-(3-Methoxy-propyl)-8-methylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-pyrimidine-5-carbonitrile       SC_3250   cis-8-Dimethylamino-8-phenyl-3-[6-(trifluoromethyl)-pyridin-3-yl]-1,3-           diazaspiro[4.5]decan-2-one       SC_3251   cis-5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-pyridine-           2-carbonitrile       SC_3252   cis-8-Dimethylamino-3-(2-morpholin-4-yl-pyrimidin-5-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3253   cis-8-Dimethylamino-3-(2-methyl-pyrimidin-5-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3254   cis-8-Dimethylamino-1-[(2-methoxyphenyl)-methyl]-3-(2-methyl-pyrimidin-5-yl)-           8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3255   cis-1-[(1-Hydroxy-cyclobutyl)-methyl]-8-methylamino-8-phenyl-3-[2-           (trifluoromethyl)-pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3256   cis-8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-3-(2-methyl-pyrimidin-5-           yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3257   cis-1-[(1-Hydroxy-cyclobutyl)-methyl]-8-methylamino-8-phenyl-3-pyrimidin-5-yl           1,3-diazaspiro[4.5]decan-2-one       SC_3258   cis-5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-4-methyl-           pyridine-2-carbonitrile       SC_3259   cis-8-Dimethylamino-3-(2-methyl-pyrimidin-5-yl)-8-phenyl-1-(pyridin-2-yl-           methyl)-1,3-diazaspiro[4.5]decan-2-one       SC_3260   cis-8-Dimethylamino-8-phenyl-3-pyrimidin-5-yl-1,3-diazaspiro[4.5]decan-2-one       SC_3261   cis-8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-8-phenyl-3-pyrimidin-5-           yl-1,3-diazaspiro[4.5]decan-2-one       SC_3262   cis-8-Amino-1-[(1-hydroxy-cyclobutyl)-methyl]-8-phenyl-3-[2-(trifluoromethyl)-           pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3263   cis-8-Dimethylamino-3-(3-fluorophenyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3264   cis-8-Dimethylamino-3-(3-methylsulfonyl-phenyl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3265   cis-8-Dimethylamino-3-(4-methylsulfonyl-phenyl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3266   cis-8-Dimethylamino-8-phenyl-3-pyridazin-3-yl-1,3-diazaspiro[4.5]decan-2-one       SC_3267   cis-3-Methoxy-4-(8-methylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           benzonitrile       SC_3268   cis-8-Dimethylamino-3-(2-fluorophenyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3269   cis-8-Dimethylamino-8-phenyl-3-(2-phenyl-pyrimidin-5-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3270   cis-8-Methylamino-1-(oxetan-3-yl-methyl)-8-phenyl-3-[2-(trifluoromethyl)-           pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3271   cis-1-(Cyclopropyl-methyl)-8-methylamino-8-phenyl-3-[2-(trifluoromethyl)-           pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3272   cis-4-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           benzonitrile       SC_3273   cis-8-Dimethylamino-3-(4-fluorophenyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3274   cis-2-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           benzonitrile       SC_3275   cis-8-Ethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-8-phenyl-3-[2-           (trifluoromethyl)-pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3276   cis-1-[(1-Hydroxy-cyclobutyl)-methyl]-8-methylamino-3-(2-methyl-pyrimidin-5-           yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3277   cis-8-Dimethylamino-3-[2-(morpholin-4-yl-methyl)-pyrimidin-5-yl]-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3278   cis-8-Dimethylamino-3-[2-(methyl-tetrahydro-pyran-4-yl-amino)-pyrimidin-5-yl]-           8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3279   cis-5-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-N-[2-[2-[2-(2-methoxy-ethoxy)-ethoxyl-ethoxy]-ethyl]-           pyrimidine-2-carboxylic acid amide       SC_3280   cis-1-(Cyclopropyl-methyl)-3-(2-fluoro-4-methylsulfonyl-phenyl)-8-methylamino-           8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3281   cis-2-[[5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidin-2-yl]-methyl-aminol-acetamide       SC_3282   cis-2-[[5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidin-2-yl]amino]-acetamide       SC_3283   cis-1-(Cyclopropyl-methyl)-8-methylamino-3-[4-methyl-6-(trifluoromethyl)-           pyridin-3-yl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3284   cis-1-(Cyclopropyl-methyl)-8-dimethylamino-3-[4-methyl-6-(trifluoromethyl)-           pyridin-3-yl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3285   cis-N-[5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidin-2-yl]-thiophene-2-carboxylic acid amide       SC_3286   cis-N-[5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidin-2-yl]-benzamide       SC_3287   cis-8-Dimethylamino-8-phenyl-3-(5-phenyl-thiophen-2-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3288   cis-1-(Cyclopropyl-methyl)-8-methylamino-3-[2-(methylsulfonyl-methyl)-           phenyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3289   cis-1-(Cyclopropyl-methyl)-8-dimethylamino-3-[2-(methylsulfonyl-methyl)-phenyl]-           8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3290   cis-8-Dimethylamino-8-(3-fluorophenyl)-3-[2-(methylsulfonyl-methyl)-phenyl]-           1,3-diazaspiro[4.5]decan-2-one       SC_3291   cis-8-Dimethylamino-8-(4-fluorophenyl)-3-[2-(methylsulfonyl-methyl)-phenyl]-           1,3-diazaspiro[4.5]decan-2-one       SC_3292   cis-8-[Methyl-(tetrahydro-furan-3-yl-methyl)-amino]-8-phenyl-3-[2-           (trifluoromethyl)-pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2-one (enantiomer 1)       SC_3293   cis-8-[Methyl-(tetrahydro-furan-3-yl-methyl)-amino]-8-phenyl-3-[2-           (trifluoromethyl)-pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2-one (enantiomer 2)       SC_3294   cis-8-Dimethylamino-8-(3-fluorophenyl)-3-(4-methyl-2-morpholin-4-yl-pyrimidin-           5-yl)-1,3-diazaspiro[4.5]decan-2-one       SC_3295   cis-3-[6-(4-Acetyl-piperazin-1-yl)-4-methyl-pyridin-3-yl]-8-dimethylamino-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3296   cis-3-[2-(4-Acetyl-piperazin-1-yl)-4-methyl-pyrimidin-5-yl]-8-dimethylamino-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3297   cis-8-Dimethylamino-3-(4-methyl-6-pyridin-4-yl-pyridin-3-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3298   cis-3-[2-(4-Acetyl-piperazin-1-yl)-4-(trifluoromethyl)-pyrimidin-5-yl]-8-           dimethylamino-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3299   cis-8-Dimethylamino-3-[2-(3-oxo-piperazin-1-yl)-4-(trifluoromethyl)-pyrimidin-5-           yl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3300   cis-8-Dimethylamino-3-isoquinolin-4-yl-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3301   cis-8-Dimethylamino-3-isoquinolin-5-yl-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3302   cis-8-Dimethylamino-8-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3303   cis-8-Dimethylamino-8-phenyl-3-(2-pyridin-4-yl-thiazol-4-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3304   cis-8-[Methyl-(tetrahydro-furan-3-yl-methyl)-amino]-3-(2-morpholin-4-yl-           pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (enantiomer 1)       SC_3305   cis-8-[Methyl-(tetrahydro-furan-3-yl-methyl)-amino]-3-(2-morpholin-4-yl-           pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (enantiomer 2)       SC_3306   cis-3-[2-(Azetidin-1-yl)-pyrimidin-5-yl]-8-dimethylamino-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3307   cis-3-[2-(3,3-Difluoro-azetidin-1-yl)-pyrimidin-5-yl]-8-dimethylamino-8-phenyl-           1,3-diazaspiro[4.5]decan-2-one       SC_3308   cis-8-Dimethylamino-3-[6-morpholin-4-yl-5-(trifluoromethyl)-pyridin-3-yl]-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3309   cis-8-Methylamino-3-[6-morpholin-4-yl-5-(trifluoromethyl)-pyridin-3-yl]-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3310   cis-8-Dimethylamino-8-phenyl-3-[5-(trifluoromethyloxy)-pyridin-2-yl]-1,3-           diazaspiro[4.5]decan-2-one       SC_3311   cis-8-Dimethylamino-3-(5-methylsulfonyl-pyridin-2-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3312   cis-6-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           nicotinonitrile       SC_3313   cis-3-[2-(4-Cyclopropyl-1H-[1,2,3]triazol-1-yl)-pyrimidin-5-yl]-8-dimethylamino-           8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3314   cis-8-Dimethylamino-3-[4-methyl-2-(3-oxo-piperazin-1-yl)-pyrimidin-5-yl]-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3315   cis-5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-pyridine-           2-carboxylic acid amide       SC_3316   cis-3-[4-(Azetidin-1-yl)-2-methyl-pyrimidin-5-yl]-8-dimethylamino-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3317   cis-2-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-benzamide       SC_3318   cis-8-Dimethylamino-3-[2-(methylsulfonyl-methyl)-phenyl]-8-thiophen-2-yl-1,3-           diazaspiro[4.5]decan-2-one       SC_3319   cis-8-Dimethylamino-8-(3-fluorophenyl)-3-[2-methyl-5-(trifluoromethyl)-2H-           pyrazol-3-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3320   cis-8-Dimethylamino-3-(4-methyl-2-morpholin-4-yl-pyrimidin-5-yl)-8-thiophen-2-           yl-1,3-diazaspiro[4.5]decan-2-one       SC_3321   cis-8-Dimethylamino-3-(6-methylsulfonyl-pyridin-3-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3322   cis-8-Dimethylamino-8-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3323   cis-N-[5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidin-2-yl]-acetamide       SC_3324   cis-3-[2-(4-Methyl-piperazin-1-yl)-pyrimidin-5-yl]-8-[methyl-(tetrahydro-furan-3-           yl-methyl)-amino]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (enantiomer 1)       SC_3325   cis-3-[2-(4-Methyl-piperazin-1-yl)-pyrimidin-5-yl]-8-[methyl-(tetrahydro-furan-3-           yl-methyl)-amino]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (enantiomer 2)       SC_3326   cis-8-Dimethylamino-3-(4,6-dimethyl-2-morpholin-4-yl-pyrimidin-5-yl)-8-phenyl-           1,3-diazaspiro[4.5]decan-2-one       SC_3327   cis-8-Dimethylamino-3-(2-morpholin-4-yl-pyrimidin-5-yl)-8-thiophen-2-yl-1,3-           diazaspiro[4.5]decan-2-one       SC_3328   cis-6-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-pyridine-           3-carboxylic acid amide       SC_3329   cis-8-Dimethylamino-3-[2-methyl-5-(trifluoromethyl)-2H-pyrazol-3-yl]-8-           thiophen-2-yl-1,3-diazaspiro[4.5]decan-2-one       SC_3330   cis-8-Dimethylamino-3-[2-[(2-hydroxy-ethyl)-methyl-amino]-pyrimidin-5-yl]-8-           thiophen-2-yl-1,3-diazaspiro[4.5]decan-2-one       SC_3331   cis-8-Dimethylamino-3-[2-(2-oxo-1,3-dihydro-indol-4-yl)-pyrimidin-5-yl]-8-           thiophen-2-yl-1,3-diazaspiro[4.5]decan-2-one       SC_3332   cis-8-Dimethylamino-3-[4-methyl-6-(3-oxo-piperazin-1-yl)-pyridin-3-yl]-8-phenyl-           1,3-diazaspiro[4.5]decan-2-one       SC_3333   cis-8-Dimethylamino-3-(4-methyl-6-pyridin-2-yl-pyridin-3-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3334   cis-8-Dimethylamino-3-(4-methylsulfonyl-pyridin-3-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3335   cis-3-(Benzothiazol-7-yl)-8-dimethylamino-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3336   cis-8-Dimethylamino-8-(4-fluorophenyl)-3-(4-methyl-2-morpholin-4-yl-pyrimidin-           5-yl)-1,3-diazaspiro[4.5]decan-2-one       SC_3337   cis-2-[8-Dimethylamino-3-[4-methyl-6-(trifluoromethyl)-pyridin-3-yl]-2-oxo-8-           phenyl-1,3-diazaspiro[4.5]decan-1-yl]-N,N-dimethyl-acetamide       SC_3338   cis-8-Dimethylamino-3-[2-(2-methyl-1-oxo-2,3-dihydro-isoindol-4-yl)-pyrimidin-           5-yl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3339   cis-2-[[5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-2-           methyl-pyrimidin-4-yl]amino]-acetamide       SC_3340   cis-2-[3-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-pyridin-           4-yl]-acetamide       SC_3341   cis-8-Dimethylamino-3-[4-(methylsulfonyl-methyl)-pyridin-3-yl]-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3342   cis-8-Dimethylamino-3-[6-(4-methyl-3-oxo-piperazin-1-yl)-pyridin-3-yl]-8-phenyl-           1,3-diazaspiro[4.5]decan-2-one       SC_3343   cis-8-Dimethylamino-3-(2,4-dimethyl-pyrimidin-5-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3344   cis-8-Dimethylamino-3-[2-(1-oxo-2,3-dihydro-isoindol-4-yl)-pyrimidin-5-yl]-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one; 2,2,2-trifluoro-acetic acid       SC_3345   cis-8-Dimethylamino-3-[6-[(2-hydroxy-ethyl)-methyl-amino]-5-(trifluoromethyl)-           pyridin-3-yl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3346   cis-8-Dimethylamino-8-phenyl-3-[2-[4-(trifluoromethyl)-1H-[1,2,3]triazol-1-yl]-           pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3347   cis-8-Dimethylamino-3-[2-(4-isopropyl-1H-[1,2,3]triazol-1-yl)-pyrimidin-5-yl]-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3348   cis-8-Dimethylamino-3-[6-(1,1-dioxo-[1,4]thiazinan-4-yl)-pyridin-3-yl]-8-phenyl-           1,3-diazaspiro[4.5]decan-2-one       SC_3349   cis-5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-2-           morpholin-4-yl-nicotinonitrile       SC_3350   cis-8-Dimethylamino-3-(1-methylsulfonyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3351   cis-8-Dimethylamino-3-(1H-indol-4-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3352   cis-8-Dimethylamino-3-(2-hydroxy-benzooxazol-7-yl)-8-phenyl-1,3           diazaspiro[4.5]decan-2-one       SC_3353   cis-8-Dimethylamino-3-[2-fluoro-4-(trifluoromethyloxy)-phenyl]-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3354   cis-4-[5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidin-2-yl]-benzamide; 2,2,2-trifluoro-acetic acid       SC_3355   cis-8-Dimethylamino-3-(1-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3356   cis-3-(1-Acetyl-1H-indol-4-yl)-8-dimethylamino-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3357   cis-8-Dimethylamino-3-(1H-indol-3-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3358   cis-6-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-5-methyl           nicotinonitrile       SC_3359   cis-6-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-5-fluoro           nicotinonitrile       SC_3360   cis-8-Dimethylamino-3-[4-methyl-6-(trifluoromethyl)-pyridin-3-yl]-1-(2-oxo-2-           pyrrolidin-1-yl-ethyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3361   cis-6-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-5-methyl           pyridine-3-carboxylic acid amide       SC_3362   cis-6-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-5-fluoro-           pyridine-3-carboxylic acid amide       SC_3363   cis-8-Dimethylamino-3-[4-methyl-6-(trifluoromethyl)-pyridin-3-yl]-8-m-tolyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3364   cis-3-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           isonicotinonitrile       SC_3365   cis-8-Dimethylamino-3-[3-fluoro-5-(2-oxo-1,3-dihydro-indol-4-yl)-pyridin-2-yl]-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3366   cis-8-Dimethylamino-3-[4-methyl-6-(trifluoromethyl)-pyridin-3-yl]-8-[3 -           (trifluoromethyloxy)-phenyl]-1,3-diazaspiro[4.5]decan-2-one       SC_3367   cis-8-Dimethylamino-3-[4-methyl-6-(trifluoromethyl)-pyridin-3-yl]-8-[3-           (trifluoromethyl)phenyl]-1,3-diazaspiro[4.5]decan-2-one       SC_3368   cis-8-Dimethylamino-8-(3-methoxyphenyl)-3-[4-methyl-6-(trifluoromethyl)-           pyridin-3-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3369   cis-8-(5-Chloro-thiophen-2-yl)-8-dimethylamino-3-[4-methyl-6-(trifluoromethyl)-           pyridin-3-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3370   cis-8-Dimethylamino-8-(3-fluorophenyl)-3-[4-methyl-6-(trifluoromethyl)-pyridin-           3-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3371   cis-8-Dimethylamino-3-(2-methylamino-pyrimidin-5-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3372   cis-8-(5-Chloro-thiophen-2-yl)-8-dimethylamino-3-(4-methyl-2-morpholin-4-yl-           pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one       SC_3373   cis-N-[5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidin-2-yl]-N-methyl-cyclopropanecarboxylic acid amide       SC_3374   cis-N-[5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidin-2-yl]-N,2,5-trimethyl-2H-pyrazole-3-carboxylic acid amide       SC_3375   cis-3-[4,6-Bis(trifluoromethyl)-pyridin-3-yl]-8-dimethylamino-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3376   cis-8-Dimethylamino-3-[2-[(2-hydroxy-ethyl)-methyl-amino]-quinazolin-6-yl]-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3377   cis-8-Dimethylamino-3-(2-morpholin-4-yl-quinazolin-6-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3378   cis-8-[Methyl-(oxetan-3-yl-methyl)-amino]-8-phenyl-3-[2-(trifluoromethyl)-           pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3379   cis-3-(1-Acetyl-1H-indol-3-yl)-8-dimethylamino-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3380   cis-8-Dimethylamino-8-phenyl-3-quinazolin-6-yl-1,3-diazaspiro[4.5]decan-2-one       SC_3381   cis-5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-2-(2-oxo-           1,3-dihydro-indol-4-yl)-isonicotinonitrile       SC_3382   cis-N-[5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidin-2-yl]-N-methyl-tetrahydro-pyran-4-carboxylic acid amide       SC_3383   cis-N-[5-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-           pyrimidin-2-yl]-N,2,2-trimethyl-propionamide       SC_3384   cis-8-Dimethylamino-3-[2-(1-methyl-2-oxo-1,3-dihydro-indol-4-yl)-pyrimidin-5-           yl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3385   cis-8-Dimethylamino-3-(2-morpholin-4-yl-1H-benzoimidazol-5-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3386   cis-8-Dimethylamino-8-(3-fluoro-5-methyl-phenyl)-3-[4-methyl-6-           (trifluoromethyl)-pyridin-3-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3387   cis-8-Dimethylamino-3-[6-(2-oxo-1,3-dihydro-indol-4-yl)-pyridin-3-yl]-8-phenyl-           1,3-diazaspiro[4.5]decan-2-one       SC_3388   cis-8-Dimethylamino-8-(3-hydroxyphenyl)-3-[4-methyl-6-(trifluoromethyl)-           pyridin-3-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3389   cis-3-[6-(Azetidin-1-yl)-5-(trifluoromethyl)-pyridin-3-yl]-8-dimethylamino-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3390   cis-3-[1-(Cyclopropyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-           diazaspiro[4.5]decan-3-yl]-isonicotinonitrile       SC_3391   cis-3-[3,5-Bis(trifluoromethyl)-pyridin-2-yl]-8-dimethylamino-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3392   cis-8-Dimethylamino-3-(5-fluoro-6-morpholin-4-yl-pyridin-3-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3393   cis-8-(3-Chlorophenyl)-8-dimethylamino-3-[4-methyl-6-(trifluoromethyl)-pyridin-           3-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3394   cis-8-Dimethylamino-3-[5-(2-oxo-1,3-dihydro-indol-4-yl)-pyridin-2-yl]-8-phenyl-           1,3-diazaspiro[4.5]decan-2-one       SC_3395   cis-8-Dimethylamino-8-phenyl-3-[5-(trifluoromethyl)-[1,3,4]thiadiazol-2-yl]-1,3-           diazaspiro[4.5]decan-2-one       SC_3396   cis-8-Dimethylamino-3-(2-oxo-1,3-dihydro-indol-4-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3397   cis-8-Dimethylamino-3-[2-[(2-hydroxy-ethyl)-methyl-amino]-1H-benzoimidazol-           5-yl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3398   cis-8-Dimethylamino-3-(5-methyl-6-morpholin-4-yl-pyridin-3-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3399   cis-1-(Cyclopropyl-methyl)-8-dimethylamino-8-(3-fluorophenyl)-3-(5-           methylsulfonyl-pyridin-2-yl)-1,3-diazaspiro[4.5]decan-2-one       SC_3400   cis-1-(Cyclopropyl-methyl)-8-(3-fluorophenyl)-8-methylamino-3-(5-           methylsulfonyl-pyridin-2-yl)-1,3-diazaspiro[4.5]decan-2-one       SC_3401   cis-1-(Cyclobutyl-methyl)-8-(3-fluorophenyl)-8-methylamino-3-[2-           (trifluoromethyl)-pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3402   cis-1-(Cyclopropyl-methyl)-8-dimethylamino-8-(3-fluorophenyl)-3-[2-           (trifluoromethyl)-pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3403   cis-1-(Cyclopropyl-methyl)-8-(3-fluorophenyl)-8-methylamino-3-[2-           (trifluoromethyl)-pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3404   cis-8-Dimethylamino-8-(3-fluorophenyl)-3-[2-(trifluoromethyl)-pyrimidin-5-yl]-           1,3-diazaspiro[4.5]decan-2-one       SC_3405   cis-1-(Cyclopropyl-methyl)-8-dimethylamino-8-(3-fluorophenyl)-3-[2-methyl-5-           (trifluoromethyl)-2H-pyrazol-3-yl]-1,3-diazaspiro[4.5]decan-2-one       SC_3406   cis-1-(Cyclopropyl-methyl)-8-(3-fluorophenyl)-8-methylamino-3-[2-methyl-5-           (trifluoromethyl)-2H-pyrazol-3-yl]1-1,3-diazaspiro[4.5]decan-2-one       SC_3407   cis-8-Methylamino-3-(4-methyl-2-morpholin-4-yl-pyrimidin-5-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3408   cis-3-[5-(Azetidin-1-yl)-3-methyl-pyridin-2-yl]-8-dimethylamino-8-(3-           fluorophenyl)-1,3-diazaspiro[4.5]decan-2-one       SC_3409   cis-8-Dimethylamino-8-(3-fluorophenyl)-3-(5-methylsulfonyl-pyridin-2-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3410   cis-3-(6-(azetidin-1-yl)-4-fluoropyridin-3-yl)-8-(dimethylamino)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3411   cis-3-(6-(azetidin-1-yl)pyridin-3-yl)-8-(dimethylamino)-8-(3-fluorophenyl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3412   cis-3-(1-(cyclopropanecarbonyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)-8-           (dimethylamino)-8-(3-fluorophenyl)-1,3-diazaspiro[4.5]decan-2-one       SC_3413   cis-8-(dimethylamino)-8-(3-fluorophenyl)-3-(1-(2-hydroxyethyl)-3-           (trifluoromethyl)-1H-pyrazol-5-yl)-1,3-diazaspiro[4.5]decan-2-one       SC_3414   cis-3-(1-(cyclopropylmethyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)-8-           (dimethylamino)-8-(3-fluorophenyl)-1,3-diazaspiro[4.5]decan-2-one       SC_3415   cis-8-(dimethylamino)-8-(3-fluorophenyl)-3-(1-(methylsulfonyl)-3-           (trifluoromethyl)-1H-pyrazol-5-yl)-1,3-diazaspiro[4.5]decan-2-one       SC_3416   cis-1-(cyclopropylmethyl)-8-(dimethylamino)-8-(3-fluorophenyl)-3-(1-           (methylsulfonyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)-1,3-diazaspiro[4.5]decan-           2-one       SC_3417   cis-2-(5-(8-(dimethylamino)-8-(3-fluorophenyl)-2-oxo-1,3-diazaspiro[4.5]decan-           3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-N,N-dimethylacetamide       SC_3418   cis-2-(5-(1-(cyclopropylmethyl)-8-(dimethylamino)-8-(3-fluorophenyl)-2-oxo-1,3-           diazaspiro[4.5]decan-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-N,N-           dimethylacetamide       SC_3419   cis-8-(dimethylamino)-3-(1-methyl1-1H-pyrrolo[2,3-b]pyridin-5-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3420   cis-8-(dimethylamino)-3-(3-fluoro-1H-pyrrolo[2,3-b]pyridin-5-yl)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3421   cis-8-(dimethylamino)-8-phenyl-3-(1H-pyrrolo[2,3-c]pyridin-4-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3422   cis-8-(dimethylamino)-8-phenyl-3-(2-(pyridazin-4-yl)pyrimidin-5-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3423   cis-8-(dimethylamino)-3-(2-(2-oxo-1,2-dihydropyridin-4-yl)pyrimidin-5-yl)-8-           phenyl-1,3-diazaspiro[4.5]decan-2-one       SC_3424   cis-8-(dimethylamino)-8-(3-fluorophenyl)-3-(1-methyl-3-(thiophen-2-yl)-1H-           pyrazol-5-yl)-1,3-diazaspiro[4.5]decan-2-one       SC_3425   cis-8-(dimethylamino)-8-(3-fluorophenyl)-3-(1-methyl-3-morpholino-1H-pyrazol-           5-yl)-1,3-diazaspiro[4.5]decan-2-one       SC_3426   cis-8-(dimethylamino)-8-phenyl-1-(2,2,2-trifluoroethyl)-3-(2-           (trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one       SC_3427   cis-8-(dimethylamino)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1-(3,3,3-           trifluoropropyl)-1,3-diazaspiro[4.5]decan-2-one       SC_3428   cis-3-(4-methyl-6-(trifluoromethyl)pyridin-3-yl)-8-(methylamino)-8-phenyl-1,3-           diazaspiro[4.5]decan-2-one       SC_3429   cis-3-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)-8-(methylamino)-8-phenyl-           1,3-diazaspiro[4.5]decan-2-one       SC_3430   cis-8-(dimethylamino)-8-(3-fluorophenyl)-3-(4-(methylsulfonyl)pyridin-3-yl)-1,3-           diazaspiro[4.5]decan-2-one       SC_3431   cis-8-(dimethylamino)-3-(1-ethyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)-8-(3-           fluorophenyl)-1,3-diazaspiro[4.5]decan-2-one       SC_3432   cis-3-(1-cyclopropyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)-8-(dimethylamino)-8-(3-           fluorophenyl)-1,3-diazaspiro[4.5]decan-2-one       SC_3433   cis-8-(dimethylamino)-8-(3-fluorophenyl)-3-(1-(oxetan-3-ylmethyl)-3-           (trifluoromethyl)-1H-pyrazol-5-yl)-1,3-diazaspiro[4.5]decan-2-one       SC_3434   cis-8-(dimethylamino)-8-(3-fluorophenyl)-3-(1-(2-(methylsulfonyl)ethyl)-3-           (trifluoromethyl)-1H-pyrazol-5-yl)-1,3-diazaspiro[4.5]decan-2-one       SC_3435   cis-8-(dimethylamino)-8-(3-fluorophenyl)-3-(4-methyl-2-(methylamino)pyrimidin-           5-yl)-1,3-diazaspiro[4.5]decan-2-one       SC_3436   cis-3-(2-cyclopropoxy-4-methylpyrimidin-5-yl)-8-(dimethylamino)-8-(3-           fluorophenyl)-1,3-diazaspiro[4.5]decan-2-one       SC_3437   cis-N-(5-(8-(dimethylamino)-8-(3-fluorophenyl)-2-oxo-1,3-diazaspiro[4.5]decan-3-           yl)-4-methylpyrimidin-2-yl)-N-methylcyclopropanecarboxamide       SC_3438   cis-N-(5-(8-(dimethylamino)-8-(3-fluorophenyl)-2-oxo-1,3-diazaspiro[4.5]decan-3-           yl)-4-methylpyrimidin-2-yl)-N-methylpivalamide       SC_3439   cis-3-(4-(azetidin-1-yl)-2-(trifluoromethyl)pyrimidin-5-yl)-8-(dimethylamino)-8-           (3-fluorophenyl)-1,3-diazaspiro[4.5]decan-2-one       SC_3440   cis-8-(dimethylamino)-8-(3-fluorophenyl)-3-(4-(oxetan-3-ylmethoxy)-2-           (trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one       SC_3441   cis-3-(2-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyrimidin-5-yl)-8-(dimethylamino)-           8-(3-fluorophenyl)-1,3-diazaspiro[4.5]decan-2-one       SC_3442   cis-3-(2-cyclopropyl-4-((2-hydroxyethyl)(methyl)amino)pyrimidin-5-yl)-8-           (dimethylamino)-8-(3-fluorophenyl)-1,3-diazaspiro[4.5]decan-2-one                    
and the physiologically acceptable salts thereof.
 
     According to the invention, unless expressly stated otherwise, “—C 1 -C 4 -alkyl”, “—C 1 -C 6 -alkyl” and any other alkyl residues can be linear or branched, saturated or unsaturated. Linear saturated alkyl includes methyl, ethyl, n-propyl, n-butyl, n-pentyl and n-hexyl. Examples of branched saturated alkyl include but are not limited to iso-propyl, sec-butyl, and tert-butyl. Examples of linear unsaturated alkyl include but are not limited to vinyl, propenyl, allyl, and propargyl. 
     According to the invention, unless expressly stated otherwise, “—C 1 -C 4 -alkyl”, “—C 1 -C 6 -alkyl” and any other alkyl residues can be unsubstituted, mono- or polysubstituted. Examples of substituted alkyl include but are not limited to —CH 2 CH 2 OH, —CH 2 CH 2 OCH 3 , —CH 2 CH 2 CH 2 OCH 3 , —CH 2 CH 2 S(═O) 2 CH 3 , —CH 2 C(═O)NH 2 , —C(CH 3 ) 2 C(═O)NH 2 , —CH 2 C(CH 3 ) 2 C(═O)NH 2 , and —CH 2 CH 2 C(═O)N(CH 3 ) 2 . 
     According to the invention, unless expressly stated otherwise, “—C 1 -C 6 -alkylene-”, “—C 1 -C 4 -alkylene” and any other alkylene residue can be unsubstituted, mono- or polysubstituted. Examples of saturated alkylene include but are not limited to —CH 2 —, —CH(CH 3 )—, —C(CH 3 ) 2 —, —CH 2 CH 2 —, —CH(CH 3 )CH 2 —, —CH 2 CH(CH 3 )—, —CH(CH 3 )—CH(CH 3 )—, —C(CH 3 ) 2 CH 2 —, —CH 2 C(CH 3 ) 2 —, —CH(CH 3 )C(CH 3 ) 2 —, —C(CH 3 ) 2 CH(CH 3 )—, C(CH 3 ) 2 C(CH 3 ) 2 —, —CH 2 CH 2 CH 2 —, and —C(CH 3 ) 2 CH 2 CH 2 —. Examples of unsaturated alkylene include but are not limited to —CH═CH—, —C≡C—, —C(CH 3 )═CH—, —CH═C(CH 3 )—, —C(CH 3 )═C(CH 3 )—, —CH 2 CH═CH—, —CH═CHCH 2 —, —CH═CH—CH═CH—, and —CH═CH—C≡C—. 
     According to the invention, unless expressly stated otherwise, “—C 1 -C 6 -alkylene-”, “—C 1 -C 4 -alkylene” and any other alkylene residue can be unsubstituted, mono- or polysubstituted. Examples of substituted —C 1 -C 6 -alkylene- include but are not limited to —CHF—, —CF 2 —, —CHOH— and —C(═O)—. 
     According to the invention, moieties may be connected through —C 1 -C 6 -alkylene-, i.e. the moieties may not be directly bound to the core structure of compound according to general formula (I), but may be connected to the core structure of compound according to general formula (I) or its periphery through a —C 1 -C 6 -alkylene-linker. 
     According to the invention, “3-12-membered cycloalkyl moiety” means a non-aromatic, monocyclic, bicyclic or tricyclic moiety comprising 3 to 12 ring carbon atoms but no heteroatoms in the ring. Examples of preferred saturated 3-12-membered cycloalkyl moieties according to the invention include but are not limited to cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, hydrindane, and decaline. Examples of preferred unsaturated 3-12-membered cycloalkyl moiety moieties according to the invention include but are not limited to cyclopropene, cyclobutene, cyclopentene, cyclopentadiene, cyclohexene, 1,3-cyclohexadiene, and 1,4-cyclohexadiene. The 3-12-membered cycloalkyl moiety, which is bonded to the compound according to the invention, in its periphery may optionally be condensed with a 3-12-membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; and/or with a 6-14-membered aryl moiety, unsubstituted, mono- or polysubstituted; and/or with a 5-14-membered heteroaryl moiety, unsubstituted, mono- or polysubstituted. Under these circumstances, the ring atoms of the condensed moieties are not included in the 3 to 12 ring atoms of the 3-12-membered cycloalkyl moiety. Examples of 3-12-membered cycloalkyl moieties condensed with 3-12-membered heterocycloalkyl moieties include but are not limited to octahydro-1H-indol, decahydroquinoline, decahydroisoquinoline, octahydro-2H-benzo[b][1,4]oxazin, and decahydro-quinoxalin, which in each case are connected through the 3-12-membered cycloalkyl moiety. Examples of 3-12-membered cycloalkyl moieties condensed with 6-14-membered aryl moieties include but are not limited to 2,3-dihydro-1H-indene and tetraline, which in each case are connected through the 3-12-membered cycloalkyl moiety. Examples of 3-12-membered cycloalkyl moieties condensed with 5-14-membered heteroaryl moieties include but are not limited to 5,6,7,8-tetrahydroquinoline and 5,6,7,8-tetrahydroquinazoline, which in each case are connected through the 3-12-membered cycloalkyl moiety. 
     According to the invention, the 3-12-membered cycloalkyl moiety may optionally be connected through —C 1 -C 6 -alkylene-, i.e. the 3-12-membered cycloalkyl moiety may not be directly bound to the compound according to general formula (I) but may be connected thereto through a —C 1 -C 6 -alkylene-linker. Examples include but are not limited to —CH 2 -cyclopropyl, —CH 2 -cyclobutyl, —CH 2 -cyclopentyl, —CH 2 -cyclohexyl, —CH 2 CH 2 -cyclopropyl, —CH 2 CH 2 -cyclobutyl, —CH 2 CH 2 -cyclopentyl, and —CH 2 CH 2 -cyclohexyl. 
     According to the invention, unless expressly stated otherwise, the 3-12-membered cycloalkyl moiety can be unsubstituted, mono- or polysubstituted. Examples of substituted 3-12-membered cycloalkyl moieties include but are not limited to —CH 2 -1-hydroxy-cyclobutyl. 
     According to the invention, “3-12-membered heterocycloalkyl moiety” means a non-aromatic, monocyclic, bicyclic or tricyclic moiety comprising 3 to 12 ring atoms, wherein each cycle comprises independently of one another 1, 2, 3, 4 or more heteroatoms independently of one another selected from the group consisting of nitrogen, oxygen and sulfur, whereas sulfur may be oxidized (S(═O) or (S(═O) 2 ), whereas the remaining ring atoms are carbon atoms, and whereas bicyclic or tricyclic systems may share common heteroatom(s). Examples of preferred saturated 3-12-membered heterocycloalkyl moieties according to the invention include but are not limited to aziridin, azetidine, pyrrolidine, imidazolidine, pyrazolidine, piperidine, piperazine, triazolidine, tetrazolidine, oxiran, oxetane, tetrahydrofurane, tetrahydropyrane, thiirane, thietane, tetrahydrothiophene, diazepane, oxazolidine, isoxazolidine, thiazolidine, isothiazolidine, thiadiazolidine, morpholine, thiomorpholine. Examples of preferred unsaturated 3-12-membered heterocycloalkyl moiety moieties according to the invention include but are not limited to oxazoline, pyrazoline, imidazoline, isoxazoline, thiazoline, isothiazoline, and dihydropyran. The 3-12-membered heterocycloalkyl moiety, which is bonded to the compound according to the invention, in its periphery may optionally be condensed with a 3-12-membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; and/or with a 6-14-membered aryl moiety, unsubstituted, mono- or polysubstituted; and/or with a 5-14-membered heteroaryl moiety, unsubstituted, mono- or polysubstituted. Under these circumstances, the ring atoms of the condensed moieties are not included in the 3 to 12 ring atoms of the 3-12-membered heterocycloalkyl moieties. Examples of 3-12-membered heterocycloalkyl moieties condensed with 3-12-membered cycloalkyl moieties include but are not limited to octahydro-1H-indol, decahydroquinoline, decahydroisoquinoline, octahydro-2H-benzo[b][1,4]oxazin, and decahydro-quinoxalin, which in each case are connected through the 3-12-membered heterocycloalkyl moiety. An examples of a 3-12-membered heterocycloalkyl moiety condensed with a 6-14-membered aryl moiety includes but is not limited to 1,2,3,4-tetrahydroquinoline, which is connected through the 3-12-membered heterocycloalkyl moiety. An example of a 3-12-membered heterocycloalkyl moiety condensed with a 5-14-membered heteroaryl moieties includes but is not limited to 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine, which is connected through the 3-12-membered heterocycloalkyl moiety. 
     According to the invention, the 3-12-membered heterocycloalkyl moiety may optionally be connected through —C 1 -C 6 -alkylene-, i.e. the 3-12-membered heterocycloalkyl moiety may not be directly bound to the compound according to general formula (I) but may be connected thereto through a —C 1 -C 6 -alkylene-linker. Said linker may be connected to a carbon ring atom or to a hetero ring atom of the 3-12-membered heterocycloalkyl moiety. Examples include but are not limited to —CH 2 -oxetane, —CH 2 -pyrrolidine, —CH 2 -piperidine, —CH 2 -morpholine, —CH 2 CH 2 -oxetane, —CH 2 CH 2 -pyrrolidine, —CH 2 CH 2 -piperidine, and —CH 2 CH 2 -morpholine. 
     According to the invention, unless expressly stated otherwise, the 3-12-membered heterocycloalkyl moiety can be unsubstituted, mono- or polysubstituted. Examples of substituted 3-12-membered heterocycloalkyl moieties include but are not limited to 2-carboxamido-N-pyrrolidinyl-, 3,4-dihydroxy-N-pyrrolidinyl, 3-hydroxy-N-pyrimidinyl, 3,4-dihydroxy-N-pyrimidinyl, 3-oxo-N-piperazinyl, -tetrahydro-2H-thiopyranyl dioxide and thiomorpholinyl dioxide. 
     According to the invention, “6-14-membered aryl moiety” means an aromatic, monocyclic, bicyclic or tricyclic moiety comprising 6 to 14 ring carbon atoms but no heteroatoms in the ring. Examples of preferred 6-14-membered aryl moieties according to the invention include but are not limited to benzene, naphthalene, anthracen, and phenanthren. The 6-14-membered aryl moiety, which is bonded to the compound according to the invention, in its periphery may optionally be condensed with a 3-12-membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; and/or with a 3-12-membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; and/or with a 5-14-membered heteroaryl moiety, unsubstituted, mono- or polysubstituted. Under these circumstances, the ring atoms of the condensed moieties are not included in the 6 to 14 ring carbon atoms of the 6-14-membered heterocycloalkyl moieties. Examples of 6-14-membered aryl moieties condensed with 3-12-membered cycloalkyl moieties include but are not limited to 2,3-dihydro-1H-indene and tetraline, which in each case are connected through the 6-14-membered aryl moiety. An example of a 6-14-membered aryl moiety condensed with a 3-12-membered heterocycloalkyl moiety includes but is not limited to 1,2,3,4-tetrahydroquinoline, which is connected through the 6-14-membered aryl moiety. Examples of 6-14-membered aryl moieties condensed with 5-14-membered heteroaryl moieties include but are not limited to quinoline, isoquinoline, phenazine and phenoxacine, which in each case are connected through the 6-14-membered aryl moiety. 
     According to the invention, the 6-14-membered aryl moiety may optionally be connected through —C 1 -C 6 -alkylene-, i.e. the 6-14-membered aryl moiety may not be directly bound to the compound according to general formula (I) but may be connected thereto through a —C 1 -C 6 -alkylene-linker. Said linker may be connected to a carbon ring atom or to a hetero ring atom of the 6-14-membered aryl moiety. Examples include but are not limited to —CH 2 —C 6 H, —CH 2 CH 2 —C 6 H5 and —CH═CH—C 6 H5. 
     According to the invention, unless expressly stated otherwise, the 6-14-membered aryl moiety can be unsubstituted, mono- or polysubstituted. Examples of substituted 6-14-membered aryl moieties include but are not limited to 2-fluorophenyl, 3-fluorophenyl, 2-methoxyphenyl and 3-methoxyphenyl. 
     According to the invention, “5-14-membered heteroaryl moiety” means an aromatic, monocyclic, bicyclic or tricyclic moiety comprising 6 to 14 ring atoms, wherein each cycle comprises independently of one another 1, 2, 3, 4 or more heteroatoms independently of one another selected from the group consisting of nitrogen, oxygen and sulfur, whereas the remaining ring atoms are carbon atoms, and whereas bicyclic or tricyclic systems may share common heteroatom(s). Examples of preferred 5-14-membered heteroaryl moieties according to the invention include but are not limited to pyrrole, pyrazole, imidazole, triazole, tetrazole, furane, thiophene, oxazole, isoxazole, thiazole, isothiazole, pyridine, pyridazine, pyrimidine, pyrazine, indolicine, 9H-chinolicine, 1,8-naphthyridine, purine, imidazo[1,2-a]pyrazine, and pteridine. The 5-14-membered heteroaryl moiety, which is bonded to the compound according to the invention, in its periphery may optionally be condensed with a 3-12-membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; and/or with a 3-12-membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; and/or with a 6-14-membered aryl moiety, unsubstituted, mono- or polysubstituted. Under these circumstances, the ring atoms of the condensed moieties are not included in the 6 to 14 ring carbon atoms of the 6-14-membered heterocycloalkyl moieties. Examples of 5-14-membered heteroaryl moieties condensed with 3-12-membered cycloalkyl moieties include but are not limited to 5,6,7,8-tetrahydroquinoline and 5,6,7,8-tetrahydroquinazoline, which in each case are connected through the 5-14-membered heteroaryl moiety. An examples of a 5-14-membered heteroaryl moiety condensed with a 3-12-membered heterocycloalkyl moiety includes but is not limited to 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine, which is connected through the 5-14-membered heteroaryl moiety. Examples of 5-14-membered heteroaryl moieties condensed with 6-14-membered aryl moieties include but are not limited to quinoline, isoquinoline, phenazine and phenoxacine, which in each case are connected through the 5-14-membered heteroaryl moiety. 
     According to the invention, the 5-14-membered heteroaryl moiety may optionally be connected through —C 1 -C 6 -alkylene-, i.e. the 5-14-membered heteroaryl moiety may not be directly bound to the compound according to general formula (I) but may be connected thereto through a —C 1 -C 6 -alkylene-linker. Said linker may be connected to a carbon ring atom or to a hetero ring atom of the 5-14-membered heteroaryl moiety. Examples include but are not limited to —CH 2 -oxazole, —CH 2 -isoxazole, —CH 2 -imidazole, —CH 2 -pyridine, —CH 2 -pyrimidine, —CH 2 -pyridazine, —CH 2 CH 2 -oxazole, —CH 2 CH 2 -isoxazole, —CH 2 CH 2 -imidazole, —CH 2 CH 2 -pyridine, —CH 2 CH 2 -pyrimidine, and —CH 2 CH 2 -pyridazine. 
     According to the invention, unless expressly stated otherwise, the 5-14-membered heteroaryl moiety can be unsubstituted, mono- or polysubstituted. Examples of 5-14-membered heteroaryl moieties include but are not limited to 2-methoxy-4-pyridinyl, 2-methoxy-5-pyridinyl, 3-methoxy-4-pyridinyl, 3-methoxy-6-pyridinyl, 4-methoxy-2-pyridinyl, 2-methylsulfonyl-5-pyridinyl, 3-methylsulfonyl-6-pyridinyl, 3-methoxy-6-pyridazinyl, 2-nitrilo-5-pyrimidinyl, 4-hydroxy-2-pyrimidinyl, 4-methoxy-pyrimidinyl, and 2-methoxy-6-pyrazinyl. 
     Preferably, the compound according to the invention has a structure according to general formula (I′) 
     
       
         
         
             
             
         
       
     
     wherein R 1  to R 5 , R 11  to R 20  are defined as above, 
     or a physiologically acceptable salt thereof. 
     In one preferred embodiment, the excess of the cis-isomer so designated is at least 50% de, more preferably at least 75% de, yet more preferably at least 90% de, most preferably at least 95% de and in particular at least 99% de. 
     In a preferred embodiment, the compound according to the invention has a structure according to general formula (IX) or (X) 
     
       
         
         
             
             
         
       
     
     wherein
 
R 2  means —H or —CH 3 ;
 
R 3  means -phenyl or -3-fluorophenyl;
 
R C  means —H or —OH;
 
R E  means —H, —CH 3 , —F, —CF 3 , -cyclopropyl, -aziridinyl, —OH; —O—C 1 -C 4 -alkyl; —OCF 3 ; —C 1 -C 4 -alkyl-CO 2 H; —O—C 1 -C 4 -alkyl-C(═O)O—C 1 -C 4 -alkyl; or —O—C 1 -C 4 -alkyl-CONH 2 ;
 
R F  means
 
—CF 3 , -cyclopropyl, —S(═O) 2 CH 3 ,
 
—NH 2 ; —NHC 1 -C 4 -alkyl; —N(C 1 -C 4 -alkyl) 2 ; —NHC 1 -C 4 -alkyl-OH; —NCH 3 C 1 -C 4 -alkyl-OH; —NH—C 1 -C 4 -alkyl-C(═O)NH 2 ; —NCH 3 —C 1 -C 4 -alkyl-C(═O)NH 2 ; —NHC(═O)—C 1 -C 4 -alkyl; —NCH 3 C(═O)—C 1 -C 4 -alkyl;
 
-6-14-membered aryl, unsubstituted, mono- or polysubstituted; or
 
-5-14-membered heteroaryl, unsubstituted, mono- or polysubstituted;
 
U means ═CH— or ═N—; and
 
V means ═CH— or ═N—;
 
or a physiologically acceptable salt thereof
 
     In a preferred embodiment, the compound according to the invention has a structure according to general formula (XI) 
     
       
         
         
             
             
         
       
     
     wherein
 
R 2  means —H or —CH 3 ;
 
R 3  means -phenyl or -3-fluorophenyl;
 
R H  means
 
—CN; —C 1 -C 4 -alkyl; —CF 3 ; —C 1 -C 4 -alkyl-C(═O)NH 2 ; —C 1 -C 4 -alkyl-S(═O) 2 —C 1 -C 4 -alkyl; —C(═O)—C 1 -C 4 -alkyl; —C(═O)OH; —C(═O)O—C 1 -C 4 -alkyl; —C(═O)NH 2 ; —C(═O)NHC 1 -C 4 -alkyl; —C(═O)N(C 1 -C 4 -alkyl) 2 ; —C(═O)NH(C 1 -C 4 -alkyl-OH); —C(═O)N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl-OH); —C(═O)NH—(CH 2 CH 2 O) 1-30 —CH 3 ;
 
-3-12-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered cycloalkyl is optionally connected through —CH 2 —, —NH—, —NCH 3 —, —NH—(CH 2 ) 1-3 —, —NCH 3 (CH 2 ) 1-3 —, —(C═O)—, —NHC(═O)—, —NCH 3 C(═O)—, —C(═O)NH—(CH 2 ) 1-3 —, —C(═O)NCH 3 —(CH 2 ) 1-3 —; or
 
-3-12-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; 6-14-membered aryl, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered heterocycloalkyl is optionally connected through —CH 2 —, —NH—, —NCH 3 —, —NH—(CH 2 ) 1-3 —, —NCH 3 (CH 2 ) 1-3 —, —(C═O)—, —NHC(═O)—, —NCH 3 C(═O)—, —C(═O)NH—(CH 2 ) 1-3 —, —C(═O)NCH 3 —(CH 2 ) 1-3 —;
 
R G  means
 
—CF 3 , —S(═O) 2 CH 3 ;
 
—NH 2 ; —NHC 1 -C 4 -alkyl; —N(C 1 -C 4 -alkyl) 2 ; —NHC 1 -C 4 -alkyl-OH; —NCH 3 C 1 -C 4 -alkyl-OH; —NH—C 1 -C 4 -alkyl-C(═O)NH 2 ; —NCH 3 —C 1 -C 4 -alkyl-C(═O)NH 2 ; —NHC(═O)—C 1 -C 4 -alkyl; —NCH 3 C(═O)—C 1 -C 4 -alkyl;
 
-3-12-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered cycloalkyl is optionally connected through —CH 2 —, —NH—, —NCH 3 —, —NH—(CH 2 ) 1-3 —, —NCH 3 (CH 2 ) 1-3 —, —(C═O)—, —NHC(═O)—, —NCH 3 C(═O)—, —C(═O)NH—(CH 2 ) 1-3 —, —C(═O)NCH 3 —(CH 2 ) 1-3 —; or
 
-3-12-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted; 6-14-membered aryl, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered heterocycloalkyl is optionally connected through —CH 2 —, —NH—, —NCH 3 —, —NH—(CH 2 ) 1-3 —, —NCH 3 (CH 2 ) 1-3 —, —(C═O)—, —NHC(═O)—, —NCH 3 C(═O)—, —C(═O)NH—(CH 2 ) 1-3 —, —C(═O)NCH 3 —(CH 2 ) 1-3 —;
 
or a physiologically acceptable salt thereof.
 
     In a preferred embodiment, the compounds according to the invention are in the form of the free bases. 
     In another preferred embodiment, the compounds according to the invention are in the form of the physiologically acceptable salts. 
     For the purposes of the description, a “salt” is to be understood as being any form of the compound in which it assumes an ionic form or is charged and is coupled with a counter-ion (a cation or anion) or is in solution. The term is also to be understood as meaning complexes of the compound with other molecules and ions, in particular complexes which are associated via ionic interactions. Preferred salts are physiologically acceptable, in particular physiologically acceptable salts with anions or acids or also a salt formed with a physiologically acceptable acid. 
     Physiologically acceptable salts with anions or acids are salts of the particular compound in question with inorganic or organic acids which are physiologically acceptable, in particular when used in humans and/or mammals. Examples of physiologically acceptable salts of particular acids include but are not limited to salts of hydrochloric acid, sulfuric acid, and acetic acid. 
     The invention also includes isotopic isomers of a compound according to the invention, wherein at least one atom of the compound is replaced by an isotope of the respective atom which is different from the naturally predominantly occurring isotope, as well as any mixtures of isotopic isomers of such a compound. Preferred isotopes are  2 H (deuterium),  3 H (tritium),  13 C and  14 C. 
     Certain compounds according to the invention are useful for modulating a pharmacodynamic response from one or more opioid receptors (mu, delta, kappa, NOP/ORL-1) either centrally or peripherally, or both. The pharmacodynamic response may be attributed to the compound either stimulating (agonizing) or inhibiting (antagonizing) the one or more receptors. Certain compounds according to the invention may antagonize one opioid receptor, while also agonizing one or more other receptors. Compounds according to the invention having agonist activity may be either full agonists or partial agonists. 
     As used herein, compounds that bind to receptors and mimic the regulatory effects of endogenous ligands are defined as “agonists”. Compounds that bind to a receptor but produce no regulatory effect, but rather block the binding of ligands to the receptor, are defined as “antagonists”. 
     In certain embodiments, the compounds according to the invention are agonists at the mu opioid (MOP) and/or kappa opioid (KOP) and/or delta opioid (DOP) and/or nociceptin opioid (NOP/ORL-1) receptors. 
     The compounds according to the invention potently bind to the MOP and/or KOP and/or DOP and/or NOP receptors. 
     The compounds according to the invention can be modulators at the MOP and/or KOP and/or DOP and/or NOP receptors, and therefore the compounds according to the invention can be used/administered to treat, ameliorate, or prevent pain. 
     In some embodiments, the compounds according to the invention are agonists of one or more opioid receptors. In some embodiments, the compounds according to the invention are agonists of the MOP and/or KOP and/or DOP and/or NOP receptors. 
     In some embodiments, the compounds according to the invention are antagonists of one or more opioid receptors. In some embodiments, the compounds according to the invention are antagonists of the MOP and/or KOP and/or DOP and/or NOP receptors. 
     In some embodiments, the compounds according to the invention have both, (i) agonist activity at the NOP receptor; and (ii) agonist activity at one or more of the MOP, KOP, and DOP receptors. 
     In some embodiments, the compounds according to the invention have both, (i) agonist activity at the NOP receptor; and (ii) antagonist activity at one or more of the MOP, KOP, and DOP receptors. 
     In some embodiments, the compounds according to the invention have both, (i) antagonist activity at the NOP receptor; and (ii) agonist activity at one or more of the MOP, KOP, and DOP receptors. 
     In some embodiments, the compounds according to the invention have both, (i) antagonist activity at the NOP receptor; and (ii) antagonist activity at one or more of the MOP, KOP, and DOP receptors. 
     In some embodiments, preferably with respect to receptors of the peripheral nervous system, the compounds according to the invention have selective agonist activity at the NOP receptor. In some embodiments, preferably with respect to receptors of the peripheral nervous system, the compounds according to the invention
         have agonist activity at the NOP receptor, but no significant activity at the MOP receptor;   have agonist activity at the NOP receptor, but no significant activity at the KOP receptor;   have agonist activity at the NOP receptor, but no significant activity at the DOP receptor;   have agonist activity at the NOP receptor, but no significant activity at the MOP receptor as well as no significant activity at the KOP receptor;   have agonist activity at the NOP receptor, but no significant activity at the MOP receptor as well as no significant activity at the DOP receptor; or   have agonist activity at the NOP receptor, but no significant activity at the MOP receptor as well as no significant activity at the KOP receptor as well as no significant activity at the DOP receptor.       

     In some embodiments, preferably with respect to receptors of the peripheral nervous system, the compounds according to the invention have balanced agonist activity at the NOP receptor as well as at the MOP receptor. In some embodiments, preferably with respect to receptors of the peripheral nervous system, the compounds according to the invention
         have agonist activity at the NOP receptor as well as agonist activity at the MOP receptor;   have agonist activity at the NOP receptor as well as agonist activity at the MOP receptor as well as agonist activity at the KOP receptor;   have agonist activity at the NOP receptor as well as agonist activity at the MOP receptor as well as agonist activity at the DOP receptor;   can be regarded as opioid pan agonists, i.e. have agonist activity at the NOP receptor as well as agonist activity at the MOP receptor as well as agonist activity at the KOP receptor as well as agonist activity at the DOP receptor;   have agonist activity at the NOP receptor as well as agonist activity at the MOP receptor, but no significant activity at the KOP receptor;   have agonist activity at the NOP receptor as well as agonist activity at the MOP receptor, but no significant activity at the DOP receptor; or   have agonist activity at the NOP receptor as well as agonist activity at the MOP receptor, but no significant activity at the KOP receptor as well as no significant activity at the DOP receptor.       

     In some embodiments, preferably with respect to receptors of the peripheral nervous system, the compounds according to the invention have balanced agonist activity at the NOP receptor as well as at the KOP receptor. In some embodiments, preferably with respect to receptors of the peripheral nervous system, the compounds according to the invention
         have agonist activity at the NOP receptor as well as agonist activity at the KOP receptor;   have agonist activity at the NOP receptor as well as agonist activity at the KOP receptor as well as agonist activity at the MOP receptor;   have agonist activity at the NOP receptor as well as agonist activity at the KOP receptor as well as agonist activity at the DOP receptor;   have agonist activity at the NOP receptor as well as agonist activity at the KOP receptor, but no significant activity at the MOP receptor;   have agonist activity at the NOP receptor as well as agonist activity at the KOP receptor, but no significant activity at the DOP receptor; or   have agonist activity at the NOP receptor as well as agonist activity at the KOP receptor, but no significant activity at the MOP receptor as well as no significant activity at the DOP receptor.       

     In some embodiments, preferably with respect to receptors of the peripheral nervous system, the compounds according to the invention have balanced agonist activity at the NOP receptor as well as at the DOP receptor. In some embodiments, preferably with respect to receptors of the peripheral nervous system, the compounds according to the invention
         have agonist activity at the NOP receptor as well as agonist activity at the DOP receptor;   have agonist activity at the NOP receptor as well as agonist activity at the DOP receptor, but no significant activity at the MOP receptor;   have agonist activity at the NOP receptor as well as agonist activity at the DOP receptor, but no significant activity at the KOP receptor; or   have agonist activity at the NOP receptor as well as agonist activity at the DOP receptor, but no significant activity at the MOP receptor as well as no significant activity at the KOP receptor.       

     In some embodiments, preferably with respect to receptors of the peripheral nervous system, the compounds according to the invention have selective agonist activity at the KOP receptor. In some embodiments, preferably with respect to receptors of the peripheral nervous system, the compounds according to the invention
         have agonist activity at the KOP receptor, but no significant activity at the MOP receptor;   have agonist activity at the KOP receptor, but no significant activity at the NOP receptor;   have agonist activity at the KOP receptor, but no significant activity at the DOP receptor;   have agonist activity at the KOP receptor, but no significant activity at the MOP receptor as well as no significant activity at the NOP receptor;   have agonist activity at the KOP receptor, but no significant activity at the MOP receptor as well as no significant activity at the DOP receptor; or   have agonist activity at the KOP receptor, but no significant activity at the MOP receptor as well as no significant activity at the NOP receptor as well as no significant activity at the DOP receptor.       

     In some embodiments, preferably with respect to receptors of the peripheral nervous system, the compounds according to the invention have agonist activity at the MOP receptor, agonist activity at the KOP receptor, and antagonist activity at the DOP receptor. In some embodiments, preferably with respect to receptors of the peripheral nervous system, the compounds according to the invention
         have agonist activity at the MOP receptor as well as agonist activity at the KOP receptor as well as antagonist activity at the DOP receptor;   have agonist activity at the MOP receptor as well as agonist activity at the KOP receptor as well as antagonist activity at the DOP receptor as well as agonist activity at the NOP receptor;   have agonist activity at the MOP receptor as well as agonist activity at the KOP receptor as well as antagonist activity at the DOP receptor as well as antagonist activity at the NOP receptor; or   have agonist activity at the MOP receptor as well as agonist activity at the KOP receptor as well as antagonist activity at the DOP receptor, no significant activity at the NOP receptor.       

     In some embodiments, preferably with respect to receptors of the central nervous system, the compounds according to the invention have selective agonist activity at the NOP receptor. In some embodiments, preferably with respect to receptors of the central nervous system, the compounds according to the invention
         have agonist activity at the NOP receptor, but no significant activity at the MOP receptor;   have agonist activity at the NOP receptor, but no significant activity at the KOP receptor;   have agonist activity at the NOP receptor, but no significant activity at the DOP receptor;   have agonist activity at the NOP receptor, but no significant activity at the MOP receptor as well as no significant activity at the KOP receptor;   have agonist activity at the NOP receptor, but no significant activity at the MOP receptor as well as no significant activity at the DOP receptor; or   have agonist activity at the NOP receptor, but no significant activity at the MOP receptor as well as no significant activity at the KOP receptor as well as no significant activity at the DOP receptor.       

     In some embodiments, preferably with respect to receptors of the central nervous system, the compounds according to the invention have selective antagonist activity at the NOP receptor. In some embodiments, preferably with respect to receptors of the central nervous system, the compounds according to the invention
         have antagonist activity at the NOP receptor, but no significant activity at the MOP receptor;   have antagonist activity at the NOP receptor, but no significant activity at the KOP receptor;   have antagonist activity at the NOP receptor, but no significant activity at the DOP receptor;   have antagonist activity at the NOP receptor, but no significant activity at the MOP receptor as well as no significant activity at the KOP receptor;   have antagonist activity at the NOP receptor, but no significant activity at the MOP receptor as well as no significant activity at the DOP receptor; or   have antagonist activity at the NOP receptor, but no significant activity at the MOP receptor as well as no significant activity at the KOP receptor as well as no significant activity at the DOP receptor.       

     In some embodiments, preferably with respect to receptors of the central nervous system, the compounds according to the invention have antagonist activity at the NOP receptor as well as agonist activity at the DOP receptor. In some embodiments, preferably with respect to receptors of the central nervous system, the compounds according to the invention
         have antagonist activity at the NOP receptor as well as agonist activity at the DOP receptor;   have antagonist activity at the NOP receptor as well as agonist activity at the DOP receptor, but no significant activity at the MOP receptor;   have antagonist activity at the NOP receptor as well as agonist activity at the DOP receptor, but no significant activity at the KOP receptor; or   have antagonist activity at the NOP receptor as well as agonist activity at the DOP receptor, but no significant activity at the MOP receptor as well as no significant activity at the KOP receptor.       

     For the purpose of the specification, “no significant activity” means that the activity (agonist/antagonist) of the given compound at this receptor is lower by a factor of 1000 or more compared to its activity (agonist/antagonist) at one or more of the other opioid receptors. 
     A further aspect of the invention relates to the compounds according to the invention as medicaments. 
     A further aspect of the invention relates to the compounds according to the invention for use in the treatment of pain. A further aspect of the invention relates to a method of treating pain comprising the administration of a pain alleviating amount of a compound according to the invention to a subject in need thereof, preferably to a human. The pain is preferably acute or chronic. The pain is preferably nociceptive or neuropathic. 
     A further aspect of the invention relates to the compounds according to the invention for use in the treatment of neurodegenerative disorders, neuroinflammatory disorders, neuropsychiatric disorders, and substance abuse/dependence. A further aspect of the invention relates to a method of treating any one of the aforementioned disorders, diseases or conditions comprising the administration of a therapeutically effective amount of a compound according to the invention to a subject in need thereof, preferably to a human. 
     Another aspect of the invention relates to a pharmaceutical composition which contains a physiologically acceptable carrier and at least one compound according to the invention. 
     Preferably, the composition according to the invention is solid, liquid or pasty; and/or contains the compound according to the invention in an amount of from 0.001 to 99 wt. %, preferably from 1.0 to 70 wt. %, based on the total weight of the composition. 
     The pharmaceutical composition according to the invention can optionally contain suitable additives and/or auxiliary substances and/or optionally further active ingredients. 
     Examples of suitable physiologically acceptable carriers, additives and/or auxiliary substances are fillers, solvents, diluents, colorings and/or binders. These substances are known to the person skilled in the art (see H. P. Fiedler, Lexikon der Hilfsstoffe fur Pharmazie, Kosmetik and angrenzende Gebiete, Editio Cantor Aulendoff). 
     The pharmaceutical composition according to the invention contains the compound according to the invention in an amount of preferably from 0.001 to 99 wt. %, more preferably from 0.1 to 90 wt. %, yet more preferably from 0.5 to 80 wt. %, most preferably from 1.0 to 70 wt. % and in particular from 2.5 to 60 wt. %, based on the total weight of the pharmaceutical composition. 
     The pharmaceutical composition according to the invention is preferably for systemic, topical or local administration, preferably for oral administration. 
     Another aspect of the invention relates to a pharmaceutical dosage form which contains the pharmaceutical composition according to the invention. 
     In one preferred embodiment, the pharmaceutical dosage form according to the invention is produced for administration twice daily, for administration once daily or for administration less frequently than once daily. Administration is preferably systemic, in particular oral. 
     The pharmaceutical dosage form according to the invention can be administered, for example, as a liquid dosage form in the form of injection solutions, drops or juices, or as a semi-solid dosage form in the form of granules, tablets, pellets, patches, capsules, plasters/spray-on plasters or aerosols. The choice of auxiliary substances etc. and the amounts thereof to be used depend on whether the form of administration is to be administered orally, perorally, parenterally, intravenously, intraperitoneally, intradermally, intramuscularly, intranasally, buccally, rectally or locally, for example to the skin, the mucosa or into the eyes. 
     Pharmaceutical dosage forms in the form of tablets, dragees, capsules, granules, drops, juices and syrups are suitable for oral administration, and solutions, suspensions, readily reconstitutable dry preparations and also sprays are suitable for parenteral, topical and inhalatory administration. Compounds according to the invention in a depot, in dissolved form or in a plaster, optionally with the addition of agents promoting penetration through the skin, are suitable percutaneous administration preparations. 
     The amount of the compounds according to the invention to be administered to the patient varies in dependence on the weight of the patient, on the type of administration, on the indication and on the severity of the disease. Usually, from 0.00005 mg/kg to 50 mg/kg, preferably from 0.001 mg/kg to 10 mg/kg, of at least one compound according to the invention is administered. 
     Another aspect of the invention relates to a process for the preparation of the compounds according to the invention. Suitable processes for the synthesis of the compounds according to the invention are known in principle to the person skilled in the art. 
     Preferred synthesis routes are described below: 
     The compounds according to the invention can be obtained via different synthesis routes. Depending on the synthesis route, different intermediates are prepared and subsequently further reacted. 
     In a preferred embodiment, the synthesis of the compounds according to the invention proceeds via a synthesis route which comprises the preparation of an intermediate according to general formula (IIIa): 
     
       
         
         
             
             
         
       
     
     wherein R 1 , R 2  and R 3  are defined as above. 
     In another preferred embodiment, the synthesis of the compounds according to the invention proceeds via a synthesis route which comprises the preparation of an intermediate according to general formula (IIIb): 
     
       
         
         
             
             
         
       
     
     wherein R 1 , R 2  and R 3  are defined as above and PG is a protecting group. 
     Preferably the protecting group is -p-methoxybenzyl. Therefore, in another preferred embodiment, the synthesis of the compounds according to the invention proceeds via a synthesis route which comprises the preparation of an intermediate according to general formula (IIIc): 
     
       
         
         
             
             
         
       
     
     wherein R 1 , R 2  and R 3  are defined as above. 
     As already indicated, in general formula (IIIc), the -p-methoxybenzyl moiety represents a protecting group which can be cleaved in the course of the synthesis route. 
     In yet another preferred embodiment, the synthesis of the compounds according to the invention proceeds via a synthesis route which comprises the preparation of
         an intermediate according to general formula (IIIa) and according to general formula (IIIb); or   an intermediate according to general formula (IIIa) and according to general formula (IIIc); or   an intermediate according to general formula (IIIb) and according to general formula (IIIc); or   an intermediate according to general formula (IIIa), according to general formula (IIIb) and according to general formula (IIIc).       

     The following examples further illustrate the invention but are not to be construed as limiting its scope. 
    
    
     EXAMPLES 
     “RT” means room temperature (23±7° C.), “M” are indications of concentration in mol/l, “aq.” means aqueous, “sat.” means saturated, “sol.” means solution, “conc.” means concentrated. 
     Further Abbreviations 
     brine saturated aqueous sodium chloride solution
 
CC column chromatography
 
cHex cyclohexane
 
dba dibenzylideneacetone
 
DCM dichloromethane
 
     DIPEA N,N-diisopropylethylamine 
     DMF N,N-dimethylformamide 
     Et ethyl
 
ether diethyl ether
 
EE ethyl acetate
 
EtOAc ethyl acetate
 
EtOH ethanol
 
h hour(s)
 
H 2 O water
 
HATU O-(7-aza-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate
 
LDA lithium diisoproylamide
 
Me methyl
 
m/z mass-to-charge ratio
 
MeOH methanol
 
MeCN acetonitrile
 
min minutes
 
MS mass spectrometry
 
     NBS N-bromosuccinimide 
     NIS N-iodosuccinimide 
     NEt 3  triethylamine
 
PE petroleum ether (60-80° C.)
 
RM reaction mixture
 
RT room temperature
 
TFA trifluoroacetic acid
 
T3P 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane-2,4,6-trioxide
 
tBME tert-butyl methyl ether
 
THF tetrahydrofurane
 
v/v volume to volume
 
w/w weight to weight
 
Xantphos 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene
 
     The yields of the compounds prepared were not optimised. All temperatures are uncorrected. 
     All starting materials, which are not explicitly described, were either commercially available (the details of suppliers such as for example Acros, Aldrich, Bachem, Butt park, Enamine, Fluka, Lancaster, Maybridge, Merck, Sigma, TCI, Oakwood, etc. can be found in the Symyx® Available Chemicals Database of MDL, San Ramon, US or the SciFinder® Database of the ACS, Washington D.C., US, respectively, for example) or the synthesis thereof has already been described precisely in the specialist literature (experimental guidelines can be found in the Reaxys® Database of Elsevier, Amsterdam, NL or the SciFinder® Database of the ACS, Washington D.C., US, respectively, for example) or can be prepared using the conventional methods known to the person skilled in the art. 
     The mixing ratios of solvents or eluents for chromatography are specified in v/v. 
     All the intermediate products and exemplary compounds were analytically characterised by mass spectrometry (MS, m/z for [M+H] + ). In addition  1 H-NMR and  13 C spectroscopy was carried out for all the exemplary compounds and selected intermediate products. 
     Remark Regarding Stereochemistry 
     CIS refers to the relative configuration of compounds described herein, in which both nitrogen atoms are drawn on the same face of the cyclohexane ring as described in the following exemplary structure. Two depictions are possible: 
     
       
         
         
             
             
         
       
     
     TRANS refers to compounds, in which both nitrogen atoms are on opposite faces of the cyclohexane ring as described in the following exemplary structure. Two depictions are possible: 
     
       
         
         
             
             
         
       
     
     Synthesis of Intermediates 
     Synthesis of INT-600: 5-(cis-8-(Dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidine-2-carbonitrile 
     
       
         
         
             
             
         
       
     
     Cs 2 CO 3  (1.1 g, 3.66 mmol) was added to the solution of CIS-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-976) (0.5 g, 1.83 mmol), Xanthphos (0.158 g, 0.274 mmol), Pd 2 (dba) 3  (0.083 g, 0.091 mmol) and 5-bromopyrimidine-2-carbonitrile (0.52 g, 2.74 mmol) in 1,4-dioxane (20 mL) under argon atmosphere. The reaction mixture was stirred for 16 h at 90° C., then cooled to RT and concentrated under reduced pressure. The residue was suspended in EtOAc (20 mL) and filtered through a plug of celite. The filtrate was concentrated under reduced pressure and the resulting residue was purified by flash chromatography on silica gel to afford 5-(cis-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidine-2-carbonitrile (INT-600) (0.4 g) as a white solid. 
     Synthesis of INT-799: CIS-8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: CIS-1-((1-(benzyloxy)cyclobutyl)methyl)-3-(3,4-dimethoxybenzyl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     NaOH (1.42 g, 35.5 mmol) was added to a solution of CIS-3-(3,4-dimethoxybenzyl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-794) (3 g, 7.09 mmol) in DMSO (90 mL) under argon atmosphere and the reaction mixture was stirred at 80° C. for 30 min. ((1-(Bromomethyl)cyclobutoxy)methyl)benzene (5.4 g, 21.3 mmol) was added and stirring was continued for 2 days at 80° C. The reaction completion was monitored by TLC. The reaction mixture was diluted with water (500 mL) and extracted with diethyl ether (4×300 mL). The combined organic extracts were dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure. The residue was purified by column chromatography (230-400mesh silica gel; 65-70% EtOAc in petroleum ether as eluent) to afford 2.5 g (59%) of CIS-1-((1-(benzyloxy)cyclobutyl)methyl)-3-(3,4-dimethoxybenzyl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (TLC system: 10% MeOH in DCM; Rf: 0.8). 
     Step 2: CIS-8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     TFA (12 mL) was added to CIS-1-((1-(benzyloxy)cyclobutyl)methyl)-3-(3,4-dimethoxybenzyl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (2.5 g, 4.18 mmol) at 0° C. and the resulting mixture was stirred at 70° C. for 6 h. The reaction completion was monitored by LCMS. The reaction mixture was concentrated under reduced pressure. To the residue sat. aq. NaHCO 3  was added (until pH 10) and the organic product was extracted with DCM (3×150 mL). The combined organic extracts were dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure. The residue was purified by column chromatography (230-400mesh silica gel; 5% MeOH in DCM as eluent) to afford 500 mg (33%) of CIS-8-dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-799) (TLC system: 10% MeOH in DCM; Rf: 0.5). [M+H]+ 358.2 
     Synthesis of INT-951: CIS-1-[(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl)-methyl]-cyclobutane-1-carbonitrile 
     
       
         
         
             
             
         
       
     
     Step 1: 1-((CIS-8-(dimethylamino)-3-(4-methoxybenzyl)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl)methyl)cyclobutanecarbonitrile 
     NaH (50% in mineral oil) (2.44 g, 50.89 mmol) was added to a solution of CIS-8-dimethylamino-3-[(4-methoxyphenyl)-methyl]-8-phenyl-1,3-diazaspiro [4.5]decan-2-one (INT-975) (5 g, 12.72 mmol) in DMF (100 mL) at 0° C. portionwise over 10 min. 1-(Bromomethyl)cyclobutanecarbonitrile (4.4 g, 25.44 mmol) was added dropwise over 10 minutes at 0° C. The reaction mixture was allowed to stir at RT for 3 h, then quenched with water and the organic product was extracted with ethyl acetate (3×200 mL). The combined organic extracts were dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure to afford 5 g (crude) of 1-((CIS-8-(dimethylamino)-3-(4-methoxybenzyl)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl)methyl)cyclobutane-carbonitrile as gummy brown liquid. The material was used for the next step without further purification. 
     Step 2: 1-((CIS-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl)methyl) cyclobutanecarboxamide 
     TFA (100 mL) was added to 1-((CIS-8-(dimethylamino)-3-(4-methoxybenzyl)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl)methyl)cyclobutanecarbonitrile (5 g, 10.28 mmol) at 0° C. and the reaction mixture at mixture was stirred at RT for 2 days. The reaction mixture was concentrated in vacuo. To the residue sat. aq. NaHCO 3  was added (until pH 10) and the organic product was extracted with dichloromethane (3×150 mL). The combined organic extracts were dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure to afford 3.5 g (crude) of 1-((CIS-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl)methyl) cyclobutanecarboxamide. The material was used for the next step without further purification. 
     Step 3: 1-((cis-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl)methyl)cyclobutane carbonitrile 
     Thionyl chloride (35 mL) was added to 1-((cis-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl)methyl)cyclobutanecarboxamide (3.5 g, 9.11 mmol) at RT and the resulting mixture was stirred at reflux for 2h. The reaction mixture was concentrated in vacuo. To the residue sat. aq. NaHCO 3  was added (until pH 10) and the organic product was extracted with dichloromethane (3×150 mL). The combined organic layer was dried over anhydrous Na 2 SO 4  and concentrated in vacuo. The residue was purified by column chromatography to afford 1.3 g (34% after three steps) of CIS-1-[(8-dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl)-methyl]-cyclobutane-1-carbonitrile (INT-951). [M+H] +  367.2. 
     Synthesis of INT-952: CIS-1-(Cyclobutyl-methyl)-8-dimethylamino-8-phenyl-3-[(4-methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     To a solution of CIS-8-dimethylamino-3-[(4-methoxyphenyl)-methyl]-8-phenyl-1,3-diazaspiro [4.5]decan-2-one (INT-975) (10 g, 25 mmol) in THF (500 mL) was added KOtBu (7.1 g, 63 mmol) at 50° C. The reaction mixture was heated up to reflux, cyclobutylmethylbromide (11.3 g, 76 mmol) was added in one portion, and stirring was continued at reflux for 12 h. KOtBu (7.1 g) and cyclobutylmethylbromide (11.3 g) were added again. The reaction mixture was allowed to stir another 2 h at reflux, then cooled to RT, diluted with water (150 mL) and the layers partitioned. The aqueous layer was extracted with EtOAc (3×300 mL). The combined organic layers were dried over Na 2 SO 4  and then concentrated in vacuo. The residue was filtered through a plug of silica gel using a DCM/MeOH (19/1 v/v) mixture. The filtrate was concentrated in vacuo and the resulting solid was recrystallized from hot ethanol to yield 7.8 g of CIS-1-(cyclobutyl-methyl)-8-dimethylamino-8-phenyl-3-[(4-methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decan-2-one (INT-952). [M+H] +  461.3. 
     Synthesis of INT-953: CIS-1-(Cyclobutyl-methyl)-8-(methyl-(2-methyl-propyl)-amino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: 1-Cyclobutylmethyl-3-(4-methoxy-benzyl)-9,12-dioxa-1,3-diaza-dispiro[4.2.4.2]tetradecan-2-one 
     To a stirred solution of 3-(4-methoxy-benzyl)-9,12-dioxa-1,3-diaza-dispiro[4.2.4.2]tetradecan-2-one (4 g, 12.04 mmol) in anhydrous DMF (60 ml) was added NaH (1.38 g, 60% dispersion in oil, 36.14 mmol) at RT. The reaction mixture was stirred for 10 min, bromomethylcyclobutane (3 ml, 26.5 mmol) was added dropwise and stirring was continued for 50 h. TLC analysis showed complete consumption of the starting material. The reaction mixture was quenched with sat. aq. NH 4 Cl (50 ml) and extracted with EtOAc (3×200 ml). The combined organic phase was dried over Na 2 SO 4  and concentrated under reduced pressure. The resulting residue was purified column chromatography (neutral aluminum oxide, EtOAc—petroleum ether (2:8)) to give 1-cyclobutylmethyl-3-(4-methoxy-benzyl)-9,12-dioxa-1,3-diaza-dispiro[4.2.4.2]tetradecan-2-one (2.4 g, 50%, white solid). TLC system: EtOAc—pet ether (6:4); R f =0.48. 
     Step 2: 1-Cyclobutylmethyl-3-(4-methoxy-benzyl)-1,3-diaza-spiro[4.5]decane-2,8-dione 
     To a stirred solution of 1-cyclobutylmethyl-3-(4-methoxy-benzyl)-9,12-dioxa-1,3-diaza-dispiro[4.2.4.2]tetradecan-2-one (1 g, 2.5 mmol) in MeOH (7 ml) was added 10% aq. HCl (8 ml) at 0° C. The reaction mixture was warmed up to RT and stirred for 16 h. TLC analysis showed complete consumption of the starting material. The reaction mixture was quenched with sat. aq. NaHCO 3  (30 ml) and extracted with EtOAc (3×50 ml). The combined organic phase was dried over Na 2 SO 4  and concentrated under reduced pressure. The resulting residue was purified by column chromatography (silica gel, 230-400 mesh, EtOAc—pet ether (1:3)→(3:7)) to give 1-cyclobutylmethyl-3-(4-methoxy-benzyl)-1,3-diaza-spiro[4.5]decane-2,8-dione (650 mg, 73%, colorless viscous oil). TLC system: EtOAc—pet ether (6:4); R f =0.40. 
     Step 3: 1-(cyclobutylmethyl)-8-(isobutyl(methyl)amino)-3-(4-methoxybenzyl)-2-oxo-1,3-diazaspiro[4.5]decane-8-carbonitrile 
     To a stirred solution of N-isobutyl-N-methylamine (1.34 ml, 11.23 mmol) and MeOH/H 2 O (8 ml, 1:1, v/v) was added 4N aq. HCl (1.5 ml) and the reaction mixture was stirred for 10 min at 0° C. (ice bath). A solution of 1-cyclobutylmethyl-3-(4-methoxy-benzyl)-1,3-diaza-spiro[4.5]decane-2,8-dione (1 g, 2.80 mmol) in MeOH (7 ml) and KCN (548 mg, 8.42 mmol) were added and the reaction mixture was stirred at 45° C. for 20 h. TLC analysis showed complete consumption of the starting material. The reaction mixture was diluted with water (30 ml), extracted with EtOAc (3×30 ml), the combined organic phase was dried over Na 2 SO 4  and concentrated under reduced pressure to give 1-(cyclobutylmethyl)-8-(isobutyl(methyl)amino)-3-(4-methoxybenzyl)-2-oxo-1,3-diazaspiro[4.5]decane-8-carbonitrile (1.3 g, viscous yellow oil). TLC system: EtOAc—pet ether (1:1); R f =0.45. The product was used for the next step without additional purification. 
     Step 4: CIS-1-(cyclobutylmethyl)-8-(isobutyl(methyl)amino)-3-(4-methoxybenzyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     A round bottom flask containing 1-(cyclobutylmethyl)-8-(isobutyl(methyl)amino)-3-(4-methoxybenzyl)-2-oxo-1,3-diazaspiro[4.5]decane-8-carbonitrile (1.3 g, 2.81 mmol) was cooled in an ice bath (˜0° C.) and a solution of phenylmagnesium bromide (26 ml, ˜2M in THF) was added slowly at 0° C.-5° C. The ice bath was removed and the reaction mixture was stirred for 30 min, then diluted with sat. aq. NH 4 Cl (25 ml) and extracted with EtOAc (4×30 ml). The combined organic phase was dried over Na 2 SO 4  and concentrated under reduced pressure to give pale yellow viscous oil. This residue was purified by column chromatography (silica gel, 230-400 mesh, eluent: EtOAc—pet ether (15:85)→(2:4)) to give CIS-1-(cyclobutylmethyl)-8-(isobutyl(methyl)amino)-3-(4-methoxybenzyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (135 mg, 10%, white solid). TLC system: EtOAc -pet ether (1:1); R f =0.6 
     Step 5: CIS-1-(Cyclobutyl-methyl)-8-(methyl-(2-methyl-propyl)-amino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     A round bottom flask containing CIS-1-(cyclobutylmethyl)-8-(isobutyl(methyl)amino)-3-(4-methoxybenzyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (130 mg, 0.25 mmol) was cooled in an ice bath and a mixture of TFA/CH 2 Cl 2  (2.6 ml, 1:1, v/v) was added slowly at 0° C.-5° C. The reaction mixture was warmed to RT and stirred for 20 h, then quenched with methanolic NH 3  (10 ml, 10% in MeOH) and concentrated under reduced pressure to give pale yellow viscous oil. This residue was purified twice by column chromatography (silica gel, 230-400 mesh, eluent: MeOH—CHCl 3  (1:99)→(2:98)) to give CIS-1-(cyclobutyl-methyl)-8-(methyl-(2-methyl-propyl)-amino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-953) (65 mg, 66%, white solid). TLC system: MeOH—CHCl 3  (5:95); R f =0.25; [M+H] +  384.3 
     Synthesis of INT-958: 4-Oxo-1-pyridin-2-yl-cyclohexane-1-carbonitrile 
     
       
         
         
             
             
         
       
     
     Step 1: Ethyl 5-cyano-2-oxo-5-(pyridin-2-yl)cyclohexanecarboxylate 
     KOtBu (57.0 g, 508.4 mmol) was added to the solution of 2-(pyridin-2-yl)acetonitrile (50.0 g, 423.7 mmol) and ethyl acrylate (89.0 g, 889.8 mmol) in THF (500 mL) at 0° C. and stirred for 16 h at RT. The reaction mixture was quenched with sat. aq. NH 4 Cl and extracted with EtOAc (2×500 mL). The combined organic layer was washed with brine, dried over Na 2 SO 4  and concentrated under reduced pressure to afford 68.0 g (60%; crude) of ethyl 5-cyano-2-oxo-5-(pyridin-2-yl)cyclohexanecarboxylate as a brown liquid (TLC system: 50% ethyl acetate in petroleum ether; Rf: 0.65). 
     Step 2: 4-Oxo-1-pyridin-2-yl-cyclohexane-1-carbonitrile 
     A solution of ethyl 5-cyano-2-oxo-5-(pyridin-2-yl)cyclohexanecarboxylate (68.0 g, 250.0 mmol) was added to a mixture of conc. aq. HCl and glacial acetic acid (170 mL/510 mL) at 0° C. The reaction mixture was heated to 100° C. for 16 h. All volatiles were evaporated under reduced pressure. The residue was diluted with sat. aq. NaHCO 3  and extracted with ethyl acetate (3×300 mL). The combined organic layer was washed with brine, dried over Na 2 SO 4  and concentrated under reduced pressure to afford 44.0 g (88%) of 4-oxo-1-pyridin-2-yl-cyclohexane-1-carbonitrile INT-958 as a brown solid (TLC system: 50% ethyl acetate in pet ether; R f : 0.45). [M+H] +  201.1 
     Synthesis of INT-961: 4-Dimethylamino-4-pyridin-2-yl-cyclohexan-1-one 
     
       
         
         
             
             
         
       
     
     Step 1: 8-(pyridin-2-yl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile 
     A solution of 4-oxo-1-pyridin-2-yl-cyclohexane-1-carbonitrile (INT-958) (44.0 g, 220.0 mmol), ethylene glycol (27.0 g, 440.0 mmol) and PTSA (4.2 g, 22.0 mmol) in toluene (450 mL) was heated to 120° C. for 16 h using Dean Stark apparatus. All volatiles were evaporated under reduced pressure. The residue was diluted with sat. aq. NaHCO 3  and extracted with ethyl acetate (3×300 mL). The combined organic layer was washed with brine, dried over Na 2 SO 4  and concentrated under reduced pressure to afford 45.0 g (85%) of 8-(pyridin-2-yl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile as a light brown solid (TLC system: 50% ethyl acetate in petroleum ether; Rf: 0.55). 
     Step 2: 8-(pyridin-2-yl)-1,4-dioxaspiro[4.5]decane-8-carboxamide 
     Potassium carbonate (50.0 g, 368.84 mmol) and 30% aq. H 2 02 (210.0 mL, 1844.2 mmol) were added to the solution of 8-(pyridin-2-yl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile (45.0 g, 184.42 mmol) in DMSO (450 mL) at 0° C. and the resulting mixture was stirred at RT for 14 h. The reaction mixture was diluted with water (1.5 L) and stirred for 1 h. The precipitated solid was separated by filtration, washed with water, petroleum ether and dried under reduced pressure to get 32.0 g (66%) of 8-(pyridin-2-yl)-1,4-dioxaspiro[4.5]decane-8-carboxamide as a white solid. (TLC system: 10% MeOH in DCM R f : 0.35). 
     Step 3: methyl 8-(pyridin-2-yl)-1,4-dioxaspiro[4.5]decan-8-ylcarbamate 
     A mixture of 8-(pyridin-2-yl)-1,4-dioxaspiro[4.5]decane-8-carboxamide (25.0 g, 95.41 mmol), sodium hypochlorite (5 wt % aq. solution, 700 mL, 477.09 mmol) and KF—Al 2 O 3  (125.0 g) in methanol (500 mL) was heated to 80° C. for 16 h. The reaction mixture was filtered through celite and the solid residue was washed with methanol. The combined filtrate was concentrated under reduced pressure. The residue was diluted with water and extracted with ethyl acetate (3×500 mL). The combined organic layer was washed with brine, dried over Na 2 SO 4  and concentrated under reduced pressure to afford 18.0 g (66%) of methyl 8-(pyridin-2-yl)-1,4-dioxaspiro[4.5]decan-8-ylcarbamate as a light brown solid. (TLC system: 5% MeOH in DCM R f : 0.52.) 
     Step 4: 8-(pyridin-2-yl)-1,4-dioxaspiro[4.5]decan-8-amine 
     A suspension of methyl 8-(pyridin-2-yl)-1,4-dioxaspiro[4.5]decan-8-ylcarbamate (18.0 g, 61.64 mmol) in 10 wt % aq. NaOH (200 mL) was heated to 100° C. for 24 h. The reaction mixture was filtered through celite pad, the solid residue was washed with water and the combined filtrate was extracted with EtOAc (4×200 mL). The combined organic layer washed with brine, dried over Na 2 SO 4  and concentrated under reduced pressure to afford 12.5 g (88%) of 8-(pyridin-2-yl)-1,4-dioxaspiro[4.5]decan-8-amine as a light brown semi-solid. (TLC system: 5% MeOH in DCM R f : 0.22.). 
     Step 5: 4-Dimethylamino-4-pyridin-2-yl-cyclohexan-1-one 
     Sodium cyanoborohydride (13.7 g, 0.213 mol) was added portionwise to a solution of 8-(pyridin-2-yl)-1,4-dioxaspiro[4.5]decan-8-amine (12.5 g, 53.418 mmol) and 35 wt % aq. formaldehyde (45 mL, 0.534 mol) in acetonitrile (130 mL) at 0° C. The reaction mixture was warmed up to room temperature and stirred for 16 h. The reaction mixture was quenched with sat. aq. NH 4 Cl and concentrated under reduced pressure. The residue was dissolved in water and extracted with EtOAc (3×200 mL). The combined organic layer was washed with brine, dried over Na 2 SO 4  and concentrated under reduced pressure to afford 10.5 g (72%) of 4-dimethylamino-4-pyridin-2-yl-cyclohexan-1-one (INT-961) as a light brown solid. (TLC system: 5% MeOH in DCM R f : 0.32.). [M+H] +  219.1 
     Synthesis of INT-965: 4-Dimethylamino-4-phenyl-cyclohexan-1-one 
     
       
         
         
             
             
         
       
     
     Step 1: 8-(Dimethylamino)-1,4-dioxaspiro[4.5]decane-8-carbonitrile 
     Dimethylamine hydrochloride (52 g, 0.645 mol) was added to the solution of 1,4-dioxaspiro-[4.5]-decan-8-one (35 g, 0.224 mmol) in MeOH (35 mL) at RT under argon atmosphere. The solution was stirred for 10 min and 40 wt % aq. dimethylamine (280 mL, 2.5 mol) and KCN (32 g, 0.492 mol) were sequentially added. The reaction mixture was stirred for 48 h at RT, then diluted with water (100 mL) and extracted with EtOAc (2×200 mL). The combined organic layer was dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure to afford 44 g of 8-(dimethylamino)-1,4-dioxaspiro-[4.5]-decane-8-carbonitrile (93%) as a white solid. 
     Step 2: N,N-dimethyl-8-phenyl-1,4-dioxaspiro [4.5] decan-8-amine 
     8-(Dimethylamino)-1,4-dioxaspiro[4.5]decane-8-carbonitrile (35 g, 0.167 mol) in THF (350 mL) was added to the solution of 3M phenylmagnesium bromide in diethyl ether (556 mL, 1.67 mol) dropwise at −10° C. under argon atmosphere. The reaction mixture was stirred for 4 h at -10° C. to 0° C. and then at RT for 18 h. The reaction completion was monitored by TLC. The reaction mixture was cooled to 0° C., diluted with sat. aq. NH 4 Cl (1 L) and extracted with EtOAc (2×600 mL). The combined organic layer was dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure to afford 60 g of, N N-dimethyl-8-phenyl-1, 4-dioxaspiro-[4.5]-decan-8-amine as a liquid. 
     Step 3: 4-(dimethylamino)-4-phenylcyclohexanone 
     A solution of N,N-dimethyl-8-phenyl-1,4-dioxaspiro[4.5]decan-8-amine (32 g, 0.123 mol) in 6N aq. HCl (320 mL) was stirred at 0° C. for 2 h and then at RT for 18 h. The reaction completion was monitored by TLC. The reaction mixture was extracted with DCM (2×150 mL). The aqueous layer was basified to pH 10 with solid NaOH and extracted with ethyl acetate (2×200 mL). The combined organic layer was dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure. The solid residue was washed with hexane and dried in vacuo to afford 7 g of 4-dimethylamino-4-phenyl-cyclohexan-1-one (INT-965) (25% over 2 steps) as a brown solid. [M+H] +  218.1 
     Synthesis of INT-966: 3-[(4-Methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decane-2,8-dione 
     
       
         
         
             
             
         
       
     
     Step 1: 9,12-Dioxa-2,4-diazadispiro[4.2.4{circumflex over ( )}{8}.2{circumflex over ( )}{5}]tetradecane-1,3-dione 
     KCN (93.8 g, 1441.6 mmol) and (NH 4 ) 2 CO 3  (271.8 g, 1729.9 mmol) were added to the solution of 1,4-dioxaspiro[4.5]decan-8-one (150 g, 961 mmol) in MeOH:H 2 O (1:1 v/v) (1.92 L) at RT under argon atmosphere. The reaction mixture was stirred at 60° C. for 16 h. The reaction completion was monitored by TLC. The reaction mixture was cooled to 0° C., the precipitated solid was filtered off and dried in vacuo to afford 120 g (55%) of 9,12-dioxa-2,4-diazadispiro[4.2.4{circumflex over ( )}{8}.2{circumflex over ( )}{5}]tetradecane-1,3-dione. The filtrate was extracted with DCM (2×1.5 L). The combined organic layer was dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure to afford additional 30 g (14%) of 9,12-dioxa-2,4-diazadispiro[4.2.4{circumflex over ( )}{8}.2{circumflex over ( )}{5}]tetradecane-1,3-dione (TLC system: 10% Methanol in DCM; Rf: 0.4). 
     Step 2: 2-[(4-Methoxyphenyl)-methyl]-9,12-dioxa-2,4-diazadispiro[4.2.4{circumflex over ( )}{8}.2{circumflex over ( )}{5}]tetradecane-1,3-dione 
     Cs 2 CO 3  (258.7 g, 796.1 mmol) was added to the solution of 73a (150 g, 663.4 mmol) in MeCN (1.5 L) under argon atmosphere and the reaction mixture was stirred for 30 min. A solution of p-methoxybenzyl bromide (96 mL, 663.4 mmol) was added. The reaction mixture was stirred at RT for 48 h. The reaction completion was monitored by TLC. The reaction mixture was quenched with sat. aq. NH 4 Cl (1.0 L) and the organic product was extracted with EtOAc (2×1.5 L). The combined organic layer was dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure. The residue was washed with diethyl ether and pentane and dried under reduced pressure to afford 151 g (65%) of 2-[(4-Methoxyphenyl)-methyl]-9,12-dioxa-2,4-diazadispiro[4.2.4{circumflex over ( )}{8}.2{circumflex over ( )}{5}]tetradecane-1,3-dione as an off white solid (TLC system: 10% MeOH in DCM; R f : 0.6). 
     Step 3: 2-[(4-Methoxyphenyl)-methyl]-9,12-dioxa-2,4-diazadispiro[4.2.4{circumflex over ( )}{8}.2{circumflex over ( )}{5}]tetradecan-3-one 
     AlCl 3  (144.3 g, 1082.6 mmol) was added to a solution of LiAlH 4  (2M in THF) (433 mL, 866.10 mmol) in THF (4.5 L) at 0° C. under argon atmosphere and the resulting mixture was stirred at RT for 1 h. 2-[(4-Methoxyphenyl)-methyl]-9,12-dioxa-2,4-diazadispiro[4.2.4{circumflex over ( )}{8}.2{circumflex over ( )}{5}]tetradecane-1,3-dione (150 g, 433.05 mmol) was added at 0° C. The reaction mixture was stirred at RT for 16 h. The reaction completion was monitored by TLC. The reaction mixture was cooled to 0° C., quenched with sat. aq. NaHCO 3  (500 mL) and filtered through celite pad. The filtrate was extracted with EtOAc (2×2.0 L). The combined organic layer was dried over anhydrous Na 2 SO 4  and concentrated in vacuo to afford 120 g (84%) of 2-[(4-methoxyphenyl)-methyl]-9,12-dioxa-2,4-diazadispiro[4.2.4{circumflex over ( )}{8}.2{circumflex over ( )}{5}]tetradecan-3-one as an off-white solid. (TLC system: 10% MeOH in DCM, R f : 0.5). 
     Step 4: 3-[(4-Methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decane-2,8-dione 
     A solution of 2-[(4-methoxyphenyl)-methyl]-9,12-dioxa-2,4-diazadispiro[4.2.4{circumflex over ( )}{8}.2{circumflex over ( )}{5}]tetradecan-3-one (120 g, 361.03 mmol) in 6N aq. HCl (2.4 L) was stirred at 0° C. for 2 h and then at RT for 18 h. The reaction completion was monitored by TLC. The reaction mixture was extracted with DCM (2×2.0 L). The aqueous layer was basified to pH 10 with 50% aq. NaOH and then extracted with DCM (2×2.0 L). Combined organic extracts were dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure. The solid residue was washed with hexane and dried in vacuo to afford 90 g of 3-[(4-Methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decane-2,8-dione (INT-966) as an off-white solid (TLC system: 10% MeOH in DCM; Rf: 0.4) [M+H] +  289.11. 
     Synthesis of INT-971: CIS-1-(Cyclobutyl-methyl)-8-dimethylamino-8-(3-hydroxyphenyl)-3-[(4-methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: CIS-8-(dimethylamino)-1-isobutyl-3-(4-methoxybenzyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     In analogy to the method described for INT-951 step 1 CIS-8-Dimethylamino-8-[3-(methoxymethyloxy)-phenyl]-3-[(4-methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decan-2-one (INT-968) was converted into CIS-1-(cyclobutylmethyl)-8-(dimethylamino)-3-(4-methoxybenzyl)-8-(3-(methoxymethoxy)phenyl)-1,3-diazaspiro[4.5]decan-2-one. 
     Step 2: CIS-1-(Cyclobutyl-methyl)-8-dimethylamino-8-(3-hydroxyphenyl)-3-[(4-methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decan-2-one 
     TFA (0.2 mL) was added to the solution of CIS-1-(cyclobutylmethyl)-8-(dimethylamino)-3-(4-methoxybenzyl)-8-(3-methoxyphenyl)-1,3-diazaspiro[4.5]decan-2-one (300 mg, 0.57 mmol) in DCM (1.5 mL) at 0° C. The reaction mixture was stirred at 0° C. for 3 h. The reaction completion was monitored by TLC. The reaction mixture was quenched with sat. aq. NaHCO 3  and the organic product was extracted with DCM (3×10 mL). The combined organic extracts were dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure. Purification of the residue by preparative TLC (3% MeOH in DCM as mobile phase) yielded 50 mg (18%) of CIS-1-(Cyclobutyl-methyl)-8-dimethylamino-8-(3-hydroxyphenyl)-3-[(4-methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decan-2-one (INT-971) as an off white solid. (TLC system: 10% MeOH in DCM; Rf: 0.20) [M+H] +  478.3 
     Synthesis of INT-974: CIS-8-Dimethylamino-8-(3-fluorophenyl)-3-[(4-methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: 8-(dimethylamino)-3-(4-methoxybenzyl)-2-oxo-1,3-diazaspiro[4.5]decane-8-carbonitrile 
     Dimethylamine hydrochloride (76.4 g, 936.4 mmol) was added to a solution of 3-[(4-methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decane-2,8-dione (INT-966) (90 g, 312.13 mmol) in MeOH (180 mL) at RT under argon atmosphere. The solution was stirred for 15 min and 40 wt % aq. dimethylamine (780 mL) and KCN (48.76 g, 749.11 mmol) were sequentially added. The reaction mixture was stirred for 48 h and the completion of the reaction was monitored by NMR. The reaction mixture was diluted with water (1.0 L) and the organic product was extracted with ethyl acetate (2×2.0 L). The combined organic layer was dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure to afford 90 g (85%) of 8-(dimethylamino)-3-(4-methoxybenzyl)-2-oxo-1,3-diazaspiro[4.5]decane-8-carbonitrile as an off white solid (TLC system: TLC system: 10% MeOH in DCM; Rf: 0.35, 0.30). 
     Step 2: CIS-8-Dimethylamino-8-(3-fluorophenyl)-3-[(4-methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decan-2-one 
     3-Fluorophenylmagnesium bromide (M in THF) (220 mL, 219.17 mmol) was added dropwise to a solution of 8-(dimethylamino)-3-(4-methoxybenzyl)-2-oxo-1,3-diazaspiro[4.5]decane-8-carbonitrile (15 g, 43.83 mmol) in THF (300 mL) at 0° C. under argon atmosphere. The reaction mixture was stirred for 16 h at RT. The reaction completion was monitored by TLC. The reaction mixture was cooled to 0° C., quenched with sat. aq. NH 4 Cl (200 mL) and the organic product was extracted with EtOAc (2×200 mL). The combined organic layer was dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure. The reaction was carried out in 4 batches (15 g×2 and 5 g×2) and the batches were combined for purification. Purification of the crude product by flash column chromatography on silica gel (230-400 mesh) (2 times) (0-20% methanol in DCM) eluent and subsequently by washing with pentane yielded 5.6 g (11%) of CTS-8-dimethylamino-8-(3-fluorophenyl)-3-[(4-methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decan-2-one (INT-974) as an off-white solid. (TLC system: 5% MeOH in DCM in presence of ammonia; Rf: 0.1). [M+H] +  412.2 
     Synthesis of INT-975: CIS-8-Dimethylamino-3-[(4-methoxyphenyl)-methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     KOtBu (1M in THF) (29.30 mL, 29.30 mmol) was added to the solution of CIS-8-Dimethylamino-8-phenyl-1,3-diazaspiro[4.5]decan-2-one INT-976 (8.0 g, 29.30 mmol) in THF (160 mL) under argon atmosphere and the reaction mixture was stirred for 30 min. 4-Methoxybenzyl bromide (4.23 mL, 29.30 mmol) was added and stirring was continued at RT for 4 h. The reaction completion was monitored by TLC. The reaction mixture was diluted with sat. aq. NH 4 Cl (150 mL) and the organic product was extracted with EtOAc (2×150 mL). The combined organic layer was dried over anhydrous Na 2 SO 4  and concentrated in vacuo. The reaction was carried out in 2 batches (8 g×2) and the batches were combined for purification. Purification of the crude product by flash column chromatography on silica gel (0-10% methanol in DCM) and subsequently by washing with pentane yielded 11 g (47%) of CIS-8-Dimethylamino-3-[(4-methoxyphenyl)-methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-975) as a white solid. [M+H] +  394.2 
     Synthesis of INT-976: CIS-8-Dimethylamino-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: 8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4,5]decane-2,4-dione 
     In a sealed tube 4-dimethylamino-4-phenyl-cyclohexan-1-one (INT-965) (2 g, 9.22 mmol) was suspended in 40 mL EtOH/H 2 O (1:1 v/v) at RT under argon atmosphere. (NH 4 ) 2 CO 3  (3.62 g, 23.04 mmol) and KCN (0.6 g, 9.22 mmol) were added. The reaction mixture was stirred at 60° C. for 18h. The reaction mixture was cooled to 0° C. and diluted with ice-water and filtered through a glass filter. The solid residue was dried under reduced pressure to afford 8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4,5]decane-2,4-dione (1.8 g, 86%) as an off white crystalline solid (TLC: 80% EtOAc in hexane; Rf: 0.25). 
     Step 2: 8-(dimethylamino)-8-phenyl-1, 3-diazaspiro [4, 5] decan-2-one 
     LiAlH 4  (2M in THF) (70 mL, 139.4 mmol) was added to the solution of 8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4,5]decane-2,4-dione (10 g, 34.8 mmol) in THF/Et 2 O (2:1 v/v) (400 mL) at 0° C. under argon atmosphere. The reaction mixture was stirred for 4 h at 60° C. The reaction completion was monitored by TLC. The reaction mixture was cooled to 0° C., quenched with saturated Na 2 SO 4  solution (100 mL) and filtered through Celite pad. The filtrate was dried over anhydrous Na 2 SO 4  and concentrated in vacuo to afford 5.7 g (59%) of 8-(dimethylamino)-8-phenyl-1, 3-diazaspiro [4, 5] decan-2-one as an off white solid. (TLC system: 10% MeOH in DCM, R f : 0.3). 
     Step 3: CIS-8-Dimethylamino-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     A mixture of CIS- and TRANS-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4,5]decan-2-one (8 g, 29.30 mmol) was purified by preparative chiral SFC (column: Chiralcel AS-H, 60% CO 2 , 40% (0,5% DEA in MeOH)) to get 5 g of CIS-8-Dimethylamino-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-976) as a white solid. [M+H] +  274.2. 
     Synthesis of INT-977: CIS-2-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl)-acetic acid; 2,2,2-trifluoro-acetic acid salt 
     
       
         
         
             
             
         
       
     
     Step 1: CIS-2-[8-Dimethylamino-3-[(4-methoxyphenyl)-methyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5] decan-1-yl]-acetic Acid Tert-Butyl Ester 
     A solution of CIS-8-Dimethylamino-3-[(4-methoxyphenyl)-methyl]-8-phenyl-1,3-diazaspiro [4.5]decan-2-one (INT-975) (5.0 g, 12.7 mmol) in THF (18 mL) was cooled to 0° C. and treated with LDA solution (2M in THF/heptane/ether, 25.4 mL, 50.8 mmol). The resulting mixture was allowed to warm up to RT over 30 min. The solution was then cooled to 0° C. again and tert-butyl-bromoacetate (5.63 mL, 38.1 mmol) was added. The reaction mixture was stirred at RT for 16 h, quenched with water and extracted with DCM (3×). The combined organic layers were dried over Na 2 SO 4 , filtered and concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel provided CIS-2-[8-dimethylamino-3-[(4-methoxyphenyl)-methyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5] decan-1-yl]-acetic acid tert-butyl ester (4.4 g). 
     Step 2: cis-2-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl)-acetic Acid Trifluoroacetic Acid Salt 
     CIS-2-[8-Dimethylamino-3-[(4-methoxyphenyl)-methyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5] decan-1-yl]-acetic acid tert-butyl ester (200 mg, 0.4 mmol) was dissolved in TFA (5 mL) and heated to reflux overnight. After cooling to RT all volatiles are removed in vacuo. The residue was taken up in THF (1 mL) and added dropwise to diethyl ether (20 mL). The resulting precipitate was filtered off and dried under reduced pressure to give CTS-2-(8-dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl)-acetic acid; 2,2,2-trifluoro-acetic acid salt (INT-977) (119 mg) as a white solid. [M+H] +  332.2 
     Synthesis of INT-978: CIS-2-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl)-N,N-dimethyl-acetamide 
     
       
         
         
             
             
         
       
     
     CIS-2-(8-Dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl)-acetic acid (INT-977) trifluoroacetic acid salt (119 mg, 0.35 mmol) was dissolved in DCM (5 mL). Triethylamine (0.21 mL, 1.6 mmol), dimethylamine (0.54 mL, 1.1 mmol) and T3P (0.63 mL, 1.1 mmol) were sequentially added. The reaction mixture was stirred at RT overnight, then diluted with 1 M aq. Na 2 CO 3  (5 mL). The aqueous layer was extracted with DCM (3×5 mL), the combined organic layers were dried over Na 2 SO 4  and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel to yield CIS-2-(8-dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl)-N,N-dimethyl-acetamide (INT-978) (39 mg) as a white solid. [M+H] +  359.2 
     Synthesis of INT-982: CIS-8-Dimethylamino-1-[(1-methyl-cyclobutyl)-methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: CIS-8-(dimethylamino)-3-(4-methoxybenzyl)-1-((1-methylcyclobutyl)methyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     A solution of NaOH (2.85 g, 71.2 mmol) in DMSO (25 mL) was stirred at RT for 10 min. CIS-8-Dimethylamino-3-[(4-methoxyphenyl)-methyl]-8-phenyl-1,3-diazaspiro[4.5] decan-2-one (INT-975) (7.00 g, 17.8 mmol) was added and stirring was continued for 15 min. 1-(Bromo-methyl)-1-methyl-cyclobutane (8.7 g, 53.4 mmol) was added at 0° C. The reaction mixture was heated to 60° C. for 16 h. After cooling down to RT, water (100 mL) was added and the mixture was extracted with DCM (3×150 mL). The combined organic layers were washed with water (70 mL), brine (100 mL), dried over Na 2 SO 4  and concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel provided CIS-8-(dimethylamino)-3-(4-methoxybenzyl)-1-((1-methylcyclobutyl)methyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (6.5 g) as a light yellow solid. 
     Step 2: CIS-8-Dimethylamino-1-[(1-methyl-cyclobutyl)-methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     To the solution of CIS-8-Dimethylamino-1-[(1-methyl-cyclobutyl)-methyl]-8-phenyl-1,3-diazaspiro [4.5]decan-2-one (6.66 g, 14.0 mmol) in DCM (65 mL) was added TFA (65 mL) and the resulting mixture was stirred at RT for 16 h. The reaction mixture was concentrated under reduced pressure. The residue was taken up in DCM (100 mL) and water (60 mL) and basified with 2M aq. NaOH to pH 10. The organic layer was separated and washed with brine (40 mL), dried over MgSO 4 , filtered and concentrated under reduced pressure. Crystallization of the residue from EtOAc provided CIS-8-Dimethylamino-1-[(1-methyl-cyclobutyl)-methyl]-8-phenyl-1,3-diazaspiro[4.5] decan-2-one (INT-982) (3.41 g) as an off-white solid. [M+H] +  356.3 
     Synthesis of INT-984: CIS-1-(Cyclobutyl-methyl)-8-(ethyl-methyl-amino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: CIS-8-(dimethylamino)-1-isobutyl-3-(4-methoxybenzyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     In analogy to the method described for INT-951 step 1 CIS-8-Dimethylamino-3-[(4-methoxyphenyl)-methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-975) was converted into CIS-8-(dimethylamino)-1-isobutyl-3-(4-methoxybenzyl)-8-phenyl-1,3-diazaspiro [4.5]decan-2-one. 
     Step 2: CIS-1-(Cyclobutyl-methyl)-8-(ethyl-methyl-amino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     In analogy to the method described for INT-982 step 2 CIS-8-(dimethylamino)-1-isobutyl-3-(4-methoxybenzyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one was converted into CIS-1-(Cyclobutyl-methyl)-8-(ethyl-methyl-amino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-984). 
     Synthesis of INT-986: CIS-1-(Cyclobutyl-methyl)-8-(ethyl-methyl-amino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: CIS-3-benzyl-1-(cyclobutylmethyl)-8-(methylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     N-Iodosuccinimide (3.11 g, 13.92 mmol) was added to the solution of CIS-1-(Cyclobutyl-methyl)-8-dimethylamino-8-phenyl-3-[phenyl-methyl]-1,3-diazaspiro[4.5]decan-2-one (INT-950) (4 g, 9.28 mmol) in a mixture of acetonitrile and THF (1:1 v/v, 80 mL) and the resulting mixture was stirred at RT for 16 h. The reaction mixture was basified with 2N aq. NaOH to pH10 and the organic product was extracted with DCM (3×10 mL). The combined organic extracts were dried over anhydrous Na 2 SO 4  and concentrated in vacuo. The residue was stirred vigorously with a mixture of 10 wt % aq. citric acid (5 mL) and DCM (10 mL) at RT for 10 min. The reaction mixture was basified with 5N aq. NaOH to pH10 and extracted with DCM (3×10 mL). The combined organic layer was dried over anhydrous Na 2 SO 4  and concentrated in vacuo to give 3.5 g (crude) of CIS-3-benzyl-1-(cyclobutylmethyl)-8-(methylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one as semi solid (TLC system: 10% MeOH in DCM; R f : 0.60.). 
     Step 2: CIS-3-benzyl-1-(cyclobutylmethyl)-8-(ethyl(methyl)amino)-8-phenyl-1,3-diazaspiro [4.5]decan-2-one 
     Sodium cyanoborohydride (1.56 g, 25.17 mmol, 3 equiv.) was added to the solution of CIS-3-benzyl-1-(cyclobutylmethyl)-8-(methylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (3.5 g, 8.39 mmol), acetaldehyde (738 mg, 16.78 mmol, 2 equiv.) and acetic acid (0.5 mL) in methanol (20 mL). The reaction mixture was stirred at RT for 3 h, then quenched with sat. aq. NaHCO 3  and the organic product was extracted with DCM (3×50 mL). The combined organic extracts were dried over anhydrous Na 2 SO 4  and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (230-400 mesh) (20-25% ethyl acetate in petroleum ether) yielded 2.3 g (62%) of CIS-3-benzyl-1-(cyclobutylmethyl)-8-(ethyl(methyl)amino)-8-phenyl-1,3-diazaspiro [4.5]decan-2-one as a solid. (TLC system: 50% EtOAc in Pet. Ether; R f : 0.65). 
     Step 3: CIS-1-(Cyclobutyl-methyl)-8-(ethyl-methyl-amino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-986) 
     Sodium metal (1.18 g, 51.68 mmol, 10 equiv.) was added to liquid ammonia (25 mL) at -78° C. The resulting mixture was stirred for 10 min at −78° C. A solution of CIS-3-benzyl-1-(cyclobutylmethyl)-8-(ethyl(methyl)amino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (2.3 g, 5.16 mmol) in THF (25 mL) was added at −78° C. The reaction mixture was stirred for 15 min, then quenched with sat. aq. NH 4 Cl, warmed to RT and stirred for 1 h. The organic product was extracted with DCM (3×50 mL). The combined organic layer was washed with water, brine and concentrated under reduced pressure to afford 1.30 g (72%) of CIS-1-(cyclobutylmethyl)-8-(ethyl(methyl)amino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-986) as an off-white solid. (TLC system: 10% MeOH in DCM R f : 0.15.). [M+H] +  356.3 
     Synthesis of INT-987: CIS-1-(Cyclobutyl-methyl)-8-dimethylamino-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     In analogy to the method as described for INT-982 step 2 CIS-1-(Cyclobutyl-methyl)-8-dimethylamino-8-phenyl-3-[(4-methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decan-2-one (INT-952) was converted into CIS-1-(Cyclobutyl-methyl)-8-dimethylamino-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-987). 
     Synthesis of INT-988: CIS-8-(dimethylamino)-1-(2-(1-methoxycyclobutyl)ethyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: CIS-8-(dimethylamino)-1-[2-(1-methoxycyclobutyl)ethyl]-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     Sodium hydroxide (78.06 mg, 4.0 equiv.) was suspended in DMSO (3.5 mL), stirred for 10 minutes, 8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-975) (192.0 mg, 1.0 equiv.) was added, the reaction mixture was stirred for 5 min followed by addition of 2-(1-methoxycyclobutyl)ethyl 4-methylbenzenesulfonate (416.2 mg, 3.0 equiv.) in DMSO (1.5 mL). The resulting mixture was stirred overnight at 50° C. The reaction mixture was quenched with water and extracted with DCM (3×20 mL). The combined organic phases were washed with brine, dried over Na 2 SO 4  and concentrated under reduced pressure. The residue (283 mg yellow oil) was purified by column chromatography on silica gel (eluent DCM/EtOH 98/2 to 96/4) to give 8-(dimethylamino)-1-[2-(1-methoxycyclobutyl)ethyl]-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 163 mg (66%). 
     Step 2: CIS-8-(dimethylamino)-1-(2-(1-methoxycyclobutyl)ethyl)-8-phenyl-1,3-diazaspiro[4.5] decan-2-one (INT-988) 
     In analogy to the method described for INT-982 step 2 CIS-8-(dimethylamino)-1-[2-(1-methoxycyclobutyl)ethyl]-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one was converted into CIS-8-(dimethylamino)-1-(2-(1-methoxycyclobutyl)ethyl)-8-phenyl-1,3-diazaspiro[4.5] decan-2-one (INT-988). Mass: m/z 386.3 (M+H)+. 
     Synthesis of INT-989: CIS-3-(2-chloropyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     CIS-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-976) (1250 mg, 4.6 mmol), 5-bromo-2-chloro-pyrimidine (1.5 equiv., 6.7 mmol, 1327 mg), Cs 2 CO 3  (2 equiv., 9.15 mmol, 2980 mg), XantPhos (0.15 equiv., 0.69 mmol, 397 mg) and Pd 2 (dba) 3  (0.05 equiv., 0.23 mmol, 209 mg) were dissolved in dry 1,4-dioxane (120 equiv., 549 mmol, 47 mL) under nitrogen atmosphere and stirred at 90° C. overnight. The reaction mixture was cooled down, diluted with water (50 mL), extracted with DCM (3×70 mL), the combined organic phases were dried over Na 2 SO 4  and concentrated under reduced pressure. The residue (2.8 g) was suspended in 10 mL DCM and stirred for 10 min. The resulting precipitate was filtered off and washed with small amount of DCM to give 1213 mg of CIS-3-(2-chloropyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-989) as a white solid. The mother liquor was concentrated under reduced pressure (1428 mg), suspended in 3 mL DCM, 3 mL pentane were slowly added and the mixture was stirred for 30 min. The precipitate was filtered off, washed with small amounts of pentane and DCM to give second portion of INT-989 (215 mg) as a light yellow solid.  1 H NMR (600 MHz, DMSO) δ 8.94 (s, 2H), 7.88 (s, 1H), 7.41-7.33 (m, 4H), 7.27 (tt, 1H), 3.65 (s, 2H), 2.49-2.32 (m, 2H), 1.98-1.88 (m, 2H), 1.96 (s, 6H), 1.87-1.73 (m, 2H), 1.53-1.47 (m, 2H). Mass: m/z 386.2 (M+H) + . 
     Synthesis of INT-991: lithium CIS-5-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidine-2-carboxylate 
     
       
         
         
             
             
         
       
     
     Methyl CIS-5-[8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]pyrimidine-2-carboxylate (INT-990) (950 mg, 2.32 mmol) was suspended in a mixture of MeOH (140 equiv., 325 mmol, 13 mL) and THF (70 equiv., 162 mmol, 13 mL). Lithium hydroxide 2M aq. sol. (1.3 mL) was added. The reaction mixture was stirred 5 days at RT. Additional 1.3 mL of lithium hydroxide 2M aq. sol. were added and the reaction mixture was stirred for 2 h at RT. The solvents were removed under reduced pressure. The residue was suspended in EtOAc (10 mL) and stirred overnight. The precipitate was filtered off (1.07 g) and washed with DCM (3 mL), pentane and dried under reduced pressure. The resulting solid (960 mg) containing INT-990 and residual lithium salts was used directly in the next steps. Mass: m/z 394.2 (M−Li) − . 
     Synthesis of INT-1008: CIS-8-ethylamino-8-phenyl-1,3-diaza-spiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1 and step 2: ethyl-(8-phenyl-1,4-dioxa-spiro[4.5]dec-8-yl)-amine hydrochloride (INT-1004) 
     A mixture of 1,4-dioxa-spiro[4.5]decan-8-one (25.0 g, 160.25 mmol, 1.0 eq.) and 2M solution of EtNH 2  in THF (200 ml, 2.5 eq. 400.64 mmol) in EtOH (30 ml) was stirred at RT for 48h. The reaction mixture was concentrated under argon atmosphere and the residue was diluted with ether (60 ml), and a freshly prepared PhLi solution was added [prepared by addition of 2.5M n-BuLi in THF (70.5 ml, 1.1 eq. 176.27 mmol) to a solution of bromobenzene (27.675 g, 1.1 eq. 176.275 mmol) in ether (100 ml) at −30° C. and stirred at RT for 1h). The reaction mixture was stirred at RT for 1.5h, quenched with saturated NH 4 Cl solution (100 ml) at 0° C. and extracted with ethyl acetate (2×750 ml). The combined organic layer was washed with water (3×350 ml), brine (300 ml), dried over Na 2 SO 4  and concentrated under reduced pressure. The resulting residue was dissolved in ethyl methyl ketone (100 ml) and trimethylsilyl chloride (37.5 ml) was added at 0° C. The resulting mixture was stirred at RT for 16h. The precipitated solid was filtered off and washed with acetone followed by THF to get ethyl-(8-phenyl-1,4-dioxa-spiro[4.5]dec-8-yl)-amine hydrochloride as an off white solid. This reaction was done in 2 batches of 25 g scale and the yield is given for 2 combined batches. Yield: 18% (17.1 g, 57.575 mmol). LCMS: m/z 262.2 (M+H) + . 
     Step 3: 4-ethylamino-4-phenyl-cyclohexanone (INT-1005) 
     To a solution of ethyl-(8-phenyl-1,4-dioxa-spiro[4.5]dec-8-yl)-amine hydrochloride (10.1 g, 34.0 mmol, 1 eq.) in water (37.5 ml) was added conc. aq. HCl (62.5 ml) at 0° C. and the resulting mixture was stirred at RT for 16 h. The reaction mixture was basified with aq. NaOH (pH 14) at 0° C. and extracted with DCM (2×750 ml). Organic layer was washed with water (400 ml), brine (400 ml), dried over Na 2 SO 4  and concentrated under reduced pressure to yield 4-ethylamino-4-phenyl-cyclohexanone which was used in the next step without further purification. This reaction was carried out in another batch of 15.1 g scale and the yield is given for 2 combined batches. Yield: 92% (17.0 g, 78.34 mmol). 
     Step 4: cis and trans mixture of 8-ethylamino-8-phenyl-1,3-diaza-spiro[4.5]decane-2,4-dione (INT-1006 and INT-1007) 
     To a solution of 4-ethylamino-4-phenyl-cyclohexanone (17 g, 78.341 mmol, 1.0 eq.) in EtOH (250 ml) and water (200 ml) was added (NH 4 ) 2 CO 3  (18.8 g, 195.85 mmol, 2.5 eq.) and the reaction mixture was stirred at RT for 15 min. KCN (5.09 g, 78.341 mmol, 1.0 eq.) was added and stirring was continued at 60° C. for 18 h. The reaction mixture was cooled down to RT. The precipitated solid was filtered off, washed with water (250 ml), EtOH (300 ml), hexane (200 ml) and dried under reduced pressure to yield cis and trans mixture of 8-ethylamino-8-phenyl-1,3-diaza-spiro[4.5]decane-2,4-dione (13.0 g, 45.29 mmol, 58%) as a white solid. Yield: 58% (13 g, 45.296 mmol). LC-MS: m/z [M+1] + =288.2. 
     Step 5: CIS-8-ethylamino-8-phenyl-1,3-diaza-spiro[4.5]decane-2,4-dione (INT-1006) 
     To a solution of cis and trans mixture of 8-ethylamino-8-phenyl-1,3-diaza-spiro[4.5]decane-2,4-dione (12 g) in MeOH-DCM (1:1, 960 ml) was added a solution of L-tartaric acid in MeOH (25 ml) and the resulting mixture stirred at RT for 2 h and then kept in refrigerator for 16 h. The precipitated solid was filtered off and washed with MeOH-DCM (1:5, 50 ml) to get tartrate salt of 8-ethylamino-8-phenyl-1,3-diaza-spiro[4.5]decane-2,4-dione (7.5 g) as a white solid. To this solid sat. aq. NaHCO 3  was added (pH8) and the resulting mixture was extracted with 25% MeOH-DCM (2×800 ml). Combined organic layer was washed with water (300 ml), brine (300 ml), dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure. The residue was triturated with 20% DCM-hexane and the resulting solid was dried under reduced pressure to afford CIS-8-ethylamino-8-phenyl-1,3-diaza-spiro[4.5]decane-2,4-dione as white solid. This step was done in 2 batches (12 g &amp; 2.4 g) and the yield is given for 2 combined batches. Yield: 31.2% (5.0 g, 17.421 mmol). LC-MS: m/z [M+1]=288.0. 
     Step 6: CIS-8-ethylamino-8-phenyl-1,3-diaza-spiro[4.5]decan-2-one (INT-1008) 
     To a slurry of LiAlH 4  (793 mg, 20.91 mmol, 3.0 eq.) in THF (15 ml) was added a suspension of CIS-8-ethylamino-8-phenyl-1,3-diaza-spiro[4.5]decane-2,4-dione (2.0 g, 6.97 mmol, 1.0 eq.) in THF (60 ml) at 0° C. and the reaction mixture was heated to 65° C. for 16 h. The reaction mixture was cooled to 0° C., quenched with sat. aq. Na 2 SO 4  (20 ml), stirred at RT for 1h and filtered through celite pad. The residue was washed with 15% MeOH-DCM (500 ml). The combined filtrate was dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure to give crude product which was triturated with 15% DCM-Hexane to afford CIS-8-ethylamino-8-phenyl-1,3-diaza-spiro[4.5]decan-2-one (INT-1008) (1.6 g, 5.86 mmol, 84%) as a white solid. Yield: 84% (1.6 g, 5.86 mmol). LC-MS: m/z [M+1] + =274.2. 
     Synthesis of INT-1026: CIS-8-(methyl((tetrahydrofuran-3-yl)methyl)amino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1:2-methyl-N-(1,4-dioxaspiro[4.5]decan-8-ylidene)propane-2-sulfinamide 
     Titanium ethoxide (58.45 g, 256.4 mmol) was added to a solution of 1,4-dioxaspiro[4.5]decan-8-one (20 g, 128.20 mmol) and 2-methylpropane-2-sulfinamide (15.51 g, 128.20 mmol) in THF (200 mL) at RT and the reaction mixture was stirred at RT for 18h. The reaction mixture was cooled to 0° C. and quenched by dropwise addition of sat. aq. NaHCO 3  (500 mL) over a period of 30 min. The organic product was extracted with EtOAc (3×100 mL). The combined organic extracts were dried over anhydrous Na 2 SO 4  and concentrated in vacuo to afford 10 g (crude) of 2-methyl-N-(1,4-dioxaspiro[4.5]decan-8-ylidene)propane-2-sulfinamide as a white solid (TLC system: 30% Ethyl acetate in hexane; Rf: 0.30). 
     Step 2: 2-methyl-N-(8-phenyl-1,4-dioxaspiro[4.5]decan-8-yl)propane-2-sulfinamide 
     Phenylmagnesium bromide (1M in THF, 116 mL, 116 mmol) was added dropwise to a solution of 2-methyl-N-(1,4-dioxaspiro[4.5]decan-8-ylidene)propane-2-sulfinamide (10 g, 38.61 mmol) in THF (500 mL) at −10° C. under argon atmosphere. The reaction mixture was stirred for 2h at −10° C. to 0° C. The reaction completion was monitored by TLC. The reaction mixture was quenched with sat. aq. NH 4 Cl (50 mL) at 0° C. and the organic product was extracted with EtOAc (3×100 mL). The combined organic extracts were dried over anhydrous Na 2 SO 4  and concentrated in vacuo. The residue was purified by column chromatography (silica gel 230-400 mesh; 40-60% ethyl acetate in hexane) to yield 6.0 g (46%) of 2-methyl-N-(8-phenyl-1,4-dioxaspiro[4.5]decan-8-yl)propane-2-sulfinamide as a liquid (TLC system: 70% Ethyl acetate in hexane; Rf: 0.30). 
     Step 3: 8-phenyl-1,4-dioxaspiro[4.5]decan-8-amine hydrochloride 
     2N solution of HCl in diethyl ether (17.80 mL, 35.60 mmol) was added to a solution of 2-methyl-N-(8-phenyl-1,4-dioxaspiro[4.5]decan-8-yl)propane-2-sulfinamide (6.0 g, 17.80 mmol) in DCM (60 mL) at 0° C. The reaction mixture was stirred at RT for 2 h. The reaction mixture was concentrated in vacuo. The residue was washed with diethyl ether to yield 3 g (crude) of 8-phenyl-1,4-dioxaspiro[4.5]decan-8-amine hydrochloride as a brown solid (TLC system: 5% MeOH in DCM; Rf: 0.10). 
     Step 4: 8-phenyl-N-((tetrahydrofuran-3-yl)methyl)-1,4-dioxaspiro[4.5]decan-8-amine 
     Sodium cyanoborohydride (2.17 g, 33.45 mmol) was added to a solution of 8-phenyl-1,4-dioxaspiro[4.5]decan-8-amine hydrochloride (3.0 g, 11.15 mmol) and tetrahydrofuran-3-carbaldehyde (4.46 mL, 22.30 mmol) and acetic acid (0.05 mL) in methanol (30 mL) at 0° C. The reaction mixture was stirred at RT for 16h. The reaction mixture was concentrated in vacuo at 30° C. and to the residue sat. aq. NaHCO 3  was added. The organic product was extracted with DCM (3×30 mL). The combined organic extracts were dried over anhydrous Na 2 SO 4  and solvent was concentrated under reduced pressure to get 3 g (crude) of 8-phenyl-N-((tetrahydrofuran-3-yl)methyl)-1,4-dioxaspiro[4.5]decan-8-amine as a semi-solid (TLC system: 10% MeOH in DCM; Rf: 0.22). 
     Step 5: N-methyl-8-phenyl-N-((tetrahydrofuran-3-yl)methyl)-1,4-dioxaspiro[4.5]decan-8-amine) 
     Sodium cyanoborohydride (1.76 g, 28.39 mmol) was added to a solution of 8-phenyl-N-((tetrahydrofuran-3-yl)methyl)-1,4-dioxaspiro[4.5]decan-8-amine (3.0 g, 9.46 mmol), 37% formaldehyde in water (7.70 mL, 94.60 mmol) and acetic acid (0.05 mL) in methanol (30 mL) at 0° C. The reaction mixture was stirred at RT for 16 h. The reaction mixture was concentrated in vacuo and to the residue sat. aq. NaHCO 3  was added. The organic product was extracted with DCM (3×30 mL). The combined organic extracts were dried over anhydrous Na 2 SO 4  and solvent was concentrated under reduced pressure. The resulting residue was purified by column chromatography (silica gel 230-400 mesh; 5-6% MeOH in DCM) to yield 2.50 g (83%) of N-methyl-8-phenyl-N-((tetrahydrofuran-3-yl)methyl)-1,4-dioxaspiro[4.5]decan-8-amine as a semi solid (TLC system: 10% MeOH in DCM; R f : 0.25). 
     Step 6: 4-(methyl((tetrahydrofuran-3-yl)methyl)amino)-4-phenylcyclohexanone 
     5% sulfuric acid in water (25 mL) was added to N-methyl-8-phenyl-N-((tetrahydrofuran-3-yl)methyl)-1,4-dioxaspiro[4.5]decan-8-amine (2.50 g, 7.55 mmol) at 0° C. and the resulting mixture was stirred at RT for 24 h. The reaction mixture was quenched with sat. aq. NaHCO 3  and the organic product was extracted with DCM (2×50 mL). The combined organic layers were dried over anhydrous Na 2 SO 4  and concentrated in vacuo to afford 2.0 g (crude) of 4-(methyl((tetrahydrofuran-3-yl)methyl)amino)-4-phenylcyclohexanone as a thick liquid (TLC system: 10% MeOH in DCM, Rf: 0.20). 
     Step 7: 8-(methyl((tetrahydrofuran-3-yl)methyl)amino)-8-phenyl-1,3-diazaspiro[4.5]decane-2,4-dione 
     4-(methyl((tetrahydrofuran-3-yl)methyl)amino)-4-phenylcyclohexanone (1.50 g, 5.22 mmol) was suspended in 30 mL of EtOH:H 2 O (1:1 v/v) at RT under argon atmosphere. (NH 4 ) 2 CO 3  (1.9 g, 13.05 mmol) and KCN (0.34 g, 5.22 mmol) were added. The reaction mixture was heated to 70° C. for 16 h. The reaction mixture was diluted with ice-water and the organic product was extracted with DCM (2×50 mL). The combined organic layer was dried over anhydrous Na 2 SO 4  and concentrated in vacuo to give 1.0 g (crude) of 8-(methyl((tetrahydrofuran-3-yl)methyl)amino)-8-phenyl-1,3-diazaspiro[4.5]decane-2,4-dione as a solid (TLC system: 70% Ethyl acetate in hexane; Rf: 0.18). 
     Step 8: CIS-8-(methyl((tetrahydrofuran-3-yl)methyl)amino)-8-phenyl-1,3-diazaspiro[4.5]decane-2,4-dione 
     Diastereomeric mixture of 8-(methyl((tetrahydrofuran-3-yl)methyl)amino)-8-phenyl-1,3-diazaspiro[4.5]decane-2,4-dione (1.0 g) was separated by reverse phase preparative HPLC to afford 400 mg of isomer 1 (CIS-8-(methyl((tetrahydrofuran-3-yl)methyl)amino)-8-phenyl-1,3-diazaspiro[4.5]decane-2,4-dione) and 60 mg of isomer 2 (TRANS-8-(methyl((tetrahydrofuran-3-yl)methyl)amino)-8-phenyl-1,3-diazaspiro[4.5]decane-2,4-dione) and 300 mg of mixture of both isomers. Reverse phase preparative HPLC conditions: mobile phase: 10 mM ammonium bicarbonate in H 2 O/acetonitrile, column: X-BRIDGE-C18 (150*30), 5 μm, gradient (T/B %): 0/35, 8/55, 8.1/98, 10/98, 10.1/35, 13/35, flow rate: 25 ml/min, diluent: mobile phase+THF. 
     Step 9: CIS-8-(methyl((tetrahydrofuran-3-yl)methyl)amino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-1026) 
     LiAlH 4  (1M in THF) (4.48 mL, 4.48 mmol) was added to a solution of CIS-8-(methyl((tetrahydrofuran-3-yl)methyl)amino)-8-phenyl-1,3-diazaspiro[4.5]decane-2,4-dione (isomer-1) (0.4 g, 1.12 mmol) in THF:Et 2 O (2:1 v/v, 15 mL) at 0° C. under argon atmosphere. The reaction mixture was stirred at 65° C. for 16 h. The mixture was cooled to 0° C., quenched with sat. aq. Na 2 SO 4  (1000 mL) and filtered through celite pad. The filtrate was dried over anhydrous Na 2 SO 4  and concentrated in vacuo. The residue was purified by column chromatography (silica gel 230-400 mesh; 5-6% MeOH in DCM) to yield 0.3 g (78%) of CIS-8-(methyl((tetrahydrofuran-3-yl)methyl)amino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-1026) as an off white solid. (TLC system: 10% MeOH in DCM, Rf: 0.2). LC-MS: m/z [M+1] + =344.2. 
     Synthesis of INT-1031: CIS-1-(Cyclobutyl-methyl)-8-dimethylamino-8-(3-fluorophenyl)-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: CIS-1-(Cyclobutyl-methyl)-8-dimethylamino-8-(3-fluorophenyl)-3-[(4-methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decan-2-one 
     In analogy to the method described for INT-952 CIS-8-dimethylamino-8-(3-fluorophenyl)-3-[(4-methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decan-2-one (INT-974) was converted into CIS-1-(cyclobutyl-methyl)-8-dimethylamino-8-(3-fluorophenyl)-3-[(4-methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decan-2-one. 
     Step 2: CIS-1-(Cyclobutyl-methyl)-8-dimethylamino-8-(3-fluorophenyl)-1,3-diazaspiro[4.5]decan-2-one 
     In analogy to the method described for INT-982 step 2 1-(cyclobutyl-methyl)-8-dimethylamino-8-(3-fluorophenyl)-3-[(4-methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decan-2-one was converted into 1-(cyclobutyl-methyl)-8-dimethylamino-8-(3-fluorophenyl)-1,3-diazaspiro[4.5]decan-2-one (INT-1031). 
     Synthesis of INT-1037: 8-(dimethylamino)-2-oxo-1,3-diazaspiro[4.5]decane-8-carbonitrile 
     
       
         
         
             
             
         
       
     
     Step 1: 9,12-dioxa-2,4-diazadispiro[4.2.4{circumflex over ( )}{8}.2{circumflex over ( )}{5}]tetradecan-3-one 
     Lithiumaluminiumhydride (2.2 equiv., 292 mmol) was suspended in THF (400 mL) and the suspension was cooled to 0° C. 8-(Dimethylamino)-8-(m-tolyl)-1,3-diazaspiro[4.5]decan-2-one (B, 75 mg, 0,261 mmol) (step 1 of INT-965) was added portionwise at 0° C. The reaction mixture was stirred 1.5 h at 0° C., then overnight at RT and then 2 h at 40° C. The reaction mixture was cooled down to 0° C., quenched carefully with sat. aq. Na 2 SO 4 , EtOAc (400 mL) was added and the resulting mixture was stirred for 2 h and then left without stirring for 2h at RT. The precipitate was filtered off and washed with EtOAc and MeOH. The resulting solid residue was suspended in methanol and stirred at RT overnight. The precipitate was filtered off and disposed. The filtrate was concentrated under reduced pressure, the residue was suspended thoroughly in water (50 mL) at 40° C., the precipitate was filtered off and dried under reduced pressure to yield 9,12-dioxa-2,4-diazadispiro[4.2.4{circumflex over ( )}{8}.2{circumflex over ( )}{5}]tetradecan-3-one (11.4 g, 41%). Mass: m/z 213.2 (M+H) + . 
     Step 2: 1,3-diazaspiro[4.5]decane-2,8-dione 
     In analogy to the method described for INT-1003 step 3 9,12-dioxa-2,4-diazadispiro[4.2.4{circumflex over ( )}{8}.2{circumflex over ( )}{5}]tetradecan-3-one was treated with conc. aq. HCl to be converted into 1,3-diazaspiro[4.5]decane-2,8-dione. Mass: m/z 169.1 (M+H) + . 
     Step 3: 8-(dimethylamino)-2-oxo-1,3-diazaspiro[4.5]decane-8-carbonitrile (INT-1037) 
     In analogy to the method described for INT-965 step 1 1,3-diazaspiro[4.5]decane-2,8-dione was treated with dimethyl amine and potassium cyanide to be converted into 8-(dimethylamino)-2-oxo-1,3-diazaspiro[4.5]decane-8-carbonitrile (INT-1037). Mass: m/z 223.2 (M+H) + . 
     Synthesis of INT-1038: CIS-8-(dimethylamino)-8-(m-tolyl)-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     To the suspension of 8-(dimethylamino)-2-oxo-1,3-diazaspiro[4.5]decane-8-carbonitrile (200 mg, 0.90 mmol) in THF (4 mL) at RT was added dropwise IM bromo(m-tolyl)magnesium in THF (4 equiv., 3.6 mmol, 3.6 mL) and the reaction mixture was stirred for 1 h at RT. Additional portion of IM bromo(m-tolyl)magnesium in THF (1 equiv., 0.8 mL) was added. The reaction mixture was stirred at RT overnight, then quenched with methanol/water. Solid NH 4 Cl and DCM were added to the resulting mixture and the precipitate was filtered off. The organic phase of the filtrate was separated and the aqueous phase was extracted with DCM (3×). The combined organic phases were dried over anhydr. Na 2 SO 4  and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (DCM/MeOH, 100/0 to 65/35) to yield CIS-8-(dimethylamino)-8-(m-tolyl)-1,3-diazaspiro[4.5]decan-2-one (INT-1038) (81 mg, 31%). Mass: m/z 288.2 (M+H) + . 
     Synthesis of INT-1059: TRANS-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: TRANS-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decane-2,4-dione 
     To a stirred solution of 4-dimethylamino-4-phenyl-cyclohexanone (250.0 g, 1.15 mol, 1.0 eq.) in EtOH (2.5 L) and water (2.1 L) was added (NH 4 ) 2 CO 3  (276.2 g, 2.87 mol, 2.5 eq.) and the reaction mixture was stirred at RT for 15 min. KCN (74.92 g, 1.15 mol, 1.0 eq.) was added. The reaction mixture was stirred at 60° C. for 18h and then filtered in hot condition to get white solid which was washed with water (2.5 L), ethanol (1 L) and hexane (2.5 L). The resulting solid was dried under reduced pressure to get CIS-8-dimethylamino-8-phenyl-1,3-diaza-spiro[4.5]decane-2,4-dione (223 g, 0.776 mol, 65%) as a white solid. The filtrate was collected from multiple batches (450 g) which contained a mixture of cis and trans isomers. The filtrate was concentrated under reduced pressure and solid obtained was filtered and washed with water (1 L) and hexane (1 L). Solid material was dried under reduced pressure to get 100 g of a mixture of cis and trans (major) isomers. Crude material was partially dissolved in hot MeOH (600 mL) and cooled to RT, filtered through sintered funnel, washed with MeOH (200 mL) followed by ether (150 mL) and dried to get TRANS-8-dimethylamino-8-phenyl-1,3-diaza-spiro[4.5]decane-2,4-dione (50 g, 0.174 mmol, 9-10%). 
     Step 2: TRANS-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-1059) 
     In analogy to the method described for INT-976 step 2 TRANS-8-dimethylamino-8-phenyl-1,3-diaza-spiro[4.5]decane-2,4-dione was treated with LiAlH 4  to be converted into TRANS-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-1059). Mass: m/z 274.2 (M+H) + . 
     Synthesis of INT-1068 and INT-1069: CIS- and TRANS-8-(dimethylamino)-8-phenyl-1-(2,2,2-trifluoroethyl)-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: 1-amino-4-dimethylamino-4-phenyl-cyclohexanecarbonitrile 
     To a stirred solution of 4-dimethylamino-4-phenyl-cyclohexanone (50 g, 230.096 mmol) in MeOH (400 mL) was added NH 4 Cl(24.6 g, 460.8 mmol) followed by NH 4 OH (400 mL) at RT and the reaction mixture was stirred for 15 min. NaCN (22.5 g, 460.83 mmol) was added and the resulting mixture was stirred for 16 h at RT. The reaction mixture was extracted with DCM (3×750 mL). Combined organic layer was washed with water (750 mL), brine (750 mL), dried over Na 2 SO 4  and concentrated under reduced pressure. The residue was triturated with DCM/hexane to get crude 1-amino-4-dimethylamino-4-phenyl-cyclohexanecarbonitrile (50 g, 90%) as an off white solid which was used in next step without further purification. LC-MS: m/z [M+H] + =244.2 (MW calc. 244.09). 
     Step 2: N-(1-cyano-4-dimethylamino-4-phenyl-cyclohexyl)-2,2,2-trifluoroacetamide 
     To a solution of 1-amino-4-dimethylamino-4-phenyl-cyclohexanecarbonitrile (5.0 g, 20.57 mmol, 1.0 eq.) in THF (100 ml) were added DIPEA (10.72 ml, 61.71 mmol, 3.0 eq), trifluoroacetic acid (1.89 ml, 24.69 mmol, 1.2 eq) and T3P (18.2 ml, 30.85 mmol, 1.5 eq) at 0° C. The reaction mixture was stirred at RT for 16h, then diluted with water (100 ml) and extracted with 10% MeOH in DCM (2×250 mL). Combined organic layer was washed with brine (100 mL), dried over Na 2 SO 4  and concentrated under reduced pressure to get crude N-(1-cyano-4-dimethylamino-4-phenyl-cyclohexyl)-2,2,2-trifluoroacetamide as a light yellow sticky material which was used in the next step without further purification. LC-MS: m/z [M+1]=339.9 (MW calc. 339.36). 
     Step 3: 1-aminomethyl-N′,N′-dimethyl-4-phenyl-N-(2,2,2-trifluoroethyl)cyclohexane-1,4-diamine 
     To suspension of LiAlH 4  (4.03 g, 106.19 mmol, 6.0 eq.) in dry THF (40 mL) was added N-(1-cyano-4-dimethylamino-4-phenyl-cyclohexyl)-2,2,2-trifluoro-acetamide (6.0 g, 17.69 mmol, 1.0 eq.) in dry THF (100 mL) dropwise at 0° C. The reaction mixture was stirred at RT for 16 h, then quenched with sat. aq. Na 2 SO 4  at 0° C., excess THF was added and the resulting mixture was stirred at RT for 2 h. The resulting suspension was filtered through celite and the filter cake was washed with 10% MeOH in DCM (150 mL). Combined filtrate was concentrated under reduced pressure to yield crude 1-aminomethyl-N′,N′-dimethyl-4-phenyl-N-(2,2,2-trifluoro-ethyl)-cyclohexane-1,4-diamine (4.2 g, crude) as a light yellow sticky material which was directly used in the next step without further purification. LC-MS: m/z [M+1]*=330.0 (MW calc. 329.40). 
     Step 4: CIS- and TRANS-8-dimethylamino-8-phenyl-1-(2,2,2-trifluoro-ethyl)-1,3-diaza-spiro[4.5]decan-2-one (INT-1068 and INT-1069) 
     To a solution of 1-aminomethyl-N′,N′-dimethyl-4-phenyl-N-(2,2,2-trifluoro-ethyl)-cyclohexane-1,4-diamine (4.2 g, 12.76 mmol, 1.0 eq.) in toluene (60 ml) was added KOH (4.29 g, 76.56 mmol, 6.0 eq.) in water (120 ml) at 0° C. followed by addition of COCl 2  (15.6 ml, 44.66 mmol, 3.5 eq., 20% in toluene) at 0° C. and stirred at RT for 16 h. Reaction mixture was basified with sat NaHCO 3  solution and extracted with DCM (2×200 ml). Combined organic layer was dried over Na 2 SO 4  and concentrated under reduced pressure to get crude product which was purified by prep HPLC to get CIS-8-dimethylamino-8-phenyl-1-(2,2,2-trifluoro-ethyl)-1,3-diaza-spiro[4.5]decan-2-one (INT-1068) (1.5 g) (major isomer, polar spot on TLC) and TRANS-8-dimethylamino-8-phenyl-1-(2,2,2-trifluoro-ethyl)-1,3-diaza-spiro[4.5]decan-2-one (INT-1069) as minor isomer (non-polar spot on TLC) (120 mg, 92.93% by HPLC) as off-white solids. CIS-isomer: LC-MS: m/z [M+1] + =356.2 (MW calc.=355.40). HPLC: 98.53%, Column: Xbridge C-18 (100×4.6), 5p, Diluent: MeOH, Mobile phase: A) 0.05% TFA in water; B) ACN flow rate: 1 ml/min, Rt=5.17 min.  1 HNMR (DMSO-d 6 , 400 MHz), δ (ppm)=7.43-7.27 (m, 5H), 6.84 (s, 1H), 3.30-3.25 (m, 4H), 2.66-2.63 (d, 2H, J=12.72 Hz), 1.89 (s, 6H), 1.58-1.51 (m, 2H), 1.46-1.43 (m, 2H), 1.33-1.23 (m, 2H). 
     For further intermediates the synthesis in analogy to previously described methods is given in the following table. The syntheses of the building blocks and intermediates have either been described previously within this application or can be performed in analogy to the herein described methods or by methods known to the person, skilled in the art. Such a person will also know which building blocks and intermediates need to be chosen for synthesis of each exemplary compound. 
     
       
         
           
               
               
               
               
               
             
               
                   
               
               
                 Inter- 
                   
                   
                 in analogy to 
                 m/z 
               
               
                 mediate 
                 Chemical Name 
                 Chemical Structure 
                 method 
                 [M + H] +   
               
               
                   
               
             
            
               
                 INT-601 
                 CIS-5-(-8- (dimethylamino)- 8-(3-fluorophenyl)-2- oxo-1,3-diazaspiro[4.5] decan-3-yl)pyrimidine- 2-carbonitrile 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-600 
                 395.1 
               
               
                   
               
               
                 INT-794 
                 CIS-3-(3,4- dimethoxybenzyl)-8- (dimethylamino)-8- phenyl-1,3- diazaspiro [4.5]decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-975 
                 424.3 
               
               
                   
               
               
                 INT-796 
                 CIS-8-Dimethylamino-3- [(4-methoxyphenyl)- methyl]-8-(3-methoxy- propyl)-1,3-diazaspiro [4.5]decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-974 
                 390.3 
               
               
                   
               
               
                 INT-797 
                 CIS-8-(Ethyl- methyl-amino)- 8-phenyl-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-976 
                 288.2 
               
               
                   
               
               
                 INT-949 
                 CIS-8-Dimethylamino- 1-ethyl-8-phenyl-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-984 
                 302.2 
               
               
                   
               
               
                 INT-950 
                 CIS-1-(Cyclobutyl- methyl)-8- dimethylamino-8- phenyl-3-[phenyl- methyl]-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-952 
                 432.3 
               
               
                   
               
               
                 INT-954 
                 4-Dimethylamino-4- (5-methyl-thiophen- 2-yl)-cyclohexan-1-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-965 
                 238.1 
               
               
                   
               
               
                 INT-955 
                 4-Dimethylamino-4- thiophen-2-yl- cyclohexan-1-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-965 
                 224.1 
               
               
                   
               
               
                 INT-956 
                 1-(1-Methyl-1H- pyrazol-3-yl)-4-oxo- cyclohexane-1- carbonitrile 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-958 
                 204.1 
               
               
                   
               
               
                 INT-957 
                 4-Oxo-1-pyrazin-2-yl- cyclohexane-1- carbonitrile 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-958 
                 202.1 
               
               
                   
               
               
                 INT-959 
                 4-Dimethylamino-4-(1- methyl-1H-pyrazol-3-yl)- cyclohexan-1-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-961 
                 222.2 
               
               
                   
               
               
                 INT-960 
                 4-Dimethylamino-4- pyrazin-2-yl-cyclohexan- 1-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-961 
                 220.1 
               
               
                   
               
               
                 INT-962 
                 4-Dimethylamino-4- (3-methoxyphenyl)- cyclohexan-1-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-965 
                 248.2 
               
               
                   
               
               
                 INT-963 
                 CIS-3-Benzyl-8- dimethylamino- 8-phenyl-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-975 
                 364.2 
               
               
                   
               
               
                 INT-964 
                 4-(Ethyl-methyl-amino)- 4-phenyl-cyclohexan-1- one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-965 
                 232.2 
               
               
                   
               
               
                 INT-967 
                 CIS-8-Dimethylamino- 8-[4- (methoxymethyloxy)- phenyl]-3-[(4- methoxyphenyl)- methyl]-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-974 
                 454.3 
               
               
                   
               
               
                 INT-968 
                 CIS-8-Dimethylamino- 8-[3- (methoxymethyloxy)- phenyl]-3-[(4- methoxyphenyl)- methyl]-1,3- diazaspiro[4.5]decan- 2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-974 
                 454.3 
               
               
                   
               
               
                 INT-969 
                 CIS-1-(Cyclobutyl- methyl)- 8-dimethylamino-8- (4-hydroxyphenyl)-3- [(4-methoxyphenyl)- methyl]-1,3-diazaspiro [4.5]decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-971 
                 478.3 
               
               
                   
               
               
                 INT-970 
                 CIS-8-Dimethylamino- 8-(4-methoxyphenyl)-3- [(4-methoxyphenyl)- methyl]-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 SC_2017 
                 424.3 
               
               
                   
               
               
                 INT-972 
                 CIS-8- Dimethylamino-8- (3-methoxyphenyl)-3- [(4-methoxyphenyl)- methyl]-1,3- diazaspiro[4.5]decan- 2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 SC_2017 
                 424.3 
               
               
                   
               
               
                 INT-973 
                 CIS-8- Dimethylamino-8- (4-fluorophenyl)-3-[(4- methoxyphenyl)- methyl]-1,3-diazaspiro [4.5]decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-974 
                 412.2 
               
               
                   
               
               
                 INT-979 
                 CIS-8-Dimethylamino- 1-(3-methoxy-propyl)-8- phenyl-1,3-diazaspiro [4.5]decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-984 
                 346.2 
               
               
                   
               
               
                 INT-980 
                 CIS-8-Dimethylamino-1- (2-methoxy-ethyl)-8- phenyl-1,3-diazaspiro [4.5]decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-984 
                 332.2 
               
               
                   
               
               
                 INT-981 
                 CIS-8-Dimethylamino-8- phenyl-1-propyl-1,3- diazaspiro[4.5]decan- 2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-984 
                 316.2 
               
               
                   
               
               
                 INT-983 
                 CIS-1-(Cyclopropyl- methyl)-8- dimethylamino-8- phenyl-1,3-diazaspiro [4.5]decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-984 
                 328.2 
               
               
                   
               
               
                 INT-985 
                 CIS-1-(Cyclobutyl- methyl)- 8-(methyl-propyl- amino)-8-phenyl-1,3- diazaspiro [4.5]decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-986 
                 370.3 
               
               
                   
               
               
                 INT-990 
                 methyl CIS-5-(8- (dimethylamino)-2-oxo- 8-phenyl-1,3-diazaspiro [4.5]decan- 3-yl)pyrimidine- 2-carboxylate 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-989 
                 410.2 
               
               
                   
               
               
                 INT-992 
                 CIS-3-(2-chloro-4- methylpyrimidin-5-yl)-8- (dimethylamino)- 8-phenyl-1,3- diazaspiro[4.5]decan- 2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-989 
                 400.2 
               
               
                   
               
               
                 INT-993 
                 4-benzyl-4- (dimethylamino) cyclochexanone 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-965 
                 232.3 
               
               
                   
               
               
                 INT-994 
                 CIS-8-benzyl-8- (dimethylamino)-1,3- diazaspiro[4.5]decan- 2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-976 
                 288.2 
               
               
                   
               
               
                 INT-995 
                 TRANS-8-benzyl-8- (dimethylamino)-1,3- diazaspiro[4.5]decan- 2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-976 
                 288.2 
               
               
                   
               
               
                 INT-997 
                 CIS-8-(dimethylamino)- 8-(thiophen-2-yl)-1,3- diazaspiro[4.5]decan- 2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-976 
                 280.1 
               
               
                   
               
               
                 INT-998 
                 TRANS-8- (dimethylamino)- 8-(thiophen-2-yl)- 1,3-diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-976 
                 280.1 
               
               
                   
               
               
                 INT-999 
                 4-(dimethylamino)- 4-(1-methyl-1H- benzo[d]imidazol-2-yl) cyclohexanone 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-965 
                 272.2 
               
               
                   
               
               
                 INT-1000 
                 CIS-8-(dimethylamino)- 8-(1-methyl-1H- benzo[d]imidazol-2-yl)- 1,3-diazaspiro [4.5]decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-976 
                 328.2 
               
               
                   
               
               
                 INT-1001 
                 TRANS-8- (dimethylamino)- 8-(1-methyl-1H- benzo[d]imidazol- 2-yl)-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-976 
                 328.2 
               
               
                   
               
               
                 INT-1002 
                 CIS-3-(2- chloropyrimidin- 4-yl)-8- (dimethylamino)-8- phenyl-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-989 
                 386.9 
               
               
                   
               
               
                 INT-1009 
                 TRANS-8-ethylamino- 8-phenyl-1,3-diaza- spiro[4.5]decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-1008 
                 274.2 
               
               
                   
               
               
                 INT-1024 
                 CIS-8-(dimethylamino)- 8-(3-fluorophenyl)-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-977 (step 2) 
                 292.2 
               
               
                   
               
               
                 INT-1025 
                 CIS-8-(dimethylamino)- 8-(4-fluorophenyl)-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-974, INT-977 (step 2) 
                 292.2 
               
               
                   
               
               
                 INT-1027 
                 CIS-3-(2- chloropyrimidin-5-yl)- 8-(dimethylamino)-8- (thiophen- 2-yl)-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-989 
                 392.1 
               
               
                   
               
               
                 INT-1039 
                 CIS-8-(dimethylamino)- 8-(3- (trifluoromethoxy) phenyl)-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-1038 
                 358.2 
               
               
                   
               
               
                 INT-1040 
                 (CIS)-8- (dimethylamino)-8-(3- (trifluoromethyl) phenyl)- 1,3-diazaspiro [4.5]decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-1038 
                 342.2 
               
               
                   
               
               
                 INT-1041 
                 (CIS)-8- (dimethylamino)- 8-(3-methoxyphenyl)- 1,3-diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-1038 
                 304.2 
               
               
                   
               
               
                 INT-1042 
                 (CIS)-8-(5- chlorothiophen-2-yl)-8- (dimethylamino)-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-1038 
                 314.1 
               
               
                   
               
               
                 INT-1043 
                 (CIS)-8- (dimethylamino)- 8-(3-fluoro-5- methylphenyl)- 1,3-diazaspiro [4.5]decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-1038 
                 306.2 
               
               
                   
               
               
                 INT-1044 
                 (CIS)-8-(3-chlorophenyl)- 8-(dimethylamino)-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-1038 
                 308.2 
               
               
                   
               
               
                 INT-1045 
                 (CIS)-3-(5-chloro- 3-fluoropyridin-2-yl)-8- (dimethylamino)- 8-phenyl-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-989 
                 403.2 
               
               
                   
               
               
                 INT-1047 
                 (CIS)-8-(methyl(oxetan- 3-ylmethyl)amino)-8- phenyl-1,3-diazaspiro [4.5]decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-1026 
                 330.5 
               
               
                   
               
               
                 INT-1048 
                 (CIS)-3-(6- chloropyridin-3-yl)-8- (dimethylamino)-8-phenyl- 1,3-diazaspiro [4.5]decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-989 
                 385.2 
               
               
                   
               
               
                 INT-1049 
                 (CIS)-3-(5- chloropyridin-2-yl)-8- (dimethylamino)- 8-phenyl-1,3- diazaspiro [4.5]decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-989 
                 385.2 
               
               
                   
               
               
                 INT-1061 
                 TRANS-1- (cyclopropyl-methyl)-8- dimethylamino-8-phenyl- 1,3-diazaspiro [4.5]decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-984 
                 328.2 
               
               
                   
               
               
                 INT-1063 
                 CIS-1- (cyclopropylmethyl)- 8-(dimethylamino)-8- (3-fluorophenyl)-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-1031 
                 346.2 
               
               
                   
               
               
                 INT-1066 
                 TRANS-1- (cyclobutylmethyl)-8- (dimethylamino)-8-phenyl- 1,3-diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-987 
                 342.3 
               
               
                   
               
               
                 INT-1070 
                 CIS-8-(dimethylamino)- 8-phenyl-1-(3,3,3- trifluoropropyl)-1,3- diazaspiro[4.5]decan- 2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-1068 
                 360.2 
               
               
                   
               
               
                 INT-1074 
                 CIS-8-(dimethylamino)- 8-(3-fluorophenyl)-1-((1- hydroxycyclobutyl) methyl)-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-1031 
                 376.2 
               
               
                   
               
               
                 INT-1076 
                 CIS-3-(2-chloro-4- methylpyrimidin-5-yl)-8- (dimethylamino)-8-(3- fluorophenyl)-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-989 
                 418.2 
               
               
                   
               
               
                 INT-1077 
                 CIS-3-(4-chloro-2- (trifluoromethyl) pyrimidin-5- yl)-8-(dimethylamino)-8- (3-fluorophenyl)-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-989 
                 472.2 
               
               
                   
               
               
                 INT-1078 
                 CIS-3-(4-chloro-2- cyclopropylpyrimidin- 5-yl)-8- (dimethylamino)-8- (3-fluorophenyl)-1,3- diazaspiro[4.5] decan-2-one 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 INT-989 
                 444.2 
               
               
                   
               
            
           
         
       
     
     Synthesis of Exemplary Compounds 
     Synthesis of SC_3013: cis-5-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile 
     
       
         
         
             
             
         
       
     
     NaH (60% in mineral oil, 0.076 g, 3.19 mmol, 3 equiv.) was added to a solution of 5-(cis-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidine-2-carbonitrile INT_600 (0.4 g, 1.06 mmol) in DMF (5 mL) at 0° C. The mixture was stirred for 30 min at RT and then cooled to 0° C. (1-(Tert-butyldimethylsilyloxy)cyclobutyl)methyl 4-methylbenzene-sulfonate (1.18 g, 3.19 mmol, 3 equiv.) was added dropwise over a period of 5 min and the reaction mixture was allowed to warm up to RT and further heated to 70° C. for 16 h. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (3×20 mL). The combined organic layers were dried over anhydrous Na 2 SO 4  and the solvent was removed in vacuo. The residue was purified by silica gel flash chromatography to afford CIS-5-[8-dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile (0.25 g). 
     Synthesis of SC_3014: cis-2-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-5-carbonitrile 
     
       
         
         
             
             
         
       
     
     cis-1-(Cyclobutylmethyl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one INT-987 (500 mg, 1.464 mmol), 2-chloropyrimidine-5-carbonitrile (409 mg, 2.928 mmol) and Cs 2 CO 3  (954 mg, 2.928 mmol) in 1,4-dioxane (6 ml) were stirred under an nitrogen atmosphere for 18 h at 105° C. The reaction mixture was cooled to RT, 2N aqueous NaOH solution (3 ml) was added and stirring was continued for 10 min. The mixture was extracted first with EtOAc and then with a blend of DCM (30 ml) and methanol (5 ml). The organic layers were combined and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (elution with a DCM/EtOAc gradient) provided cis-2-[1-(cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-5-carbonitrile SC_3014 (57 mg). 
     Synthesis of SC_3016: cis-2-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-5-carboxylic Acid Amide 
     
       
         
         
             
             
         
       
     
     cis-2-[1-(Cyclobutylmethyl)-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]pyrimidine-5-carbonitrile SC_3014 (40 mg, 0.09 mmol) was dissolved in DMSO (1.2 mL) and K 2 CO 3  (25 mg, 0.18 mmol) and hydrogen peroxide (30%, 0.13 mL 1.260 mmol) were added. The reaction mixture was stirred at RT for 20 h, then diluted with 2N NaOH (10 mL) and extracted with DCM (3×20 mL). The combined organic layers were dried over Na 2 SO 4 , concentrated in vacuo. The residue was purified by flash chromatography to yield cis-2-[1-(cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-5-carboxylic acid amide SC_3016 (40 mg) as a white solid. 
     Synthesis of SC_3022: cis-1-(Cyclobutylmethyl)-8-(dimethylamino)-8-phenyl-3-[2-(trifluoromethyl)pyrimidin-5-yl]-1, 3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     cis-1-(Cyclobutylmethyl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one INT-987 (240 mg, 0.7 mmol), Pd-XPhos Generation 2 (138 mg, 0.17 mmol), Cs 2 CO 3  (457 mg, 1.4 mmol) and 5-bromo-2-(trifluoromethyl)pyrimidine (319 mg, 1.4 mmol) were suspended in anhydrous 1,4-dioxane (3 mL) under nitrogen atmosphere and the resulting mixture was stirred at 100° C. overnight. The reaction mixture was cooled to RT and water (3 mL) was added. The aqueous layer was extracted with DCM (3×10 mL), the combined organic layers were dried over Na 2 SO 4  and concentrated in vacuo. The residue was purified by flash chromatography on silica gel to yield the title compound. Final purification using a strong cation exchange resin gave cis-1-(cyclobutylmethyl)-8-(dimethylamino)-8-phenyl-3-[2-(trifluoromethyl)pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2-one SC_3022 (145 mg) as a white solid. 
     Synthesis of SC_3028: cis-4-[1-(cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-N,N-dimethyl-benzamide 
     
       
         
         
             
             
         
       
     
     Step 1: Lithium 4-(cis-1-(cyclobutylmethyl)-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)benzoate 
     Methyl 4-(cis-1-(cyclobutylmethyl)-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro [4.5]decan-3-yl)benzoate SC_3081 (400 mg) was dissolved in methanol (5 mL) and DCM (5 mL). Lithium hydroxide solution (2 M in water, 1 mL) was added and the resulting mixture was stirred overnight at RT. All volatiles were removed in vacuo to yield lithium 4-(cis-1-(cyclobutylmethyl)-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)benzoate (403 mg). 
     Step 2 cis-4-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro [4.5]decan-3-yl]-N,N-dimethyl-benzamide (SC_3028) 
     Lithium 4-(cis-1-(cyclobutylmethyl)-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro [4.5]decan-3-yl)benzoate (80 mg, 0.17 mmol) was suspended in DCM (1 mL) and triethylamine (0.23 mL, 1.7 mmol) and dimethylamine (2M solution in THF, 0.17 mL) and T3P (0.20 mL, 0.34 mmol) were sequentially added. The resulting mixture was stirred for 18 h at RT. Water (10 mL) was added and the mixture was extracted with DCM (3×20 mL). The combined organic layers were dried over Na 2 SO 4 , concentrated in vacuo and the residue was purified by flash chromatography to yield cis-4-[1-(cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-N,N-dimethyl-benzamide SC_3028 (28 mg) as white solid. 
     Synthesis of SC_3045: cis-4-Methoxy-5-[1-(3-methoxypropyl)-8-(methylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]pyrimidine-2-carbonitrile 
     
       
         
         
             
             
         
       
     
     N-iodosuccinimide (150 mg, 0.67 mmol) was added to a suspension of cis-5-[8-(dimethylamino)-1-(3-methoxypropyl)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-4-methoxy-pyrimidine-2-carbonitrile SC_3040 (214 mg, 0.44 mmol) in acetonitrile/THF (2/1 v/v, 10 mL) at RT and the resulting mixture was stirred for 16 h at RT. The reaction mixture was basified with 2N NaOH solution to pH10 and the organic product was extracted with DCM (10 mL×3). The combined organic extracts were dried over anhydrous Na 2 SO 4 , the solvent was removed in vacuo and the residue was purified by preparative flash chromatography to give cis-4-methoxy-5-[1-(3-methoxypropyl)-8-(methylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]pyrimidine-2-carbonitrile SC_3045 (81 mg) as a solid. 
     Synthesis of SC_3064: cis-2-[3-(2-cyano-pyrimidin-5-yl)-8-dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl]-N-propyl-acetamide 
     
       
         
         
             
             
         
       
     
     Sodium hydroxide (51 mg, 1.3 mmol) was added to anhydrous DMSO (4.5 mL) and stirred for 10 minutes at room temperature. cis-5-[8-(Dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]pyrimidine-2-carbonitrile INT_600 (80 mg, 0.21 mmol) was added and the resulting mixture was stirred at room temperature for 5 min and then heated to 50° C. 2-Bromo-N-propyl-acetamide (153 mg, 0.85 mmol) was added and stirring was continued at 50° C. for one hour. The reaction mixture was quenched with water (25 mL) and extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with water (5 mL) and brine (5 mL), dried over Na 2 SO 4  and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel to yield cis-2-[3-(2-cyano-pyrimidin-5-yl)-8-dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl]-N-propyl-acetamide SC_3064 (22 mg) as a solid. 
     Synthesis of SC_3065: 5-(cis-1-(Cyclobutylmethyl)-8-(ethyl(methyl)amino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-4-methoxypyrimidine-2-carbonitrile 
     
       
         
         
             
             
         
       
     
     Cs 2 CO 3  (274 mg, 0.84 mmol) was added to the solution of cis-1-(cyclobutylmethyl)-8-(ethyl(methyl)amino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one INT_986 (150 mg, 0.42 mmol), Xanthphos (36 mg, 0.063 mmol), Pd 2 (dba) 3  (19 mg, 0.0211 mmol) and 5-bromo-4-methoxypyrimidine-2-carbonitrile (135 mg, 0.633 mmol) in 1,4-dioxane (10 mL) under argon atmosphere. The mixture was flushed again with argon for 5 min and the reaction mixture was stirred at 90° C. for 5h. The reaction mixture was cooled to room temperature. The residue was diluted with water (20 mL) and the organic product was extracted with ethyl acetate (3×10 mL). The combined organic extracts were dried over anhydrous Na 2 SO 4  and the solvent was concentrated under reduced pressure. The residue was purified by preparative TLC (EtOAc/petroleum ether 1/9) to afford a white solid (0.15 g), which was further washed with n-pentane to give 0.1 g of 5-(cis-1-(cyclobutylmethyl)-8-(ethyl(methyl)amino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-4-methoxypyrimidine-2-carbonitrile SC_3065. 
     Synthesis of SC_3008: cis-2-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-5-methylsulfonyl-benzonitrile 
     
       
         
         
             
             
         
       
     
     cis-2-[1-(Cyclobutylmethyl)-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-5-methylsulfanyl-benzonitrile (320 mg, 0.66 mmol, prepared from 2-iodo-5-(methylthio)benzonitrile and INT-987 analogously to SC_3022) was dissolved in a mixture of methanol (9 mL) and water (8 mL). Oxone® (807 mg, 1.3 mmol) was added at RT and the resulting mixture was stirred at RT for 18 h. Water (10 mL) was added and the mixture was extracted with DCM (3×20 mL). The combined organic layers were dried over Na 2 SO 4 , concentrated in vacuo. The residue was purified by flash chromatography on silica gel to yield cis-2-[1-(cyclobutylmethyl)-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-5-methylsulfonyl-benzonitrile SC_3008 (66 mg) as a white solid. 
     Synthesis of SC_3023: cis-8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-3-(2-hydroxy-pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Boron tribromide (1M in DCM, 0.38 mL, 0.387 mmol) was added to the solution of cis-8-dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-3-(2-methoxy-pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one SC_3015 (180 mg, 0.387 mmol) in DCM (2 mL) at 0° C. The reaction mixture was stirred for 30 min at 0° C. and then for 16 h at room temperature, quenched with methanol (2 mL), the solvents were removed under reduced pressure and the residue was purified by normal phase preparative HPLC to yield cis-8-dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-3-(2-hydroxy-pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one SC_3023 (60 mg, 34%) as a white solid.  1 H NMR (400 MHz, DMSO-d 6 , δ in ppm): 6 8.43 (s, 2H), 7.35-7.25 (m, 5H), 5.50 (s, 1H), 3.67 (s, 2H), 3.19 (s, 2H), 2.69-2.65 (m, 2H), 2.19-2.10 (m, 4H), 1.98-1.85 (m, 8H), 1.68-1.61 (m, 1H), 1.51-1.39 (m, 5H). 
     Synthesis of SC_3025: cis-5-[8-Dimethylamino-1-(2-hydroxy-ethyl)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile 
     
       
         
         
             
             
         
       
     
     Step 1: 5-(cis-1-(2-(tert-Butyldimethylsilyloxy)ethyl)-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidine-2-carbonitrile 
     NaH (60% in mineral oil, 63.8 mg, 1.59 mmol) was added at 0° C. to the solution of 5-(cis-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidine-2-carbonitrile INT-600 (0.2 g, 0.53 mmol) in DMF (8 mL) for 10 min at 0° C. The reaction mixture was stirred at RT for 30 min, (3-bromopropoxy)(tert-butyl)dimethylsilane (252 mg, 1.06 mmol) was added dropwise over 5 min at 0° C. and the mixture was stirred for further 16 h at RT. The reaction mixture was diluted with water (15 mL) and extracted with diethyl ether (3×25 mL). The combined organic extracts were dried over anhydrous Na 2 SO 4 , the solvents were removed under reduced pressure and the residue was purified by flash chromatography on silica gel to afford 5-(cis-1-(2-(tert-butyldimethylsilyloxy)ethyl)-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidine-2-carbonitrile (100 mg, 34%) as a white solid. 
     Step 2: cis-5-[8-Dimethylamino-1-(2-hydroxy-ethyl)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile (SC_3025) 
     1M TBAF solution in THF (0.36 mL, 0.36 mmol) was added to 5-(cis-1-(2-(tert-butyldimethylsilyloxy)ethyl)-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidine-2-carbonitrile (0.1 g, 0.18 mmol) in THF (5 mL) at 0° C. The reaction mixture was stirred at RT for 30 min, diluted with water (10 mL) and extracted with diethyl ether (3×25 mL). The combined organic extracts were washed with sat. aq. NaHCO 3 , water and brine and dried over anhydrous Na 2 SO 4 . The solvents were evaporated under reduced pressure and the residue was purified by preparative TLC (ethyl acetate/n-hexane=45:55) and then washed with n-pentane (5 mL) to give of cis-5-[8-dimethylamino-1-(2-hydroxy-ethyl)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile (70 mg, 80%) as a white solid.  1 H NMR (400 MHz, DMSO-d 6 , δ in ppm): δ 9.18 (s, 2H), 7.38-7.26 (m, 5H), 4.84 (t, 1H), 3.82 (s, 2H), 3.55-3.51 (m, 2H), 3.26-3.20 (m, 2H), 2.73-2.70 (m, 2H), 2.17-2.11 (m, 2H), 2.00 (s, 6H), 1.57-1.43 (m, 4H). 
     Synthesis of SC_3097: CIS-8-dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-3-(2-morpholin-4-yl-pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     starting from here until the end of the section all procedures were added 
     Step 1: 4-(5-bromopyrimidin-2-yl)morpholine 
     K 2 CO 3  (14.2 g, 103 mmol) was added to the solution of morpholine (9.0 g, 103 mmol) in acetonitrile (900 mL) and the resulting suspension was stirred at RT for 1 h. 5—Bromo-2-chloropyrimidine (20 g, 103 mmol) was added portionwise. The reaction mixture was stirred for 16h at 80° C., then cooled down to RT and diluted with EtOAc (100 mL) and water (50 mL). The organic product was extracted with EtOAc (2×100 mL). The combined organic layer was washed with brine (100 mL), dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel (100-200 mesh) (20% EtOAc in petroleum ether) to afford 18.0 g (71%) of 4-(5-bromopyrimidin-2-yl)morpholine as an off white solid (TLC system: 30% EtOAc in pet ether, R f : 0.6). 
     Step 2: CIS-8-dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-3-(2-morpholin-4-yl-pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (SC_3097) 
     K 2 CO 3  (0.53 g, 3.85 mmol, 2.5 equiv.) was added to the suspension of CIS-8-(dimethylamino)-1-((1-hydroxycyclobutyl)methyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-799) (0.55 g, 1.54 mmol, 1 equiv.) and 4-(5-bromopyrimidin-2-yl)morpholine (0.37 g, 1.54 mmol, 1 equiv.) in dioxane (20 mL) and the resulting suspension was purged with nitrogen for 5 min. Copper(I) iodide (0.29 g, 1.54 mmol, 1 equiv.) and trans-1,2-diaminocyclohexane (0.35 g, 3.085 mmol, 2 equiv.) were sequentially added, the reaction vessel was sealed and the reaction mixture was stirred at 130° C. for 4 h. The reaction mixture was cooled down to RT and diluted with EtOAc (20 mL) and aq. ammonia (10 mL). The organic product was extracted with EtOAc (2×50 mL). The combined organic layer was washed with brine (50 mL), dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure. Purification of the resulting residue by column chromatography on silica gel (100-200 mesh) (60-70% EtOAc in petroleum ether) afforded 0.35 g (48%) of CIS-8-(dimethylamino)-1-((1-hydroxycyclobutyl)methyl)-3-(2-morpholin-4-yl-pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (SC_3097) as an off white solid (TLC system: EtOAc, R f : 0.7).  1 H NMR (DMSO-d 6 ): δ 8.60 (s, 2H), 7.36-7.35 (m, 4H), 7.27-7.24 (m, 1H), 5.50 (s, 1H), 3.72 (s, 2H), 3.62-3.61 (m, 8H), 3.21 (s, 2H), 2.70-2.66 (m, 2H), 2.19-2.11 (m, 4H), 1.98 (s, 6H), 1.93-1.85 (m, 2H), 1.66-1.64 (m, 1H), 1.53-1.42 (m, 5H). Mass: m/z 521.3 (M+H) + . 
     Synthesis of SC_3099: CIS-1-[(1-hydroxy-cyclobutyl)-methyl]-8-methylamino-3-(2-morpholin-4-yl-pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     N-Iodosuccinimide (162 mg, 0.72 mmol) was added to the solution CIS-8-(dimethylamino)-1-((1-hydroxycyclobutyl)methyl)-3-(2-morpholinopyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (SC-3097) (250 mg, 0.48 mmol) in acetonitrile (8.0 mL) and THF (8.0 mL) at 0° C. and the resulting mixture was stirred for 16 h at RT. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in EtOAc (2×30 mL), the organic layer was washed with 2N aq. NaOH solution, dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure. The residue was purified by reverse phase prep. HPLC to yield 0.12 g (49%) of CIS-1-((1-hydroxycyclobutyl)methyl)-8-(methylamino)-3-(2-morpholinopyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (SC_3099) as an off white solid (TLC system 5% MeOH in DCM R f : 0.5.). Preparative reverse phase HPLC conditions: column: Luna-Phenyl-Hexyl-C18 (150*19 mm) 5 μm; mobile phase: 10 mM ammonium bicarbonate/acetonitrile, gradient (T/% B): 0/50, 7/85, 7.1/98, 9/98, 9.1/50, 12/50; flow Rate: 25 ml/min; diluent: mobile phase+THF.  1 H NMR (DMSO-d6): δ 8.63 (s, 2H), 7.49-7.47 (m, 2H), 7.34-7.30 (t, 2H), 7.21-7.17 (m, 1H), 5.60 (s, 1H), 3.76 (s, 2H), 3.64-3.62 (m, 8H), 3.35 (m, 2H), 2.26-2.20 (m, 3H), 2.12-2.08 (m, 2H), 1.90-1.88 (m, 7H), 1.79-1.73 (m, 2H), 1.65-1.63 (m, 1H), 1.52-1.44 (m, 3H). Mass: m/z 507.3 (M+H) + . 
     Synthesis of SC_3100: CIS-8-dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-8-phenyl-3-(2-piperazin-1-yl-pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one Hydrochloride 
     
       
         
         
             
             
         
       
     
     Step 1: tert-butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate 
     In analogy to the method described for SC_3097 step 1 tert-butyl piperazine-1-carboxylate was reacted with 5-bromo-2-chloropyrimidine to be converted into tert-butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate. 
     Step 2: tert-butyl 4-(5-((cis)-8-(dimethylamino)-1-((1-hydroxycyclobutyl)methyl)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidin-2-yl)piperazine-1-carboxylate 
     K 2 CO 3  (0.38 g, 2.8 mmol, 2.5 equiv.) was added to the suspension of CIS-8-(dimethylamino)-1-((1-hydroxycyclobutyl)methyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (0.4 g, 1.12 mmol, 1 equiv.) (INT-799) and tert-butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate (0.38 g, 1.12 mmol, 1 equiv.) in dioxane (25 mL) and the resulting mixture was purged with nitrogen for 5 min. Copper(I) iodide (0.21 g, 1.12 mmol, 1 equiv.) and trans-1,2-diaminocyclohexane (0.25 g, 2.24 mmol, 2 equiv.) were sequentially added, the reaction vessel was sealed and the reaction mixture was stirred for 10h at 130° C. The reaction mixture was cooled down to RT and diluted with EtOAc (20 mL) and aq. ammonia (10 mL). The organic product was extracted with e EtOAc (2×50 mL). The combined organic layer was washed with brine (50 mL), dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel (100-200 mesh) (60-70% EtOAc in petroleum ether) afforded 0.5 g (72%) of tert-butyl 4-(5-((cis)-8-(dimethylamino)-1-((1-hydroxycyclobutyl)methyl)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidin-2-yl)piperazine-1-carboxylate as an off white solid (TLC system: 1:1 EtOAc/pet ether, R f : 0.3). 
     Step 3: CIS-8-(dimethylamino)-1-((1-hydroxycyclobutyl)methyl)-8-phenyl-3-(2-(piperazin-1-yl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one hydrochloride (SC_3100) 
     4N HCl in dioxane (2 mL) was added to tert-butyl 4-(5-(cis-8-(dimethylamino)-1-((1-hydroxycyclobutyl)methyl)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidin-2-yl)piperazine-1-carboxylate (0.15 g, 0.24 mmol). The resulting mixture was stirred at 0° C. for 6 h and then concentrated under reduced pressure to give a pale yellow solid which was triturated with n-pentane and lyophilized with water for 16 h to yield 0.14 g of CIS-8-(dimethylamino)-1-((1-hydroxycyclobutyl)methyl)-8-phenyl-3-(2-(piperazin-1-yl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one hydrochloride (SC_3100) as a pale yellow solid.  1 H NMR (DMSO-d6): δ 10.42 (br s, 1H), 9.34 (br s, 2H), 8.63 (s, 2H), 7.70-7.68 (m, 2H), 7.54-7.50 (m, 3H), 3.88-3.86 (m, 4H), 3.77 (m, 4H), 3.16-3.11 (m, 6H), 2.52-2.49 (m, 6H), 2.47 (m, 2H), 2.10-2.07 (m, 2H), 2.00-1.95 (t, 2H), 1.87-1.81 (m, 3H), 1.70-1.68 (m, 2H), 1.58 (m, 1H). Mass: m/z 520.3 (M+H) + . 
     Synthesis of SC_3103: CIS-1-(cyclobutyl-methyl)-8-dimethylamino-3-[4-methyl-6-(trifluoromethyl)-pyridin-3-yl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Cs 2 CO 3  (2 g, 6.451 mmol) was added to an argon purged solution of CIS-1-(cyclobutylmethyl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-987) (1.1 g, 3.225 mmol, 1 equiv.), Xantphos (279 mg, 0.483 mmol, 0.15 equiv.), Pd 2 (dba) 3  (295 mg, 0.322 mmol, 0.1 equiv.) and 5-bromo-4-methyl-2-(trifluoromethyl)pyridine (774 mg, 3.225 mmol, 1 equiv.) in 1,4-dioxane (55 mL). The mixture was purged again with argon for 15 min. The reaction mixture was stirred at 90° C. for 18 h, then cooled down to RT, filtered through Celite and washed with EtOAc (80 mL). The filtrate was concentrated under reduced pressure. The resulting residue was purified by flash chromatography (neutral alumina, 0-3% methanol in DCM) to afford 0.6 g (37%) of CIS-1-(cyclobutylmethyl)-8-(dimethylamino)-3-(4-methyl-6-(trifluoromethyl)pyridin-3-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (SC_3103) as an off white solid. (TLC system: 5% MeOH in DCM; Rf: 0.5).  1 H NMR (DMSO-d6): δ 8.56 (s, 1H), 7.80 (s, 1H), 7.34-7.24 (m, 5H), 3.71 (s, 2H), 3.17 (d, 2H), 2.70-2.56 (m, 3H), 2.31 (s, 3H), 2.17-2.11 (m, 2H), 2.03-2.00 (m, 8H), 1.82-1.73 (m, 4H), 1.54-1.41 (m, 4H). Mass: m/z 501.3 (M+H) + . 
     Synthesis of SC_3105: CIS-1-(cyclopropyl-methyl)-8-dimethylamino-3-(4-methylsulfonyl-phenyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     NaH (60% in mineral oil) (36.80 mg, 0.92 mmol) was added portionwise to the solution of CIS-8-(dimethylamino)-3-(4-(methylsulfonyl)phenyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (200 mg, 0.46 mmol, prepared from INT-976 and 1-bromo-4-(methylsulfonyl)benzene by analogy with SC_3103) in DMF (30 mL) at 0° C. under argon atmosphere and the resulting mixture was stirred for 10 min. (Bromomethyl)cyclopropane (122 mg, 0.92 mmol) was added dropwise at 0° C., ice bath was removed and the reaction mixture was further stirred for 4h at room temperature. The reaction progress was monitored by TLC. The reaction mixture was diluted with water (30 mL) and the precipitated solid was filtered. Purification by column chromatography (silica gel 100-200mesh, 50-60% ethyl acetate in hexane as eluent) to get 80 mg (35%) of CIS-1-(cyclopropylmethyl)-8-(dimethylamino)-3-(4-(methylsulfonyl)phenyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (SC_3105) as off white solid (TLC system: 10% MeOH in DCM; R f : 0.70). 1H NMR (CDCl3): δ 7.85-7.83 (d, 2H), 7.73-7.71 (d, 2H), 7.39-7.36 (m, 2H), 7.32-7.27 (m, 3H), 3.64 (s, 2H), 3.20 (d, 2H), 3.00 (s, 3H), 2.75-2.71 (m, 2H), 2.43-2.36 (m, 2H), 2.07 (s, 6H), 1.57 (m, 2H), 1.50 (m, 2H), 1.11-1.06 (m, 1H), 0.59-0.54 (m, 2H), 0.41-0.37 (m, 2H). Mass: m/z 482.2 (M+H) + . 
     Synthesis of SC_3109: CIS-2-[8-Dimethylamino-1-[2-(1-methoxy-cyclobutyl)-ethyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-benzamide 
     
       
         
         
             
             
         
       
     
     Step 1: CIS-2-(8-(dimethylamino)-1-(2-(1-methoxycyclobutyl)ethyl)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)benzonitrile 
     In analogy to the method described for SC_3103 CIS-8-(dimethylamino)-1-(2-(1-methoxycyclobutyl)ethyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one was reacted with 2-bromobenzonitrile to be converted into CIS-2-(8-(dimethylamino)-1-(2-(1-methoxycyclobutyl)ethyl)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)benzonitrile. 
     Step 2: CIS-2-[8-Dimethylamino-1-[2-(1-methoxy-cyclobutyl)-ethyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-benzamide SC_3109 
     CIS-2-[8-(dimethylamino)-1-[2-(1-methoxycyclobutyl)ethyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]benzonitrile (57.0 mg, 1.0 equiv.) was dissolved in DMSO (1.6 mL), hydrogen peroxide (0.167 mL, 14.0 equiv., 30 mass % in water solution) and K 2 CO 3  (32.4 mg, 2.0 equiv.) were added and the reaction mixture was stirred at RT for 18 h. The reaction mixture was then quenched with 10 mL water, extracted with DCM (3×10 mL), the combined organic extracts were dried over Na 2 SO 4  and concentrated under reduced pressure (24 mg crude product). The aqueous phase was concentrated to dryness (91 mg), suspended in DCM, the precipitate was filtered off and the organic solution was concentrated under reduced pressure to give additional 56 mg of the crude product. The combined crude product was purified by column chromatography on silica gel (DCM/EtOH 95/5) to give 37 mg (62%) of CIS-2-[8-dimethylamino-1-[2-(1-methoxy-cyclobutyl)-ethyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-benzamide (SC_3109) as a white solid.  1 H NMR (600 MHz, DMSO) δ 7.52-7.48 (s, 1H), 7.47-7.31 (m, 7H), 7.29-7.23 (m, 1H), 7.25-7.22 (s, 1H), 7.24-7.18 (m, 1H), 3.68-3.65 (s, 3H), 3.13-3.10 (s, 2H), 3.09-3.02 (m, 2H), 2.71-2.65 (m, 2H), 2.21-2.12 (m, 2H), 2.09-1.99 (m, 2H), 2.02-1.98 (s, 6H), 1.97-1.86 (m, 4H), 1.77-1.67 (m, 1H), 1.64-1.52 (m, 3H), 1.44-1.36 (td, 2H). Mass: m/z 505.32 (M+H)*. 
     Synthesis of SC_3112: CIS-2-(1-((1-hydroxycyclobutyl)methyl)-8-(methylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)benzonitrile 
     
       
         
         
             
             
         
       
     
     Step 1: CIS-2-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)benzonitrile 
     In analogy to the method described for SC_3103 1-bromo-2-cyanobenzene was reacted with CIS-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-976) to be converted into CIS-2-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)benzonitrile. 
     Step 2: CIS-2-(8-(dimethylamino)-1-((1-hydroxycyclobutyl)methyl)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)benzonitrile 
     To a solution of CIS-2-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)benzonitrile (500 mg, 1.336 mmol, 1.0 equiv.) in DMSO (16 ml) was added sodium hydroxide (213 mg, 5.334 mmol, 4.0 equiv.) and the mixture was stirred at 60° C. for 30 min. A solution of 1-oxa-spiro[2.3]hexane (237 mg, 6.68 mmol, 5.0 equiv.) in DMSO (4 ml) was added at RT and the reaction mixture was stirred at 55° C. for 16h. The reaction mixture was diluted with water (100 ml) and extracted with EtOAc (100 ml). The organic layer was washed with water (50 ml) and brine (50 ml), dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (EtOAc/Hexane, 7/3) to yield CIS-2-(8-(dimethylamino)-1-((1-hydroxycyclobutyl)methyl)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)benzonitrile (200 mg, 0.436 mmol, 32%) as an off white solid. Mass: m/z 459.4 (M+H)+ 
     Step 3: CIS-2-(1-((1-hydroxycyclobutyl)methyl)-8-(methylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)benzonitrile (SC_3112) 
     In analogy to the method described for SC_3099 CIS-2-(8-(dimethylamino)-1-((1-hydroxycyclobutyl)methyl)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)benzonitrile was reacted with N-iodosuccinimide to be converted into CIS-2-(1-((1-hydroxycyclobutyl)methyl)-8-(methylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)benzonitrile (SC_3112). Yield: 29%.  1 H NMR (DMSO-d6, 400 MHz), δ (ppm)=7.75 (dd, 1H, J=7.76 Hz, 1.16 Hz), 7.70-7.65 (m, 1H), 7.50 (d, 1H, J=8.16 Hz), 7.44-7.42 (m, 2H), 7.35-7.25 (m, 3H), 7.17-7.15 (m, 1H), 5.49 (s, 1H), 3.85 (s, 2H), 3.32 (s, 2H), 2.29-2.23 (m, 2H), 2.12-2.23 (m, 2H), 1.87 (bs, 6H), 1.73-1.46 (m, 6H). Mass: m/z 445.26 (M+H) + . 
     Synthesis of SC_3120: CIS-8-(dimethylamino)-3-(2-(3-oxopiperazin-1-yl)pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     CIS-3-(2-chloropyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-989) (100 mg, 0.259 mmol) was placed into a reaction vial for microwave reactor (5 mL), the vial was flushed with nitrogen, anhydrous n-butanol (50 equiv., 13.0 mmol, 1.2 mL), diisopropylethylamine (5 equiv., 1.30 mmol, 0.224 mL) and piperazine-2-one (1.2 equiv., 0.311 mmol, 31 mg) were added, the vial was sealed and the reaction mixture was stirred for 2.5 h at 140° C. (conventional heating). The reaction mixture was cooled down, transferred into a 1-neck flask and concentrated under reduced pressure. The resulting residue (128 mg) was purified by flash chromatography on aluminium oxide (neutral) (DCM/MeOH gradient 100/0 to 97/3) to yield 65 mg (56%) CIS-8-(dimethylamino)-3-(2-(3-oxopiperazin-1-yl)pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro-[4.5]decan-2-one (SC_3120).  1 H NMR (600 MHz, DMSO) δ 8.60 (s, 2H), 8.01 (s, 1H), 7.46 (s, 1H), 7.43-7.30 (m, 4H), 7.27 (td, 1H), 4.09 (s, 2H), 3.91-3.75 (m, 2H), 3.62-3.40 (m, 2H), 3.30-3.09 (m, 2H), 2.61-2.51 (m, 2H), 2.44-2.25 (m, 2H), 1.97 (s, 6H), 1.93-1.80 (m, 2H), 1.55-1.41 (m, 2H). Mass: m/z 437.27 (M+H) + . 
     Synthesis of SC_3129: CIS-3-(5-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidin-2-yl)benzonitrile 
     
       
         
         
             
             
         
       
     
     CIS-3-(2-chloropyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-989) (1 equiv., 0.47 mmol, 180 mg), Pd(PPh 3 ) 4  (0.1 equiv., 0,047 mmol, 54 mg) and (3-cyanophenyl)boronic acid (1.5 equiv., 0.70 mmol, 103 mg) were dissolved in degassed dry tetrahydrofurane (9.5 mL) and sodium carbonate 1M aq. sol. (1.9 equiv., 0.89 mmol, 0.89 mL) was added. The resulting clear reaction mixture was stirred overnight at 70° C. Additional portion of Pd(PPh 3 ) 4  (0.1 equiv., 0,047 mmol, 54 mg) was added and the reaction was stirred further 12 h at 70° C. The reaction mixture was diluted with EtOAc (50 mL), stirred for 10 min, the precipitate was filtered off and the filtrate was concentrated under reduced pressure. The resulting residue (285 mg) was purified by flash chromatography on silica gel (gradient DCM/MeOH, 100/0 to 80/20) to yield 130 mg (62%) of CIS-3-(5-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidin-2-yl)benzonitrile (SC_3129).  1 H NMR (600 MHz, DMSO) δ 9.13 (s, 2H), 8.60 (dp, 2H), 7.93 (dt, 1H), 7.88 (s, 1H), 7.72 (dd, 1H), 7.42-7.35 (m, 5H), 7.28 (d, 1H), 3.73 (s, 2H), 2.01-1.91 (m, 2H), 1.98 (s, 10H), 1.57-1.48 (m, 2H). Mass: m/z 453.24 (M+H) + . 
     Synthesis of SC_3130: CIS-8-(dimethylamino)-3-(2-(4-(methylsulfonyl)piperazin-1-yl)pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     CIS-8-(dimethylamino)-8-phenyl-3-(2-(piperazin-1-yl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one (SC_3124) (100 mg, 0.23 mmol) was dissolved in DCM (150 equiv., 34 mmol, 2.2 mL) under nitrogen atmosphere. To the resulting solution 4-dimethylaminopyridine (0.05 equiv., 0.012 mmol, 1.4 mg) and diisopropylethylamine (3 equiv., 0.67 mmol, 0.119 mL) were added and the mixture was cooled to 0° C. Methansulfonylchloride (2 equiv., 0.46 mmol, 0.036 mL) was added, ice bath was removed and the reaction mixture was stirred for 2 h at RT. The reaction mixture was quenched with water (5 mL), diluted with DCM (10 mL), the resulting brown suspension was filtered through a glass filter, the filtrate transferred to a separating funnel, the organic phase separated and the aqueous phase extracted with DCM (2×10 mL). The combined organic phases were dried over MgSO 4  and concentrated under reduced pressure. The resulting residue (81 mg) was purified by flash chromatography on aluminium oxide (gradient DCM/EtOH 97/3 to 96/4) to yield 51 mg (43%) of CIS-8-(dimethylamino)-3-(2-(4-(methylsulfonyl)piperazin-1-yl)pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro-[4.5]decan-2-one (SC_3130).  1 H NMR (600 MHz, DMSO) δ 8.59 (s, 2H), 7.46 (s, 1H), 7.39 (d, 1H), 7.37 (s, 3H), 7.28 (d, 1H), 3.79-3.74 (m, 4H), 3.54 (s, 2H), 3.18-3.13 (m, 4H), 2.87 (s, 3H), 2.43-2.32 (m, 2H), 1.97 (s, 6H), 1.92-1.87 (m, 2H), 1.51-1.41 (m, 2H). Mass: m/z 514.26 (M+H) + . 
     Synthesis of SC_3132: CIS-8-((cyclopropylmethyl)(methyl)amino)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: CIS-8-(methylamino)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one 
     In analogy to the method described for SC_3099 CIS-8-(dimethylamino)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one (SC_3245) was reacted with N-iodosuccinimide to be converted into CIS-8-(methylamino)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one. 
     Step 2: CIS-1-(4-methoxybenzyl)-8-(methylamino)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one 
     NaH (60% in mineral oil) (296.3 mg, 7.407 mmol, 1.5 equiv.) was added portionwise to the solution CIS-8-(methylamino)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one (2 g, 4.938 mmol, 1 equiv.) in DMF (20 mL) at 0° C. under argon atmosphere and the resulting mixture was stirred for 10 min. 1-(Bromomethyl)-4-methoxybenzene (1.092 g, 5.432 mmol, 1.1 equiv.) was added dropwise. The reaction mixture was allowed to warm up to RT and stirred for 16h. The reaction progress was monitored by LCMS. The reaction mixture was diluted with water (150 mL) and the organic product was extracted with EtOAc (3×60 mL). The combined organic extracts were dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (silica gel 230-400 mesh; 04% MeOH/DCM) to afford 2 g (77%) of CIS-1-(4-methoxybenzyl)-8-(methylamino)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one as an off white solid (TLC system 5% MeOH in DCM R f : 0.55). 
     Step 3: CIS-8-((cyclopropylmethyl)(methyl)amino)-1-(4-methoxybenzyl)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one 
     (Bromomethyl)cyclopropane (0.461 mL, 4.762 mmol, 5 equiv.) was added dropwise to a mixture of CIS-1-(4-methoxybenzyl)-8-(methylamino)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro-[4.5]decan-2-one (500 mg, 0.952 mmol, 1 equiv.) and K 2 CO 3  (657 mg, 4.762 mmol, 5 equiv.) in acetonitrile (20 mL) at RT under argon atmosphere. The reaction vessel was sealed and the mixture was stirred at 95° C. for 24h. Reaction progress was monitored by LCMS. The reaction mixture was diluted with water (50 mL) and the organic product was extracted with EtOAc (2×50 mL). The combined organic extracts were dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (silica gel 230-400 mesh; 0-40% EtOAc/petroleum ether) to afford 220 mg (39%) of CIS-8-((cyclopropylmethyl)(methyl)amino)-1-(4-methoxybenzyl)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one as an off white solid (TLC 50% EtOAc in petroleum ether, Rf: 0.65) and 230 mg of the unreacted starting material. 
     Step 4: CIS-8-((cyclopropylmethyl)(methyl)amino)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one (SC_3132) 
     TFA (4.2 mL) was added drop wise to a solution of CIS-8-((cyclopropylmethyl)(methyl)amino)-1-(4-methoxybenzyl)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one (210 mg, 0.363 mmol) in DCM (0.05 mL) at 0° C. under argon atmosphere. The reaction mixture was allowed to warm up to RT and stirred for 16h. The reaction progress was monitored by LCMS. The excess of TFA was evaporated under reduced pressure and the residual amount of TFA was removed as an azeotropic mixture with DCM (2×5 mL). The crude product was purified by preparative HPLC to yield 105 mg (63%) of CIS-8-((cyclopropylmethyl)(methyl)amino)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one (SC_3132) as an off white solid (TLC system 50% EtOAc in pe ether, Rf: 0.35).  1 H NMR (DMSO-d6): δ 9.17 (s, 2H), 8.10 (br s, 1H), 7.35-7.33 (m, 4H), 7.25-7.22 (m, 1H), 3.72 (s, 2H), 2.43 (m, 2H), 2.13 (s, 3H), 1.97-1.82 (m, 6H), 1.49 (m, 2H), 0.75-0.71 (m, 1H), 0.41-0.39 (m, 2H), 0.06-0.01 (m, 2H). Mass: m/z=460.2 (M+H). 
     Synthesis of SC_3133:CIS-8-Dimethylamino-3-[2-(4-methyl-piperazine-1-carbonyl)-pyrimidin-5-yl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     1-Methylpiperazine (2 equiv., 0.5 mmol, 55 μL) and [5-[8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]pyrimidine-2-carbonyl]oxylithium (INT-990) (100 mg, 0.25 mmol) were suspended in DCM (1.6 mL), triethylamine (10 equiv., 2.5 mmol, 336 μL) and propylphosphonic anhydride (&gt;50 wt. % solution in ethyl acetate) (2 equiv., 0.5 mmol, 297 μL) were sequentially added and the reaction mixture was stirred at RT for 2 h. The resulting mixture was quenched with 2M aq. NaOH (2 mL), organic phase was separated and aqueous phase was extracted with dichloromethane (3×10 mL). The combined organic extracts were dried over Na 2 SO 4  and concentrated under reduced pressure. The residue (88 mg) was dissolved in 3 mL DCM and 6 mL pentane were slowly added. The resulting mixture was stirred for 30 min. The precipitate was filtered off and dried under reduced pressure to give 69 mg (58%) of CIS-8-dimethylamino-3-[2-(4-methyl-piperazine-1-carbonyl)-pyrimidin-5-yl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (SC_3133). H NMR (600 MHz, DMSO) δ 9.03 (s, 2H), 7.87 (s, 1H), 7.42-7.34 (m, 5H), 7.28 (d, 1H), 3.69 (s, 2H), 3.62 (dd, 2H), 3.17-3.12 (m, 2H), 2.57-2.51 (m, 2H), 2.36 (t, 2H), 2.25-2.21 (m, 2H), 2.21 (s, 3H), 1.98-1.89 (m, 2H), 1.96 (s, 6H), 1.56-1.46 (m, 2H). Mass: m/z 478.29 (M+H). 
     Synthesis of SC_3146: CIS-5-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidine-2-carboxamide 
     
       
         
         
             
             
         
       
     
     Methyl CIS-5-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidine-2-carboxylate (INT-990) (100 mg, 0.244 mmol) was dissolved in 7N NH 3  in methanol (25 equiv. NH 3 , 0.9 mL) in a microwave reactor vial. The reaction vessel was sealed, the reaction mixture was stirred for 5 days at RT and then concentrated under reduced pressure. The residue was purified by flash chromatography on neutral aluminum oxide (DCM/EtOH, gradient 90/10 to 74/26) to yield 38 mg (39%) of CIS-5-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidine-2-carboxamide (SC_3140).  1 H NMR (600 MHz, DMSO) δ 9.07 (s, 2H), 8.02 (d, 1H), 7.93 (s, 1H), 7.59-7.55 (m, 1H), 7.38 (d, 4H), 7.28 (ddd, 1H), 3.72 (s, 2H), 2.49-2.37 (m, 2H), 1.99-1.92 (m, 8H), 1.88-1.75 (m, 2H), 1.56-1.45 (m, 2H). Mass: m/z 395.22 (M+H) + . 
     Synthesis of SC_3146: methyl CIS-2-(4-(5-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidin-2-yl)piperazin-1-yl)acetate 
     
       
         
         
             
             
         
       
     
     CIS-8-(dimethylamino)-8-phenyl-3-(2-(piperazin-1-yl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one (SC_3124) (200 mg, 0.46 mmol) was dissolved in dry acetonitrile (5 mL) under nitrogen atmosphere, KCO 3  (1.2 equiv., 0.55 mmol, 76 mg) and methyl-2-chloroacetate (1.5 equiv., 0.69 mmol, 0.06 mL) were sequentially added and the reaction mixture was stirred at reflux for 5 h. A new portion of methyl-2-chloroacetate (1.5 equiv., 0.69 mmol, 0.06 mL) was added and the reaction mixture was stirred at reflux overnight. The reaction mixture was concentrated under reduced pressure. The residue was suspended in DCM, the precipitate was filtered off and washed with DCM. The combined filtrate was concentrated under reduced pressure to give 106 mg of crude product. Flash chromatography on silica gel (eluent DCM/EtOH gradient 98/2 to 96/4) yielded 168 mg (72%) of methyl CIS-2-(4-(5-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidin-2-yl)piperazin-1-yl)acetate (SC_3146).  1 H NMR (600 MHz, DMSO) δ 8.54 (s, 2H), 7.42 (s, 1H), 7.37 (m, 4H), 7.27 (m, 1H), 3.63 (t, 7H), 3.52 (s, 2H), 3.27 (s, 2H), 2.54 (t, 4H), 2.45-2.30 (m, 2H), 1.96 (s, 6H), 1.93-1.83 (m, 4H), 1.52-1.42 (m, 2H). Mass: m/z 508.4 (M+H) + . 
     Synthesis of SC_3162: CIS-8-(dimethylamino)-8-phenyl-3-(2-(pyridin-2-yl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     CIS-3-(2-chloropyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-989) (200 mg, 0.52 mmol), tributyl(2-pyridyl)stannane (1.5 equiv., 0.78 mmol, 286 mg) and Pd(PPh 3 ) 4  (0.1 equiv., 0.052 mmol, 60 mg) were dissolved in degassed anhydrous DMF (150 equiv., 77.7 mmol, 6 mL) under nitrogen atmosphere. Cesium fluoride (2.2 equiv., 1.14 mmol, 173 mg) was added and the reaction mixture was stirred at 90° C. overnight. The resulting suspension was cooled down to RT, diluted with water (10 mL), extracted with ethylacetate (30 mL), then DCM (30 mL), the DCM phase was dried over MgSO 4  and concentrated under reduced pressure to give 320 mg of crude product. Flash chromatography on silica gel (eluent DCM/0.1N NH 3  in MeOH, gradient 95/5 to 70/30) yielded 72 mg (33%) of CIS-8-(dimethylamino)-8-phenyl-3-(2-(pyridin-2-yl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one (SC_3162).  1 H NMR (600 MHz, DMSO) δ 9.13 (s, 2H), 8.71-8.67 (m, 1H), 8.30 (d, 1H), 7.92 (td, 1H), 7.86 (s, 1H), 7.46 (dd, 1H), 7.43-7.35 (m, 5H), 7.31-7.25 (m, 1H), 3.73 (s, 2H), 2.48-2.33 (m, 2H), 2.00-1.78 (m, 10H), 1.57-1.47 (m, 2H). Mass: m/z 429.2 (M+H) + . 
     Synthesis of SC_3169: CIS-2-(2-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)phenoxy)acetic Acid 
     
       
         
         
             
             
         
       
     
     Step 1: CIS-2-(2-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)phenoxy)acetonitrile 
     In analogy to the method described for SC_3103 CIS-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-976) was reacted with 2-(2-bromophenoxy)acetonitrile to be converted into CIS-2-(2-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)phenoxy)acetonitrile. 
     Step 2: CIS-2-(2-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)phenoxy)acetic Acid (SC_3169) 
     CIS-2-(2-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)phenoxy)acetonitrile (134 mg, 0.331 mmol) was dissolved in conc. aq. HCl (1.4 mL, 50 equiv.). The reaction mixture was heated to 100° C. for 2 h and cooled down to RT. The precipitate was filtered off, washed with water (2×) and dried under reduced pressure to give 31 mg (22%) of CIS-2-(2-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)phenoxy)acetic acid (SC_3169).  1 H NMR (600 MHz, DMSO) δ 7.75-7.71 (m, 1H), 7.59-7.48 (m, 4H), 7.27 (dd, 1H), 7.15 (ddd, 1H), 6.97-6.90 (m, 2H), 4.65 (s, 2H), 3.43 (s, 2H), 2.70 (d, 2H), 2.56 (s, 6H), 2.31 (t, 2H), 1.93-1.86 (m, 2H), 1.33-1.22 (m, 2H). Mass: m/z 424.2 (M+H) + . 
     Synthesis of SC_3173: CIS-8-(dimethylamino)-8-phenyl-3-(2-(piperazine-1-carbonyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: CIS-tert-butyl 4-(5-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidine-2-carbonyl)piperazine-1-carboxylate 
     In analogy to the method described for SC_3133 lithium CIS-5-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidine-2-carboxylate (INT-990) was reacted with 1-(tert-butoxycarbonyl)piperazine to be converted into CIS-tert-butyl 4-(5-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidine-2-carbonyl)piperazine-1-carboxylate. 
     Step 2: CIS-8-(dimethylamino)-8-phenyl-3-(2-(piperazine-1-carbonyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one (SC_3173) 
     CIS-tert-butyl 4-(5-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidine-2-carbonyl)piperazine-1-carboxylate (230 mg, 0.41 mmol) was dissolved in TFA (2.2 mL, 28.6 mmol, 70 equiv.). The reaction mixture was stirred at RT for 2.5 h and then concentrated under reduced pressure. The residue was dissolved in DCM and aq. sat Na 2 CO 3  was added (until pH 10). The organic phase was separated and the aq. phase was extracted with DCM (2×). The combined organic extracts were dried over MgSO 4  and concentrated under reduced pressure. Recrystallization of the residue from DCM/pentane gave 105 mg (56%) of CIS-8-(dimethylamino)-8-phenyl-3-(2-(piperazine-1-carbonyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one (SC_3173).  1 H NMR (600 MHz, DMSO) δ 9.04 (s, 2H), 7.89 (s, 1H), 7.42-7.32 (m, 4H), 7.31-7.26 (m, 1H), 3.69 (s, 2H), 3.65 (t, 2H), 3.21 (t, 2H), 2.90 (t, 2H), 2.79-2.74 (m, 2H), 2.43 (s, 2H), 1.98 (s, 9H), 1.89-1.75 (m, 1H), 1.53-1.47 (m, 2H). Mass: m/z 464.3 (M+H) + . 
     Synthesis of SC_3182: CIS-8-(dimethylamino)-3-(2-(4-hydroxypiperidin-1-yl)pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Et 3 N (0.39 g, 3.89 mmol) was added to the solution of CIS-3-(2-chloropyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-989) (0.5 g, 1.29 mmol) and piperidin-4-ol (0.32 g, 3.24 mmol) in DMF (10 mL) at RT. The reaction mixture was stirred at 130° C. for 16h, cooled down to RT and concentrated under reduced pressure. The residue was diluted with 10% aq. NaOH and the organic product was extracted with 1/9 v/v MeOH/DCM. The combined organic layer was dried over anhydrous Na 2 SO 4  and concentrated in vacuo. The residue was purified by preparative TLC using 10% MeOH/DCM as eluent to afford 130 mg of CIS-8-(dimethylamino)-3-(2-(4-hydroxypiperidin-1-yl)pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (SC_3182) as an off-white solid (TLC system: 10% MeOH in DCM; Rf: 0.1).  1 H NMR (DMSO-d6): δ 8.50 (s, 2H), 7.39-7.26 (m, 6H), 4.68 (d, 1H), 4.19-4.16 (m, 2H), 3.69-3.67 (m, 1H), 3.51 (s, 2H), 3.14 (t, 2H), 2.33 (m, 2H), 1.94-1.71 (m, 12H), 1.45 (m, 2H), 1.30-1.23 (m, 2H). Mass: m/z 451.2 (M+H) + . 
     Synthesis of SC_3186: CIS-8-(dimethylamino)-3-(3-methylpyridin-2-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Compound was synthesized within a parallel array. An argon-flushed dry reaction vessel equipped with a septum was loaded with the solutions of INT-976 (0.1 M, 1 mL) and 1-bromo-2-methylbenzene (0.15 M, 1 mL) in dioxane. To the resulting mixture Cs 2 CO 3  (200 μmol), XantPhos (10 μmol) and Pd 2 (dba) 3  (5 μmol) were added. The reaction vessel was flushed with argon once again, sealed and the reaction mixture was shaken at 100° C. overnight. The resulting mixture was cooled down to RT and the solvent was removed under reduced pressure. The residue was taken up in 3 mL dichloromethane and 3 mL water, the organic phase was separated, the aqueous phase was extracted with dichloromethane (2×3 mL). Combined organic phases were concentrated under reduced pressure. The residue was purified by HPLC to give CIS-8-(dimethylamino)-3-(3-methylpyridin-2-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (SC_3186). Mass: m/z 363.2 (M+H) + . 
     Synthesis of SC_3208: CIS-4-(5-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidin-2-yl)indolin-2-one 
     
       
         
         
             
             
         
       
     
     CIS-3-(2-chloropyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-989) (150 mg, 0.38 mmol), Pd(t-Bu 3 P) 2  (0.1 equiv., 0.02 mmol, 10 mg) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indolin-2-one (2 equiv., 0.78 mmol, 201 mg) were dissolved in degassed anhydrous THF (80 equiv., 31 mmol, 2.5 mL) and IM aq. Na 2 CO 3  (5.5 equiv., 2.14 mmol, 2.14 mL) was added. The resulting mixture was stirred at 60° C. for 8 h and then at RT overnight. The reaction mixture was diluted with water until precipitation occurred. The precipitate was filtered off, suspended in 30 mL DCM, filtered off again, washed with pentane (5 mL) and dried under reduced pressure to give 143 mg (76%) of CIS-4-(5-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidin-2-yl)indolin-2-one (SC_3208).  1 H NMR (600 MHz, DMSO) δ 10.45 (s, 1H), 9.10 (s, 2H), 7.87 (d, 1H), 7.84-7.80 (m, 1H), 7.39 (d, 5H), 7.29 (dt, 2H), 6.91 (d, 1H), 3.82 (s, 2H), 3.72 (s, 2H), 2.41 (d, 2H), 2.03-1.74 (m, 9H), 1.60-1.44 (m, 3H). Mass: m/z 484.26 (M+H) + . 
     Synthesis of SC_3221: CIS-8-(dimethylamino)-3-(2-((2-hydroxyethyl)amino)pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: CIS-8-(dimethylamino)-3-(2-((2-methoxyethyl)amino)pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     In analogy to the method described for SC_3103 2-methoxyethanamine was reacted with CIS-3-(2-chloropyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-989) to be converted into CIS-8-(dimethylamino)-3-(2-((2-methoxyethyl)amino)pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one. 
     Step 2: CIS-8-(dimethylamino)-3-(2-((2-hydroxyethyl)amino)pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (SC_3221) 
     BBr 3  (IM in DCM) (2.2 mL, 2.22 mmol) was added to the solution of CIS-8-(dimethylamino)-3-(2-((2-methoxyethyl)amino)pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (0.55 g, 1.06 mmol) in DCM (20 mL) at −78° C. over 15 min. The reaction mixture was stirred at RT for 4 h, then quenched with water and concentrated under reduced pressure. The residue was purified by preparative reverse phase HPLC to afford 82 mg (19%) of CIS-8-(dimethylamino)-3-(2-((2-hydroxyethyl)amino)pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (SC_3221) (TLC system: 10% MeOH in DCM (Ammonia atmosphere); R f : 0.3).  1 H NMR (DMSO-d6): δ 8.41 (s, 2H), 7.39-7.24 (m, 6H), 6.70 (t, 1H), 4.64 (br, s, 1H), 3.50-3.45 (m, 4H), 3.28-3.25 (m, 2H), 2.37 (br m, 2H), 1.94-1.86 (m, 10H), 1.45 (m, 2H). Mass: m/z 411.2 (M+H)+ 
     Synthesis of SC_3224: CIS-3-(2-(1H-indazol-1-yl)pyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     K 2 CO 3  (0.53 g, 3.89 mmol) was added to the solution of CIS-3-(2-chloropyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (500 mg, 1.29 mmol) and 1H-indazole (306 mg, 2.59 mmol) in DMF (10 mL). The reaction mixture was stirred at 140° C. for 48h, cooled down to RT and concentrated under reduced pressure. The residue was diluted with DCM (50 mL), filtered through Celite and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography using neutral alumina (0-10% MeOH/DCM) followed by reverse phase HPLC to afford 77 mg (13%) of CIS-3-(2-(1H-indazol-1-yl)pyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (SC_3224) as off-white solid (TLC system: 10% MeOH in DCM; Rf: 0.6).  1 H NMR (DMSO-d6): δ 9.10 (s, 2H), 8.57-8.55 (d, 1H), 8.41 (s, 1H), 7.89-7.87 (d, 1H), 7.82 (br s, 1H), 7.57-7.53 (t, 1H), 7.39-7.28 (m, 6H), 3.72 (s, 2H), 2.45 (m, 2H), 1.98-1.93 (m, 10H), 1.52 (m, 2H). Mass: m/z 468.2 (M+H) + . 
     Synthesis of SC_3235: CIS-methyl 2-(2-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)phenoxy)acetate 
     
       
         
         
             
             
         
       
     
     CIS-2-(2-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)phenoxy)acetic acid (120 mg, 0.28 mmol) was dissolved in methanol (1.4 mL, 125 equiv.) and thionyl chloride (4 equiv., 1.13 mmol, 83 μL) was added dropwise. The reaction mixture was stirred at RT overnight, diluted with aq. sat. NaHCO 3  and extracted with DCM (3×). The combined organic phases were dried over MgSO 4  and concentrated under reduced pressure. The residue (112 mg) was purified by flash chromatography on silica get (gradient DCM/MeOH 97/3 to 88/12) to give 92 mg (74%) of CIS-methyl 2-(2-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)phenoxy)acetate (SC_3235).  1 H NMR (600 MHz, DMSO) δ 7.40-7.33 (m, 4H), 7.29 (dd, 1H), 7.28-7.24 (m, 1H), 7.13 (td, 1H), 6.99-6.91 (m, 2H), 4.76 (s, 2H), 3.67 (s, 3H), 3.55 (s, 2H), 2.45-2.26 (m, 2H), 2.07 (s, 2H), 1.98 (s, 6H), 1.94-1.75 (m, 4H), 1.52-1.45 (m, 2H). Mass: m/z 438.2 (M+H) + . 
     Synthesis of SC_3238: CIS-2-(5-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidin-2-yl)benzonitrile 
     
       
         
         
             
             
         
       
     
     CIS-3-(2-chloropyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-989) (240 mg, 0.56 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.05 equiv., 0.028 mmol, 23 mg) and (2-cyanophenyl)boronic acid (1.125 equiv., 0.63 mmol, 92 mg) were dissolved in degassed 1,2-dimethoxyethane (100 equiv., 56 mmol, 5.8 mL) and Cs 2 CO 3  (3.3 equiv., 1.84 mmol, 600 mg) in water (175 equiv., 98 mmol, 1.8 mL) was added. The resulting clear reaction mixture was stirred 3 days at 60° C. The reaction mixture was diluted with water (15 mL) and extracted with EtOAc (2×15 mL). Combined organic phases were dried over MgSO 4  and concentrated under reduced pressure. The residue (355 mg) was purified by flash chromatography on silica get (gradient DCM/MeOH 95/5 to 70/30) to give 60 mg of product, which was further purified by HPLC to give 15.4 mg (6%) of CIS-2-(5-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidin-2-yl)benzonitrile (SC_3238).  1 H NMR (600 MHz, DMSO) δ 9.17 (s, 2H), 8.27 (dd, 1H), 7.94 (dd, 1H), 7.81 (td, 1H), 7.65 (td, 1H), 7.42-7.35 (m, 5H), 7.28 (ddt, 1H), 3.75 (s, 2H), 2.49-2.34 (m, 1H), 2.00-1.76 (m, 11H), 1.55-1.51 (m, 2H). Mass: m/z 453.24 (M+H) + . 
     Synthesis of SC_3239: CIS-3-(2-aminopyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Microwave reactor vial was loaded with CIS-3-(2-chloropyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-989) (250 mg, 0.65 mmol), flushed with nitrogen, 7N solution of NH 3  in methanol (108 equiv., 70 mmol, 10 mL) and dioxane (37 equiv., 24 mmol, 2 mL) were added, the vial was sealed and the reaction mixture was stirred at 115° C. for 12 h in the microwave reactor. The reaction mixture was then cooled down to 4° C. overnight. The precipitate formed was filtered off, washed with DCM (small amount), water (2×), ether (2×) and dried under reduced pressure to give 180 mg (76%) of CIS-3-(2-aminopyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (SC_3239) as an off-white solid.  1 H NMR (600 MHz, DMSO) δ 8.39 (s, 2H), 7.40-7.32 (m, 5H), 7.26 (tt, 1H), 6.25 (s, 2H), 3.51 (s, 2H), 2.37 (s, 2H), 2.07 (s, 2H), 1.96 (s, 6H), 1.94-1.68 (m, 4H), 1.47 (d, 2H). Mass: m/z 367.23 (M+H) + . 
     Synthesis of SC_3240: CIS-N-(5-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidin-2-yl)cyclopropanecarboxamide 
     
       
         
         
             
             
         
       
     
     CIS-3-(2-aminopyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (SC_3239) (50 mg, 0.14 mmol) and 4-dimethylaminopyridine (1.3 equiv., 0.18 mmol, 22 mg) were dissolved in dry pyridine (200 equiv., 27 mmol, 2.2 mL) under nitrogen atmosphere. Cyclopropancarbonyl chloride (1.3 equiv., 0.18 mmol, 16 μL) was added in one portion and the reaction mixture was stirred at RT for 3 h. Additional portion of cyclopropancarbonyl chloride (3 equiv., 0.42 mmol, 37 μL) was added and the reaction mixture was stirred at 90° C. for 1 h. The reaction mixture was diluted with water (5 mL) and aq. sat. NaHCO 3  (5 mL), extracted with DCM (3×10 mL), organic phases were washed with brine, dried over Na 2 SO 4  and the solvent was removed under reduced pressure. The residue was suspended thoroughly in 3 mL DCM, the precipitate was filtered off, washed with ether and dried under reduced pressure to give 47 mg (79%) of CIS-N-(5-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidin-2-yl)cyclopropanecarboxamide (SC_3240) as a white solid.  1 H NMR (600 MHz, DMSO) δ 10.66 (s, 1H), 8.81 (s, 2H), 7.67 (s, 1H), 7.41-7.33 (m, 4H), 7.31-7.21 (m, 1H), 3.62 (s, 2H), 2.45-2.32 (m, 2H), 2.01 (td, 1H), 1.96 (s, 6H), 1.93-1.78 (m, 3H), 1.52-1.47 (m, 2H), 0.82-0.72 (m, 4H). Mass: m/z 435.3 (M+H) + . 
     Synthesis of SC_3242: CIS-8-(dimethylamino)-8-phenyl-3-(6-(piperazin-1-yl)pyridin-3-yl)-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: 4-(5-bromopyrimidin-2-yl)piperazine 
     In analogy to the method described for SC_3097 step 1 5-bromo-2-chloro-pyridine was reacted with piperazine to be converted into 4-(5-bromopyrimidin-2-yl)piperazine. 
     Step 2: CIS-8-(dimethylamino)-8-phenyl-3-(6-(piperazin-1-yl)pyridin-3-yl)-1,3-diazaspiro [4.5]decan-2-one (SC_3242) 
     CIS-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-976) (80 mg, 0.29 mmol), 4-(5-bromopyrimidin-2-yl)piperazine (2 equiv., 0.56 mmol, 142 mg) and potassium phosphate (4 equiv., 1.17 mmol, 248 mg) were suspended in N,N′-dimethylethylenediamine (18 equiv., 5.27 mmol, 0.6 mL) under nitrogen atmosphere. The reaction mixture was stirred at 80° C. for 2 h, diluted with water (10 mL) and extracted with DCM (3×15 mL). The combined organic phases contained a precipitate which was filtered off, washed with isopropanol and dried under reduced pressure to give 79 mg (62%) of CIS-8-(dimethyl-amino)-8-phenyl-3-(6-(piperazin-1-yl)pyridin-3-yl)-1,3-diazaspiro [4.5]decan-2-one (SC_3242).  1 H NMR (600 MHz, DMSO) δ 8.15 (d, 1H), 7.85 (dd, 1H), 7.41-7.33 (m, 4H), 7.32-7.23 (m, 2H), 6.74 (d, 1H), 3.51 (s, 2H), 3.30-3.25 (m, 4H), 2.78-2.73 (m, 4H), 2.43-2.31 (m, 2H), 1.96 (s, 6H), 1.93-1.79 (m, 4H), 1.50-1.42 (m, 2H). Mass: m/z 435.3 (M+H) + . 
     Synthesis of SC_3275: CIS-8-(ethylamino)-1-((1-hydroxycyclobutyl)methyl)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     CIS-8-amino-1-((1-hydroxycyclobutyl)methyl)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one (70 mg, 0.15 mmol) was dissolved in anhydrous DCM (3.8 mL) under nitrogen atmosphere. Acetic acid (0.1 equiv., 0.015 mmol, 0.8 μL) and acetaldehyde (1.1 equiv., 0.16 mmol, 9 μL) were sequentially added and the resulting mixture was stirred at RT for 1 h. Sodium triacetoxyborohydride (2 equiv., 0.29 mmol, 62 mg) was added and the reaction mixture was stirred at RT overnight and then at 50° C. for 5 h. Additional amounts of acetaldehyde (1.1 equiv., 0.16 mmol, 9 μL) and sodium triacetoxyborohydride (2 equiv., 0.29 mmol, 62 mg) were added and the reaction mixture was stirred further 24 h at 50° C. The resulting mixture was cooled down to RT, quenched with aq. sat. NaHCO 3  until pH&gt;7, diluted with water and extracted with DCM (3×). The combined organic layers were dried over Na 2 SO 4  and concentrated under reduced pressure. The residue (70 mg) was purified by flash chromatography on silica gel (DCM/EtOH gradient 99/1 to 95/5) to yield 43 mg (58%) of CIS-8-(ethylamino)-1-((1-hydroxycyclobutyl)methyl)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one (SC_3275).  1 H NMR (600 MHz, DMSO) δ 9.26 (s, 2H), 7.55-7.49 (m, 2H), 7.33 (t, 2H), 7.21 (d, 1H), 3.92 (s, 2H), 2.38 (td, 2H), 2.17-2.06 (m, 3H), 2.00-1.87 (m, 4H), 1.81 (td, 2H), 1.72-1.64 (m, 1H), 1.60-1.50 (m, 1H), 1.49-1.43 (m, 2H), 0.99 (t, 3H). Mass: m/z 504.3 (M+H) +   
     Synthesis of SC_3292 and SC_3293: enantiomer 1 and enantiomer 2 of CIS-8-(methyl((tetrahydrofuran-3-yl)methyl)amino)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Cs 2 CO 3  (0.85 g, 2.61 mmol) was added to an argon purged solution of CIS-8-(methyl((tetrahydrofuran-3-yl)methyl)amino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-1026) (0.3 g, 0.87 mmol), Xanthphos (45 mg, 0.087 mmol), Pd 2 (dba) 3  (80 mg, 0.087 mmol) and 5-bromo-2-(trifluoromethyl)pyrimidine (0.29 g, 1.30 mmol) in 1,4-dioxane (15 mL). The mixture was purged with argon for 5 min and stirred at 90° C. for 16 h. The reaction mixture was cooled to RT, diluted with EtOAc (20 mL), filtered through Celite and the filtrate was concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel 230-400 mesh; 3% MeOH in DCM) to get the compound which was further purified by reverse phase preparative HPLC to afford 0.1 g (23%) of CIS-8-(methyl((tetrahydrofuran-3-yl)methyl)amino)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one (TLC system: 10% MeOH in DCM; Rf: 0.4) as a mixture of enantiomers. Reverse phase preparative HPLC conditions: mobile phase: 10 mM ammonium bicarbonate in H 2 O/acetonitrile; column: X-BRIDGE-C18 (150*19), 5 μm; mobile phase gradient (min/% B): 0/30, 8/82, 8.1/100, 10/100, 10.1/30, 12/30; flow rate: 19 ml/min; diluent: mobile phase+THF. Enantiomeric mixture of CIS-8-(methyl((tetrahydrofuran-3-yl)methyl)amino)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one (100 mg) was separated by chiral SFC to afford 35 mg of enantiomer 1 (SC-3292) and 40 mg of enantiomer 2 (SC-3293) as off-white solids. Preparative SFC conditions: column: Chiralpak IA (250×30) mm, 5 μm; % CO 2 : 50.0%; % co-solvent: 50.0% (100% Methanol); total flow: 70.0 g/min; back pressure: 100.0 bar; UV: 256 nm; stack time: 13.5 min; load/inj.: 9.5 mg; no. of injections: 11. SC-3292:  1 H NMR (DMSO-d6): δ 9.15 (s, 2H), 8.23 (broad s, 1H), 7.37-7.25 (m, 5H), 3.68-3.58 (m, 5H), 3.37-3.36 (m, 1H), 2.32 (m, 3H), 2.13-1.89 (m, 10H), 1.47 (m, 3H). SC-3293:  1 H NMR (DMSO-d6): δ 9.15 (s, 2H), 8.23 (broad s, 1H), 7.37-7.36 (m, 4H), 7.26-7.24 (m, 1H), 3.68-3.56 (m, 5H), 3.37-3.36 (m, 1H), 2.31-2.28 (m, 3H), 2.13-1.86 (m, 10H), 1.48 (m, 3H). Mass: m/z 490.3 (M+H) + . 
     Synthesis of SC_3313: CIS-3-(2-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)pyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: 5-bromo-2-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)pyrimidine 
     2-Azido-5-bromo-pyrimidine (400 mg, 1.94 mmol) and ethynylcyclopropane (1.3 equiv., 2.522 mmol, 0.21 mL) were dissolved in tert-butanol (5 mL). The solutions of sodium ascorbate (0.1 equiv., 0.194 mmol, 38 mg) in water (2.5 mL) and copper(II) sulfate pentahydrate (0.1 equiv., 0.194 mmol, 48 mg) in water (2.5 mL) were sequentially added. The reaction mixture was stirred under ambient conditions for 18 h, then diluted with 20 mL 1M aq. NH 4 OH and extracted with EtOAc (3×30 mL). The combined organic extracts were washed with brine, dried over Na 2 SO 4  and concentrated under reduced pressure. Crude product (510 mg) was purified by flash chromatography on silica gel (DCM/EtOH 99/1) to yield 143 mg of 5-bromo-2-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)pyrimidine as a white solid. Mass: m/z 266.0 (M+H) + . 
     Step 2: CIS-3-(2-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)pyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (SC_3313) 
     In analogy to the method described for SC_3103 CIS-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-976) was reacted with 5-bromo-2-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)pyrimidine to be converted into CIS-3-(2-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)pyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (SC_3313).  1 H NMR (600 MHz, DMSO) δ 9.09 (d, 2H), 8.50 (d, 1H), 7.91 (s, 1H), 7.42-7.34 (m, 2H), 7.38 (s, 3H), 7.31-7.25 (m, 1H), 3.72 (s, 2H), 2.48-2.31 (m, 2H), 2.10-2.01 (m, 1H), 1.99-1.77 (m, 10H), 1.58-1.46 (m, 2H), 1.00-0.91 (m, 2H), 0.84 (tt, 2H). Mass: m/z 459.3 (M+H) + . 
     Synthesis of SC_3319: CIS-8-(methyl((tetrahydrofuran-3-yl)methyl)amino)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Cs 2 CO 3  (145 mg, 0.45 mmol, 2 equiv.), CIS-8-(dimethylamino)-8-(3-fluorophenyl)-1,3-diazaspiro[4.5]decan-2-one (INT-1024) (65 mg, 0.223 mmol, 1 equiv.), Xanthphos (19 mg, 0.033 mmol, 0.15 equiv.), Pd 2 (dba) 3  (10 mg, 0.011 mmol, 0.05 equiv.) and 5-bromo-1-methyl-3-(trifluoromethyl)pyrazole (102 mg, 0.446 mmol, 2 equiv.) were loaded into a microwave reactor vial (2-5 mL), the vial was sealed and flushed with nitrogen (3×). 1,4-Dioxane (1.5 mL) was added via syringe and the reaction mixture was stirred at 110° C. in the microwave reactor for 10 h. The resulting mixture was cooled down to RT, solution of Xanthphos (19 mg, 0.033 mmol, 0.15 equiv.) and Pd 2 (dba) 3  (10 mg, 0.011 mmol, 0.05 equiv.) in 1,4 dioxane (1 mL) was added, and the reaction mixture was stirred at 130° C. in the microwave reactor for further 10 h. The resulting suspension was cooled to RT, quenched with water and extracted with DCM (3×). The combined organic layer was dried over Na 2 SO 4  and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (gradient 0% to 16% MeOH in DCM) to yield 41 mg (42%) of CIS-8-(methyl((tetrahydrofuran-3-yl)methyl)amino)-8-phenyl-3-(2-(trifluoromethyl)pyrimidin-5-yl)-1,3-diazaspiro[4.5]decan-2-one (SC_3319).  1 H NMR (600 MHz, DMSO) δ 7.71 (s, 1H), 7.41 (q, 1H), 7.21-7.12 (m, 2H), 7.09 (td, 1H), 6.63 (s, 1H), 3.75 (s, 2H), 3.55 (s, 2H), 2.42-2.27 (m, 2H), 1.99-1.89 (m, 8H), 1.88-1.73 (m, 2H), 1.56-1.49 (m, 2H). Mass: m/z 440.2 (M+H) + . 
     Synthesis of SC_3340: CIS-2-(3-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyridin-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Step 1: CIS-2-(3-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyridin-4-yl)acetonitrile 
     In analogy to the method described for SC_3097 step 2 CIS-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-976) was reacted with (3-bromo-pyridin-4-yl)-acetonitrile to be converted into CIS-2-(3-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyridin-4-yl)acetonitrile. 
     Step 2: CIS-2-(3-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyridin-4-yl)acetamide (SC_3340) 
     To a solution of CIS-2-(3-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyridin-4-yl)acetonitrile (600 mg, 1.54 mmol, 1.0 equiv.) in EtOH (50 ml) was added NaOH (247 mg, 6.16 mmol, 4.0 equiv.). The reaction mixture was stirred at reflux for 16 h and then concentrated under reduced pressure. The resulting residue was purified by column chromatography (neutral alumina; 4% MeOH in DCM) and finally by preparative HPLC (column: Gemini NX-C 18  (50×4.6), 3 μm, diluent: DMSO, mobile phase: gradient 0.05% HCOOH in water/ACN flow rate: 1 ml/min) to yield CIS-2-(3-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyridin-4-yl)acetamide (SC_3340) (40 mg, 0,098 mmol, 4% yield after two steps) as an off white solid.  1 HNMR (DMSO, 400 MHz) δ 8.40 (s, 1H), 8.32 (d, 1H, J=4.92 Hz), 7.49 (s, 1H), 7.36-7.24 (m, 7H), 6.99 (s, 1H), 3.49-3.46 (m, 4H), 2.32 (bs, 2H), 1.94-1.77 (m, 10H), 1.52 (bs, 2H). Mass: m/z 408.2 (M+H) + . 
     Synthesis of SC_3352: CIS-8-(dimethylamino)-3-(2-hydroxybenzo[d]oxazol-7-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: CIS-7-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-3-((2-(trimethylsilyl)ethoxy)methyl)benzo[d]oxazol-2(3H)-one 
     In analogy to the method described for SC_3103 CIS-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-976) was reacted with 7-bromo-3-(2-trimethylsilanyl-ethoxymethyl)-3H-benzooxazol-2-one (prepared from 7-bromobenzo[d]oxazol-2(3H)-one and trimethylsilylethoxymethylchloride following a standard procedure) to be converted into CIS-7-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-3-((2-(trimethylsilyl)ethoxy)methyl)benzo[d]oxazol-2(3H)-one. Mass: m/z 537.2 (M+H) + . 
     Step 2: CIS-8-(dimethylamino)-3-(2-hydroxybenzo[d]oxazol-7-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (SC_3352) 
     To a solution of CIS-7-[8-dimethylamino-2-oxo-8-phenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1,3-diaza-spiro[4.5]dec-3-yl]-3H-benzooxazol-2-one (350 mg, 0.65 mmol, 1.0 eq) in 1,4-dioxane (2 mL) was added 4M HCl in dioxane (6 mL) dropwise at 0° C. The reaction mixture was stirred at RT for 48 h and then concentrated under reduced pressure. The residue was taken in DCM (200 mL) and washed with sat. aq. NaHCO 3  (100 mL). Organic layer was dried over Na 2 SO 4  and concentrated under reduced pressure to get the crude product which was purified by column chromatography (neutral alumina; 2% MeOH/DCM) to yield CIS-7-(8-dimethylamino-2-oxo-8-phenyl-1,3-diaza-spiro[4.5]dec-3-yl)-3H-benzooxazol-2-one (SC_3352) (85 mg, 0.21 mmol, 32%) as an off white solid.  1 HNMR (DMSO-d6, 400 MHz at 100° C.), δ (ppm)=11.19 (bs, 1H), 7.37-7.23 (m, 6H), 7.14 (s, 1H), 7.04 (t, 1H, J=8.06), 6.76 (d, 1H, J=7.68 Hz), 3.69 (s, 2H), 2.38-2.26 (m, 2H), 2.08-1.76 (m, 10H), 1.56-1.51 (m, 2H). Mass: m/z 407.1 (M+H) + . 
     Synthesis of SC_3354: CIS-4-(5-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidin-2-yl)benzamide Trifluoroacetate Salt 
     
       
         
         
             
             
         
       
     
     3-(2-chloropyrimidin-5-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT 989) (200 mg, 0.52 mmol, 1 equiv.), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (129 mg, 0.52 mmol, 1 equiv.), Pd 2 (dba) 3  (95 mg, 0.10 mmol, 0.2 equiv.), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (X-Phos) (99 mg, 0.21 mmol, 0.4 equiv.) were loaded into microwave reactor vessel and flushed with nitrogen (2×). Anhydrous 1,4-dioxane (9 mL) and sodium carbonate (213 mg, 2.07 mmol, 4 equiv.) were sequentially added. The reaction mixture was stirred 8 h at 120° C. in the microwave reactor and then concentrated under reduced pressure. The residue was suspended in EtOAc/water (1/1, v/v) and filtered through a glass filter. The solid residue was dissolved in MeOH/DCM/TFA, filtered through Celite pad and the filtrate was concentrated under reduced pressure to give 75 mg (25%) of CIS-4-(5-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)pyrimidin-2-yl)benzamide trifluoroacetate salt (SC_3354).  1 H NMR (600 MHz, DMSO) δ 9.05 (s, 2H), 8.42 (s, 1H), 8.34 (d, 2H), 8.03 (s, 1H), 7.98 (d, 2H), 7.74-7.65 (m, 2H), 7.58 (t, 2H), 7.56-7.52 (m, 1H), 7.40 (s, 1H), 3.58 (s, 2H), 2.70 (d, 2H), 2.60 (s, 6H), 2.25 (t, 2H), 1.91 (d, 2H), 1.39 (t, 2H). Mass: m/z 471.3 (M+H) + . 
     Synthesis of SC_3357: CIS-8-(dimethylamino)-3-(1H-indol-3-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: CIS-8-(dimethylamino)-8-phenyl-3-(1-tosyl-1H-indol-3-yl)-1,3 diazaspiro[4.5]decan-2-one 
     In analogy to the method described for SC_3103 CIS-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-976) was reacted with 3-bromo-1-(toluene-4-sulfonyl)-1H-indole to be converted into CIS-8-(dimethylamino)-8-phenyl-3-(1-tosyl-1H-indol-3-yl)-1,3-diazaspiro[4.5]decan-2-one. Mass: m/z 543.1 (M+H) + . 
     Step 2: CIS-8-(dimethylamino)-3-(1H-indol-3-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (SC_3357) 
     To a solution of 8-dimethylamino-8-phenyl-3-[1-(toluene-4-sulfonyl)-1H-indol-3-yl]-1,3-diaza-spiro[4.5]decan-2-one (275 mg, 0.51 mmol, 1.0 eq.) in EtOH (24 mL) was added ION aq. NaOH (1.2 mL) at RT. The reaction mixture was heated to reflux for 1.5 h, then concentrated, diluted with water (50 mL) and extracted with EtOAc (150 mL). Organic layer was dried over Na 2 SO 4  and concentrated under reduced pressure. The residue was purified by column chromatography (neutral alumina; 2% MeOH/DCM) to afford CIS-8-dimethylamino-3-(1H-indol-3-yl)-8-phenyl-1,3-diaza-spiro[4.5]decan-2-one (SC_3357) (130 mg, 0.33 mmol, 65%) as light brown solid.  1 H NMR (DMSO-d6, 400 MHz at 100° C.), δ (ppm)=10.55 (bs, 1H), 7.62-7.60 (d, 1H, J=7.96 Hz), 7.37-7.23 (m, 7H), 7.04 (t, 1H, J=7.48 Hz), 6.92 (t, 1H, J=7.44 Hz), 6.71 (bs, 1H), 3.61 (s, 2H), 2.38-2.33 (m, 2H), 2.04-1.82 (m, 10H), 1.59-1.54 (m, 2H). Mass: m/z 389.3 (M+H) + . 
     Synthesis of SC_3379: CIS-3-(1-acetyl-1H-indol-3-yl)-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     To a solution of 8-dimethylamino-3-(1H-indol-3-yl)-8-phenyl-1,3-diaza-spiro[4.5]decan-2-one (SC_3357) (150 mg, 0.38 mmol, 1.0 eq.) in DCM (6 mL) were added NaOH (39 mg, 0.96 mmol, 2.5 eq.) and Bu 4 NHSO 4  (129 mg, 0.38 mmol, 1.0 eq.) at 0° C. and the reaction mixture was stirred for 30 min followed by addition of acetyl chloride (54 μl, 0.76 mmol, 2.0 eq.). The reaction mixture was stirred at RT for 16 h, then diluted with DCM (150 ml) and washed with water (50 mL) and brine (50 mL). Organic layer was dried over Na 2 SO 4  and concentrated under reduced pressure. The residue was purified by column chromatography (neutral alumina; 1% MeOH/DCM) followed by prep HPLC to afford 3-(1-acetyl-H-indol-3-yl)-8-dimethylamino-8-phenyl-1,3-diaza-spiro[4.5]decan-2-one (SC_3379) as off white solid. Note: Two batches of same reactions were done and yield was calculated accordingly. Yield: 13% (45 mg, 0.1 mmol). 1HNMR (DMSO-d6, 400 MHz at 100° C.), δ (ppm)=8.34-8.32 (d, 1H, J=7.88 Hz), 7.90 (d, 1H, J=7.36 Hz), 7.67 (s, 1H), 7.37-7.10 (m, 8H), 3.71 (s, 2H), 2.57 (s, 3H), 2.38-2.32 (m, 2H), 2.04-1.88 (m, 10H), 1.61-1.59 (m, 2H). Mass: m/z 431.2 (M+H) + . 
     Synthesis of SC_3388: CIS-8-(dimethylamino)-8-(3-hydroxyphenyl)-3-(4-methyl-6-(trifluoromethyl)pyridin-3-yl)-1,3-diazaspiro[4.5]decan-2-one 
     
       
         
         
             
             
         
       
     
     CIS-8-(dimethylamino)-8-(3-methoxyphenyl)-3-[4-methyl-6-(trifluoromethyl)-3-pyridyl]-1,3-diazaspiro[4.5]decan-2-one (SC_3368) (42 mg, 0.091 mmol) was dissolved in DCM (2 mL) and the solution was cooled to 0° C. Boron tribromide (1M sol. in DCM, 4 equiv., 0.36 mmol, 0.36 mL) was added in one portion. The reaction mixture was allowed to stir at RT overnight, then quenched with methanol and diluted with water. The resulting mixture was extracted with DCM (2×), the combined organic phases were dried over Na 2 SO 4  and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent gradient DCM/EtOH) to yield 16 mg (39%) of CIS-8-(dimethylamino)-8-(3-hydroxyphenyl)-3-(4-methyl-6-(trifluoromethyl)pyridin-3-yl)-1,3-diazaspiro[4.5]decan-2-one (SC_3388).  1 H NMR (600 MHz, DMSO) δ 8.57 (s, 1H), 7.80 (s, 1H), 7.52 (s, 1H), 7.14 (t, 1H), 6.77 (d, 1H), 6.74 (s, 1H), 6.66 (dd, 1H), 3.61 (s, 2H), 2.32 (s, 3H), 2.31-2.19 (m, 2H), 2.01-1.89 (m, 8H), 1.88-1.70 (m, 2H), 1.54 (t, 2H). Mass: m/z 449.2 (M+H) + . 
     Synthesis of SC_3396: CIS-4-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)indolin-2-one 
     
       
         
         
             
             
         
       
     
     Step 1: CIS-4-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-1-(4-methoxybenzyl)indoline-2,3-dione 
     In analogy to the method described for SC_3242 CIS-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one (INT-976) was reacted with 4-bromo-1-(4-methoxy-benzyl)-1H-indole-2,3-dione to be converted into CIS-4-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-1-(4-methoxybenzyl)indoline-2,3-dione. Mass: m/z 539.2 (M+H) + . 
     Step 2: CIS-4-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)-1-(4-methoxybenzyl)indolin-2-one 
     To a solution of CIS-4-(8-dimethylamino-2-oxo-8-phenyl-1,3-diaza-spiro[4.5]dec-3-yl)-1-(4-methoxy-benzyl)-1H-indole-2,3-dione (600 mg, 1.11 mmol, 1.0 eq) in EtOH (9 mL) was added hydrazine hydrate (9 mL) at RT. The reaction mixture was stirred at reflux for 16 h, then concentrated, diluted with water (50 mL) and extracted with EtOAc (200 mL). Organic layer was dried over Na 2 SO 4 , filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography (neutral alumina, 0.5% MeOH/DCM) to afford 8-dimethylamino-3-[I-(4-methoxy-benzyl)-2-oxo-2,3-dihydro-1H-indol-4-yl]-8-phenyl-1,3-diaza-spiro[4.5]decan-2-one (275 mg, 0.52 mmol, 47%) as a brown solid. Mass: m/z 525.2 (M+H)*. 
     Step 3: CIS-4-(8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl)indolin-2-one (SC_3396) 
     A solution of CIS-8-dimethylamino-3-[1-(4-methoxy-benzyl)-2-oxo-2,3-dihydro-1H-indol-4-yl]-8-phenyl-1,3-diaza-spiro[4.5]decan-2-one (275 mg, 0.52 mmol, 1.0 eq.) in TFA (4 mL) was stirred at 90° C. in a sealed tube for 16 h. The reaction mixture was cooled to RT, concentrated under reduced pressure, diluted with water (50 mL), basified with sat. aq. NaHCO 3  and extracted with EtOAc (200 mL). The organic phase was washed with brine (50 mL), dried over Na 2 SO 4 , filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography (neutral alumina, 5% MeOH in DCM) to afford CIS-8-dimethylamino-3-(2-oxo-2,3-dihydro-1H-indol-4-yl)-8-phenyl-1,3-diaza-spiro[4.5]decan-2-one (SC_3396) (60 mg, 0.14 mmol, 28%) as an off-white solid.  1 H NMR (DMSO-d6, 400 MHz, 100° C.): δ (ppm)=9.98 (bs, 1H), 7.36-7.22 (m, 5H), 7.09 (t, 1H, J=7.94 Hz), 6.95-6.88 (m, 2H), 6.59 (d, 1H, J=7.52 Hz), 3.57 (s, 2H), 3.49 (s, 2H), 2.36-2.31 (m, 2H), 2.03 (s, 6H), 1.97-1.85 (m, 4H), 1.55-1.51 (m, 2H). Mass: m/z 405.3 (M+H) + . 
     The following compounds were prepared in analog and by combining previously described methods: 
     
       
         
           
               
               
               
               
               
               
             
               
                   
               
               
                   
                   
                   
                   
                 in analogy 
                 m/z 
               
               
                 Example 
                 Chemical Name 
                 Reactant I 
                 Reactant II 
                 to method 
                 [M + H] +   
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 SC_3001 
                 cis-5-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT-987 
                 5-bromopyrimidine-2- 
                 SC-3022 
                 445.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2- 
                   
                 carbonitrile 
               
               
                   
                 carbonitrile 
               
               
                 SC_3002 
                 cis-5-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT-987 
                 5-bromopyrazine-2- 
                 SC-3022 
                 445.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrazine-2-carbonitrile 
                   
                 carbonitrile 
               
               
                 SC_3003 
                 cis-5-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT-987 
                 5-bromo-4- 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-4-methoxy-pyrimidine- 
                   
                 methoxypyrimidine-2- 
                 SC-3022 
                 475.3 
               
               
                   
                 2-carbonitrile 
                   
                 carbonitrile 
               
               
                 SC_3004 
                 cis-5-[8-Dimethylamino-1-(2-methoxy-ethyl)-2-oxo-8-phenyl- 
                 INT-980 
                 5-bromopyrimidine-2- 
                 SC-3022 
                 435.2 
               
               
                   
                 1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile 
                   
                 carbonitrile 
               
               
                 SC_3005 
                 cis-5-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 SC_3001 
                 — 
                 SC_3016 
                 463.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carboxylic 
               
               
                   
                 acid amide 
               
               
                 SC_3006 
                 cis-5-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT-987 
                 5-bromo-2-(methylthio)- 
                 SC-3022 
                 523.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-2-methylsulfonyl- 
                   
                 pyrimidine-4-carbonitrile 
                 (step 1); 
               
               
                   
                 pyrimidine-4-carbonitrile 
                   
                   
                 SC_3008 
               
               
                   
                   
                   
                   
                 (step 2) 
               
               
                 SC_3007 
                 cis-5-[1-(2-Methoxy-ethyl)-8-methylamino-2-oxo-8-phenyl- 
                 SC_3004 
                 — 
                 SC_3045 
                 421.2 
               
               
                   
                 1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile 
               
               
                 SC_3008 
                 cis-2-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT-987 
                 2-iodo-5- 
                 SC-3022 
                 521.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-5-methylsulfonyl- 
                   
                 (methylthio)benzonitrile 
                 (step 1); 
               
               
                   
                 benzonitrile 
                   
                 (step 1) 
                 SC_3008 
               
               
                   
                   
                   
                   
                 (step 2) 
               
               
                 SC_3009 
                 cis-2-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 SC_3090 
                 — 
                 SC_3016 
                 461.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-benzamide 
               
               
                 SC_3010 
                 cis-3-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 SC_3072 
                 — 
                 SC_3016 
                 461.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-benzamide 
               
               
                 SC_3011 
                 cis-5-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2- 
                 SC_3013 
                 — 
                 SC_3016 
                 479.3 
               
               
                   
                 oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2- 
               
               
                   
                 carboxylic acid amide 
               
               
                 SC_3012 
                 cis-5-[1-(Cyclobutyl-methyl)-8-methylamino-2-oxo-8-phenyl- 
                 SC_3003 
                 — 
                 SC_3045 
                 461.3 
               
               
                   
                 1,3-diazaspiro[4.5]decan-3-yl]-4-methoxy-pyrimidine-2- 
               
               
                   
                 carbonitrile 
               
               
                 SC_3013 
                 cis-5-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2- 
                 INT-600 
                 — 
                 SC_3013 
                 461.3 
               
               
                   
                 oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2- 
               
               
                   
                 carbonitrile 
               
               
                 SC_3014 
                 cis-2-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT-987 
                 2-chloropyrimidine-5- 
                 SC_3014 
                 445.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-5- 
                   
                 carbonitrile 
               
               
                   
                 carbonitrile 
               
               
                 SC_3015 
                 cis-8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-3-(2- 
                 INT-976 
                 5-bromo-2- 
                 SC_3013 
                 466.3 
               
               
                   
                 methoxy-pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                 methoxypyrimidine 
               
               
                   
                 one 
                   
                 (step 1); 
               
               
                   
                   
                   
                 1-(tert-butyldimethyl- 
               
               
                   
                   
                   
                 silyloxy)cyclobutyl)methyl 
               
               
                   
                   
                   
                 4-methylbenzene-sulfonate 
               
               
                   
                   
                   
                 (step 2) 
               
               
                 SC_3016 
                 cis-2-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 SC_3014 
                 — 
                 SC_3016 
                 463.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-5-carboxylic 
               
               
                   
                 acid amide 
               
               
                 SC_3017 
                 cis-4-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 SC_3081 
                 methanamine 
                 SC_3028 
                 475.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-N-methyl-benzamide 
               
               
                 SC_3018 
                 cis-5-(8-Dimethylamino-2-oxo-8-phenyl-1-propyl-1,3- 
                 INT-600 
                 1-bromopropane 
                 SC_3013 
                 419.2 
               
               
                   
                 diazaspiro[4.5]decan-3-yl)-pyrimidine-2-carbonitrile 
               
               
                 SC_3019 
                 cis-5-[8-Dimethylamino-1-(3-methoxy-propyl)-2-oxo-8- 
                 INT-600 
                 1-bromo-3-methoxypropane 
                 SC-3013 
                 449.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2- 
               
               
                   
                 carbonitrile 
               
               
                 SC_3020 
                 cis-5-[1-(Cyclopropyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT-600 
                 (bromomethyl)cyclopropane 
                 SC-3013 
                 431.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2- 
               
               
                   
                 carbonitrile 
               
               
                 SC_3021 
                 cis-4-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 SC_3081 
                 ammonia 
                 SC-3028 
                 461.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-benzamide 
               
               
                 SC_3022 
                 cis-1-(Cyclobutyl-methyl)-8-dimethylamino-8-phenyl-3-[2- 
                 INT-987 
                 5-bromo-2- 
                 SC_3022 
                 488.3 
               
               
                   
                 (trifluoromethyl)-pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2- 
                   
                 (trifluoromethyl)pyrimidine 
               
               
                   
                 one 
               
               
                 SC_3023 
                 cis-8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-3-(2- 
                 SC_3015 
                 — 
                 SC_3023 
                 452.3 
               
               
                   
                 hydroxy-pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2- 
               
               
                   
                 one 
               
               
                 SC_3024 
                 cis-5-[8-Dimethylamino-1-(2-methyl-propyl)-2-oxo-8-phenyl- 
                 INT-600 
                 1-bromo-2-methylpropane 
                 SC_3013 
                 433.3 
               
               
                   
                 1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile 
               
               
                 SC_3025 
                 cis-5-[8-Dimethylamino-1-(2-hydroxy-ethyl)-2-oxo-8-phenyl- 
                 INT-600 
                 (3-bromopropoxy)(tert- 
                 SC-3025 
                 421.2 
               
               
                   
                 1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile 
                   
                 butyl)dimethylsilane 
               
               
                 SC_3026 
                 cis-5-[1-(Cyclobutyl-methyl)-8-methylamino-2-oxo-8-phenyl- 
                 SC_3078 
                 — 
                 SC_3045 
                 444.3 
               
               
                   
                 1,3-diazaspiro[4.5]decan-3-yl]-4-methyl-pyridine-2- 
               
               
                   
                 carbonitrile 
               
               
                 SC_3027 
                 cis-1-(Cyclobutyl-methyl)-3-(5-methoxy-pyrazin-2-yl)-8- 
                 SC_3075 
                 — 
                 SC_3045 
                 436.3 
               
               
                   
                 methylamino-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
               
               
                 SC_3028 
                 cis-4-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 SC_3081 
                 — 
                 SC_3028 
                 489.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-N,N-dimethyl- 
               
               
                   
                 benzamide 
               
               
                 SC_3029 
                 cis-4-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 SC_3081 
                 — 
                 SC_3028 
                 533.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-N-ethyl-N-(2-hydroxy- 
               
               
                   
                 ethyl)-benzamide 
               
               
                 SC_3030 
                 cis-2-[1-(Cyclobutyl-methyl)-8-methylamino-2-oxo-8-phenyl- 
                 SC_3008 
                 — 
                 SC_3045 
                 507.2 
               
               
                   
                 1,3-diazaspiro[4.5]decan-3-yl]-5-methylsulfonyl-benzonitrile 
               
               
                 SC_3031 
                 cis-1-(Cyclobutyl-methyl)-8-methylamino-3-[2- 
                 SC_3084 
                 — 
                 SC_3031 
                 550.2 
               
               
                   
                 methylsulfonyl-4-(trifluoromethyl)-phenyl]-8-phenyl-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3032 
                 cis-4-[1-(Cyclobutyl-methyl)-8-methylamino-2-oxo-8-phenyl- 
                 SC_3089 
                 — 
                 SC_3032 
                 579.3 
               
               
                   
                 1,3-diazaspiro[4.5]decan-3-yl]-N,N-dimethyl-3- 
               
               
                   
                 (trifluoromethyl)-benzenesulfonic acid amide 
               
               
                 SC_3033 
                 cis-4-[1-(Cyclobutyl-methyl)-8-(ethyl-methyl-amino)-2-oxo-8- 
                 INT-797 
                 4-bromobenzonitrile 
                 SC_3013 
                 457.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-benzonitrile 
                   
                 (step 1); 
               
               
                   
                   
                   
                 (bromomethyl)cyclobutane 
               
               
                   
                   
                   
                 (step 2) 
               
               
                 SC_3034 
                 cis-1-(Cyclobutyl-methyl)-8-(ethyl-methyl-amino)-8-phenyl-3- 
                 INT-797 
                 5-bromo-2- 
                 SC-3013 
                 502.3 
               
               
                   
                 [2-(trifluoromethyl)-pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan- 
                   
                 (trifluoromethyl)pyrimidine 
               
               
                   
                 2-one 
                   
                 (step 1); 
               
               
                   
                   
                   
                 (bromomethyl)cyclobutane 
               
               
                   
                   
                   
                 (step 2) 
               
               
                 SC_3035 
                 cis-5-[1-(Cyclobutyl-methyl)-8-(ethyl-methyl-amino)-2-oxo-8- 
                 INT-797 
                 5-bromopyrimidine-2- 
                 SC_3013 
                 459.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2- 
                   
                 carbonitrile (step 1); 
               
               
                   
                 carbonitrile 
                   
                 (bromomethyl)cyclobutane 
               
               
                   
                   
                   
                 (step 2) 
               
               
                 SC_3036 
                 cis-5-[8-Dimethylamino-1-[(1-methyl-cyclobutyl)-methyl]-2- 
                 INT-982 
                 5-bromopyrimidine-2- 
                 SC_3022 
                 459.3 
               
               
                   
                 oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2- 
                   
                 carbonitrile 
               
               
                   
                 carbonitrile 
               
               
                 SC_3037 
                 cis-2-[3-(2-Cyano-pyrimidin-5-yl)-8-dimethylamino-2-oxo-8- 
                 INT-978 
                 5-bromopyrimidine-2- 
                 SC_3065 
                 462.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-1-yl]-N,N-dimethyl- 
                   
                 carbonitrile 
               
               
                   
                 acetamide 
               
               
                 SC_3038 
                 cis-1-(Cyclobutyl-methyl)-8-methylamino-8-phenyl-3-[2- 
                 SC_3022 
                 — 
                 SC_3038 
                 474.2 
               
               
                   
                 (trifluoromethyl)-pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2- 
               
               
                   
                 one 
               
               
                 SC_3039 
                 cis-5-[8-Dimethylamino-8-(3-fluorophenyl)-1-(4-methoxy- 
                 INT-601 
                 1-bromo-4-methoxybutane 
                 SC_3064 
                 481.3 
               
               
                   
                 butyl)-2-oxo-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2- 
               
               
                   
                 carbonitrile 
               
               
                 SC_3040 
                 cis-5-[8-Dimethylamino-1-(3-methoxy-propyl)-2-oxo-8- 
                 INT-979 
                 5-bromo-4- 
                 SC_3022 
                 479.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-4-methoxy-pyrimidine- 
                   
                 methoxypyrimidine-2- 
               
               
                   
                 2-carbonitrile 
                   
                 carbonitrile 
               
               
                 SC_3041 
                 cis-5-[1-[(1-Cyano-cyclobutyl)-methyl]-8-dimethylamino-2- 
                 INT_600 
                 (1-cyanocyclobutyl)methyl 
                 SC_3013 
                 470.3 
               
               
                   
                 oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2- 
                   
                 4-methylbenzenesulfonate 
               
               
                   
                 carbonitrile 
               
               
                 SC_3042 
                 cis-N-(Cyclobutyl-methyl)-5-[1-(cyclobutyl-methyl)-8- 
                 INT-601 
                 (bromomethyl)cyclobutane 
                 SC_3064 
                 549.3 
               
               
                   
                 dimethylamino-8-(3-fluorophenyl)-2-oxo-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carboxylic acid amide 
               
               
                 SC_3043 
                 cis-5-[1-(3-Methoxy-propyl)-8-methylamino-2-oxo-8-phenyl- 
                 SC_3019 
                 — 
                 SC_3043 
                 435.2 
               
               
                   
                 1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile 
               
               
                 SC_3044 
                 cis-5-[8-Dimethylamino-8-(3-fluorophenyl)-1-methyl-2-oxo- 
                 INT_600 
                 iodomethane 
                 SC_3013 
                 409.2 
               
               
                   
                 1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile 
               
               
                 SC_3045 
                 cis-4-Methoxy-5-[1-(3-methoxy-propyl)-8-methylamino-2- 
                 SC_3040 
                 — 
                 SC_3045 
                 465.3 
               
               
                   
                 oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2- 
               
               
                   
                 carbonitrile 
               
               
                 SC_3046 
                 cis-4-[8-Dimethylamino-1-(2-methoxy-ethyl)-2-oxo-8-phenyl- 
                 INT-980 
                 4-bromopyrimidine-2- 
                 SC_3022 
                 435.2 
               
               
                   
                 1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2-carbonitrile 
                   
                 carbonitrile 
               
               
                 SC_3047 
                 cis-5-[8-Dimethylamino-1-(2-methoxy-ethyl)-2-oxo-8-phenyl- 
                 INT-980 
                 5-bromo-4- 
                 SC_3022 
                 465.3 
               
               
                   
                 1,3-diazaspiro[4.5]decan-3-yl]-4-methoxy-pyrimidine-2- 
                   
                 methoxypyrimidine-2- 
               
               
                   
                 carbonitrile 
                   
                 carbonitrile 
               
               
                 SC_3048 
                 cis-4-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT-987 
                 4-bromopyrimidine-2- 
                 SC_3022 
                 445.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2- 
                   
                 carbonitrile 
               
               
                   
                 carbonitrile 
               
               
                 SC_3049 
                 cis-1-(Cyclobutyl-methyl)-8-dimethylamino-3-(6- 
                 INT-987 
                 4-bromo-6-(methylthio)- 
                 SC_3022 
                 466.3 
               
               
                   
                 methylsulfanyl-pyrimidin-4-yl)-8-phenyl-1,3- 
                   
                 pyrimidine 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3050 
                 cis-2-[3-(2-Cyano-pyrimidin-4-yl)-8-dimethylamino-2-oxo-8- 
                 SC_3022 
                 4-bromopyrimidine-2- 
                 SC_3022 
                 462.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-1-yl]-N,N-dimethyl- 
                   
                 carbonitrile 
               
               
                   
                 acetamide 
               
               
                 SC_3051 
                 cis-6-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT-987 
                 6-bromopyrimidine-4- 
                 SC_3022 
                 445.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-4- 
                   
                 carbonitrile 
               
               
                   
                 carbonitrile 
               
               
                 SC_3052 
                 cis-2-(8-Dimethylamino-2-oxo-3,8-diphenyl-1,3- 
                 INT-987 
                 bromobenzene 
                 SC_3022 
                 435.3 
               
               
                   
                 diazaspiro[4.5]decan-1-yl)-N,N-dimethyl-acetamide 
               
               
                 SC_3053 
                 cis-1-(Cyclobutyl-methyl)-8-dimethylamino-3,8-diphenyl-1,3- 
                 INT-987 
                 bromobenzene 
                 SC_3022 
                 418.3 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3054 
                 cis-2-[8-Dimethylamino-1-(2-methoxy-ethyl)-2-oxo-8-phenyl- 
                 INT-980 
                 5-chloropyrimidine-2- 
                 SC_3022 
                 435.2 
               
               
                   
                 1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-5-carbonitrile 
                   
                 carbonitrile 
               
               
                 SC_3055 
                 cis-8-Dimethylamino-1-(2-methoxy-ethyl)-3,8-diphenyl-1,3- 
                 INT-980 
                 bromobenzene 
                 SC_3022 
                 408.3 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3056 
                 cis-5-[8-Dimethylamino-1-(2-methoxy-ethyl)-2-oxo-8-phenyl- 
                 INT-980 
                 5-bromo-4- 
                 SC_3022 
                 448.3 
               
               
                   
                 1,3-diazaspiro[4.5]decan-3-yl]-4-methyl-pyridine-2- 
                   
                 methylpicolinonitrile 
               
               
                   
                 carbonitrile 
               
               
                 SC_3057 
                 cis-N,N-Dimethyl-2-(8-methylamino-2-oxo-3,8-diphenyl-1,3- 
                 SC_3052 
                 — 
                 SC_3045 
                 421.3 
               
               
                   
                 diazaspiro[4.5]decan-1-yl)-acetamide 
               
               
                 SC_3058 
                 cis-5-[1-[(1-Cyano-cyclobutyl)-methyl]-8-methylamino-2-oxo- 
                 SC_3041 
                 — 
                 SC_3058 
                 456.2 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyrimidine-2- 
               
               
                   
                 carbonitrile 
               
               
                 SC_3059 
                 cis-5-[1-[(1-Cyano-cyclobutyl)-methyl]-8-(ethyl-methyl- 
                 INT-797 
                 5-bromopyrimidine-2- 
                 SC_3013 
                 484.3 
               
               
                   
                 amino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]- 
                   
                 carbonitrile (step 1); 
               
               
                   
                 pyrimidine-2-carbonitrile 
                   
                 1-(bromo- 
               
               
                   
                   
                   
                 methyl)cyclobutane- 
               
               
                   
                   
                   
                 carbonitrile 
               
               
                   
                   
                   
                 (step 2) 
               
               
                 SC_3060 
                 CIS-4-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]- 
                 INT-987 
                 4-bromobenzonitrile 
                 SC_3013 
                 459.3 
               
               
                   
                 2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-benzonitrile 
                   
                 (step 1); (1-(tert- 
               
               
                   
                   
                   
                 butyldimethylsilyloxy)cyclo- 
               
               
                   
                   
                   
                 butyl)methyl 4- 
               
               
                   
                   
                   
                 methylbenzene-sulfonate 
               
               
                   
                   
                   
                 (2 step) 
               
               
                 SC_3061 
                 cis-3-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2- 
                 INT-987 
                 3-bromobenzonitrile 
                 SC_3013 
                 459.3 
               
               
                   
                 oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-benzonitrile 
                   
                 (step 1); (1-(tert- 
               
               
                   
                   
                   
                 butyldimethylsilyloxy)cyclo- 
               
               
                   
                   
                   
                 butyl)methyl 4- 
               
               
                   
                   
                   
                 methylbenzene-sulfonate 
               
               
                   
                   
                   
                 (step 2) 
               
               
                 SC_3063 
                 cis-5-[1-[(1-Cyano-cyclobutyl)-methyl]-8-dimethylamino-2- 
                 INT-987 
                 5-bromopicolinonitrile (step 
                 SC_3013 
                 469.3 
               
               
                   
                 oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyridine-2- 
                   
                 1); 1-(bromomethyl)cyclo- 
               
               
                   
                 carbonitrile 
                   
                 butanecarbonitrile (step 2) 
               
               
                 SC_3064 
                 cis-2-[3-(2-Cyano-pyrimidin-5-yl)-8-dimethylamino-2-oxo-8- 
                 INT-600 
                 2-bromo-N-propylacetamide 
                 SC_3064 
                 476.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-1-yl]-N-propyl-acetamide 
               
               
                 SC_3065 
                 cis-5-[1-(Cyclobutyl-methyl)-8-(ethyl-methyl-amino)-2-oxo-8- 
                 INT-986 
                 5-bromo-4- 
                 SC_3065 
                 489.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-4-methoxy-pyrimidine- 
                   
                 methoxypyrimidine-2- 
               
               
                   
                 2-carbonitrile 
                   
                 carbonitrile 
               
               
                 SC_3066 
                 cis-4-[1-(Cyclobutyl-methyl)-8-methylamino-2-oxo-8-phenyl- 
                 SC_3080 
                 — 
                 SC_3066 
                 459.3 
               
               
                   
                 1,3-diazaspiro[4.5]decan-3-yl]-3-methoxy-benzonitrile 
               
               
                 SC_3067 
                 cis-5-[8-Dimethylamino-1-(3-methoxy-propyl)-2-oxo-8- 
                 INT-979 
                 5-bromo-6- 
                 SC_3022 
                 478.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-6-methoxy-pyridine-2- 
                   
                 methoxypicolinonitrile 
               
               
                   
                 carbonitrile 
               
               
                 SC_3068 
                 cis-4-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2- 
                 SC_3060 
                 — 
                 SC_3016 
                 477.3 
               
               
                   
                 oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-benzamide 
               
               
                 SC_3069 
                 cis-5-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2- 
                 INT-976 
                 5-bromopicolinonitrile (step 
                 SC_3013 
                 460.3 
               
               
                   
                 oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-pyridine-2- 
                   
                 1); 1-(tert-butyldimethyl- 
               
               
                   
                 carbonitrile 
                   
                 silyloxy)cyclobutyl)methyl 
               
               
                   
                   
                   
                 4-methylbenzene-sulfonate 
               
               
                   
                   
                   
                 (step 2) 
               
               
                 SC_3070 
                 cis-5-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2- 
                 INT-976 
                 5-bromopicolinonitrile (step 
                 SC_3013 
                 562.3 
               
               
                   
                 oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-N-[(1-hydroxy- 
                   
                 1); 1-(tert-butyldimethyl- 
               
               
                   
                 cyclobutyl)-methyl]-pyridine-2-carboxylic acid amide 
                   
                 silyloxy)cyclobutyl)methyl 
               
               
                   
                   
                   
                 4-methylbenzene-sulfonate 
               
               
                   
                   
                   
                 (step 2) 
               
               
                 SC_3071 
                 cis-2-[8-Dimethylamino-1-[(1-hydroxy-cyclobutyl)-methyl]-2- 
                 INT-976 
                 2-bromobenzonitrile (step 
                 SC_3013 
                 459.3 
               
               
                   
                 oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]-benzonitrile 
                   
                 1); 1-(tert-butyldimethyl- 
               
               
                   
                   
                   
                 silyloxy)cyclobutyl)methyl 
               
               
                   
                   
                   
                 4-methylbenzene-sulfonate 
               
               
                   
                   
                   
                 (step 2) 
               
               
                 SC_3072 
                 cis-3-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT-987 
                 3-iodobenzonitrile 
                 SC_3022 
                 443.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-benzonitrile 
               
               
                 SC_3073 
                 cis-1-(Cyclobutyl-methyl)-8-dimethylamino-8-phenyl-3-[2- 
                 INT-987 
                 5-bromo-2- 
                 SC_3022 
                 488.3 
               
               
                   
                 (trifluoromethyl)-pyrimidin-5-yl]-1,3-diazaspiro[4.5]decan-2- 
                   
                 (trifluoromethyl)pyrimidine 
               
               
                   
                 one 
               
               
                 SC_3074 
                 cis-5-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT-987 
                 methyl 5-bromo-4-methyl- 
                 SC_3022 
                 491.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-4-methyl-pyridine-2- 
                   
                 picolinate 
               
               
                   
                 carboxylic acid methyl ester 
               
               
                 SC_3075 
                 cis-1-(Cyclobutyl-methyl)-8-dimethylamino-3-(5-methoxy- 
                 INT-987 
                 2-bromo-5-methoxypyrazine 
                 SC_3022 
                 450.3 
               
               
                   
                 pyrazin-2-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
               
               
                 SC_3076 
                 cis-1-(Cyclobutyl-methyl)-8-dimethylamino-3-(2-methoxy- 
                 INT-987 
                 5-bromo-2- 
                 SC_3022 
                 450.3 
               
               
                   
                 pyrimidin-5-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
                   
                 methoxypyrimidine 
               
               
                 SC_3077 
                 cis-4-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT-987 
                 4-iodobenzonitrile 
                 SC_3022 
                 443.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-benzonitrile 
               
               
                 SC_3078 
                 cis-5-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT-987 
                 5-bromo-4- 
                 SC_3022 
                 458.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-4-methyl-pyridine-2- 
                   
                 methylpicolinonitrile 
               
               
                   
                 carbonitrile 
               
               
                 SC_3079 
                 cis-1-(Cyclobutyl-methyl)-8-dimethylamino-3-(5-fluoro- 
                 INT-987 
                 2-bromo-5-fluoropyrimidine 
                 SC_3022 
                 438.3 
               
               
                   
                 pyrimidin-2-yl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
               
               
                 SC_3080 
                 cis-4-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT-987 
                 4-bromo-3- 
                 SC_3022 
                 473.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-3-methoxy-benzonitrile 
                   
                 methoxybenzonitrile 
               
               
                 SC_3081 
                 cis-4-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT-987 
                 methyl 4-iodobenzoate 
                 SC_3022 
                 476.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-benzoic acid methyl 
               
               
                   
                 ester 
               
               
                 SC_3082 
                 cis-1-(Cyclobutyl-methyl)-8-dimethylamino-8-phenyl-3-(2- 
                 INT-987 
                 4-iodo-2-(pyrrolidin-1- 
                 SC_3022 
                 489.3 
               
               
                   
                 pyrrolidin-1-yl-pyrimidin-4-yl)-1,3-diazaspiro[4.5]decan-2-one 
                   
                 yl)pyrimidine 
               
               
                 SC_3083 
                 cis-1-(Cyclobutyl-methyl)-8-dimethylamino-8-phenyl-3-(5- 
                 INT-987 
                 2-(5-bromothiophen-2- 
                 SC_3022 
                 501.3 
               
               
                   
                 pyridin-2-yl-thiophen-2-yl)-1,3-diazaspiro[4.5]decan-2-one 
                   
                 yl)pyridine 
               
               
                 SC_3084 
                 cis-1-(Cyclobutyl-methyl)-8-dimethylamino-3[2- 
                 INT-987 
                 1-bromo-2- 
                 SC_3022 
                 564.2 
               
               
                   
                 methylsulfonyl-4-(trifluoromethyl)-phenyl]-8-phenyl-1,3- 
                   
                 (methylsulfonyl)-4- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                 (trifluoromethyl)benzene 
               
               
                 SC_3085 
                 cis-1-(Cyclobutyl-methyl)-8-dimethylamino-8-phenyl-3-[6- 
                 INT-987 
                 5-bromo-2- 
                 SC_3022 
                 487.3 
               
               
                   
                 (trifluoromethyl)-pyridin-3-yl]-1,3-diazaspiro[4.5]decan-2-one 
                   
                 (trifluoromethyl)pyridine 
               
               
                 SC_3086 
                 cis-1-(Cyclobutyl-methyl)-3-(2,4-dimethoxy-phenyl)-8- 
                 INT-987 
                 1-bromo-2,4- 
                 SC_3022 
                 478.3 
               
               
                   
                 dimethylamino-8-phenyl-1,3-diazaspiro[4.5]decan-2-one 
                   
                 dimethoxybenzene 
               
               
                 SC_3087 
                 cis-2-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT 987 
                 2-iodo-4-(methylthio)- 
                 SC_3022/ 
                 521.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-4-methylsulfonyl- 
                   
                 benzonitrile (SC_3022) 
                 SC_3008 
               
               
                   
                 benzonitrile 
               
               
                 SC_3088 
                 cis-5-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT-987 
                 5-bromo-2- 
                 SC_3022 
                 461.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-2-fluoro-benzonitrile 
                   
                 fluorobenzonitrile 
               
               
                 SC_3089 
                 cis-4-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT-987 
                 4-bromo-N,N-dimethyl-3- 
                 SC_3022 
                 593.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-N,N-dimethyl-3- 
                   
                 (trifluoromethyl)benzene- 
               
               
                   
                 (trifluoromethyl)-benzenesulfonic acid amide 
                   
                 sulfonamide 
               
               
                 SC_3090 
                 cis-2-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT-987 
                 2-bromobenzonitrile 
                 SC_3022 
                 443.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-benzonitrile 
               
               
                 SC_3091 
                 cis-1-(Cyclobutyl-methyl)-8-dimethylamino-3-(2-methyl- 
                 INT-987 
                 6-bromo-2- 
                 SC_3022 
                 473.3 
               
               
                   
                 imidazo[1,2-a]pyrazin-6-yl)-8-phenyl-1,3- 
                   
                 methylimidazo[1,2- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                 a]pyrazine 
               
               
                 SC_3092 
                 cis-1-(Cyclobutyl-methyl)-8-dimethylamino-3-(4- 
                 INT-987 
                 (4- 
                 SC_3022/ 
                 496.3 
               
               
                   
                 methylsulfonyl-phenyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                 iodophenyl)(methyl)sulfane 
                 SC_3008 
               
               
                   
                 one 
               
               
                 SC_3093 
                 cis-2-[1-(Cyclobutyl-methyl)-8-dimethylamino-2-oxo-8- 
                 INT-987 
                 2-bromo-5- 
                 SC_3022 
                 473.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3-yl]-5-methoxy-benzonitrile 
                   
                 methoxybenzonitrile 
               
               
                 SC_3094 
                 cis-1-(Cyclobutyl-methyl)-8-dimethylamino-3,8-diphenyl-1,3- 
                 INT-987 
                 bromobenzene 
                 SC_3022 
                 418.3 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3096 
                 cis-1-(Cyclobutyl-methyl)-8-dimethylamino-8-phenyl-3- 
                 INT-987 
                 2-bromopyrazine 
                 SC_3022 
                 420.3 
               
               
                   
                 pyrazin-2-yl-1,3-diazaspiro[4.5]decan-2-one 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
               
             
               
                   
               
               
                 Example 
                 Chemical name 
                 Reactant I 
                 Reactant II 
                 in analogy to method 
                   1 H NMR data 
                 m/z (M + H) +   
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 SC_3098 
                 cis-8-Dimethylamino-1-[(1- 
                 INT-799 
                 5-bromo-2-(4-methylpiperazin-1- 
                 SC_3097 
                 1H NMR (DMSO-d6): δ 8.56 (s, 2H), 7.36- 
                 534.4 
               
               
                   
                 hydroxy-cyclobutyl)-methyl]-3- 
                   
                 yl)pyrimidine 
                   
                 7.35 (m, 4H), 7.27-7.24 (m, 1H), 5.52 (s, 
               
               
                   
                 [2-(4-methyl-piperazin-1-yl)- 
                   
                   
                   
                 1H), 3.71 (s, 2H), 3.64 (m, 4H), 3.21 (s, 2H), 
               
               
                   
                 pyrimidin-5-yl]-8-phenyl-1,3- 
                   
                   
                   
                 2.69-2.67 (m, 2H), 2.32 (m, 4H), 2.19-2.11 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (m, 7H), 1.98 (s, 6H), 1.92-1.86 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 1.66-1.64 (m, 1H), 1.52-1.42 (m, 5H). 
               
               
                 SC_3101 
                 cis-1-[(1-Hydroxy-cyclobutyl)- 
                 SC_3098 
                   
                 SC_3099 
                 1H NMR (DMSO-d6): δ 8.58 (s, 2H), 7.48 
                 520.4 
               
               
                   
                 methyl]-8-methylamino-3-[2-(4- 
                   
                   
                   
                 (d, 2H), 7.32 (t, 2H), 7.19 (t, 1H), 5.61 (s, 
               
               
                   
                 methyl-piperazin-1-yl)-pyrimidin- 
                   
                   
                   
                 1H), 3.75 (s, 2H), 3.66-3.64 (m, 4H), 3.30 (s, 
               
               
                   
                 5-yl]-8-phenyl-1,3- 
                   
                   
                   
                 2H), 2.35-2.32 (m, 4H), 2.25-2.19 (m, 5H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2.12-2.07 (m, 2H), 1.90-1.88 (m, 7H), 1.79- 
               
               
                   
                   
                   
                   
                   
                 1.73 (m, 2H), 1.65-1.63 (m, 1H), 1.50-1.44 
               
               
                   
                   
                   
                   
                   
                 (m, 3H) 
               
               
                 SC_3102 
                 cis-1-[(1-Hydroxy-cyclobutyl)- 
                 SC_3100 
                   
                 SC_3099 
                 1H NMR (DMSO-d6): δ 9.51 (br s, 2H), 
                 506.3 
               
               
                   
                 methyl]-8-methylamino-8-phenyl- 
                   
                   
                   
                 9.15 (br s, 2H), 8.65 (s, 2H), 7.69-7.68 (m, 
               
               
                   
                 3-(2-piperazin-1-yl-pyrimidin-5- 
                   
                   
                   
                 2H), 7.50-7.41 (m, 3H), 3.88-3.86 (m, 4H), 
               
               
                   
                 yl)-1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.79 (m, 2H), 3.65 (m, 2H), 3.16-3.13 (m, 
               
               
                   
                 dihydrochloride 
                   
                   
                   
                 4H), 2.64-2.62 (m, 2H), 2.38-2.33 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.16-2.04 (m, 7H), 1.90-1.84 (m, 2H), 1.76- 
               
               
                   
                   
                   
                   
                   
                 1.70 (m, 3H), 1.60-1.58 (m, 1H). 
               
               
                 SC_3104 
                 cis-1-(Cyclobutyl-methyl)-8- 
                 SC_3103 
                   
                 SC_3099 
                 1H NMR (DMSO-d6): δ 8.59 (s, 1H), 7.81 
                 487.3 
               
               
                   
                 methylamino-3-[4-methyl-6- 
                   
                   
                   
                 (s, 1H), 7.44 (d, 2H), 7.30 (t, 2H), 7.17 (t, 
               
               
                   
                 (trifluoromethyl)-pyridin-3-yl]-8- 
                   
                   
                   
                 1H), 3.76 (s, 2H), 3.21 (d, 2H), 2.61-2.57 (m, 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 1H), 2.32 (s, 3H), 2.29-2.17 (m, 3H), 2.03- 
               
               
                   
                 one 
                   
                   
                   
                 1.97 (m, 2H), 1.91-1.88 (m, 5H), 1.84-1.67 
               
               
                   
                   
                   
                   
                   
                 (m, 6H), 1.51-1.48 (m, 2H). 
               
               
                 SC_3106 
                 cis-1-(Cyclopropyl-methyl)-8- 
                 SC_3105 
                   
                 SC_3099 
                 1H NMR (DMSO-d6): δ 7.90-7.88 (d, 2H), 
                 468.2 
               
               
                   
                 methylamino-3-(4-methylsulfonyl- 
                   
                   
                   
                 7.82-7.80 (d, 2H), 7.50-7.48 (d, 2H), 7.35- 
               
               
                   
                 phenyl)-8-phenyl-1,3- 
                   
                   
                   
                 7.32 (m, 2H), 7.22-7.19 (m, 1H), 3.80 (s, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2H), 3.14-3.10 (m, 5H), 2.29-2.23 (m, 3H), 
               
               
                   
                   
                   
                   
                   
                 1.91-1.79 (m, 7H), 1.42-1.39 (m, 2H), 1.05- 
               
               
                   
                   
                   
                   
                   
                 1.04 (m, 1H), 0.50-0.47 (m, 2H), 0.34-0.32 
               
               
                   
                   
                   
                   
                   
                 (m, 2H). 
               
               
                 SC_3107 
                 cis-1-(Cyclopropyl-methyl)-8- 
                 INT-983 
                 1-bromo-2-fluoro-4- 
                 SC3103 (step 1), 
                 1H NMR (DMSO-d6): δ 7.85 (t, 1H), 7.79- 
                 500.2 
               
               
                   
                 dimethylamino-3-(2-fluoro-4- 
                   
                 (methylsulfonyl)benzene (step 1), 
                 SC_3105 (step 2) 
                 7.76 (m, 1H), 7.72-7.69 (m, 1H), 7.37-7.33 
               
               
                   
                 methylsulfonyl-phenyl)-8-phenyl- 
                   
                 (Bromomethyl)cyclopropane (step 2) 
                   
                 (m, 4H), 7.27-7.24 (m, 1H), 3.81 (s, 2H), 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.24 (s, 3H), 3.07 (d, 2H), 2.71-2.68 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.28-2.22 (m, 2H), 1.99 (s, 6H), 1.53-1.42 
               
               
                   
                   
                   
                   
                   
                 (m, 4H), 1.00-0.99 (m, 1H), 0.53-0.49 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 0.34-0.30 (m, 2H). 
               
               
                 SC_3108 
                 cis-2-[8-Dimethylamino-1-[(1- 
                 SC_3071 
                   
                 SC_3016 
                 1H NMR (600 MHz, DMSO) δ 7.59-7.55 
                 477.3 
               
               
                   
                 hydroxy-cyclobutyl)-methyl]-2- 
                   
                   
                   
                 (s, 1H), 7.47-7.39 (m, 2H), 7.39-7.31 (m, 
               
               
                   
                 oxo-8-phenyl-1,3- 
                   
                   
                   
                 5H), 7.30-7.21 (m, 3H), 3.77-3.73 (s, 
               
               
                   
                 diazaspiro[4.5]decan-3-yl]- 
                   
                   
                   
                 2H), 3.21-3.17 (s, 1H), 2.72-2.66 (d, 2H), 
               
               
                   
                 benzamide; formic acid 
                   
                   
                   
                 2.17-2.09 (m, 5H), 2.02-1.99 (s, 6H), 
               
               
                   
                   
                   
                   
                   
                 1.95-1.86 (m, 2H), 1.71-1.60 (m, 3H), 
               
               
                   
                   
                   
                   
                   
                 1.49-1.37 (m, 3H) 
               
               
                 SC_3109 
                 cis-2-[8-Dimethylamino-1-[2-(1- 
                 INT988 
                 2-bromobenzonitrile 
                 SC_3097 (step 1), 
                 1H NMR (600 MHz, DMSO) δ 7.52-7.48 
                 505.3 
               
               
                   
                 methoxy-cyclobutyl)-ethyl]-2-oxo- 
                   
                   
                 SC_3109 (step 2) 
                 (s, 1H), 7.47-7.31 (m, 7H), 7.29-7.23 (m, 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                   
                   
                 1H), 7.25-7.22 (s, 1H), 7.24-7.18 (m, 
               
               
                   
                 3-yl]-benzamide 
                   
                   
                   
                 1H), 3.68-3.65 (s, 3H), 3.13-3.10 (s, 2H), 
               
               
                   
                   
                   
                   
                   
                 3.09-3.02 (m, 2H), 2.71-2.65 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.21-2.12 (m, 2H), 2.09-1.99 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.02-1.98 (s, 6H), 1.97-1.86 (m, 4H), 
               
               
                   
                   
                   
                   
                   
                 1.77-1.67 (m, 1H), 1.64-1.52 (m, 3H), 
               
               
                   
                   
                   
                   
                   
                 1.44-1.36 (td, 2H). 
               
               
                 SC_3110 
                 cis-8-Dimethylamino-1-[2-(1- 
                 INT-988 
                 5-bromo2-methyl-pyrimidine 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.94-8.90 
                 478.3 
               
               
                   
                 methoxy-cyclobutyl)-ethyl]-3-(2- 
                   
                   
                   
                 (s, 2H), 7.41-7.34 (d, 4H), 7.32-7.24 
               
               
                   
                 methyl-pyrimidin-5-yl)-8-phenyl- 
                   
                   
                   
                 (ddd, 1H), 3.76-3.72 (s, 2H), 3.15-3.08 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (m, 5H), 2.72-2.65 (m, 2H), 2.57-2.52 (s, 
               
               
                   
                   
                   
                   
                   
                 3H), 2.25-2.16 (m, 2H), 2.11-2.02 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 2.03-1.99 (s, 6H), 1.99-1.86 (m, 
               
               
                   
                   
                   
                   
                   
                 4H), 1.78-1.68 (tq, 1H), 1.65-1.51 (m, 
               
               
                   
                   
                   
                   
                   
                 3H), 1.50-1.44 (d, 2H). 
               
               
                 SC_3111 
                 cis-5-[1-[(1-Hydroxy-cyclobutyl)- 
                 INT-799 
                 5-bromo-2-cyanopyrimidine 
                 SC_3103 (step 1), 
                 1H NMR (600 MHz, DMSO) δ 9.24-9.20 
                 447.3 
               
               
                   
                 methyl]-8-methylamino-2-oxo-8- 
                   
                   
                 SC_3099 (step 2) 
                 (s, 2H), 7.53-7.48 (m, 2H), 7.37-7.31 (t, 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 2H), 7.25-7.19 (t, 1H), 3.93-3.89 (s, 2H), 
               
               
                   
                 yl]-pyrimidine-2-carbonitrile 
                   
                   
                   
                 3.42-3.36 (m, 2H), 2.35-2.26 (td, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.18-2.10 (tt, 2H), 2.09-2.04 (s, 1H), 1.97- 
               
               
                   
                   
                   
                   
                   
                 1.88 (m, 2H), 1.93-1.90 (s, 6H), 1.86- 
               
               
                   
                   
                   
                   
                   
                 1.77 (td, 2H), 1.72-1.62 (s, 1H), 1.59- 
               
               
                   
                   
                   
                   
                   
                 1.54 (d, 1H), 1.48-1.43 (d, 2H). 
               
               
                 SC_3113 
                 cis-4-[1-[(1-Hydroxy-cyclobutyl)- 
                 INT-976 
                 1-bromo-4-cyano-2- 
                 SC_3112 
                 1HNMR (DMSO-d6, 400 MHz), δ (ppm) = 
                 475.3 
               
               
                   
                 methyl]-8-methylamino-2-oxo-8- 
                   
                 methoxybenzene (step 1) 
                   
                 7.54 (s, 1H), 7.50 (d, 1H, J = 8.16 Hz), 7.46- 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 7.39 (m, 3H), 7.30 (t, 2H, J = 7.48 Hz), 7.18 
               
               
                   
                 yl]-3-methoxy-benzonitrile 
                   
                   
                   
                 (t, 1H, J = 7.16 Hz), 5.59 (s, 1H), 3.85 (s, 
               
               
                   
                   
                   
                   
                   
                 3H), 3.73 (s, 2H), 3.30 (s, 2H, merged with 
               
               
                   
                   
                   
                   
                   
                 DMSO-water), 2.32-2.08 (m, 4H), 1.91-1.87 
               
               
                   
                   
                   
                   
                   
                 (m, 7H), 1.68-1.47 (m, 6H). 
               
               
                 SC_3114 
                 cis-4-[8-Ethylamino-1-[(1- 
                 INT-1008 
                 4-Bromo-3-methoxy- 
                 SC_3112 (step 1, step 2) 
                 1HNMR (DMSO-d6, 400 MHz), δ (ppm) = 
                 489.1 
               
               
                   
                 hydroxy-cyclobutyl)-methyl]- 
                   
                 benzonitrile (step 1) 
                   
                 7.54 (s, 1H), 7.51-7.45 (m, 3H), 7.40 (d, 1H, 
               
               
                   
                 2-oxo-8-phenyl-1,3- 
                   
                   
                   
                 J = 8.24 Hz), 7.29 (t, 2H, J = 7.58 Hz), 7.17 
               
               
                   
                 diazaspiro[4.5]decan-3- 
                   
                   
                   
                 (t, 1H, J = 7.12 (Hz), 5.60 (s, 1H), 3.85 (s, 
               
               
                   
                 yl]-3-methoxy-benzonitrile 
                   
                   
                   
                 3H), 3.73 (s, 2H), 3.21 (s, 2H, merged with 
               
               
                   
                   
                   
                   
                   
                 DMSO—H2O), 2.32-2.27 (m, 2H), 2.08 (bs, 
               
               
                   
                   
                   
                   
                   
                 5H), 1.96-1.87 (m, 4H), 1.68-1.46 (m, 6H), 
               
               
                   
                   
                   
                   
                   
                 0.97 (t, 3H, J = 4.0 Hz). 
               
               
                 SC_3115 
                 cis-2-[8-Ethylamino-1-[(1- 
                 INT-1008 
                 2-bromo-benzonitrile (step 1) 
                 SC_3112 (step 1, step 2) 
                 1HNMR (DMSO-d6, 400 MHz), δ (ppm) = 
                 458.9 
               
               
                   
                 hydroxy-cyclobutyl)-methyl]- 
                   
                   
                   
                 7.82 (d, 1H, J = 7.56 Hz), 7.71 (t, 1H, J = 
               
               
                   
                 2-oxo-8-phenyl-1,3- 
                   
                   
                   
                 6.98 Hz), 7.53-7.47 (m, 3H), 7.37-7.27 (m, 
               
               
                   
                 diazaspiro[4.5]decan-3- 
                   
                   
                   
                 3H), 7.19-7.17 (m, 1H), 5.55 (s, 1H), 3.87 (s, 
               
               
                   
                 yl]-benzonitrile 
                   
                   
                   
                 2H), 3.38 (s, 2H), 2.36-2.32 (m, 2H), 2.10 
               
               
                   
                   
                   
                   
                   
                 (bs, 4H), 1.94-1.86 (m. 4H), 1.75-1.48 (6H), 
               
               
                   
                   
                   
                   
                   
                 0.98 (bs, 3H). 
               
               
                 SC_3116 
                 cis-5-[1-[(1-Hydroxy-cyclobutyl)- 
                 INT-799 
                 5-bromo-4-methoxy-pyrimidine-2- 
                 SC_3103 (step 1), 
                 1HNMR (DMSO-d6, 400 MHz, at 100 0 C.), 
                 477.2 
               
               
                   
                 methyl]-8-methylamino-2-oxo-8- 
                   
                 carbonitrile (step 1) 
                 SC_3099 (step 2) 
                 δ (ppm) = 8.79 (s, 1H), 7.46 (d, 2H, J = 7.84 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 Hz), 7.32 (t, 2H, J = 7.12 Hz), 7.19 (t, 1H, J = 
               
               
                   
                 yl]-4-methoxy-pyrimidine-2- 
                   
                   
                   
                 7.28 Hz), 5.09 (bs, 1H), 4.05 (s, 3H), 3.85 
               
               
                   
                 carbonitrile 
                   
                   
                   
                 (s, 2H), 3.38 (s, 2H), 2.31-2.15 (m, 4H), 1.98 
               
               
                   
                   
                   
                   
                   
                 (m, 7H), 1.74-1.51 (m, 6H). 
               
               
                 SC_3117 
                 cis-2-[8-Dimethylamino-1-(oxetan- 
                 SC_3274 
                 toluene-4-sulfonic acid oxetan-3- 
                 SC_3105 (step 1), 
                 1HNMR (DMSO-d6, 400 MHz), δ (ppm) = 
                 463.4 
               
               
                   
                 3-yl-methyl)-2-oxo-8-phenyl-1,3- 
                   
                 ylmethyl ester (step 1) 
                 SC_3016 (step 2) 
                 7.52 (s,1H), 7.43-7.33 (m, 6H), 7.30-7.17 
               
               
                   
                 diazaspiro[4.5]decan-3-yl]- 
                   
                   
                   
                 (m, 4H), 4.63 (t, 2H, J = 6.9 Hz), 4.39 (t, 2H, 
               
               
                   
                 benzamide 
                   
                   
                   
                 J = 6.08 Hz), 3.64 (s, 2H), 3.38 (d, 2H, J = 
               
               
                   
                   
                   
                   
                   
                 7.32 Hz), 3.21-3.15 (m, 1H), 2.70-2.66 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 2.08-1.98 (m, 8H), 1.54-1.35 (m, 4H). 
               
               
                 SC_3118 
                 cis-4-Methoxy-5-(8-methylamino- 
                 INT-976 
                 5-bromo-4-methoxy-pyrimidine-2- 
                 SC_3103 (step 1), 
                 1HNMR (DMS0-d6, 400 MHz), δ (ppm) = 
                 393.0 
               
               
                   
                 2-oxo-8-phenyl-1,3- 
                   
                 carbonitrile (step 1) 
                 SC_3099 (step 2) 
                 8.80 (s, 1H), 7.86 (bs, 1H), 7.43 (d, 2H, J = 
               
               
                   
                 diazaspiro[4.5]decan-3-yl)- 
                   
                   
                   
                 7.84 Hz), 7.32 (t, 2H, J = 7.32 Hz), 7.21-7.18 
               
               
                   
                 pyrimidine-2-carbonitrile 
                   
                   
                   
                 (m, 1H), 4.02 (s, 3H), 3.83 (s, 2H), 2.07-2.00 
               
               
                   
                   
                   
                   
                   
                 (m, 3H), 1.90-1.74 (m, 7H), 1.48 (d, 2H, J = 
               
               
                   
                   
                   
                   
                   
                 13.8 Hz). 
               
               
                 SC_3119 
                 cis-2-(8-Methylamino-2-oxo-8- 
                 INT-976 
                 2-bromo-benzonitrile (step 1) 
                 SC_3103 (step 1), 
                 1HNMR (DMSO-d6, 400 MHz) δ 7.51 (bs, 
                 379.4 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                 SC_3099 (step 2), 
                 1H), 7.43-7.37 (m, 4H), 7.33-2.29 (m, 3H, 
               
               
                   
                 yl)-benzamide 
                   
                   
                 SC_3016 (step 3) 
                 J = 8.28 Hz), 7.22-7.16 (m, 3H), 6.93 (bs, 1H), 
               
               
                   
                   
                   
                   
                   
                 3.64 (s, 2H), 2.03-1.97 (m, 2H), 1.86 (bs, 
               
               
                   
                   
                   
                   
                   
                 5H), 1.73-1.58 (m, 4H). 
               
               
                 SC_3121 
                 cis-3-(2-Cyclopropyl-pyrimidin-5- 
                 INT-976 
                 5-bromo-2-cyclopropyl- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.80 (s, 2H), 
                 392.3 
               
               
                   
                 yl)-8-dimethylamino-8-phenyl-1,3- 
                   
                 pyrimidine 
                   
                 7.67 (s, 1H), 7.41-7.32 (m, 4H), 7.31- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 7.22 (ddt, 1H), 3.60 (s, 2H), 2.42-2.36 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 2.18-2.08 (m, 1H), 1.98-1.85 (m, 
               
               
                   
                   
                   
                   
                   
                 4H), 1.96 (s, 6H), 1.47 (s, 2H), 0.98-0.91 
               
               
                   
                   
                   
                   
                   
                 (m, 2H), 0.93-0.86 (m, 2H). 
               
               
                 SC_3122 
                 cis-8-Dimethylamino-3-[4-methyl- 
                 INT-976 
                 5-bromo-4-methyl-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.57 (s, 1H), 
                 433.2 
               
               
                   
                 6-(trifluoromethyl)-pyridin-3-yl]-8- 
                   
                 (trifluoromethyl)pyridine 
                   
                 7.79 (s, 1H), 7.52 (s, 1H), 7.40-7.32 (m, 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 4H), 7.30-7.22 (tt, 1H), 3.61 (s, 2H), 2.39- 
               
               
                   
                 one 
                   
                   
                   
                 2.30 (m, 5H), 1.96 (s, 6H), 2.00-1.91 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 1.84 (s, 2H), 1.57-1.53 (s, 2H). 
               
               
                 SC_3123 
                 cis-8-Dimethylamino-3-(2- 
                 INT-976 
                 1-bromo-2-methylsulfonyl- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 7.98-7.92 
                 428.2 
               
               
                   
                 methylsulfonyl-phenyl)-8-phenyl- 
                   
                 benzene 
                   
                 (dd, 1H), 7.81-7.74 (td, 1H), 7.61-7.54 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (td, 1H), 7.52-7.46 (m, 2H), 7.41-7.31 
               
               
                   
                   
                   
                   
                   
                 (m, 2H), 7.35 (s, 2H), 7.29-7.22 (tt, 1H), 
               
               
                   
                   
                   
                   
                   
                 3.49 (s, 2H), 3.25 (s, 3H), 2.37 (s, 2H), 1.99- 
               
               
                   
                   
                   
                   
                   
                 1.96 (m, 1H), 1.98-1.94 (s, 6H), 1.95- 
               
               
                   
                   
                   
                   
                   
                 1.91 (d, 1H), 1.83-1.79 (m, 2H), 1.58- 
               
               
                   
                   
                   
                   
                   
                 1.55 (s, 2H). 
               
               
                 SC_3124 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-989 
                 Piperazine-2-one 
                 SC_3120 
                 1H NMR (600 MHz, DMSO) δ 8.52 (s, 2H), 
                 436.3 
               
               
                   
                 (2-piperazin-1-yl-pyrimidin-5-yl)- 
                   
                   
                   
                 7.41-7.31 (m, 5H), 3.59-3.54 (m, 4H), 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.52 (s, 2H), 2.76-2.70 (m, 4H), 2.55 (s, 
               
               
                   
                   
                   
                   
                   
                 3H), 2.49-2.33 (m, 2H), 1.96 (s, 6H), 1.93- 
               
               
                   
                   
                   
                   
                   
                 1.83 (m, 4H), 1.51-1.43 (s, 2H). 
               
               
                 SC_3125 
                 trans-2-(8-Ethylamino-2-oxo-8- 
                 SC_3127 
                   
                 SC_3016 
                 1HNMR (DMSO-d6, 400 MHz), δ (ppm) = 
                 393.1 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 7.56-7.20 (m, 12H), 3.60 (s, 2H), 2.08-1.92 
               
               
                   
                 yl)-benzamide 
                   
                   
                   
                 (m, 6H), 1.69 (bs, 2H), 1.56 (bs, 2H), 0.93 (t, 
               
               
                   
                   
                   
                   
                   
                 3H). 
               
               
                 SC_3126 
                 cis--2-(8-Ethylamino-2-oxo-8- 
                 SC_3128 
                   
                 SC_3016 
                   1 HNMR (DMSO-d 6 , 400 MHz), δ (ppm) = 
                 393.4 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 7.51-2.38 (m, 5H), 7.32-7.30 (m, 3H), 7.22- 
               
               
                   
                 yl)-benzamide 
                   
                   
                   
                 7.18 (m, 3H), 6.93 (s, 1H), 3.63 (s, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.07-1.98 (m, 4H), 1.86-1.72 (m, 4H), 1.60- 
               
               
                   
                   
                   
                   
                   
                 1.57 (m, 2H), 0.93 (t, 3H). 
               
               
                 SC_3127 
                 cis-2-(8-Ethylamino-2-oxo-8- 
                 INT-1009 
                 2-bromo-benzonitrile 
                 SC_3103 
                 1HNMR (DMSO-d6, 400 MHz), δ (ppm) = 
                 375.1 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 7.77 (d, 1H, J = 6.8 Hz), 7.69-7.65 (m, 1H), 
               
               
                   
                 yl)-benzonitrile 
                   
                   
                   
                 7.51 (d, 1H, J = 8.4 Hz), 7.44 (d, 2H, J = 7.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.39 (s, 1H), 7.34-7.28 (m, 3H), 7.17 (t, 
               
               
                   
                   
                   
                   
                   
                 1H, 7.2 Hz), 3.77 (s, 2H), 2.10-2.04 (m, 4H), 
               
               
                   
                   
                   
                   
                   
                 1.91-1.88 (m, 2H), 1.80-1.74 (m, 3H), 1.61- 
               
               
                   
                   
                   
                   
                   
                 1.58 (m, 2H), 0.94 (t, 3H, J = 6.8 Hz). 
               
               
                 SC_3128 
                 cis-2-(8-Ethylamino-2-oxo-8- 
                 INT-1008 
                 2-bromo-benzonitrile 
                 SC_3103 
                   1 HNMR (DMSO-d 6 , 400 MHz), δ (ppm) = 
                 375.1 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 7.89 (bs, 1H), 7.79 (d, 1H, J = 7.6), 7.69 (t, 
               
               
                   
                 yl)-benzonitrile 
                   
                   
                   
                 1H, J = 7.6 Hz), 7.54-7.50 (m, 3H), 7.36- 
               
               
                   
                   
                   
                   
                   
                 7.30 (m, 3H), 7.18 (t, 1H, J = 7.2 Hz), 3.73 
               
               
                   
                   
                   
                   
                   
                 (s, 2H), 2.08-1.92 (m, 7H), 1.71 (bs, 2H), 
               
               
                   
                   
                   
                   
                   
                 1.59 (bs, 2H,), 0.93 (t, 3H, J = 6.4 Hz). 
               
               
                 SC_3131 
                 cis-3-[5-(8-Dimethylamino-2-oxo- 
                 SC_3129 
                   
                 SC_3016 
                 1H NMR (600 MHz, DMSO) δ 9.11 (s, 2H), 
                 471.3 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                   
                   
                 8.79 (t, 1H), 8.43 (dt, 1H), 8.09 (s, 1H), 7.94 
               
               
                   
                 3-yl)-pyrimidin-2-yl]-benzamide 
                   
                   
                   
                 (dt, 1H), 7.84 (s, 1H), 7.56 (t, 1H), 7.41- 
               
               
                   
                   
                   
                   
                   
                 7.35 (m, 4H), 7.28 (ddd, 1H), 3.72 (s, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.00-1.84 (m, 2H), 1.98 (s, 6H), 1.53 (s, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3134 
                 trans-4-(8-Ethylamino-2-oxo-8- 
                 INT-1009 
                 4-Bromo-3-methoxy-benzonitrile 
                 SC_3103 
                 1HNMR (DMSO-d6, 400 MHz), δ (ppm) = 
                 405.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 7.71 (bs, 1H), 7.56-7.49 (m, 4H), 7.37 (d, 
               
               
                   
                 yl)-3-methoxy-benzonitrile 
                   
                   
                   
                 1H, J = 6.6 Hz), 7.31 (t, 2H, J = 7.10 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.19-7.17 (m, 1H), 3.87 (s, 3H), 3.62 (s, 
               
               
                   
                   
                   
                   
                   
                 2H), 2.06-1.90 (m, 7H), 1.69-1.53 (m, 4H), 
               
               
                   
                   
                   
                   
                   
                 0.92 (t, 3H, J = 6.70 Hz). 
               
               
                 SC_3135 
                 cis-4-(8-Ethylamino-2-oxo-8- 
                 INT-1008 
                 4-Bromo-3-methoxy-benzonitrile 
                 SC_3103 
                 1HNMR (DMSO-d6, 400 MHz), δ (ppm) = 
                 405.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 7.52-7.50 (m, 2H), 7.44-7.43 (m, 2H), 736 
               
               
                   
                 yl)-3-methoxy-benzonitrile 
                   
                   
                   
                 (d, 1H, J = 8.04 Hz), 7.30-7.19 (m, 4H), 3.83 
               
               
                   
                   
                   
                   
                   
                 (s, 3H), 3.63 (s, 2H), 2.05-1.72 (m, 8H), 
               
               
                   
                   
                   
                   
                   
                 1.53-1.50 (m, 2H), 0.92 (t, 3H). 
               
               
                 SC_3136 
                 cis-3-[2-(4-Acetyl-piperazin-1-yl)- 
                 SC_3124 
                 acetyl chloride 
                 SC_3130 
                   
                 478.3 
               
               
                   
                 pyrimidin-5-yl]-8-dimethylamino- 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
               
               
                   
                 2-one 
               
               
                 SC_3137 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-989 
                 pyridine-4-boronic acid 
                 SC_3129 
                 1H NMR (600 MHz, DMSO) δ 9.16 (s, 2H), 
                 429.2 
               
               
                   
                 (2-pyridin-4-yl-pyrimidin-5-yl)-1,3- 
                   
                   
                   
                 8.70 (d, 1H), 8.18 (s, 1H), 7.91 (s, 1H), 7.42- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 7.35 (m, 4H), 7.28 (tt, 1H), 3.73 (s, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.49-2.37 (m, 2H), 1.98 (s, 6H), 2.01-1.87 
               
               
                   
                   
                   
                   
                   
                 (m, 2H), 1.58-1.47 (m, 2H). 
               
               
                 SC_3138 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-989 
                 pyridine-3-boronic acid 
                 SC_3129 
                 1H NMR (600 MHz, DMSO) δ 9.43 (dd, 
                 429.2 
               
               
                   
                 (2-pyridin-3-yl-pyrimidin-5-yl)-1,3- 
                   
                   
                   
                 1H), 9.13 (s, 2H), 8.65 (dd, 1H), 8.58 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (dt, 1H), 7.52 (ddd, 1H), 7.42-7.36 (m, 4H), 
               
               
                   
                   
                   
                   
                   
                 7.28 (ddd, 1H), 3.72 (s, 2H), 1.98 (s, 6H), 
               
               
                   
                   
                   
                   
                   
                 2.02-1.89 (m, 4H), 1.57-1.46 (m, 4H). 
               
               
                 SC_3139 
                 cis-5-(8-Dimethylamino-2-oxo-8- 
                 INT-991 
                 2-aminoethanol 
                 SC_3133 
                 1H NMR (600 MHz, DMSO) δ 9.08 (s, 2H), 
                 439.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 8.59 (t, 1H), 7.94 (s, 1H), 7.43-7.30 (m, 
               
               
                   
                 yl)-N-(2-hydroxy-ethyl)- 
                   
                   
                   
                 5H), 7.30-7.21 (m, 1H), 3.72 (s, 2H), 3.51 
               
               
                   
                 pyrimidine-2-carboxylic acid amide 
                   
                   
                   
                 (q, 2H), 2.49-2.37 (m, 2H), 2.00-1.90 (m, 
               
               
                   
                   
                   
                   
                   
                 10H), 1.89-1.74 (m, 2H), 1.57-1.48 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 1.38-1.32 (m, 1H). 
               
               
                 SC_3141 
                 cis-8-Dimethylamino-3-[2- 
                 INT-976 
                 4-[5-bromo-4- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.59 (d, 1H), 
                 505.3 
               
               
                   
                 morpholin-4-yl-4-(trifluoromethyl)- 
                   
                 (trifluoromethyl)pyrmidin-2- 
                   
                 7.39-7.35 (m, 5H), 7.27 (d, 1H), 3.73 (t, 
               
               
                   
                 pyrimidin-5-yl]-8-phenyl-1,3- 
                   
                 yl]morpholine 
                   
                 4H), 3.67 (q, 4H), 3.28-3.22 (m, 1H), 2.41- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2.28 (m, 2H), 1.98 (s, 6H), 1.94-1.80 (m, 
               
               
                   
                   
                   
                   
                   
                 3H), 1.53-1.42 (m, 2H). 
               
               
                 SC_3142 
                 cis-4-[5-(8-Dimethylamino-2-oxo- 
                 INT-989 
                 4-cyanophenylboronic acid 
                 SC_3129 
                 1H NMR (600 MHz, DMSO) δ 9.15 (s, 2H), 
                 453.2 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                   
                   
                 8.49-8.43 (m, 2H), 7.99-7.92 (m, 2H), 
               
               
                   
                 3-yl)-pyrimidin-2-yl]-benzonitrile 
                   
                   
                   
                 7.89 (s, 1H), 7.38 (m, 4H), 7.28 (td, 1H), 
               
               
                   
                   
                   
                   
                   
                 3.73 (s, 2H), 2.48-2.35 (m, 1H), 2.03-1.90 
               
               
                   
                   
                   
                   
                   
                 (m, 10H), 1.55-1.48 (m, 2H). 
               
               
                 SC_3143 
                 cis-5-(8-Ethylamino-2-oxo-8- 
                 INT-1008 
                 5-Bromo-4-methoxy-pyrimidine-2- 
                 SC_3103 
                 (DMSO-d6, 400 MHz), δ (ppm) = 8.79 (s, 
                 407.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                 carbonitrile 
                   
                 1H), 7.60 (s, 1H), 7.41 (d, 2H, J = 7.72 Hz), 
               
               
                   
                 yl)-4-methoxy-pyrimidine-2- 
                   
                   
                   
                 7.28 (t, 2H, J = 7.54 Hz), 7.16 (t, 1H, J = 
               
               
                   
                 carbonitrile 
                   
                   
                   
                 7.32 Hz), 3.97 (s, 3H), 3.72 (s, 2H), 2.02 (bs, 
               
               
                   
                   
                   
                   
                   
                 4H), 1.90-1.69 (m, 5H), 1.51-1.48 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 0.89 (t, 3H, J = 6.56 Hz). 
               
               
                 SC_3144 
                 trans-5-(8-Ethylamino-2-oxo-8- 
                 INT-1009 
                 5-Bromo-4-methoxy-pyrimidine-2- 
                 SC_3103 
                 1HNMR (DMSO-d6, 400 MHz), δ (ppm) = 
                 407.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                 carbonitrile 
                   
                 8.87 (s, 1H), 8.10 (bs, 1H), 7.50 (d, 2H, J = 
               
               
                   
                 yl)-4-methoxy-pyrimidine-2- 
                   
                   
                   
                 7.52 Hz), 7.31 (t, 2H, J = 7.20 Hz), 7.18 (t, 
               
               
                   
                 carbonitrile 
                   
                   
                   
                 1H, J = 6.88 Hz), 4.04 (s, 3H), 3.74 (s, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.07-1.95 (m, 6H), 1.70-1.54 (m, 4H), 0.93 
               
               
                   
                   
                   
                   
                   
                 (t, 3H, J = 6.62 Hz). 
               
               
                 SC_3145 
                 cis-8-Dimethylamino-3-[2- 
                 INT-991 
                 morpholine 
                 SC_3133 
                 1H NMR (600 MHz, DMSO) δ 9.04 (s, 2H), 
                 478.3 
               
               
                   
                 (morpholine-4-carbonyl)- 
                   
                   
                   
                 7.88 (s, 1H), 7.42-7.30 (m, 5H), 7.30- 
               
               
                   
                 pyrimidin-5-yl]-8-phenyl-1,3- 
                   
                   
                   
                 7.22 (m, 1H), 3.75-3.58 (m, 6H), 3.51 (t, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2H), 3.20 (t, 2H), 2.50-2.33 (m, 2H), 1.99- 
               
               
                   
                   
                   
                   
                   
                 1.90 (m, 8H), 1.89-1.74 (m, 2H), 1.54- 
               
               
                   
                   
                   
                   
                   
                 1.44 (m, 2H). 
               
               
                 SC_3147 
                 cis-8-Dimethylamino-3-[2- 
                 INT-976 
                 1-bromo-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 7.47 (d, 1H), 
                 442.2 
               
               
                   
                 (methylsulfonyl-methyl)-phenyl]-8- 
                   
                 (methylsulfonylmethyl)benzene 
                   
                 7.42-7.31 (m, 6H), 7.30-7.22 (m, 3H), 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 4.50 (s, 2H), 3.56 (s, 2H), 2.88 (s, 3H), 2.42- 
               
               
                   
                 one 
                   
                   
                   
                 2.28 (m, 2H), 2.07 (s, 2H), 1.98-1.90 (m, 
               
               
                   
                   
                   
                   
                   
                 8H), 1.89-1.69 (m, 2H), 1.61-1.48 (d, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3148 
                 cis-8-Dimethylamino-3-(4-methyl- 
                 INT-992 
                 morpholine 
                 SC_3120 
                 1H NMR (600 MHz, DMSO) δ 8.14 (s, 1H), 
                 451.3 
               
               
                   
                 2-morpholin-4-yl-pyrimidin-5-yl)- 
                   
                   
                   
                 7.40-7.32 (m, 4H), 7.26 (td, 1H), 7.21 (s, 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                   
                   
                 1H), 3.69-3.60 (m, 8H), 3.38 (s, 2H), 2.41- 
               
               
                   
                 2-one 
                   
                   
                   
                 2.27 (m, 2H), 2.20 (s, 3H), 1.97 (s, 6H), 1.95- 
               
               
                   
                   
                   
                   
                   
                 1.76 (m, 4H), 1.54-1.45 (s, 2H). 
               
               
                 SC_3149 
                 cis-8-Dimethylamino-3-[2-(1,1- 
                 INT-989 
                 thiomorpholine-1,1-dioxide 
                 SC_3120 
                 1H NMR (600 MHz, DMSO) δ 8.63 (s, 2H), 
                 485.2 
               
               
                   
                 dioxo-[1,4]thiazinan-4-yl)- 
                   
                 hydrochloride 
                   
                 7.50 (br s, 1H), 7.41-7.33 (m, 4H), 7.27 (td, 
               
               
                   
                 pyrimidin-5-yl]-8-phenyl-1,3- 
                   
                   
                   
                 1H), 4.17-4.12 (m, 4H), 3.55 (s, 2H), 3.12- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.06 (m, 4H), 2.47-2.27 (m, 2H), 2.04- 
               
               
                   
                   
                   
                   
                   
                 1.74 (m, 10H), 1.51-1.42 (m, 2H). 
               
               
                 SC_3150 
                 cis-8-Dimethylamino-3-(4-fluoro- 
                 INT-976 
                 3-bromo-4-fluoro-pyridine 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.70 (d, 1H), 
                 369.2 
               
               
                   
                 pyridin-3-yl)-8-phenyl-1,3- 
                   
                   
                   
                 8.36 (dd, 1H), 7.54 (s, 1H), 7.36 (td, 5H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 7.26 (s, 1H), 3.61 (s, 2H), 2.44-2.28 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 2.01-1.74 (m, 10H), 1.92 (d, 2H), 1.56- 
               
               
                   
                   
                   
                   
                   
                 1.45 (m, 2H). 
               
               
                 SC_3151 
                 cis-5-(8-Dimethylamino-2-oxo-8- 
                 INT-991 
                 2-(methylamino)ethanol 
                 SC_3133 
                 1H NMR (600 MHz, DMSO) δ 9.03 (d, 2H), 
                 453.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 7.86 (s, 1H), 7.40-7.23 (m, 5H), 3.69 (s, 
               
               
                   
                 yl)-N-(2-hydroxy-ethyl)-N-methyl- 
                   
                   
                   
                 2H), 3.61 (q, 1H), 3.50 (t, 1H), 3.45 (d, 1H), 
               
               
                   
                 pyrimidine-2-carboxylic acid amide 
                   
                   
                   
                 3.17 (t, 1H), 3.01 and 2.83 (both s, together 
               
               
                   
                   
                   
                   
                   
                 3H, amide rotamers), 2.49-2.36 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.00-1.89 (m, 8H), 1.89-1.73 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 1.55-1.47 (m, 2H). 
               
               
                 SC_3152 
                 cis-5-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 5-bromo-2-morpholino-pyridine- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.24 (s, 1H), 
                 461.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                 4-carbonitrile 
                   
                 7.67-7.30 (m, 5H), 7.29 (s, 1H), 3.70-3.65 
               
               
                   
                 yl)-2-morpholin-4-yl- 
                   
                   
                   
                 (m, 4H), 3.51-3.44 (m, 4H), 2.37-2.22 (m, 
               
               
                   
                 isonicotinonitrile 
                   
                   
                   
                 2H), 2.10-1.87 (m, 10H), 1.53-1.31 (m, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3153 
                 cis-4-(8-Dimethylamino-2-oxo-8- 
                 SC_3272 
                   
                 SC_3016 
                 1H NMR (600 MHz, DMSO) δ 7.79 (d, 2H), 
                 393.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 7.62 (d, 2H), 7.41-7.34 (m, 4H), 7.27 (td, 
               
               
                   
                 yl)-benzamide 
                   
                   
                   
                 1H), 7.13-7.09 (m, 1H), 3.62 (s, 2H), 2.46- 
               
               
                   
                   
                   
                   
                   
                 2.35 (m, 2H), 1.97 (s, 6H), 1.93-1.76 (m, 
               
               
                   
                   
                   
                   
                   
                 4H), 1.51-1.45 (m, 2H). 
               
               
                 SC_3154 
                 cis-8-Dimethylamino-3-(2-fluoro- 
                 INT-976 
                 1-bromo-2-fluoro-4- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 7.89-7.83 
                 446.2 
               
               
                   
                 4-methylsulfonyl-phenyl)-8- 
                   
                 methylsulfonyl- 
                   
                 (m, 1H), 7.76 (dd, 1H), 7.70 (dd, 1H), 7.40- 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                 benzene 
                   
                 7.32 (m, 5H), 7.29-7.23 (m, 1H), 3.69 (s, 
               
               
                   
                 one 
                   
                   
                   
                 2H), 3.23 (s, 3H), 2.43-2.30 (m, 2H), 1.96 
               
               
                   
                   
                   
                   
                   
                 (s, 6H), 1.94-1.88 (m, 2H), 1.53-1.47 (m, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3155 
                 cis-4-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 4-bromo-3-fluoro-benzonitrile 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 7.85-7.79 
                 393.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 (m, 2H), 7.73 (s, 1H), 7.62 (dd, 1H), 7.40- 
               
               
                   
                 yl)-3-fluoro-benzonitrile 
                   
                   
                   
                 7.31 (m, 4H), 7.26 (tt, 1H), 3.69 (s, 2H), 2.40- 
               
               
                   
                   
                   
                   
                   
                 2.31 (m, 2H), 1.95 (s, 6H), 1.94-1.87 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 1.87-1.75 (m, 2H), 1.52-1.46 (m, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3156 
                 cis-4-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 4-bromo-3,5-difluoro- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 7.85 (d, 2H), 
                 411.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                 benzonitrile 
                   
                 7.61 (s, 1H), 7.39-7.31 (m, 4H), 7.25 (tt, 
               
               
                   
                 yl)-3,5-difluoro-benzonitrile 
                   
                   
                   
                 1H), 3.53 (s, 2H), 2.42-2.33 (m, 2H), 1.98- 
               
               
                   
                   
                   
                   
                   
                 1.89 (m, 8H), 1.82-1.78 (m, 2H), 1.54- 
               
               
                   
                   
                   
                   
                   
                 1.47 (m, 2H). 
               
               
                 SC_3157 
                 cis-8-Dimethylamino-3-(2- 
                 INT-989 
                 methanol instead of 
                 SC_3120 
                 1H NMR (600 MHz, DMSO) δ 8.76 (s, 2H), 
                 382.2 
               
               
                   
                 methoxy-pyrimidin-5-yl)-8-phenyl- 
                   
                 n-butanol as a solvent 
                   
                 7.41-7.33 (m, 5H), 7.27 (ddt, 1H), 3.86 (s, 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3H), 3.60 (s, 2H), 2.47-2.30 (m, 2H), 2.01- 
               
               
                   
                   
                   
                   
                   
                 1.74 (m, 10H), 1.52-1.45 (m, 2H). 
               
               
                 SC_3158 
                 cis-3-[2-(Benzylamino)-pyrimidin- 
                 INT-989 
                 benzylamine 
                 SC_3120 
                 1H NMR (600 MHz, DMSO) δ 8.43 (s, 2H), 
                 457.3 
               
               
                   
                 5-yl]-8-dimethylamino-8-phenyl- 
                   
                   
                   
                 7.50-7.45 (m, 1H), 7.46-7.33 (m, 5H), 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 7.31-7.23 (m, 4H), 7.19 (tq, 1H), 4.46 (d, 
               
               
                   
                   
                   
                   
                   
                 2H), 4.02 (s, 1H), 3.50 (s, 2H), 2.41-2.31 
               
               
                   
                   
                   
                   
                   
                 (m, 2H), 1.97 (s, 6H), 1.88 (s, 2H), 1.49- 
               
               
                   
                   
                   
                   
                   
                 1.41 (m, 2H). 
               
               
                 SC_3159 
                 cis-8-Dimethylamino-3-[2-(4- 
                 INT-989 
                 (4-fluorophenyl)boronic acid 
                 SC_3129 
                 1H NMR (600 MHz, DMSO) δ 9.07 (s, 2H), 
                 446.2 
               
               
                   
                 fluorophenyl)-pyrimidin-5-yl]-8- 
                   
                   
                   
                 8.37-8.30 (m, 2H), 7.83 (s, 1H), 7.44- 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 7.35 (m, 4H), 7.34-7.25 (m, 3H), 3.69 (s, 
               
               
                   
                 one 
                   
                   
                   
                 2H), 2.47-2.30 (m, 2H), 2.08-1.80 (m, 
               
               
                   
                   
                   
                   
                   
                 10H), 1.55-1.46 (m, 2H). 
               
               
                 SC_3160 
                 trans-8-Benzyl-8-dimethylamino-3- 
                 INT-995 
                 4-(5-bromopyrimidin- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.57 (s, 2H), 
                 451.3 
               
               
                   
                 (2-morpholin-4-yl-pyrimidin-5-yl)- 
                   
                 2-yl)morpholine 
                   
                 7.60 (s, 1H), 7.27 (t, 2H), 7.22-7.15 (m, 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3H), 3.68-3.62 (m, 4H), 3.64-3.57 (m, 
               
               
                   
                   
                   
                   
                   
                 4H), 3.49 (s, 2H), 2.66 (s, 2H), 2.22 (s, 6H), 
               
               
                   
                   
                   
                   
                   
                 1.80-1.70 (m, 4H), 1.51-1.43 (m, 4H). 
               
               
                 SC_3161 
                 cis-8-Benzyl-8-dimethylamino-3- 
                 INT-994 
                 4-(5-bromopyrimidin- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.45 (s, 2H), 
                 451.3 
               
               
                   
                 (2-morpholin-4-yl-pyrimidin-5-yl)- 
                   
                 2-yl)morpholine 
                   
                 7.27 (t, 2H), 7.22-7.15 (m, 3H), 7.11 (s, 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 1H), 3.68-3.56 (m, 8H), 2.64 (s, 2H), 2.26 
               
               
                   
                   
                   
                   
                   
                 (s, 6H), 1.87-1.77 (m, 4H), 1.42 (d, 2H), 
               
               
                   
                   
                   
                   
                   
                 1.15 (dt, 2H). 
               
               
                 SC_3163 
                 cis-4-(8-Dimethylamino-2-oxo-8- 
                 SC_3156 
                   
                 SC_3016 
                 1H NMR (600 MHz, DMSO) δ 8.08 (s, 1H), 
                 429.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 7.65-7.58 (m, 2H), 7.48 (br s, 1H), 7.39- 
               
               
                   
                 yl)-3,5-difluoro-benzamide 
                   
                   
                   
                 7.31 (m, 4H), 7.28-7.22 (m, 1H), 3.49 (s, 
               
               
                   
                   
                   
                   
                   
                 2H), 2.40-2.32 (m, 2H), 1.96 (s, 6H), 1.95- 
               
               
                   
                   
                   
                   
                   
                 1.90 (m, 2H), 1.87-1.77 (m, 2H), 1.54- 
               
               
                   
                   
                   
                   
                   
                 1.49 (m, 2H). 
               
               
                 SC_3164 
                 cis-4-(8-Dimethylamino-2-oxo-8- 
                 SC_3155 
                   
                 SC_3016 
                 1H NMR (600 MHz, DMSO) δ 7.95 (s, 1H), 
                 411.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 7.72-7.64 (m, 2H), 7.61 (t, 1H), 7.54-7.50 
               
               
                   
                 yl)-3-fluoro-benzamide 
                   
                   
                   
                 (m, 1H), 7.40-7.32 (m, 5H), 7.26 (tt, 1H), 
               
               
                   
                   
                   
                   
                   
                 3.62 (s, 2H), 2.41-2.31 (m, 2H), 1.96 (s, 
               
               
                   
                   
                   
                   
                   
                 6H), 1.93-1.88 (m, 2H), 1.86-1.75 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 1.53-1.45 (m, 2H). 
               
               
                 SC_3165 
                 cis-8-Benzyl-8-dimethylamino-3- 
                 INT-994 
                 5-bromo-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 9.07 (s, 2H), 
                 434.2 
               
               
                   
                 [2-(trifluoromethyl)-pyrimidin-5- 
                   
                 (trifluoromethyl)pyrimidine 
                   
                 7.77 (s, 1H), 7.29 (t, 2H), 7.24-7.17 (m, 
               
               
                   
                 yl]-1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3H), 3.55 (s, 2H), 2.66 (s, 2H), 2.26 (s, 6H), 
               
               
                   
                   
                   
                   
                   
                 1.86 (dt, 4H), 1.44 (d, 2H), 1.25-1.17 (m, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3166 
                 trans-8-Benzyl-8-dimethylamino-3- 
                 INT-995 
                 5-bromo-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 9.16 (s, 2H), 
                 434.2 
               
               
                   
                 [2-(trifluoromethyl)-pyrimidin-5- 
                   
                 (trifluoromethyl)pyrimidine 
                   
                 8.28 (s, 1H), 7.27 (t, 2H), 7.22-7.16 (m, 
               
               
                   
                 yl]-1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3H), 3.67 (s, 2H), 2.66 (s, 2H), 2.24 (s, 6H), 
               
               
                   
                   
                   
                   
                   
                 1.84-1.72 (m, 4H), 1.49 (q, 4H). 
               
               
                 SC_3167 
                 cis-8-Dimethylamino-8-thiophen-2- 
                 INT-997 
                 5-bromo-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 9.19 (d, 2H), 
                 426.1 
               
               
                   
                 yl-3-[2-(trifluoromethyl)- 
                   
                 (trifluoromethyl)pyrimidine 
                   
                 7.97 (s, 1H), 7.43 (t, 1H), 7.07 (dd, 1H), 6.97 
               
               
                   
                 pyrimidin-5-yl]-1,3- 
                   
                   
                   
                 (d, 1H), 3.78 (s, 2H), 2.40-2.27 (m, 2H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2.04 (s, 6H), 1.96 (t, 2H), 1.90-1.79 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 1.60-1.52 (m, 2H). 
               
               
                 SC_3168 
                 trans-8-Dimethylamino-8-thiophen- 
                 INT-998 
                 5-bromo-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 9.20 (s, 2H), 
                 426.1 
               
               
                   
                 2-yl-3-[2-(trifluoromethyl)- 
                   
                 (trifluoromethyl)pyrimidine 
                   
                 8.00 (s, 1H), 7.45 (dd, 1H), 7.09 (dd, 1H), 
               
               
                   
                 pyrimidin-5-yl]-1,3- 
                   
                   
                   
                 7.02-6.97 (m, 1H), 3.81 (s, 2H), 2.12 (d, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 4H), 2.03 (s, 6H), 1.85 (t, 2H), 1.62-1.54 
               
               
                   
                   
                   
                   
                   
                 (m, 2H). 
               
               
                 SC_3170 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-989 
                 piperidine 
                 SC_3120 
                 1H NMR (DMSO-d6): δ 8.49 (s, 2H), 7.39- 
                 435.3 
               
               
                   
                 (2-piperidin-1-yl-pyrimidin-5-yl)- 
                   
                   
                   
                 7.24 (m, 6H), 3.65-3.63 (m, 4H), 3.50 (s, 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2H), 2.36-2.32 (m, 2H), 1.95-1.86 (m, 10H), 
               
               
                   
                   
                   
                   
                   
                 1.61-1.56 (m, 2H), 1.50-1.44 (m, 6H). 
               
               
                 SC_3171 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-989 
                 pyrrolidine 
                 SC_3120 
                 1H NMR (CDCl3): δ 8.43 (s, 2H), 7.41-7.38 
                 421.3 
               
               
                   
                 (2-pyrrolidin-1-yl-pyrimidin-5-yl)- 
                   
                   
                   
                 (m, 2H), 7.32-7.30 (m, 3H), 5.05 (br s, 1H), 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.53 (t, 4H), 3.45 (s, 2H), 2.30-2.06 (m, 
               
               
                   
                   
                   
                   
                   
                 10H), 1.99-1.96 (m, 6H), 1.62-1.58 (m, 2H). 
               
               
                 SC_3172 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-989 
                 pyrimidin-5-ylboronic acid 
                 SC_3129 
                 1H NMR (600 MHz, DMF) δ 9.56 (s, 2H), 
                 430.2 
               
               
                   
                 (2-pyrimidin-5-yl-pyrimidin-5-yl)- 
                   
                   
                   
                 9.27 (s, 1H), 9.17 (s, 2H), 8.35 (s, 1H), 7.89 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (d, 2H), 7.63 (dq, 3H), 3.73 (s, 2H), 3.04 (d, 
               
               
                   
                   
                   
                   
                   
                 2H), 2.81 (s, 6H), 2.57 (td, 2H), 2.06 (d, 2H), 
               
               
                   
                   
                   
                   
                   
                 1.58 (td, 2H). 
               
               
                 SC_3174 
                 trans-8-Benzyl-8-dimethylamino-3- 
                 INT-995 
                 5-bromo-4-methyl-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.57 (s, 1H), 
                 447.2 
               
               
                   
                 [4-methyl-6-(trifluoromethyl)- 
                   
                 (trifluoromethyl)pyridine 
                   
                 7.80 (s, 1H), 7.67 (s, 1H), 7.27 (t, 2H), 7.23- 
               
               
                   
                 pyridin-3-yl]-1,3- 
                   
                   
                   
                 7.15 (m, 3H), 3.58 (d, 2H), 2.67 (s, 2H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2.31 (s, 3H), 2.22 (d, 6H), 1.82-1.72 (m, 
               
               
                   
                   
                   
                   
                   
                 4H), 1.56 (dd, 2H), 1.48 (td, 2H). 
               
               
                 SC_3175 
                 cis-5-(8-Dimethylamino-2-oxo-8- 
                 SC_3152 
                   
                 SC_3016 
                   
                 480.6 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
               
               
                   
                 yl)-2-morpholin-4-yl-pyridine-4- 
               
               
                   
                 carboxylic acid amide 
               
               
                 SC_3176 
                 cis-8-Dimethylamino-3-[2-(3,5- 
                 INT-989 
                 (3,5-dimethylisoxazol-4- 
                 SC_3129 
                 1H NMR (600 MHz, DMSO) δ 9.05 (s, 2H), 
                 447.2 
               
               
                   
                 dimethyl-isoxazol-4-yl)-pyrimidin- 
                   
                 yl)boronic acid 
                   
                 7.80 (s, 1H), 7.43-7.34 (m, 4H), 7.28 (tt, 
               
               
                   
                 5-yl]-8-phenyl-1,3- 
                   
                   
                   
                 1H), 3.68 (s, 2H), 2.69 (s, 3H), 2.47 (s, 3H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2.43-2.35 (m, 2H), 2.01-1.79 (m, 10H), 
               
               
                   
                   
                   
                   
                   
                 1.50 (s, 2H). 
               
               
                 SC_3177 
                 cis-3-[2-(Benzothiazol-6-yl)- 
                 INT-989 
                 1,3-benzothiazol-6- 
                 SC_3129 
                 1H NMR (600 MHz, DMSO) δ 9.46 (s, 1H), 
                 485.2 
               
               
                   
                 pyrimidin-5-yl]-8-dimethylamino- 
                   
                 ylboronic acid 
                   
                 9.12 (s, 2H), 9.07 (s, 1H), 8.49 (d, 1H), 8.16 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                   
                   
                 (d, 1H), 7.84 (s, 1H), 7.39 (d, 4H), 7.29 (d, 
               
               
                   
                 2-one 
                   
                   
                   
                 1H), 3.73 (s, 2H), 2.42 (d, 2H), 1.97 (d, 
               
               
                   
                   
                   
                   
                   
                 10H), 1.54 (d, 2H). 
               
               
                 SC_3178 
                 cis-8-Dimethylamino-3-[2-fluoro- 
                 INT-976 
                 1-bromo-2-fluoro-4- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 7.80 (t, 1H), 
                 436.2 
               
               
                   
                 4-(trifluoromethyl)-phenyl]-8- 
                   
                 (trifluoromethyl)benzene 
                   
                 7.65 (dd, 1H), 7.53 (dd, 1H), 7.40-7.32 (m, 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 4H), 7.29-7.23 (m, 1H), 3.66 (s, 2H), 2.36 
               
               
                   
                 one 
                   
                   
                   
                 (s, 2H), 1.97-1.88 (m, 8H), 1.85-1.75 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 1.53-1.46 (m, 2H). 
               
               
                 SC_3179 
                 cis-8-Dimethylamino-3-(6- 
                 INT-976 
                 4-(5-bromo-2- 
                 as SC_3097 step 2 
                 1H NMR (600 MHz, DMSO) δ 8.20 (d, 1H), 
                 436.3 
               
               
                   
                 morpholin-4-yl-pyridin-3-yl)-8- 
                   
                 pyridyl)morpholine 
                   
                 7.89 (dd, 1H), 7.37 (p, 5H), 7.27 (d, 1H), 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 6.79 (d, 1H), 3.71-3.66 (m, 4H), 3.53 (s, 
               
               
                   
                 one 
                   
                   
                   
                 2H), 2.43-2.32 (m, 2H), 1.96 (s, 7H), 1.91- 
               
               
                   
                   
                   
                   
                   
                 1.85 (m, 5H), 1.49-1.42 (m, 2H). 
               
               
                 SC_3180 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 4-bromo-2-phenylthiazole 
                 SC_3103 
                 1H NMR (DMSO-d6): δ 7.89-7.87 (m, 2H), 
                 433.2 
               
               
                   
                 (2-phenyl-thiazol-4-yl)-1,3- 
                   
                   
                   
                 7.55 (br s, 1H), 7.43-7.35 (m, 8H), 7.29-7.26 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (m, 1H), 3.82 (s, 2H), 2.45 (br m, 2H), 1.96- 
               
               
                   
                   
                   
                   
                   
                 1.79 (m, 10H), 1.53-1.50 (m, 2H). 
               
               
                 SC_3181 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-989 
                 tetrahydro-2H-pyran-4-amine 
                 SC_3103 
                 1H NMR (DMSO-d6): δ 8.42 (s, 2H), 7.39- 
                 451.3 
               
               
                   
                 [2-(tetrahydro-pyran-4-ylamino)- 
                   
                   
                   
                 7.35 (m, 5H), 7.27-7.24 (m, 1H), 6.83 (d, 
               
               
                   
                 pyrimidin-5-yl]-1,3- 
                   
                   
                   
                 1H), 3.84-3.79 (m, 3H), 3.50 (s, 2H), 3.38- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.35 (m, 2H), 2.36-2.32 (m, 2H), 1.94-1.77 
               
               
                   
                   
                   
                   
                   
                 (m, 12H), 1.50-1.40 (m, 4H). 
               
               
                 SC_3183 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 2-bromo-4-phenylthiazole 
                 SC_3103 
                 1H NMR (DMSO-d6): δ 8.09 (br s, 1H), 
                 433.2 
               
               
                   
                 (4-phenyl-thiazol-2-yl)-1,3- 
                   
                   
                   
                 7.87 (d, 2H), 7.51 (s, 1H), 7.37-7.24 (m, 8H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.87 (s, 2H), 2.43 (m, 2H), 1.96-1.84 (m, 
               
               
                   
                   
                   
                   
                   
                 10H), 1.54 (m, 2H). 
               
               
                 SC_3184 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 1H-pyrrolo[2,3-b]pyridine 
                 SC_3103 
                 1H NMR (DMSO-d6): δ 9.07 (s, 2H), 8.35- 
                 468.2 
               
               
                   
                 [2-(1H-pyrrolo[2,3-b]pyridin-1-yl)- 
                   
                   
                   
                 8.33 (m, 1H), 8.10-8.04 (m, 2H), 7.83 (br s, 
               
               
                   
                 pyrimidin-5-yl]-1,3- 
                   
                   
                   
                 1H), 7.41-7.37 (m, 4H), 7.29-7.21 (m, 2H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 6.72-6.71 (d, 1H), 3.71 (s, 2H), 2.49 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 1.97 (m, 10H), 1.52 (m, 2H). 
               
               
                 SC_3185 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-989 
                 (3,4,5-trifluorophenyl)boronic 
                 SC_3129 
                 1H NMR (600 MHz, DMSO) δ 9.11 (s, 2H), 
                 481.2 
               
               
                   
                 [2-(3,4,5-trifluoro-phenyl)- 
                   
                 acid 
                   
                 8.12-8.03 (m, 2H), 7.89 (s, 1H), 7.42- 
               
               
                   
                 pyrimidin-5-yl]-1,3- 
                   
                   
                   
                 7.34 (m, 4H), 7.28 (dq, 1H), 3.71 (s, 2H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2.48-2.35 (m, 2H), 1.99-1.79 (m, 10H), 
               
               
                   
                   
                   
                   
                   
                 1.58-1.47 (m, 2H). 
               
               
                 SC_3187 
                 cis-8-Dimethylamino-3-m-tolyl-8- 
                 INT-976 
                 1-bromo-3-methylbenzene 
                 SC_3186 
                   
                 363.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
               
               
                   
                 one 
               
               
                 SC_3188 
                 cis-8-Dimethylamino-8-phenyl-3-p- 
                 INT-976 
                 1-bromo-4-methylbenzene 
                 SC_3186 
                   
                 363.2 
               
               
                   
                 tolyl-1,3-diazaspiro[4.5]decan-2- 
               
               
                   
                 one 
               
               
                 SC_3189 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 1-bromo-4- 
                 SC_3186 
                   
                 417.2 
               
               
                   
                 [4-(trifluoromethyl)-phenyl]-1,3- 
                   
                 trifluoromethylbenzene 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3190 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 1-bromo-3- 
                 SC_3186 
                   
                 433.2 
               
               
                   
                 [3-(trifluoromethyloxy)-phenyl]- 
                   
                 (trifluoromethoxy)benzene 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
               
               
                 SC_3191 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 1-bromo-4- 
                 SC_3186 
                   
                 433.2 
               
               
                   
                 [4-(trifluoromethyloxy)-phenyl]- 
                   
                 (trifluoromethoxy)benzene 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
               
               
                 SC_3192 
                 cis-2-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 methyl 2-bromobenzoate 
                 SC_3186 
                   
                 407.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
               
               
                   
                 yl)-benzoic acid methyl ester 
               
               
                 SC_3193 
                 cis-3-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 methyl 3-bromobenzoate 
                 SC_3186 
                   
                 407.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
               
               
                   
                 yl)-benzoic acid methyl ester 
               
               
                 SC_3194 
                 cis-4-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 methyl 4-bromobenzoate 
                 SC_3186 
                   
                 407.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
               
               
                   
                 yl)-benzoic acid methyl ester 
               
               
                 SC_3195 
                 cis-3-(1,3-Benzodioxol-5-yl)-8- 
                 INT-976 
                 5-bromobenzo[d][1,3]dioxole 
                 SC_3186 
                   
                 393.2 
               
               
                   
                 dimethylamino-8-phenyl-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3196 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 5-bromoquinoline 
                 SC_3186 
                   
                 400.2 
               
               
                   
                 quinolin-5-yl-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3197 
                 cis-3-(2,3-Dihydro-1H-indol-6-yl)- 
                 INT-976 
                 6-bromoindoline 
                 SC_3186 
                   
                 390.2 
               
               
                   
                 8-dimethylamino-8-phenyl-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3198 
                 cis-5-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 methyl 5-bromo-4- 
                 SC_3186 
                   
                 422.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                 methylpicolinate 
               
               
                   
                 yl)-4-methyl-pyridine-2-carboxylic 
               
               
                   
                 acid methyl ester 
               
               
                 SC_3199 
                 cis-8-Dimethylamino-3-(6- 
                 INT-976 
                 5-bromo-2-methoxy- 
                 SC_3186 
                   
                 394.2 
               
               
                   
                 methoxy-4-methyl-pyridin-3-yl)-8- 
                   
                 4-methylpyridine 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
               
               
                   
                 one 
               
               
                 SC_3200 
                 cis-8-Dimethylamino-3-[2-methyl- 
                 INT-976 
                 5-bromo-1-methyl-3- 
                 SC_3186 
                   
                 421.2 
               
               
                   
                 5-(trifluoromethyl)-2H-pyrazol-3- 
                   
                 (trifluoromethyl)-1H-pyrazole 
               
               
                   
                 yl]-8-phenyl-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3201 
                 cis-8-Dimethylamino-3-(3- 
                 INT-976 
                 2-bromo-3-methoxypyridine 
                 SC_3186 
                   
                 380.2 
               
               
                   
                 methoxy-pyridin-2-yl)-8-phenyl- 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
               
               
                 SC_3202 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 2-bromo-5- 
                 SC_3186 
                   
                 418.2 
               
               
                   
                 [5-(trifluoromethyl)-pyridin-2-yl]- 
                   
                 trifluoromethylpyridine 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
               
               
                 SC_3203 
                 cis-5-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 3-bromo-5-cyanopyridine 
                 SC_3186 
                   
                 375.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
               
               
                   
                 yl)-nicotinonitrile 
               
               
                 SC_3204 
                 cis-8-Dimethylamino-3-(3-methyl- 
                 INT-976 
                 2-bromo-3-methylpyridine 
                 SC_3186 
                   
                 364.2 
               
               
                   
                 pyridin-2-yl)-8-phenyl-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3205 
                 cis-8-Dimethylamino-3-(6- 
                 INT-976 
                 5-bromo-2-methoxypyridine 
                 SC_3186 
                   
                 380.2 
               
               
                   
                 methoxy-pyridin-3-yl)-8-phenyl- 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
               
               
                 SC_3206 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 1-bromo-3- 
                 SC_3186 
                   
                 417.2 
               
               
                   
                 [3-(trifluoromethyl)phenyl]-1,3- 
                   
                 trifluoromethylbenzene 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3207 
                 cis-3-(1,3-Benzodioxol-4-yl)-8- 
                 INT-976 
                 4-bromobenzo[d][1,3]dioxole 
                 SC_3186 
                   
                 393.2 
               
               
                   
                 dimethylamino-8-phenyl-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3209 
                 cis-8-Dimethylamino-3-[2-(3,5- 
                 INT-976 
                 3,5-dimethyl-1H-pyrazole 
                 SC_3103 
                 1H NMR (DMSO-d6): δ 9.00 (s, 2H), 7.81 
                 446.2 
               
               
                   
                 dimethyl-1H-pyrazol-1-yl)- 
                   
                   
                   
                 (br s, 1H), 7.38-7.27 (m, 5H), 6.07 (s, 1H), 
               
               
                   
                 pyrimidin-5-yl]-8-phenyl-1,3- 
                   
                   
                   
                 3.69 (s, 2H), 2.45 (m, 5H), 2.17 (s, 3H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 1.96-1.91 (m, 10H), 1.51(br m, 2H). 
               
               
                 SC_3210 
                 cis-8-Dimethylamino-3-[2-(3- 
                 INT-989 
                 rac-piperidin-3-ol 
                 SC_3182 
                 1H NMR (DMS0-d6): 8.48 (s, 2H), 7.39- 
                 451.2 
               
               
                   
                 hydroxy-piperidin-1-yl)-pyrimidin- 
                   
                   
                   
                 7.35 (m, 5H), 7.27-7.24 (m, 1H), 4.82 (d, 
               
               
                   
                 5-yl]-8-phenyl-1,3- 
                   
                   
                   
                 1H), 4.39-4.36 (m, 1H), 4.24-4.21 (m, 1H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.51 (s, 2H), 3.41-3.36 (m, 1H), 2.92-2.87 
               
               
                   
                   
                   
                   
                   
                 (m, 1H), 2.77-2.72 (m, 1H), 2.42-2.32 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 2.00-1.66 (m, 12H), 1.46-1.39 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 1.34 (t, 2H). 
               
               
                 SC_3211 
                 cis-8-Dimethylamino-3-[2-(3- 
                 INT-989 
                 rac-piperidin-3-ol 
                 SC_3182 
                 1H NMR (DMSO-d6): 8.48 (s, 2H), 7.35 (m, 
                 451.3 
               
               
                   
                 hydroxy-piperidin-1-yl)-pyrimidin- 
                   
                   
                   
                 5H), 7.25 (m, 1H), 4.82 (d, 1H), 4.39-4.37 
               
               
                   
                 5-yl]-8-phenyl-1,3- 
                   
                   
                   
                 (m, 1H), 4.24-4.21 (m, 1H), 3.51 (s, 2H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.40-3.39 (m, 1H), 2.90-2.87 (m, 1H), 2.77- 
               
               
                   
                   
                   
                   
                   
                 2.72 (m, 1H), 2.37 (m, 2H), 2.00-1.66 (m, 
               
               
                   
                   
                   
                   
                   
                 12H), 1.45 (m, 2H), 1.34 (t, 2H). 
               
               
                 SC_3212 
                 cis-8-Dimethylamino-3-[2-[4-(2- 
                 INT-989 
                 2-piperazin-1-ylethanol 
                 SC_3120 
                 1H NMR (600 MHz, DMSO) δ 8.53 (s, 2H), 
                 480.3 
               
               
                   
                 hydroxy-ethyl)-piperazin-1-yl]- 
                   
                   
                   
                 7.37 (p, 5H), 7.27 (d, 1H), 3.62 (t, 4H), 3.53 
               
               
                   
                 pyrimidin-5-yl]-8-phenyl-1,3- 
                   
                   
                   
                 (q, 4H), 2.49-2.27 (m, 7H), 1.96 (s, 6H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 1.94-1.73 (m, 4H), 1.51-1.40 (m, 2H). 
               
               
                 SC_3213 
                 cis-2-[4-[5-(8-Dimethylamino-2- 
                 SC_3146 
                   
                 INT-991 
                 1H NMR (600 MHz, DMSO) δ 8.53 (s, 2H), 
                 494.3 
               
               
                   
                 oxo-8-phenyl-1,3- 
                   
                   
                   
                 7.57 (s, 1H), 7.42 (d, 4H), 7.33 (d, 1H), 3.68 
               
               
                   
                 diazaspiro[4.5]decan-3-yl)- 
                   
                   
                   
                 (t, 4H), 3.19 (s, 2H), 2.62 (t, 4H), 2.37 (d, 
               
               
                   
                 pyrimidin-2-yl]-piperazin-1-yl]- 
                   
                   
                   
                 2H), 2.20-1.96 (m, 8H), 1.88 (t, 2H), 1.43 
               
               
                   
                 acetic acid 
                   
                   
                   
                 (t, 2H). 
               
               
                 SC_3214 
                 cis-8-Dimethylamino-3-[2-(1- 
                 INT-989 
                 1-methyl-4-(4,4,5,5- 
                 SC_3208 
                 1H NMR (600 MHz, DMSO + 2 vol % TFA) 
                 484.3 
               
               
                   
                 methyl-1H-pyrrolo[2,3-b]pyridin-4- 
                   
                 tetramethyl-1,3,2- 
                   
                 δ 9.85 (s, 1H), 9.13 (s, 2H), 8.41 (d, 2H), 
               
               
                   
                 yl)-pyrimidin-5-yl]-8-phenyl-1,3- 
                   
                 dioxaborolan-2-yl)- 
                   
                 7.99 (s, 1H), 7.72 (s, 2H), 7.66-7.46 (m, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                 2,3-dihydropyrrolo[2,3- 
                   
                 4H), 7.30 (s, 1H), 3.88 (s, 2H), 3.60 (s, 6H), 
               
               
                   
                   
                   
                 b]pyridine 
                   
                 2.77-2.71 (m, 2H), 2.30-2.26 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 1.94-1.89 (m, 2H), 1.75 (s, 3H), 1.41- 
               
               
                   
                   
                   
                   
                   
                 1.35 (m, 2H). 
               
               
                 SC_3215 
                 cis-8-Benzyl-8-dimethylamino-3- 
                 INT-994 
                 5-bromo-4-methyl-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.52 (s, 1H), 
                 447.2 
               
               
                   
                 [4-methyl-6-(trifluoromethyl)- 
                   
                 (trifluoromethyl)pyridine 
                   
                 7.76 (s, 1H), 7.23 (dd, 2H), 7.19-7.11 (m, 
               
               
                   
                 pyridin-3-yl]-1,3- 
                   
                   
                   
                 4H), 2.62 (s, 2H), 2.27 (s, 6H), 2.25 (s, 3H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 1.86 (td, 2H), 1.80 (dt, 2H), 1.57-1.49 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 1.09 (td, 2H). 
               
               
                 SC_3216 
                 trans-8-Dimethylamino-3-[4- 
                 INT-998 
                 5-bromo-4-methyl-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.61 (s, 1H), 
                 439.2 
               
               
                   
                 methyl-6-(trifluoromethyl)-pyridin- 
                   
                 (trifluoromethyl)pyridine 
                   
                 7.83 (s, 1H), 7.53-7.49 (m, 1H), 7.45 (dd, 
               
               
                   
                 3-yl]-8-thiophen-2-yl-1,3- 
                   
                   
                   
                 1H), 7.09 (dd, 1H), 6.99 (dd, 1H), 3.70 (s, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2H), 2.35 (s, 3H), 2.19-2.05 (m, 4H), 2.02 
               
               
                   
                   
                   
                   
                   
                 (s, 6H), 1.93-1.85 (m, 2H), 1.64 (dt, 2H). 
               
               
                 SC_3217 
                 cis-8-Dimethylamino-3-[4-methyl- 
                 INT-997 
                 5-bromo-4-methyl-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.58 (s, 1H), 
                 439.2 
               
               
                   
                 6-(trifluoromethyl)-pyridin-3-yl]-8- 
                   
                 (trifluoromethyl)pyridine 
                   
                 7.80 (s, 1H), 7.45 (s, 1H), 7.42 (dd, 1H), 
               
               
                   
                 thiophen-2-yl-1,3- 
                   
                   
                   
                 7.05 (dd, 1H), 6.95 (dd, 1H), 3.67 (s, 2H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2.33 (s, 3H), 2.32-2.25 (m, 2H), 2.04 (s, 
               
               
                   
                   
                   
                   
                   
                 6H), 2.00-1.92 (m, 2H), 1.89-1.76 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 1.62 (dt, 2H). 
               
               
                 SC_3218 
                 cis-8-Dimethylamino-3-[2-(1,1- 
                 INT-976 
                 4-[5-bromo-4- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.65 (s, 1H), 
                 553.2 
               
               
                   
                 dioxo-[1,4]thiazinan-4-yl)-4- 
                   
                 (trifluoromethyl)pyrimidin-2-yl]-1,4- 
                   
                 7.42 (s, 1H), 7.41-7.31 (m, 5H), 7.25 (tt, 
               
               
                   
                 (trifluoromethyl)-pyrimidin-5-yl]- 
                   
                 thiazinane 1,1- 
                   
                 1H), 4.23 (t, 4H), 3.22 (t, 4H), 2.40-2.26 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                 dioxide (prepared as SC_3097 step 1) 
                   
                 (m, 2H), 1.97-1.88 (m, 8H), 1.87-1.75 
               
               
                   
                 2-one 
                   
                   
                   
                 (m, 2H), 1.54-1.42 (m, 2H). 
               
               
                 SC_3219 
                 cis-8-Dimethylamino-8-(1-methyl- 
                 INT-1000 
                 5-bromo-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 9.14 (s, 2H), 
                 474.2 
               
               
                   
                 1H-benzoimidazol-2-yl)-3-[2- 
                   
                 (trifluoromethyl)pyrimidine 
                   
                 8.65 (s, 1H), 7.63 (d, 1H), 7.51 (d, 1H), 7.25 
               
               
                   
                 (trifluoromethyl)-pyrimidin-5-yl]- 
                   
                   
                   
                 (ddd, 1H), 7.19 (ddd, 1H), 4.02 (s, 3H), 3.61 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (s, 2H), 2.26 (d, 2H), 2.18 (s, 6H), 2.16- 
               
               
                   
                   
                   
                   
                   
                 2.09 (m, 2H), 1.87 (s, 2H), 1.78 (d, 2H). 
               
               
                 SC_3220 
                 cis-8-Dimethylamino-8-(1-methyl- 
                 INT-1000 
                 5-bromo-4-methyl-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.56 (s, 1H), 
                 487.3 
               
               
                   
                 1H-benzoimidazol-2-yl)-3-[4- 
                   
                 (trifluoromethyl)pyridine 
                   
                 8.10 (s, 1H), 7.80 (s, 1H), 7.60 (d, 1H), 7.50 
               
               
                   
                 methyl-6-(trifluoromethyl)-pyridin- 
                   
                   
                   
                 (d, 1H), 7.23 (ddd, 1H), 7.17 (td, 1H), 4.02 
               
               
                   
                 3-yl]-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 (s, 3H), 3.50 (s, 2H), 2.34-2.25 (m, 5H), 
               
               
                   
                 one 
                   
                   
                   
                 2.19-2.09 (m, 8H), 1.90-1.74 (m, 4H). 
               
               
                 SC_3222 
                 cis-3-[2-(Benzyl-methyl-amino)- 
                 INT-976 
                 N-benzyl-5-bromo-N- 
                 SC_3103 
                 1H NMR (DMSO-d6): δ 8.52 (s, 2H), 7.39- 
                 471.2 
               
               
                   
                 pyrimidin-5-yl]-8-dimethylamino- 
                   
                 methylpyrimidin-2-amine 
                   
                 7.33 (m, 5H), 7.30-7.17 (m, 6H), 4.81 (s, 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                   
                   
                 2H), 3.52 (s, 2H), 3.03 (s, 3H), 2.45-2.32 (m, 
               
               
                   
                 2-one 
                   
                   
                   
                 2H), 1.95-1.86 (m, 10H), 1.47-1.43 (m, 2H). 
               
               
                 SC_3223 
                 cis-5-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 ethyl 5-bromopyrimidine-2- 
                 SC_3103 (step 1), 
                 1H NMR (DMSO-d6): δ 9.04 (s, 2H), 8.24- 
                 585.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                 carboxylate (step 1), 2,5,8,11- 
                 INT-991 (step 2), 
                 8.23 (m, 1H), 7.42-7.39 (m, 2H), 7.32-7.31 
               
               
                   
                 yl)-N-[2-[2-[2-(2-methoxy-ethoxy)- 
                   
                 tetraoxatridecan-13-amine (step 3) 
                 SC_3133 (step 3) 
                 (m, 3H), 5.70 (s, 1H), 3.70-3.60 (m, 16H), 
               
               
                   
                 ethoxy]-ethoxy]-ethyl]-pyrimidine- 
                   
                   
                   
                 3.54-3.52 (m, 2H), 3.35 (s, 3H), 2.21-2.00 
               
               
                   
                 2-carboxylic acid amide 
                   
                   
                   
                 (m, 12H), 1.66-1.64 (m, 2H). 
               
               
                 SC_3225 
                 cis-8-Dimethylamino-3-[2-[(2- 
                 INT-989 
                 2-(methylamino)ethanol 
                 SC_3182 
                 1H NMR (DMSO-d6): δ 8.46 (s, 2H), 7.39- 
                 425.2 
               
               
                   
                 hydroxy-ethyl)-methyl-amino]- 
                   
                   
                   
                 7.33 (m, 5H), 7.27-7.24 (m, 1H), 4.62 (t, 
               
               
                   
                 pyrimidin-5-yl]-8-phenyl-1,3- 
                   
                   
                   
                 1H), 3.61-3.50 (m, 6H), 3.08 (s, 3H), 2.36- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2.33 (m, 2H), 1.95-1.86 (m, 10H), 1.47-1.45 
               
               
                   
                   
                   
                   
                   
                 (m, 2H). 
               
               
                 SC_3226 
                 cis-3-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 5-bromo-4-methyl-2- 
                 SC_3103 (step 1), 
                   
                 487.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                 (trifluoromethyl)pyridine 
                 SC_3016 (step 2) 
               
               
                   
                 yl)-benzamide 
               
               
                 SC_3227 
                 cis-8-Dimethylamino-3-[3-fluoro- 
                 INT-976 
                 2-bromo-3-fluoro-5- 
                 SC_3186 
                   
                 417.1 
               
               
                   
                 5-(trifluoromethyl)-pyridin-2-yl]-8- 
                   
                 (trifluoromethyl)pyridine 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
               
               
                   
                 one 
               
               
                 SC_3228 
                 cis-8-Dimethylamino-3-(5-methyl- 
                 INT-976 
                 2-bromo-5-methylpyrazine 
                 SC_3186 
                   
                 459.1 
               
               
                   
                 pyrazin-2-yl)-8-phenyl-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3229 
                 cis-8-Dimethylamino-3-(5-fluoro- 
                 INT-976 
                 4-bromo-5-fluoropyrimidine 
                 SC_3186 
                   
                 433.2 
               
               
                   
                 pyrimidin-4-yl)-8-phenyl-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3230 
                 cis-8-Dimethylamino-3-(5-fluoro- 
                 INT-976 
                 2-bromo-5-fluoropyrimidine 
                 SC_3186 
                   
                 458.1 
               
               
                   
                 pyrimidin-2-yl)-8-phenyl-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3231 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 2-bromopyrazine 
                 SC_3186 
                   
                 471.1 
               
               
                   
                 pyrazin-2-yl-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3232 
                 cis-3-([2,1,3]Benzoxadiazol-5-yl)- 
                 INT-976 
                 5-bromobenzo[c][1,2,5]- 
                 SC_3186 
                   
                 444.1 
               
               
                   
                 8-dimethylamino-8-phenyl-1,3- 
                   
                 oxadiazole 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3233 
                 cis-2-[2-(8-Dimethylamino-2-oxo- 
                 SC_3169 
                 ammonium chloride 
                 SC_3133 
                 1H NMR (600 MHz, DMSO) δ 7.73 (s, 1H), 
                 423.2 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                   
                   
                 7.40-7.32 (m, 4H), 7.31 (s, 1H), 7.26 (dd, 
               
               
                   
                 3-yl)-phenoxy]-acetamide 
                   
                   
                   
                 1H), 7.18 (td, 1H), 6.98-6.91 (m, 2H), 4.50 
               
               
                   
                   
                   
                   
                   
                 (s, 2H), 3.52 (s, 2H), 2.42-2.29 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.01-1.71 (m, 10H), 1.55-1.48 (m, 2H). 
               
               
                 SC_3234 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 4-(5-bromothiophen-2-yl)pyridine 
                 SC_3103 
                 1H NMR (DMSO-d6): δ 8.45-8.43 (d, 2H), 
                 433.2 
               
               
                   
                 (5-pyridin-4-yl-thiophen-2-yl)-1,3- 
                   
                   
                   
                 7.87 (br s, 1H), 7.54-7.53 (d, 1H), 7.49-7.48 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (m, 2H), 7.38-7.27 (m, 5H), 6.35-6.34 (d, 
               
               
                   
                   
                   
                   
                   
                 2H), 3.64 (s, 2H), 2.42 (m, 2H), 1.96-1.90 
               
               
                   
                   
                   
                   
                   
                 (m, 10H), 1.51-1.49 (m, 2H). 
               
               
                 SC_3236 
                 cis-8-Dimethylamino-3-(2- 
                 INT-1002 
                 morpholine 
                 SC_3120 
                 1H NMR (600 MHz, DMSO) δ 8.07 (d, 1H), 
                 437.3 
               
               
                   
                 morpholin-4-yl-pyrimidin-4-yl)-8- 
                   
                   
                   
                 7.93 (s, 1H), 7.37 (dt, 5H), 7.27 (t, 1H), 3.65 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 (s, 2H), 3.58 (s, 8H), 2.40-2.27 (m, 2H), 
               
               
                   
                 one 
                   
                   
                   
                 1.94 (s, 6H), 1.92-1.80 (m, 4H), 1.43 (d, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3237 
                 cis-3-[2-(3,4-Difluoro-phenyl)- 
                 INT-989 
                 (3,4-difluorophenyl)boronic acid 
                 SC_3129 
                 1H NMR (600 MHz, DMSO) δ 9.08 (s, 2H), 
                 463.2 
               
               
                   
                 pyrimidin-5-yl]-8-dimethylamino- 
                   
                   
                   
                 8.22-8.12 (m, 2H), 7.54 (dt, 1H), 7.41- 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                   
                   
                 7.37 (m, 4H), 7.29 (s, 1H), 3.70 (s, 2H), 2.06- 
               
               
                   
                 2-one 
                   
                   
                   
                 1.75 (m, 12H), 1.50 (d, 2H). 
               
               
                 SC_3241 
                 cis-2-[4-[5-(8-Dimethylamino-2- 
                 SC_3213 
                 ammonium chloride 
                 SC_3133 
                 1H NMR (600 MHz, DMSO) δ 8.53 (s, 2H), 
                 493.3 
               
               
                   
                 oxo-8-phenyl-1,3- 
                   
                   
                   
                 7.38 (d, 5H), 7.27 (s, 1H), 7.23 (s, 1H), 7.11 
               
               
                   
                 diazaspiro[4.5]decan-3-yl)- 
                   
                   
                   
                 (s, 1H), 3.67 (t, 4H), 3.54-3.50 (m, 2H), 
               
               
                   
                 pyrimidin-2-yl]-piperazin-1-yl]- 
                   
                   
                   
                 2.89 (s, 2H), 2.47 (t, 4H), 2.39-2.35 (m, 
               
               
                   
                 acetamide 
                   
                   
                   
                 2H), 1.96 (s, 7H), 1.93-1.82 (m, 3H), 1.48- 
               
               
                   
                   
                   
                   
                   
                 1.44 (m, 2H). 
               
               
                 SC_3243 
                 cis-8-Dimethylamino-3-[6-(4- 
                 INT-976 
                 1-(5-bromo-2-pyridyl)-4-methyl- 
                 SC_3242 (step 2) 
                 1H NMR (600 MHz, DMSO) δ 8.16 (d, 1H), 
                 449.3 
               
               
                   
                 methyl-piperazin-1-yl)-pyridin-3- 
                   
                 piperazine 
                   
                 7.86 (dd, 1H), 7.41-7.33 (m, 4H), 7.32 (s, 
               
               
                   
                 yl]-8-phenyl-1,3- 
                   
                   
                   
                 1H), 7.27 (t, 1H), 6.78 (d, 1H), 3.51 (s, 2H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2.55-2.45 (m, 4H), 2.42-2.27 (m, 6H), 
               
               
                   
                   
                   
                   
                   
                 2.21 (s, 3H), 1.96 (s, 6H), 1.93-1.73 (m, 
               
               
                   
                   
                   
                   
                   
                 4H), 1.46 (t, 2H). 
               
               
                 SC_3244 
                 cis-8-Dimethylamino-3-[2-(1,1- 
                 INT-976 
                 4-(5-bromo-4-methyl- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.20 (s, 1H), 
                 499.3 
               
               
                   
                 dioxo-[1,4]thiazinan-4-yl)-4- 
                   
                 pyrimidin-2-yl)-1,4- 
                   
                 7.36 (h, 4H), 7.30-7.17 (m, 2H), 4.23- 
               
               
                   
                 methyl-pyrimidin-5-yl]-8-phenyl- 
                   
                 thiazinane 1,1-dioxide 
                   
                 4.17 (m, 4H), 3.13 (t, 4H), 2.44-2.28 (m, 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2H), 2.24 (s, 3H), 1.97 (s, 6H), 1.91 (d, 4H), 
               
               
                   
                   
                   
                   
                   
                 1.55-1.44 (m, 2H). 
               
               
                 SC_3245 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 5-bromo-2-(trifluoromethyl)- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 9.17 (s, 2H), 
                 419.2 
               
               
                   
                 [2-(trifluoromethyl)-pyrimidin-5- 
                   
                 pyrimidine 
                   
                 8.03 (s, 1H), 7.38 (s, 4H), 7.28 (tt, 1H), 3.73 
               
               
                   
                 yl]-1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (s, 2H), 2.49-2.35 (m, 2H), 1.97 (s, 6H), 
               
               
                   
                   
                   
                   
                   
                 1.97-1.92 (m, 2H), 1.90-1.73 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 1.55-1.49 (m, 2H). 
               
               
                 SC_3246 
                 cis-2-[8-Dimethylamino-1-(3- 
                 INT-979 
                 2-chloropyrimidine- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 9.02 (s, 2H), 
                 449.3 
               
               
                   
                 methoxy-propyl)-2-oxo-8-phenyl- 
                   
                 5-carbonitrile 
                   
                 7.40-7.31 (m, 5H), 3.86 (s, 2H), 3.26 (s, 
               
               
                   
                 1,3-diazaspiro[4.5]decan-3-yl]- 
                   
                   
                   
                 3H), 3.29-3.19 (m, 2H), 2.73-2.67 (m, 
               
               
                   
                 pyrimidine-5-carbonitrile 
                   
                   
                   
                 2H), 2.16 (td, 2H), 2.00 (s, 7H), 1.83 (dt, 
               
               
                   
                   
                   
                   
                   
                 2H), 1.50-1.40 (m, 5H). 
               
               
                 SC_3247 
                 cis-8-Dimethylamino-3-[2-(4- 
                 INT-989 
                 1-Methylpiperazin 
                 SC_3120 
                 1H NMR (600 MHz, DMSO) δ 8.54 (s, 2H), 
                 450.3 
               
               
                   
                 methyl-piperazin-1-yl)- 
                   
                   
                   
                 7.48-7.33 (m, 5H), 7.31-7.21 (m, 1H), 
               
               
                   
                 pyrimidin-5-yl]-8-phenyl-1,3- 
                   
                   
                   
                 3.63 (dd, 4H), 2.45-2.29 (m, 6H), 2.20 (s, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3H), 1.96 (s, 6H), 1.94-1.78 (m, 4H), 1.51- 
               
               
                   
                   
                   
                   
                   
                 1.42 (m, 2H). 
               
               
                 SC_3248 
                 cis-8-Dimethylamino-1-[(1- 
                 SC_3245 
                 [1-[tert-butyl(dimethyl)silyl]- 
                 INT-988 (step 1) 
                 1H NMR (600 MHz, DMSO) δ 9.24 (s, 2H), 
                 504.3 
               
               
                   
                 hydroxy-cyclobutyl)-methyl]-8- 
                   
                 oxycyclobutyl]methyl 
                   
                 7.38 (d, 4H), 7.27 (p, 1H), 3.89 (s, 2H), 2.73- 
               
               
                   
                 phenyl-3-[2-(trifluoromethyl)- 
                   
                 4-methylbenzenesulfonate 
                   
                 2.67 (m, 2H), 2.26 (ddd, 2H), 2.19 (tt, 2H), 
               
               
                   
                 pyrimidin-5-yl]-1,3- 
                   
                   
                   
                 2.08 (s, 1H), 2.00 (s, 6H), 1.92 (qd, 2H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 1.73-1.64 (m, 1H), 1.60-1.50 (m, 3H), 
               
               
                   
                   
                   
                   
                   
                 1.50-1.45 (m, 2H). 
               
               
                 SC_3249 
                 cis-2-[1-(3-Methoxy-propyl)-8- 
                 SC_3246 
                   
                 SC_3099 
                 1H NMR (600 MHz, DMSO) δ 9.05 (s, 2H), 
                 435.3 
               
               
                   
                 methylamino-2-oxo-8-phenyl-1,3- 
                   
                   
                   
                 7.49-7.44 (m, 2H), 7.34 (t, 2H), 7.21 (t, 
               
               
                   
                 diazaspiro[4.5]decan-3-yl]- 
                   
                   
                   
                 1H), 3.90 (s, 2H), 3.26 (s, 3H), 2.23 (td, 2H), 
               
               
                   
                 pyrimidine-5-carbonitrile 
                   
                   
                   
                 2.07 (s, 1H), 1.91 (d, 5H), 1.86-1.78 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 1.73 (tt, 2H), 1.42 (d, 2H). 
               
               
                 SC_3250 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 5-bromo-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.88 (d, 1H), 
                 419.3 
               
               
                   
                 [6-(trifluoromethyl)-pyridin-3-yl]- 
                   
                 (trifluoromethyl)pyridine 
                   
                 8.24 (dd, 1H), 7.86 (s, 1H), 7.78 (d, 1H), 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 7.41-7.34 (m, 4H), 7.27 (t, 1H), 3.69 (s, 
               
               
                   
                   
                   
                   
                   
                 2H), 2.42 (s, 2H), 1.97 (s, 6H), 1.96-1.74 
               
               
                   
                   
                   
                   
                   
                 (m, 4H), 1.53-1.47 (m, 2H). 
               
               
                 SC_3251 
                 cis-5-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 5-bromopyridine-2-carbonitrile 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.92 (d, 1H), 
                 376.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 8.15 (dd, 1H), 7.95 (br s, 1H), 7.90 (d, 1H), 
               
               
                   
                 yl)-pyridine-2-carbonitrile 
                   
                   
                   
                 7.41-7.34 (m, 4H), 7.27 (t, 1H), 3.69 (s, 
               
               
                   
                   
                   
                   
                   
                 2H), 2.44-2.40 (m, 2H), 1.97 (s, 6H), 1.96- 
               
               
                   
                   
                   
                   
                   
                 1.89 (m, 3H), 1.90-1.70 (m, 1H), 1.53- 
               
               
                   
                   
                   
                   
                   
                 1.46 (m, 2H). 
               
               
                 SC_3252 
                 cis-8-Dimethylamino-3-(2- 
                 INT-989 
                 morpholine 
                 SC_3120 
                 1H NMR (600 MHz, DMSO) δ 8.57 (s, 2H), 
                 437.3 
               
               
                   
                 morpholin-4-yl-pyrimidin-5-yl)-8- 
                   
                   
                   
                 7.46-7.42 (m, 1H), 7.40-7.34 (m, 4H), 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 7.27 (td, 1H), 3.64 (dd, 4H), 3.59 (dd, 4H), 
               
               
                   
                 one 
                   
                   
                   
                 3.54 (s, 2H), 2.46-2.29 (m, 2H), 1.96 (s, 
               
               
                   
                   
                   
                   
                   
                 7H), 1.93-1.73 (m, 3H), 1.50-1.44 (m, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3253 
                 cis-8-Dimethylamino-3-(2-methyl- 
                 INT-976 
                 5-bromo-2-methyl-pyrimidine 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.86 (s, 2H), 
                 366.3 
               
               
                   
                 pyrimidin-5-yl)-8-phenyl-1,3- 
                   
                   
                   
                 7.69 (s, 1H), 7.41-7.33 (m, 5H), 7.31- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 7.19 (m, 1H), 3.62 (s, 2H), 2.53 (s, 3H), 2.48- 
               
               
                   
                   
                   
                   
                   
                 2.31 (m, 2H), 1.97 (s, 6H), 1.95-1.77 (m, 
               
               
                   
                   
                   
                   
                   
                 4H), 1.52-1.46 (m, 2H). 
               
               
                 SC_3254 
                 cis-8-Dimethylamino-1-[(2- 
                 SC_3253 
                 2-methoxybenzyl bromide 
                 SC_3105 
                 1H NMR (DMSO-d6): δ 8.90 (s, 2H), 7.39- 
                 486.2 
               
               
                   
                 methoxyphenyl)-methyl]-3-(2- 
                   
                   
                   
                 7.34 (m, 3H), 7.28-7.22 (m, 4H), 6.95-6.87 
               
               
                   
                 methyl-pyrimidin-5-yl)-8-phenyl- 
                   
                   
                   
                 (m, 2H), 4.58 (s, 2H), 3.89 (s, 3H), 3.63 (s, 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2H), 2.68-2.64 (m, 5H), 2.35-2.28 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.01(s, 6H), 1.49-1.43 (m, 4H). 
               
               
                 SC_3255 
                 cis-1-[(1-Hydroxy-cyclobutyl)- 
                 SC_3248 
                   
                 SC_3099 
                 1H NMR (600 MHz, DMSO) δ 9.26 (s, 2H), 
                 490.3 
               
               
                   
                 methyl]-8-methylamino-8-phenyl- 
                   
                   
                   
                 7.51 (d, 2H), 7.34 (t, 2H), 7.22 (t, 1H), 3.92 
               
               
                   
                 3-[2-(trifluoromethyl)-pyrimidin-5- 
                   
                   
                   
                 (s, 2H), 3.41 (s, 1H), 2.31 (td, 2H), 2.15 (td, 
               
               
                   
                 yl]-1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2H), 2.07 (d, 1H), 1.93 (d, 7H), 1.83 (dt, 
               
               
                   
                   
                   
                   
                   
                 2H), 1.67 (t, 1H), 1.56 (q, 1H), 1.47 (d, 2H). 
               
               
                 SC_3256 
                 cis-8-Dimethylamino-1-[(1- 
                 SC_3253 
                 [1-[tert-butyl(dimethyl)silyl]- 
                 INT-988 (step 1) 
                 1H NMR (600 MHz, DMSO) δ 8.92 (s, 2H), 
                 450.3 
               
               
                   
                 hydroxy-cyclobutyl)-methyl]-3-(2- 
                   
                 oxycyclobutyl]methyl 
                   
                 7.37 (d, 4H), 7.27 (td, 1H), 3.79 (s, 2H), 3.27 
               
               
                   
                 methyl-pyrimidin-5-yl)-8-phenyl- 
                   
                 4-methylbenzenesulfonate 
                   
                 (s, 1H), 2.72-2.65 (m, 2H), 2.54 (s, 3H), 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2.25-2.19 (m, 2H), 2.16 (tt, 2H), 2.07 (s, 
               
               
                   
                   
                   
                   
                   
                 2H), 2.00 (s, 6H), 1.95-1.86 (m, 2H), 1.67 
               
               
                   
                   
                   
                   
                   
                 (qd, 1H), 1.55 (td, 2H), 1.51-1.42 (m, 3H). 
               
               
                 SC_3257 
                 cis-1-[(1-Hydroxy-cyclobutyl)- 
                 SC_3260 
                   
                 SC_3099 
                 1H NMR (600 MHz, DMSO) δ 9.07 (s, 2H), 
                 422.3 
               
               
                   
                 methyl]-8-methylamino-8-phenyl- 
                   
                   
                   
                 8.81 (s, 1H), 7.53-7.48 (m, 2H), 7.33 (t, 
               
               
                   
                 3-pyrimidin-5-yl-1,3- 
                   
                   
                   
                 2H), 7.24-7.18 (m, 1H), 3.86 (s, 2H), 2.29 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (td, 2H), 2.14 (tt, 2H), 2.07 (s, 1H), 1.96- 
               
               
                   
                   
                   
                   
                   
                 1.87 (m, 8H), 1.82 (td, 2H), 1.71-1.62 (m, 
               
               
                   
                   
                   
                   
                   
                 1H), 1.54 (dp, 1H), 1.49-1.43 (m, 2H). 
               
               
                 SC_3258 
                 cis-5-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 5-bromo-4-methyl-pyridine-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.57 (s, 1H), 
                 390.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                 carbonitrile 
                   
                 7.92 (s, 1H), 7.61-7.57 (m, 1H), 7.42- 
               
               
                   
                 yl)-4-methyl-pyridine-2- 
                   
                   
                   
                 7.32 (m, 4H), 7.25 (tt, 1H), 3.63 (s, 2H), 2.38 
               
               
                   
                 carbonitrile 
                   
                   
                   
                 (d, 2H), 2.28 (s, 3H), 2.00-1.90 (m, 9H), 
               
               
                   
                   
                   
                   
                   
                 1.90-1.72 (m, 1H), 1.59-1.49 (m, 2H). 
               
               
                 SC_3259 
                 cis-8-Dimethylamino-3-(2-methyl- 
                 SC_3253 
                 2-(bromomethyl)pyridine 
                 SC_3105 
                 1H NMR (DMSO-d6): δ 8.94 (s, 2H), 8.52- 
                 457.2 
               
               
                   
                 pyrimidin-5-yl)-8-phenyl-1- 
                   
                   
                   
                 8.51 (m, 1H), 7.77-7.74 (m, 1H), 7.45-7.42 
               
               
                   
                 (pyridin-2-yl-methyl)-1,3- 
                   
                   
                   
                 (d, 1H), 7.38-7.22 (m, 6H), 4.47 (s, 2H), 3.84 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (s, 2H), 2.66-2.63 (m, 2H), 2.54 (s, 3H), 
               
               
                   
                   
                   
                   
                   
                 2.06-2.03 (m, 2H), 1.92(s, 6H), 1.57-1.42 
               
               
                   
                   
                   
                   
                   
                 (m, 4H). 
               
               
                 SC_3260 
                   
                 INT-976 
                 5-bromopyrimidine 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.98 (s, 2H), 
                 352.2 
               
               
                   
                   
                   
                   
                   
                 8.76 (s, 1H), 7.78 (s, 1H), 7.41-7.34 (m, 
               
               
                   
                   
                   
                   
                   
                 4H), 7.31-7.24 (m, 1H), 3.65 (s, 2H), 2.49- 
               
               
                   
                   
                   
                   
                   
                 2.34 (m, 2H), 1.97 (s, 6H), 1.95-1.76 (m, 
               
               
                   
                   
                   
                   
                   
                 4H), 1.50 (t, 2H). 
               
               
                 SC_3261 
                 cis-8-Dimethylamino-1-[(1- 
                 SC_3260 
                 [1-[tert-butyl(dimethyl)silyl]- 
                 INT-988 (step 1) 
                 1H NMR (600 MHz, DMSO) δ 9.04 (s, 2H), 
                 436.3 
               
               
                   
                 hydroxy-cyclobutyl)-methyl]-8- 
                   
                 oxycyclobutyl]methyl 
                   
                 8.80 (s, 1H), 7.37 (d, 4H), 7.27 (p, 1H), 3.83 
               
               
                   
                 phenyl-3-pyrimidin-5-yl-1,3- 
                   
                 4-methylbenzenesulfonate 
                   
                 (s, 2H), 3.28 (s, 1H), 2.72-2.65 (m, 2H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2.23 (td, 1H), 2.17 (tt, 1H), 2.07 (s, 2H), 2.00 
               
               
                   
                   
                   
                   
                   
                 (s, 6H), 1.91 (dt, 2H), 1.72-1.63 (m, 1H), 
               
               
                   
                   
                   
                   
                   
                 1.60-1.45 (m, 5H). 
               
               
                 SC_3262 
                 cis-8-Amino-1-[(1-hydroxy- 
                 SC_3255 
                   
                 SC_3099 
                 1H NMR (600 MHz, DMSO) δ 9.29 (s, 2H), 
                 476.2 
               
               
                   
                 cyclobutyl)-methyl]-8-phenyl-3-[2- 
                   
                   
                   
                 7.68-7.63 (m, 2H), 7.33 (t, 2H), 7.26-7.18 
               
               
                   
                 (trifluoromethyl)-pyrimidin-5-yl]- 
                   
                   
                   
                 (m, 1H), 3.97 (s, 2H), 3.45 (s, 2H), 2.43 (td, 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2H), 2.14 (tt, 2H), 1.99 (td, 2H), 1.96-1.90 
               
               
                   
                   
                   
                   
                   
                 (m, 2H), 1.71-1.54 (m, 4H), 1.52-1.47 
               
               
                   
                   
                   
                   
                   
                 (m, 2H). 
               
               
                 SC_3263 
                 cis-8-Dimethylamino-3-(3- 
                 INT-976 
                 1-bromo-3-fluoro-benzene 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 7.58-7.50 
                 368.2 
               
               
                   
                 fluorophenyl)-8-phenyl-1,3- 
                   
                   
                   
                 (m, 2H), 7.41-7.33 (m, 4H), 7.33-7.23 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (m, 3H), 6.77-6.71 (m, 1H), 3.58 (s, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.48-2.31 (m, 2H), 1.97 (s, 6H), 1.92- 
               
               
                   
                   
                   
                   
                   
                 1.80 (m, 4H), 1.47 (t, 2H). 
               
               
                 SC_3264 
                 cis-8-Dimethylamino-3-(3- 
                 INT-976 
                 1-bromo-3- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.13 (t, 1H), 
                 428.2 
               
               
                   
                 methylsulfonyl-phenyl)-8-phenyl- 
                   
                 methylsulfonylbenzene 
                   
                 7.88 (d, 1H), 7.65 (s, 1H), 7.53 (t, 1H), 7.47 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (dt, 1H), 7.41-7.35 (m, 4H), 7.28 (qd, 1H), 
               
               
                   
                   
                   
                   
                   
                 3.66 (s, 2H), 3.16 (s, 3H), 2.49-2.36 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 1.97 (s, 6H), 1.96-1.74 (m, 4H), 1.53- 
               
               
                   
                   
                   
                   
                   
                 1.47 (m, 2H). 
               
               
                 SC_3265 
                 cis-8-Dimethylamino-3-(4- 
                 INT-976 
                 1-bromo-4- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 7.83-7.70 
                 428.2 
               
               
                   
                 methylsulfonyl-phenyl)-8-phenyl- 
                   
                 methylsulfonylbenzene 
                   
                 (m, 5H), 7.41-7.34 (m, 4H), 7.27 (tt, J = 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 7.1, 1.9 Hz, 1H), 3.65 (s, 2H), 3.12 (s, 3H), 
               
               
                   
                   
                   
                   
                   
                 2.49-2.31 (m, 2H), 1.97 (s, 6H), 1.95- 
               
               
                   
                   
                   
                   
                   
                 1.75 (m, 4H), 1.49 (t, J = 8.6 Hz, 2H). 
               
               
                 SC_3266 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 3-bromopyridazine 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.82 (dd, J = 
                 352.2 
               
               
                   
                 pyridazin-3-yl-1,3- 
                   
                   
                   
                 4.6, 1.4 Hz, 1H), 8.45 (dd, J = 9.2, 1.4 Hz, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 1H), 7.95 (br s, 1H), 7.55 (dd, J = 9.2, 4.5 
               
               
                   
                   
                   
                   
                   
                 Hz, 1H), 7.42-7.34 (m, 4H), 7.28 (t, J = 6.8 
               
               
                   
                   
                   
                   
                   
                 Hz, 1H), 3.83 (s, 2H), 2.47-2.29 (m, 1H), 
               
               
                   
                   
                   
                   
                   
                 1.97 (s, 10H), 1.54-1.48 (m, 2H). 
               
               
                 SC_3267 
                 cis-3-Methoxy-4-(8-methylamino- 
                 INT-976 
                 4-bromo-3-methoxy- 
                 SC_3103 (for step 1), 
                 1HNMR (DMSO-d6, 400 MHz), δ (ppm) = 
                 391.2 
               
               
                   
                 2-oxo-8-phenyl-1,3- 
                   
                 benzonitrile (step 1) 
                 SC_3099 (for step 2) 
                 7.50-7.50 (m, 2H), 7.42-7.31 (m, 5H), 7.18 
               
               
                   
                 diazaspiro[4.5]decan-3-yl)- 
                   
                   
                   
                 (bs, 2H), 3.83 (s, 3H), 3.64 (s, 2H), 2.05- 
               
               
                   
                 benzonitrile 
                   
                   
                   
                 21.99 (m, 2H), 1.85 (bs, 5H), 1.70 (bs, 2H), 
               
               
                   
                   
                   
                   
                   
                 1.53-1.50 (m, 2H). 
               
               
                 SC_3268 
                 cis-8-Dimethylamino-3-(2- 
                 INT-976 
                 1-bromo-2-luorobenzene 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 7.46 (td, J = 
                 368.2 
               
               
                   
                 fluorophenyl)-8-phenyl-1,3- 
                   
                   
                   
                 8.0, 1.6 Hz, 1H), 7.40-7.32 (m, 5H), 7.26 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (td, J = 6.7, 3.3 Hz, 1H), 7.24-7.12 (m, 
               
               
                   
                   
                   
                   
                   
                 3H), 3.53 (s, 2H), 2.37-2.33 (m, 2H), 1.96 
               
               
                   
                   
                   
                   
                   
                 (s, 6H), 1.95-1.74 (m, 4H), 1.49 (t, J = 9.3 
               
               
                   
                   
                   
                   
                   
                 Hz, 2H). 
               
               
                 SC_3269 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 5-bromo-2-phenyl-pyrimidine 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 9.07 (s, 2H), 
                 428.3 
               
               
                   
                 (2-phenyl-pyrimidin-5-yl)-1,3- 
                   
                   
                   
                 8.34-8.28 (m, 2H), 7.82 (s, 1H), 7.52- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 7.42 (m, 4H), 7.39 (s, 1H), 7.38 (s, 3H), 7.28 
               
               
                   
                   
                   
                   
                   
                 (t, J = 4.8 Hz, 1H), 3.70 (s, 2H), 2.43-2.39 
               
               
                   
                   
                   
                   
                   
                 (m, 2H), 2.06-1.72 (m, 10H), 1.52 (d, J = 
               
               
                   
                   
                   
                   
                   
                 10.8 Hz, 2H). 
               
               
                 SC_3270 
                 cis-8-Methylamino-1-(oxetan-3-yl- 
                 SC_3245 
                 oxetan-3-ylmethyl 4- 
                 SC_3099 (for step1), 
                 1H NMR (DMSO-d6): δ 9.24 (s, 2H), 7.49 
                 476.2 
               
               
                   
                 methyl)-8-phenyl-3-[2- 
                   
                 methylbenzenesulfonate (step 2) 
                 SC_3105 (for step 2) 
                 (d, 2H), 7.34 (t, 2H), 7.21 (t, 1H), 4.66-4.62 
               
               
                   
                 (trifluoromethyl)-pyrimidin-5-yl]- 
                   
                   
                   
                 (m, 2H), 4.44 (t, 2H), 3.87 (s, 2H), 3.55 (d, 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2H), 3.28-3.23 (m, 1H), 2.36 (m, 1H), 2.20- 
               
               
                   
                   
                   
                   
                   
                 2.14 (m, 2H), 1.95-1.91 (m, 5H), 1.84-1.77 
               
               
                   
                   
                   
                   
                   
                 (m, 2H), 1.43-1.40 (m, 2H). 
               
               
                 SC_3271 
                 cis-1-(Cyclopropyl-methyl)-8- 
                 SC_3245 
                 (bromomethyl)-cyclopropane 
                 SC_3099 (for step1), 
                 1H NMR (DMSO-d6): δ 9.26 (s, 2H), 7.50 
                 460.1 
               
               
                   
                 methylamino-8-phenyl-3-[2- 
                   
                   
                 SC_3105 (for step 2) 
                 (d, 2H), 7.35 (t, 2H), 7.22 (t, 1H), 3.89 (s, 
               
               
                   
                 (trifluoromethyl)-pyrimidin-5-yl]- 
                   
                   
                   
                 2H), 3.13 (d, 2H), 2.29-2.23 (m, 3H), 1.92- 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 1.82 (m, 7H), 1.47-1.44 (m, 2H), 1.08-1.05 
               
               
                   
                   
                   
                   
                   
                 (m, 1H), 0.52-0.48 (m, 2H), 0.36-0.36-0.32 
               
               
                   
                   
                   
                   
                   
                 (m, 2H). 
               
               
                 SC_3272 
                 cis-4-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 4-bromobenzonitrile 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 7.82-7.71 
                 375.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 (m, 3H), 7.72-7.67 (m, 2H), 7.41-7.33 
               
               
                   
                 yl)-benzonitrile 
                   
                   
                   
                 (m, 4H), 7.30-7.23 (m, 1H), 3.63 (s, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.45-2.39 (m, 2H), 1.97 (s, 6H), 1.95- 
               
               
                   
                   
                   
                   
                   
                 1.72 (m, 4H), 1.51-1.44 (m, 2H). 
               
               
                 SC_3273 
                 cis-8-Dimethylamino-3-(4- 
                 INT-976 
                 1-bromo-4-fluoro-benzene 
                 SC_3103 
                   
                 368.2 
               
               
                   
                 fluorophenyl)-8-phenyl-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3274 
                 cis-2-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 2-bromobenzonitrile 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 7.77 (dd, J = 
                 375.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 7.5, 1.6 Hz, 1H), 7.66 (ddd, J = 8.3, 7.5, 1.6 
               
               
                   
                 yl)-benzonitrile 
                   
                   
                   
                 Hz, 1H), 7.60 (s, 1H), 7.48 (dd, J = 8.3, 1.1 
               
               
                   
                   
                   
                   
                   
                 Hz, 1H), 7.39-7.34 (m, 4H), 7.32 (td, J = 
               
               
                   
                   
                   
                   
                   
                 7.5, 1.1 Hz, 1H), 7.26 (tt, J = 7.5, 1.6 Hz, 
               
               
                   
                   
                   
                   
                   
                 1H), 3.68 (s, 2H), 2.46-2.30 (m, 2H), 2.01- 
               
               
                   
                   
                   
                   
                   
                 1.75 (m, 10H), 1.59-1.50 (m, 2H). 
               
               
                 SC_3276 
                 cis-1-[(1-Hydroxy-cyclobutyl)- 
                 SC_3256 
                   
                 SC_3099 
                 1H NMR (600 MHz, DMSO) δ 8.94 (s, 2H), 
                 436.3 
               
               
                   
                 methyl]-8-methylamino-3-(2- 
                   
                   
                   
                 7.53-7.47 (m, 2H), 7.39-7.30 (m, 2H), 
               
               
                   
                 methyl-pyrimidin-5-yl)-8-phenyl- 
                   
                   
                   
                 7.24-7.17 (m, 1H), 3.83 (s, 2H), 3.54- 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.36 (m, 2H), 2.56 (s, 3H), 2.28 (td, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.18-2.09 (m, 2H), 1.97-1.86 (m, 7H), 
               
               
                   
                   
                   
                   
                   
                 1.81 (td, 2H), 1.71-1.61 (m, 1H), 1.59- 
               
               
                   
                   
                   
                   
                   
                 1.47 (m, 1H), 1.49-1.42 (m, 2H). 
               
               
                 SC_3277 
                 cis-8-Dimethylamino-3-[2- 
                 INT-976 
                 4-[(5-bromopyrimidin-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.93 (s, 2H), 
               
               
                   
                 (morpholin-4-yl-methyl)- 
                   
                 yl)methyl]morpholine 
                   
                 7.87-7.65 (m, 1H), 7.42-7.34 (m, 4H), 
               
               
                   
                 pyrimidin-5-yl]-8-phenyl-1,3- 
                   
                   
                   
                 7.28 (dq, 1H), 3.66-3.62 (m, 2H), 3.61 (s, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2H), 3.54 (t, 4H), 2.43 (t, 4H), 1.98 (s, 6H), 
               
               
                   
                   
                   
                   
                   
                 1.96-1.74 (m, 4H), 1.52-1.46 (m, 2H). 
               
               
                 SC_3278 
                 cis-8-Dimethylamino-3-[2-(methyl- 
                 INT-989 
                 N-methyltetrahydro- 
                 SC_3120 
                 1H NMR (DMSO-d6): δ 8.50 (s, 2H), 7.39- 
                 465.2 
               
               
                   
                 tetrahydro-pyran-4-yl-amino)- 
                   
                 2H-pyran-4-amine 
                   
                 7.35 (m, 5H), 7.27-7.24 (m, 1H), 4.74-4.67 
               
               
                   
                 pyrimidin-5-yl]-8-phenyl-1,3- 
                   
                   
                   
                 (m, 1H), 3.94-3.90 (m, 2H), 3.50 (s, 2H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.39 (t, 2H), 2.93 (s, 3H), 2.35 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 1.99-1.71 (m, 12H), 1.50-1.44 (m, 4H). 
               
               
                 SC_3279 
                 cis-5-[8-Dimethylamino-1-[(1- 
                 INT-990 
                 (1-(tert- 
                 SC_3105 (step 1), 
                 1H NMR (DMSO-d6): δ 9.12 (s, 2H), 8.63 
                 669.4 
               
               
                   
                 hydroxy-cyclobutyl)-methyl]-2- 
                   
                 butyldimethylsilyloxy)cyclobutyl)methyl 
                 SC_3133 (step 2) 
                 (t, 1H), 7.36-7.33 (m, 4H), 7.26-7.23 (m, 
               
               
                   
                 oxo-8-phenyl-1,3- 
                   
                 4-methylbenzenesulfonate (step 1), 
                   
                 1H), 5.25 (s, 1H), 3.85 (s, 2H), 3.52-3.34 (m, 
               
               
                   
                 diazaspiro[4.5]decan-3-yl]-N-[2-[2- 
                   
                 2,5,8,11-tetraoxatridecan-13- 
                   
                 16H), 3.35 (m, 2H), 3.19 (s, 3H), 2.69-2.66 
               
               
                   
                 [2-(2-methoxy-ethoxy)-ethoxy]- 
                   
                 amine (step 2) 
                   
                 (m, 2H), 2.25-2.13 (m, 4H), 1.97 (s, 6H), 
               
               
                   
                 ethoxy]-ethyl]-pyrimidine-2- 
                   
                   
                   
                 1.92-1.87 (m, 2H), 1.57-1.44 (m, 6H). 
               
               
                   
                 carboxylic acid amide 
               
               
                 SC_3280 
                 cis-1-(Cyclopropyl-methyl)-3-(2- 
                 INT-976 
                 1-bromo-2-fluoro-4- 
                 SC_3103 (for step 1), 
                 1H NMR (DMS0-d6): δ 7.86 (t, 1H), 7.81- 
                 486.2 
               
               
                   
                 fluoro-4-methylsulfonyl-phenyl)-8- 
                   
                 (methylsulfonyl)benzene (step 1), 
                 SC_3105 (step 2), 
                 7.77 (m, 1H), 7.73-7.70 (m, 1H), 7.45 (d, 
               
               
                   
                 methylamino-8-phenyl-1,3- 
                   
                 (Bromomethyl)cyclopropane (step 2) 
                 SC_3099 (step 3) 
                 2H), 7.31 (t, 2H), 7.19 (t, 1H), 3.85 (s, 2H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.24 (s, 3H), 3.09 (d, 2H), 2.29-2.22 (m, 3H), 
               
               
                   
                   
                   
                   
                   
                 1.93-1.90 (m, 5H), 1.74-1.68 (m, 2H), 1.49- 
               
               
                   
                   
                   
                   
                   
                 1.46 (m, 2H), 1.04 (m, 1H), 0.51-0.46 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 0.34-0.30 (m, 2H). 
               
               
                 SC_3281 
                 cis-2-[[5-(8-Dimethylamino-2-oxo- 
                 INT-989 
                 2-(methylamino)acetamide 
                 SC_3120 
                 1H NMR (DMSO-d6): δ 8.48 (s, 2H), 7.39- 
                 438.2 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                 hydrochloride 
                   
                 7.35 (m, 5H), 7.27-7.25 (m, 2H), 6.89 (s, 
               
               
                   
                 3-yl)-pyrimidin-2-yl]-methyl- 
                   
                   
                   
                 1H), 4.08 (s, 2H), 3.51 (s, 2H), 3.07 (s, 3H), 
               
               
                   
                 amino]-acetamide 
                   
                   
                   
                 2.36-2.33 (m, 2H), 1.94-1.86 (m, 10H), 1.45 
               
               
                   
                   
                   
                   
                   
                 (m, 2H). 
               
               
                 SC_3282 
                 cis-2-[[5-(8-Dimethylamino-2-oxo- 
                 INT-976 
                 tert-butyl (5-bromopyrimidin-2- 
                 SC_3103 (for step 1), 
                 1H NMR (DMS0-d6): δ 8.45 (s, 2H), 7.39- 
                 424.2 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                 yl)(cyanomethyl)carbamate (step 1) 
                 SC_3100 step 3 (for step 2) 
                 7.33 (m, 5H), 7.27-7.22 (m, 2H), 6.92 (s, 
               
               
                   
                 3-yl)-pyrimidin-2-yl]amino]- 
                   
                   
                   
                 1H), 6.86 (t, 1H), 3.74 (d, 2H), 3.51 (s, 2H), 
               
               
                   
                 acetamide 
                   
                   
                   
                 2.46-2.28 (m, 2H), 1.95-1.86 (m, 10H), 1.45 
               
               
                   
                   
                   
                   
                   
                 (m, 2H). 
               
               
                 SC_3283 
                 cis-1-(Cyclopropyl-methyl)-8- 
                 SC_3284 
                   
                 SC_3099 
                 1H NMR (DMS0-d6): δ 8.61 (s, 1H), 7.82 
                 473.3 
               
               
                   
                 methylamino-3-[4-methyl-6- 
                   
                   
                   
                 (s, 1H), 7.46-7.44 (m, 2H), 7.30 (t, 2H), 7.18 
               
               
                   
                 (trifluoromethyl)-pyridin-3-yl]-8- 
                   
                   
                   
                 (t, 1H), 3.80 (s, 2H), 3.08 (d, 2H), 2.33-2.25 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 (m, 6H), 1.92-1.89 (m, 5H), 1.72 (t, 2H), 
               
               
                   
                 one 
                   
                   
                   
                 1.56-1.53 (m, 2H), 1.04 (m, 1H), 0.51-0.46 
               
               
                   
                   
                   
                   
                   
                 (m, 2H), 0.33-0.30 (m, 2H). 
               
               
                 SC_3284 
                 cis-1-(Cyclopropyl-methyl)-8- 
                 INT-984 
                 5-bromo-4-methyl-2- 
                 SC_3103 
                 1H NMR(DMSO-d6): δ 8.59 (s, 1H), 7.82 
                 487.3 
               
               
                   
                 dimethylamino-3-[4-methyl-6- 
                   
                 (trifluoromethyl)pyridine 
                   
                 (s, 1H), 7.35-7.34 (m, 4H), 7.27-7.23 (m, 
               
               
                   
                 (trifluoromethyl)-pyridin-3-yl]-8- 
                   
                   
                   
                 1H), 3.75 (s, 2H), 3.06 (d, 2H), 2.71-2.68 (m, 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 2H), 2.33-2.24 (m, 5H), 2.00 (m, 6H), 1.59- 
               
               
                   
                 one 
                   
                   
                   
                 1.56 (m, 2H), 1.46 (t, 2H), 1.02-0.99 (m, 
               
               
                   
                   
                   
                   
                   
                 1H), 0.53-0.48 (m, 2H), 0.33-0.30 (m, 2H). 
               
               
                 SC_3285 
                 cis-N-[5-(8-Dimethylamino-2-oxo- 
                 SC_3239 
                 thiophene-2-carbonyl chloride 
                 SC_3240 
                 1H NMR (600 MHz, DMSO) δ 8.90 (s, 2H), 
                 477.2 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                   
                   
                 8.08-8.04 (m, 1H), 7.84 (dd, 1H), 7.71 (s, 
               
               
                   
                 3-yl)-pyrimidin-2-yl]-thiophene-2- 
                   
                   
                   
                 1H), 7.38 (d, 5H), 7.27 (td, 1H), 7.19 (dd, 
               
               
                   
                 carboxylic acid amide 
                   
                   
                   
                 1H), 3.66 (s, 2H), 2.48-2.34 (m, 2H), 1.99- 
               
               
                   
                   
                   
                   
                   
                 1.75 (m, 10H), 1.54-1.48 (m, 2H). 
               
               
                 SC_3286 
                 cis-N-[5-(8-Dimethylamino-2-oxo- 
                 SC_3239 
                 benzoyl chloride 
                 SC_3240 
                 1H NMR (600 MHz, DMSO) δ 10.84 (s, 
                 471.3 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                   
                   
                 1H), 8.91 (s, 2H), 7.98-7.93 (m, 2H), 7.62- 
               
               
                   
                 3-yl)-pyrimidin-2-yl]-benzamide 
                   
                   
                   
                 7.55 (m, 1H), 7.50 (t, 2H), 7.39 (d, 4H), 
               
               
                   
                   
                   
                   
                   
                 7.28 (dt, 1H), 3.67 (s, 2H), 2.48-2.32 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 2.05-1.76 (m, 10H), 1.55-1.49 (m, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3287 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 2-bromo-5-phenylthiophene 
                 SC_3103 
                 1H NMR (DMSO-d6): δ 7.80-7.70 (br s, 
                 432.2 
               
               
                   
                 (5-phenyl-thiophen-2-yl)-1,3- 
                   
                   
                   
                 1H), 7.52 (d, 2H), 7.38-7.28 (m, 7H), 7.20- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 7.17 (m, 2H), 6.27 (d, 1H), 3.61 (s, 2H), 2.49 
               
               
                   
                   
                   
                   
                   
                 (m, 2H), 1.95-1.91 (m, 10H), 1.48 (m, 2H). 
               
               
                 SC_3288 
                 cis-1-(Cyclopropyl-methyl)-8- 
                 INT-984 
                 1-bromo-2- 
                 SC_3103 
                 1H NMR (CDCl3): δ 7.49 (d, 1H), 7.41-7.22 
                 496.3 
               
               
                   
                 dimethylamino-3-[2- 
                   
                 (methylsulfonylmethyl)benzene 
                   
                 (m, 8H), 4.45 (s, 2H), 3.64 (s, 2H), 3.15 (d, 
               
               
                   
                 (methylsulfonyl-methyl)-phenyl]-8- 
                   
                   
                   
                 2H), 2.79 (s, 3H), 2.71-2.67 (m, 2H), 2.37 (t, 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 2H), 2.06 (s, 6H), 1.67-1.64 (m, 2H), 1.55- 
               
               
                   
                 one 
                   
                   
                   
                 1.44 (m, 2H), 1.10-1.06 (m, 1H), 0.57-0.52 
               
               
                   
                   
                   
                   
                   
                 (m, 2H), 0.39-0.35 (m, 2H). 
               
               
                 SC_3289 
                 cis-1-(Cyclopropyl-methyl)-8- 
                 SC_3288 
                   
                 SC_3099 
                 1H NMR (DMSO-d6): δ 7.49-7.37 (m, 5H), 
                 482.3 
               
               
                   
                 methylamino-3-[2-(methylsulfonyl- 
                   
                   
                   
                 7.32-7.30 (m, 3H), 7.19-7.15 (m, 1H), 4.49 
               
               
                   
                 methyl)-phenyl]-8-phenyl-1,3- 
                   
                   
                   
                 (s, 2H), 3.71 (s, 2H), 3.05 (d, 2H), 2.87 (s, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3H), 2.26-2.20 (m, 3H), 1.91-1.87 (m, 5H), 
               
               
                   
                   
                   
                   
                   
                 1.71-1.56 (m, 4H), 1.03-1.01 (m, 1H), 0.49- 
               
               
                   
                   
                   
                   
                   
                 0.45 (m, 2H), 0.31-0.28 (m, 2H). 
               
               
                 SC_3290 
                 cis-8-Dimethylamino-8-(3- 
                 INT-1024 
                 1-bromo-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 7.46 (dd, 
                 460.3 
               
               
                   
                 fluorophenyl)-3-[2- 
                   
                 (methylsulfonylmethyl)benzene 
                   
                 1H), 7.39 (td, 2H), 7.33 (dd, 1H), 7.31-7.21 
               
               
                   
                 (methylsulfonyl-methyl)-phenyl]- 
                   
                   
                   
                 (m, 1H), 7.18 (d, 1H), 7.15 (dd, 1H), 7.08 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (td, 1H), 4.50 (s, 2H), 3.56 (s, 2H), 2.88 (s, 
               
               
                   
                   
                   
                   
                   
                 3H), 2.42-2.24 (m, 2H), 1.99-1.89 (m, 
               
               
                   
                   
                   
                   
                   
                 8H), 1.88-1.75 (m, 2H), 1.60-1.48 (m, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3291 
                 cis-8-Dimethylamino-8-(4- 
                 INT-1025 
                 1-bromo-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 7.46 (dd, 
                 460.3 
               
               
                   
                 fluorophenyl)-3-[2- 
                   
                 (methylsulfonylmethyl)benzene 
                   
                 1H), 7.43-7.34 (m, 3H), 7.33 (dd, 1H), 7.28 
               
               
                   
                 (methylsulfonyl-methyl)-phenyl]- 
                   
                   
                   
                 (td, 2H), 7.16 (t, 2H), 4.49 (s, 2H), 3.55 (s, 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2H), 2.88 (s, 3H), 2.35-2.32 (m, 2H), 1.95 
               
               
                   
                   
                   
                   
                   
                 (s, 6H), 1.94-1.88 (m, 2H), 1.88-1.65 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 1.59-1.47 (m, 2H). 
               
               
                 SC_3294 
                 cis-8-Dimethylamino-8-(3- 
                 INT-1024 
                 4-(5-bromo-4-methyl- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.13 (s, 1H), 
                 469.3 
               
               
                   
                 fluorophenyl)-3-(4-methyl-2- 
                   
                 pyrimidin-2-yl)morpholine 
                   
                 7.40 (td, 1H), 7.22-7.11 (m, 4H), 7.08 (td, 
               
               
                   
                 morpholin-4-yl-pyrimidin-5-yl)- 
                   
                   
                   
                 1H), 3.69-3.60 (m, 8H), 2.34-2.31 (m, 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2H), 2.20 (s, 3H), 1.96 (s, 6H), 1.96-1.70 
               
               
                   
                   
                   
                   
                   
                 (m, 4H), 1.56-1.43 (m, 2H). 
               
               
                 SC_3295 
                 cis-3-[6-(4-Acetyl-piperazin-1-yl)- 
                 INT-976 
                 1-[4-(5-bromo-4-methyl-pyridin-2-yl)- 
                 SC_3103 
                 1HNMR (DMSO-d6, 400 MHz at 100 0 C.), δ 
                 491.3 
               
               
                   
                 4-methyl-pyridin-3-yl]-8- 
                   
                 piperazin-1-yl]-ethanone 
                   
                 (ppm) = 7.88 (s, 1H), 7.35-7.22 (m, 5H), 
               
               
                   
                 dimethylamino-8-phenyl-1,3- 
                   
                   
                   
                 6.73 (s, 1H), 6.64 (s, 1H), 3.53-3.50 (m, 8H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.38 (s, 2H), 2.33-2.30 (m, 2H), 2.14 (s, 3H), 
               
               
                   
                   
                   
                   
                   
                 2.03-1.88 (m, 13H), 1.56-1.51 (m, 2H). 
               
               
                 SC_3296 
                 cis-3-[2-(4-Acetyl-piperazin-1-yl)- 
                 INT-976 
                 1-[4-(5-bromo-4-methyl-pyrimidin-2- 
                 SC_3103 
                 1H-NMR (DMSO-d6, 400 MHz at 100 0 C.), 
                 492.3 
               
               
                   
                 4-methyl-pyrimidin-5-yl]-8- 
                   
                 yl)-piperazin-1-yl]-ethanone 
                   
                 δ (ppm) = 8.11 (s, 1H), 7.35-7.24 (m, 5H), 
               
               
                   
                 dimethylamino-8-phenyl-1,3- 
                   
                   
                   
                 6.88 (s, 1H), 3.73 (bs, 4H), 3.52 (bs, 4H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.38 (s, 2H), 2.33 (bs, 2H), 2.22 (s, 3H), 
               
               
                   
                   
                   
                   
                   
                 2.03-1.87 (m, 13H), 1.56-1.53 (m, 2H). 
               
               
                 SC_3297 
                 cis-8-Dimethylamino-3-(4-methyl- 
                 INT-976 
                 5-bromo-2-chloro-4- 
                 SC_3103 (for step 1), 
                 1H-NMR (DMSO-d6, 400 MHz at 100 0 C.), 
                 442.3 
               
               
                   
                 6-pyridin-4-yl-pyridin-3-yl)-8- 
                   
                 methyl-pyridine (step 1), 
                 SC_3129 (for step 2) 
                 δ (ppm) = 8.65 (d, 2H, J = 5.92 Hz), 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                 4-pyridinylboronic acid (step 2) 
                   
                 8.50 (s, 1H), 7.96 (d, 2H, J = 5.96 Hz), 7.91 
               
               
                   
                 one 
                   
                   
                   
                 (s, 1H), 7.36-7.23 (m, 5H), 7.07 (s, 1H), 3.57 
               
               
                   
                   
                   
                   
                   
                 (s, 2H), 2.38-2.33 (m, 5H), 2.04 (s, 6H), 
               
               
                   
                   
                   
                   
                   
                 2.00-1.88 (m, 4H), 1.61-1.57 (m, 2H). 
               
               
                 SC_3298 
                 cis-3-[2-(4-Acetyl-piperazin-1-yl)- 
                 INT-976 
                 1-[4-(5-bromo-4-trifluoromethyl- 
                 SC_3103 
                 1H-NMR (DMSO-d6, 400 MHz at 100 0 C.), 
                 546.3 
               
               
                   
                 4-(trifluoromethyl)-pyrimidin-5- 
                   
                 pyrimidin-2-yl)-piperazin-1-yl]- 
                   
                 δ (ppm) = 8.52 (s, 1H), 7.35-7.22 (m, 5H), 
               
               
                   
                 yl]-8-dimethylamino-8-phenyl-1,3- 
                   
                 ethanone 
                   
                 7.07 (s, 1H), 3.79-3.78 (t, 4H, 5.08 Hz), 3.57 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (t, 4H, 5.26 Hz), 3.39 (s, 2H), 2.36-2.32 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 2.04-1.85 (m, 13H), 1.54-1.50 (m, 2H). 
               
               
                 SC_3299 
                 cis-8-Dimethylamino-3-[2-(3-oxo- 
                 INT-976 
                 4-(5-bromo-4-trifluoromethyl- 
                 SC_3103 
                 1HNMR (DMSO-d6, 400 MHz), δ (ppm) = 
                 518.2 
               
               
                   
                 piperazin-1-yl)-4-(trifluoromethyl)- 
                   
                 pyrimidin-2-yl)-piperazin-2-one 
                   
                 8.55 (s, 1H), 7.77 (bs, 1H), 7.35-7.23 (m, 
               
               
                   
                 pyrimidin-5-yl]-8-phenyl-1,3- 
                   
                   
                   
                 5H), 7.09 (s, 1H), 4.20 (s, 2H), 3.92 (t, 2H, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 J = 5.04 Hz), 3.39 (s, 2H), 3.33 (bs, 2H), 2.36- 
               
               
                   
                   
                   
                   
                   
                 2.33 (m, 2H), 2.03-1.85 (m, 10H), 1.54-1.39 
               
               
                   
                   
                   
                   
                   
                 (m, 2H). 
               
               
                 SC_3300 
                 cis-8-Dimethylamino-3- 
                 INT-976 
                 4-bromo-isoquinoline 
                 SC_3103 
                 1HNMR (DMSO-d6, 400 MHz at 100 0 C.), δ 
                 401.2 
               
               
                   
                 isoquinolin-4-yl-8-phenyl-1,3- 
                   
                   
                   
                 (ppm) = 9.16 (s, 1H), 8.41 (s, 1H), 8.13 (d, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 1H, J = 8.12 Hz), 7.91 (d, 1H, J = 8.64 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.71 (t, 1H, J = 7.58 Hz), 7.67 (t, 1H, J = 
               
               
                   
                   
                   
                   
                   
                 7.46 Hz), 7.36-7.23 (m, 5H), 7.14 (s, 1H), 
               
               
                   
                   
                   
                   
                   
                 3.67 (s, 2H), 2.41-2.36 (m, 2H), 2.10-1.89 
               
               
                   
                   
                   
                   
                   
                 (m, 10H), 1.68-1.64 (m, 2H). 
               
               
                 SC_3301 
                 cis-8-Dimethylamino-3- 
                 INT-976 
                 5-bromo-isoquinoline 
                 SC_3103 
                 1HNMR (DMSO-d6, 400 MHz at 100 0 C.), δ 
                 401.2 
               
               
                   
                 isoquinolin-5-yl-8-phenyl-1,3- 
                   
                   
                   
                 (ppm) = 9.29 (s, 1H), 8.48 (d, 1H, J = 5.92 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 Hz) 7.98-7.96 (m, 1H), 7.70-7.64 (m, 3H), 
               
               
                   
                   
                   
                   
                   
                 7.36-7.23 (m, 5H), 7.13 (s, 1H), 3.65 (s, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.41-2.36 (m, 2H), 2.10-1.90 (m, 10H), 1.68- 
               
               
                   
                   
                   
                   
                   
                 1.63 (m, 2H). 
               
               
                 SC_3302 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 4-bromo-1H-pyrrolo[2,3-b]pyridine 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 11.42 (s, 
                 390.2 
               
               
                   
                 (1H-pyrrolo[2,3-b]pyridin-4-yl)- 
                   
                   
                   
                 1H), 7.99 (d, 1H), 7.66 (br s, 1H), 7.43- 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 7.33 (m, 5H), 7.27 (t, 1H), 7.22 (t, 1H), 6.65- 
               
               
                   
                   
                   
                   
                   
                 6.60 (m, 1H), 3.91 (s, 2H), 2.45-2.27 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 1.98-1.82 (m, 10H), 1.56-1.49 (m, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3303 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 4-bromo-2-(pyridin-4-yl)thiazole 
                 SC_3103 
                 1H NMR (DMSO-d6): δ 8.62 (d, 2H), 7.82 
                 434.1 
               
               
                   
                 (2-pyridin-4-yl-thiazol-4-yl)-1,3- 
                   
                   
                   
                 (d, 2H), 7.61 (broad s, 1H), 7.54 (s, 1H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 7.40-7.37 (m, 4H), 7.29-7.27 (m, 1H), 3.84 
               
               
                   
                   
                   
                   
                   
                 (s, 2H), 2.49 (m, 2H), 1.96-1.79 (m, 10H), 
               
               
                   
                   
                   
                   
                   
                 1.51 (m, 2H). 
               
               
                 SC_3304 
                 cis-8-[Methyl-(tetrahydro-furan-3- 
                 INT-1026 
                 4-(5-bromopyrimidin-2-yl)morpholine 
                 step 2 of SC_3097 (for synthesis), 
                 1H NMR (DMSO-d6): δ 8.56 (s, 2H), 7.65 
                 507.3 
               
               
                   
                 yl-methyl)-amino]-3-(2-morpholin- 
                   
                   
                 SC_3292 and SC_3293 
                 (broad s, 1H), 7.36-7.23 (m, 5H), 3.66-3.55 
               
               
                   
                 4-yl-pyrimidin-5-yl)-8-phenyl-1,3- 
                   
                   
                 (for separation of enantiomers) 
                 (m, 10H), 3.49 (s, 2H), 3.38 (m, 1H), 2.32- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2.26 (m, 3H), 2.11-1.94 (m, 6H), 1.86-1.82 
               
               
                   
                 (enantiomer 1) 
                   
                   
                   
                 (m, 3H), 1.50-1.41(m, 3H). 
               
               
                 SC_3305 
                 cis-8-[Methyl-(tetrahydro-furan-3- 
                 INT-1026 
                 4-(5-bromopyrimidin-2-yl)morpholine 
                 step 2 of SC_3097 (for synthesis), 
                 1H NMR (DMSO-d6): δ 8.56 (s, 2H), 7.66 
                 507.2 
               
               
                   
                 yl-methyl)-amino]-3-(2-morpholin- 
                   
                   
                 SC_3292 and SC_3293 
                 (broad s, 1H), 7.35-7.24 (m, 5H), 3.63-3.49 
               
               
                   
                 4-yl-pyrimidin-5-yl)-8-phenyl-1,3- 
                   
                   
                 (for separation of enantiomers) 
                 (m, 12H), 3.31 (m, 1H), 2.27 (m, 3H), 2.11- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 1.84 (m, 10H), 1.42 (m, 3H). 
               
               
                   
                 (enantiomer 2) 
               
               
                 SC_3306 
                 cis-3-[2-(Azetidin-1-yl)-pyrimidin- 
                 INT-976 
                 2-azetidin-1-yl-5-bromo-pyrimidine 
                 step 2 of SC_3242 
                 1HNMR (DMSO-d6, 400 MHz at 100 0 C.), δ 
                 407.2 
               
               
                   
                 5-yl]-8-dimethylamino-8-phenyl- 
                   
                   
                   
                 (ppm) = 8.48 (s, 2H), 7.36-7.26 (m, 5H), 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 7.07 (s, 1H), 3.99 (t, 4H, J = 7.18 Hz), 3.50 
               
               
                   
                   
                   
                   
                   
                 (s, 2H), 2.35-2.26 (m, 4H), 2.03 (s, 6H), 
               
               
                   
                   
                   
                   
                   
                 1.95-1.91 (m, 2H), 1.52-1.50 (m, 2H). 
               
               
                 SC_3307 
                 cis-3-[2-(3,3-Difluoro-azetidin-1- 
                 INT-976 
                 5-bromo-2-(3,3-difluoro-azetidin-1- 
                 step 2 of SC_3242 
                 1HNMR (DMSO-d6, 400 MHz at 100 0 C.), δ 
                 443.2 
               
               
                   
                 yl)-pyrimidin-5-yl]-8- 
                   
                 yl)-pyrimidine 
                   
                 (ppm) = 8.62 (s, 2H), 7.37-7.25 (m, 5H), 
               
               
                   
                 dimethylamino-8-phenyl-1,3- 
                   
                   
                   
                 7.20 (s, 1H), 4.38 (t, 4H, J = 12.40 Hz), 3.55 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (s, 2H), 2.36-233 (m, 2H), 2.03 (s, 6H) 1.97- 
               
               
                   
                   
                   
                   
                   
                 1.89 (m, 4H), 1.53-1.51 (m, 2H). 
               
               
                 SC_3308 
                 cis-8-Dimethylamino-3-[6- 
                 INT-976 
                 4-(5-bromo-3-trifluoromethyl- 
                 SC_3103 
                 1HNMR (DMSO-d6, 400 MHz at 100 0 C.), δ 
                 504.3 
               
               
                   
                 morpholin-4-yl-5-(trifluoromethyl)- 
                   
                 pyridin-2-yl)-morpholine 
                   
                 (ppm) = 8.63 (s, 1H), 8.38 (s, 1H), 7.37-7.25 
               
               
                   
                 pyridin-3-yl]-8-phenyl-1,3- 
                   
                   
                   
                 (m, 6H), 3.71 (bs, 4H), 3.65 (s, 2H), 3.03 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (bs, 4H), 2.37-2.32 (m, 2H), 2.03 (s, 6H), 
               
               
                   
                   
                   
                   
                   
                 1.98-1.88 (m, 4H), 1.55-1.52 (m, 2H). 
               
               
                 SC_3309 
                 cis-8-Methylamino-3-[6- 
                 SC_3308 
                   
                 SC_3099 
                 1HNMR (DMSO-d6, 400 MHz at 100 0 C.), δ 
                 490.4 
               
               
                   
                 morpholin-4-yl-5-(trifluoromethyl)- 
                   
                   
                   
                 (ppm) = 8.68 (s, 1H), 8.42 (s, 1H), 7.48 (d, 
               
               
                   
                 pyridin-3-yl]-8-phenyl-1,3- 
                   
                   
                   
                 2H, J = 8.12 Hz), 7.33 (t, 2H, J = 7.62 Hz), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 7.20 (t, 1H, J = 7.38 Hz), 7.14 (s, 1H), 3.75- 
               
               
                   
                   
                   
                   
                   
                 3.71 (m, 6H), 3.03 (t, 4H, J = 8.88 Hz), 2.08- 
               
               
                   
                   
                   
                   
                   
                 2.02 (m, 2H), 1.95-1.79 (m, 8H), 1.58-1.55 
               
               
                   
                   
                   
                   
                   
                 (m, 2H). 
               
               
                 SC_3310 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 2-bromo-5-(trifluoromethoxy)- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.32-8.26 
                 435.2 
               
               
                   
                 [5-(trifluoromethyloxy)-pyridin-2- 
                   
                 pyridine 
                   
                 (m, 2H), 7.86-7.82 (m, 1H), 7.79 (dd, 1H), 
               
               
                   
                 yl]-1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 7.41-7.33 (m, 4H), 7.27 (t, 1H), 3.71 (s, 
               
               
                   
                   
                   
                   
                   
                 2H), 2.46-2.33 (m, 2H), 1.96 (s, 6H), 1.94- 
               
               
                   
                   
                   
                   
                   
                 1.72 (m, 4H), 1.47 (t, 2H). 
               
               
                 SC_3311 
                 cis-8-Dimethylamino-3-(5- 
                 INT-976 
                 2-bromo-5- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.66 (dd, 
                 429.2 
               
               
                   
                 methylsulfonyl-pyridin-2-yl)-8- 
                   
                 methylsulfonylpyridine 
                   
                 1H), 8.39 (dd, 1H), 8.14 (dd, 1H), 8.06 (s, 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 1H), 7.42-7.33 (m, 4H), 7.28 (t, 1H), 3.77 
               
               
                   
                 one 
                   
                   
                   
                 (s, 2H), 3.21 (s, 3H), 2.46-2.32 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.03-1.68 (m, 10H), 1.52-1.46 (m, 2H). 
               
               
                 SC_3312 
                 cis-6-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 6-bromopyridine-3- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.66 (d, 1H), 
                 376.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                 carbonitrile 
                   
                 8.34 (d, 1H), 8.08 (dd, 1H), 7.41-7.33 (m, 
               
               
                   
                 yl)-nicotinonitrile 
                   
                   
                   
                 4H), 7.28 (t, 1H), 3.74 (s, 2H), 2.46-2.30 
               
               
                   
                   
                   
                   
                   
                 (m, 2H), 1.96 (s, 6H), 1.94-1.73 (m, 4H), 
               
               
                   
                   
                   
                   
                   
                 1.51-1.44 (m, 2H). 
               
               
                 SC_3314 
                 cis-8-Dimethylamino-3-[4-methyl- 
                 INT-976 
                 4-(5-bromo-4-methyl-pyrimidin- 
                 SC_3103 
                 1HNMR (DMSO-d6, 400 MHz at 100° C.), δ 
                 464.2 
               
               
                   
                 2-(3-oxo-piperazin-1-yl)-pyrimidin- 
                   
                 2-yl)-piperazin-2-one 
                   
                 (ppm) = 8.14 (s, 1H), 7.65 (bs, 1H), 7.34- 
               
               
                   
                 5-yl]-8-phenyl-1,3- 
                   
                   
                   
                 7.23 (m, 5H), 6.89 (s, 1H), 4.16 (s, 2H), 3.88 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (bs, 2H), 3.39 (s, 2H), 3.29 (bs, 2H), 2.33 
               
               
                   
                   
                   
                   
                   
                 (bs, 2H), 2.24 (s, 3H), 2.03-1.87 (m, 10H), 
               
               
                   
                   
                   
                   
                   
                 1.53 (bs, 2H). 
               
               
                 SC_3315 
                 cis-5-(8-Dimethylamino-2-oxo-8- 
                 SC_3312 
                   
                 SC_3016 
                 1H NMR (600 MHz, DMSO) δ 8.80 (d, 1H), 
                 394.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 8.10 (dd, 1H), 7.95-7.89 (m, 2H), 7.79 (s, 
               
               
                   
                 yl)-pyridine-2-carboxylic acid 
                   
                   
                   
                 1H), 7.42-7.35 (m, 5H), 7.28 (s, 1H), 3.67 
               
               
                   
                 amide 
                   
                   
                   
                 (s, 2H), 2.48-2.28 (m, 2H), 1.95 (d, 10H), 
               
               
                   
                   
                   
                   
                   
                 1.53-1.46 (m, 2H). 
               
               
                 SC_3316 
                 cis-3-[4-(Azetidin-1-yl)-2-methyl- 
                 INT-976 
                 4-azetidin-1-yl-5- 
                 step 2 of SC_3242 
                 1HNMR (DMSO-d6, 400 MHz at 100 0 C.), δ 
                 421.2 
               
               
                   
                 pyrimidin-5-yl]-8-dimethylamino- 
                   
                 bromo-2-methyl-pyrimidine 
                   
                 (ppm) = 7.85 (s, 1H), 7.34-7.23 (m, 5H), 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                   
                   
                 6.93 (s, 1H), 4.11 (t, 4H, J = 7.40 Hz), 3.33 
               
               
                   
                 2-one 
                   
                   
                   
                 (s, 2H), 2.33-2.30 (m, 7H), 2.02 (s, 6H), 
               
               
                   
                   
                   
                   
                   
                 1.96-1.87 (m, 4H), 1.53-1.48 (m, 2H). 
               
               
                 SC_3317 
                 cis-2-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 2-bromobenzonitrile 
                 SC_3103 (step 1), 
                 1H NMR (600 MHz, DMSO) δ 7.50 (s, 1H), 
                 393.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                 SC_3016 (step 2) 
                 7.42 (dd, 1H), 7.42-7.32 (m, 5H), 7.31 (d, 
               
               
                   
                 yl)-benzamide 
                   
                   
                   
                 1H), 7.26 (t, 1H), 7.23-7.13 (m, 3H), 3.53 
               
               
                   
                   
                   
                   
                   
                 (s, 2H), 2.41-2.27 (m, 2H), 1.96 (s, 6H), 
               
               
                   
                   
                   
                   
                   
                 1.90 (t, 2H), 1.86-1.68 (m, 2H), 1.52-1.48 
               
               
                   
                   
                   
                   
                   
                 (m, 2H). 
               
               
                 SC_3318 
                 cis-8-Dimethylamino-3-[2- 
                 INT-997 
                 1-bromo-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 7.47 (dd, 
                 448.2 
               
               
                   
                 (methylsulfonyl-methyl)-phenyl]-8- 
                   
                 (methylsulfonylmethyl)-benzene 
                   
                 1H), 7.43-7.36 (m, 2H), 7.34 (dd, 1H), 7.29 
               
               
                   
                 thiophen-2-yl-1,3- 
                   
                   
                   
                 (ddd, 1H), 7.19 (s, 1H), 7.05 (ddd, 1H), 6.94 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (d, 1H), 4.50 (s, 2H), 3.61 (s, 2H), 2.89 (s, 
               
               
                   
                   
                   
                   
                   
                 3H), 2.35-2.21 (m, 2H), 2.04 (s, 6H), 1.98- 
               
               
                   
                   
                   
                   
                   
                 1.90 (m, 2H), 1.86-1.70 (m, 2H), 1.66- 
               
               
                   
                   
                   
                   
                   
                 1.59 (m, 2H). 
               
               
                 SC_3320 
                 cis-8-Dimethylamino-3-(4-methyl- 
                 INT-997 
                 4-(5-bromo-4-methyl- 
                 SC_3319 
                 1H NMR (600 MHz, DMSO) δ 8.15 (d, 1H), 
                 457.2 
               
               
                   
                 2-morpholin-4-yl-pyrimidin-5-yl)- 
                   
                 pyrimidin-2-yl)morpholine 
                   
                 7.41 (dt, 1H), 7.13 (s, 1H), 7.05 (ddd, 1H), 
               
               
                   
                 8-thiophen-2-yl-1,3- 
                   
                   
                   
                 6.94 (dd, 1H), 3.71-3.60 (m, 8H), 3.44 (s, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2H), 2.32-2.24 (m, 2H), 2.21 (s, 3H), 2.04 
               
               
                   
                   
                   
                   
                   
                 (s, 6H), 1.98-1.88 (m, 2H), 1.87-1.75 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 1.62-1.54 (m, 2H). 
               
               
                 SC_3321 
                 cis-8-Dimethylamino-3-(6- 
                 INT-976 
                 5-bromo-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.89 (d, J = 
                 429.2 
               
               
                   
                 methylsulfonyl-pyridin-3-yl)-8- 
                   
                 methylsulfonylpyridine 
                   
                 2.6 Hz, 1H), 8.28 (dd, J = 8.9, 2.6 Hz, 1H), 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 7.93 (d, 1H), 7.42-7.34 (m, 4H), 7.31- 
               
               
                   
                 one 
                   
                   
                   
                 7.25 (m, 1H), 3.71 (s, 2H), 3.18 (s, 3H), 2.48- 
               
               
                   
                   
                   
                   
                   
                 2.33 (m, 2H), 2.04-1.76 (m, 10H), 1.54- 
               
               
                   
                   
                   
                   
                   
                 1.48 (m, 2H). 
               
               
                 SC_3322 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 tert-butyl 5-bromopyrrolo[2,3- 
                 SC_3103 (for step 1), 
                 1H NMR (600 MHz, DMSO) δ 11.45 (s, 
                 390.2 
               
               
                   
                 (1H-pyrrolo[2,3-b]pyridin-5-yl)- 
                   
                 b]pyridine-1-carboxylate (step 1) 
                 SC_3173 (for step 2) 
                 1H), 8.38 (s, 1H), 8.00 (d, 1H), 7.85-7.81 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (m, 1H), 7.70-7.66 (m, 2H), 7.57-7.53 
               
               
                   
                   
                   
                   
                   
                 (m, 3H), 7.41 (t, 1H), 6.35 (dd, 1H), 3.54 (s, 
               
               
                   
                   
                   
                   
                   
                 2H), 2.75-2.41 (m, 8H, overlapps with 
               
               
                   
                   
                   
                   
                   
                 solvent residual peak), 2.30-2.26 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 1.89 (d, 2H), 1.41-1.37 (m, 2H). 
               
               
                 SC_3323 
                 cis-N-[5-(8-Dimethylamino-2-oxo- 
                 SC_3239 
                 acetyl chloride 
                 SC_3240 
                 1H NMR (600 MHz, DMSO) δ 10.36 (s, 
                 409.2 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                   
                   
                 1H), 8.82 (s, 2H), 8.40 (s, rotamer), 7.67 (s, 
               
               
                   
                 3-yl)-pyrimidin-2-yl]-acetamide 
                   
                   
                   
                 1H), 7.44-7.31 (m, 4H), 7.27 (td, 1H), 3.62 
               
               
                   
                 (enantiomer 1) 
                   
                   
                   
                 (s, 2H), 2.46-2.30 (m, 2H), 2.11 (s, 3H), 
               
               
                   
                   
                   
                   
                   
                 2.08 (s, rotamer), 1.96 (s, 6H), 1.97 (s, 
               
               
                   
                   
                   
                   
                   
                 rotamer), 1.95-1.75 (m, 4H), 1.52-1.47 
               
               
                   
                   
                   
                   
                   
                 (m, 2H). 
               
               
                 SC_3324 
                 cis-3-[2-(4-Methyl-piperazin-1-yl)- 
                 INT-1026 
                 5-bromo-2-(4-methylpiperazin-1- 
                 step 2 of SC_3097 (for synthesis), 
                 1H NMR (DMSO-d6): δ 8.52 (s, 2H), 7.64 
                 518.3 
               
               
                   
                 pyrimidin-5-yl]-8-[methyl- 
                   
                 yl)pyrimidine 
                 SC_3292 and SC_3293 
                 (broad s, 1H), 7.36-7.23 (m, 5H), 3.66-3.55 
               
               
                   
                 (tetrahydro-furan-3-yl-methyl- 
                   
                   
                 (for separation of enantiomers) 
                 (m, 7H), 3.48 (s, 2H), 3.37-3.36 (m, 1H), 
               
               
                   
                 amino]-8-phenyl-1,3- 
                   
                   
                   
                 2.33-2.13 (m, 11H), 2.01-1.82 (m, 9H), 1.50- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 1.41 (m, 3H). 
               
               
                   
                 (enantiomer 2) 
               
               
                 SC_3325 
                 cis-3-[2-(4-Methyl-piperazin-1-yl)- 
                 INT-1026 
                 5-bromo-2-(4-methylpiperazin-1- 
                 step 2 of SC_3097 (for synthesis), 
                 1H NMR (DMSO-d6): δ 8.52 (s, 2H), 7.64 
                 518.3 
               
               
                   
                 pyrimidin-5-yl]-8-[methyl- 
                   
                 yl)pyrimidine 
                 SC_3292 and SC_3293 
                 (broad s, 1H), 7.36-7.24 (m, 5H), 3.66-3.55 
               
               
                   
                 (tetrahydro-furan-3-yl-methyl- 
                   
                   
                 (for separation of enantiomers) 
                 (m, 7H), 3.48 (s, 2H), 3.36 (m, 1H), 2.34- 
               
               
                   
                 amino]-8-phenyl-1,3- 
                   
                   
                   
                 2.13 (m, 10H), 2.01-1.83 (m, 10H), 1.50- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 1.41 (m, 3H). 
               
               
                 SC_3326 
                 cis-8-Dimethylamino-3-(4,6- 
                 INT-976 
                 4-(5-bromo-4,6-dimethyl-pyrimidin- 
                 SC_3103 
                 — 
                 465.3 
               
               
                   
                 dimethyl-2-morpholin-4-yl- 
                   
                 2-yl)morpholine 
               
               
                   
                 pyrimidin-5-yl)-8-phenyl-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3327 
                 cis-8-Dimethylamino-3-(2- 
                 INT-1027 
                 morpholine 
                 SC_3120 
                 1H NMR (600 MHz, DMSO) δ 8.58 (s, 2H), 
                 443.2 
               
               
                   
                 morpholin-4-yl-pyrimidin-5-yl)-8- 
                   
                   
                   
                 7.43 (dd, 1H), 7.40-7.32 (m, 1H), 7.07 (dd, 
               
               
                   
                 thiophen-2-yl-1,3- 
                   
                   
                   
                 1H), 6.96 (dd, 1H), 3.67-3.61 (m, 4H), 3.62- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.57 (m, 6H), 2.31-2.27 (m, 2H), 2.04 (s, 
               
               
                   
                   
                   
                   
                   
                 6H), 1.91 (t, 2H), 1.86-1.82 (m, 2H), 1.56- 
               
               
                   
                   
                   
                   
                   
                 1.50 (m, 2H). 
               
               
                 SC_3328 
                 cis-6-(8-Dimethylamino-2-oxo-8- 
                 SC_3312 
                   
                 SC_3016 
                 1H NMR (600 MHz, DMSO) δ 8.71 (d, J = 
                 394.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 2.3 Hz, 1H), 8.24 (d, J = 8.9 Hz, 1H), 8.12 
               
               
                   
                 yl)-pyridine-3-carboxylic acid 
                   
                   
                   
                 (dd, J = 9.0, 2.4 Hz, 1H), 7.95 (s, 1H), 7.86 
               
               
                   
                 amide 
                   
                   
                   
                 (s, 1H), 7.36 (dq, J = 13.7, 6.6, 5.6 Hz, 5H), 
               
               
                   
                   
                   
                   
                   
                 7.27 (t, J = 7.2 Hz, 1H), 3.74 (s, 2H), 2.41- 
               
               
                   
                   
                   
                   
                   
                 2.37 (m, 2H), 1.96 (s, 6H), 1.94-1.87 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 1.86-1.80 (m, 2H), 1.51-1.44 (m, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3329 
                 cis-8-Dimethylamino-3-[2-methyl- 
                 INT-997 
                 5-bromo-1-methyl-3- 
                 SC_3319 
                 1H NMR (600 MHz, DMSO) δ 7.66-7.63 
                 428.2 
               
               
                   
                 5-(trifluoromethyl)-2H-pyrazol-3- 
                   
                 (trifluoromethyl)pyrazole 
                   
                 (m, 1H), 7.42 (dd, 1H), 7.06 (dd, 1H), 6.95 
               
               
                   
                 yl]-8-thiophen-2-yl-1,3- 
                   
                   
                   
                 (dd, 1H), 6.64 (s, 1H), 3.75 (s, 3H), 3.60 (s, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2H), 2.30-2.26 (m, 2H), 2.04 (s, 6H), 1.98- 
               
               
                   
                   
                   
                   
                   
                 1.90 (m, 2H), 1.83-1.79 (m, 2H), 1.64- 
               
               
                   
                   
                   
                   
                   
                 1.57 (m, 2H). 
               
               
                 SC_3330 
                 cis-8-Dimethylamino-3-[2-[(2- 
                 INT-1027 
                 2-(methylamino)ethanol 
                 SC_3120 
                 1H NMR (600 MHz, DMSO) δ 8.48 (s, 2H), 
                 431.2 
               
               
                   
                 hydroxy-ethyl)-methyl-amino]- 
                   
                   
                   
                 7.43 (d, 1H), 7.30 (s, 1H), 7.07 (dd, 1H), 
               
               
                   
                 pyrimidin-5-yl]-8-thiophen-2-yl- 
                   
                   
                   
                 6.96 (d, 1H), 3.61 (dd, 2H), 3.58-3.51 (m, 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 4H), 3.09 (s, 3H), 2.34-2.22 (m, 2H), 2.04 
               
               
                   
                   
                   
                   
                   
                 (s, 6H), 1.96-1.76 (m, 4H), 1.56-1.50 (m, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3331 
                 cis-8-Dimethylamino-3-[2-(2-oxo- 
                 INT-1027 
                 4-(4,4,5,5-tetramethyl-1,3,2- 
                 SC_3208 
                 1H NMR (600 MHz, DMSO) δ 10.46 (s, 
                 489.2 
               
               
                   
                 1,3-dihydro-indol-4-yl)-pyrimidin- 
                   
                 dioxaborolan-2-yl)indolin-2-one 
                   
                 1H), 9.12 (s, 2H), 7.87 (d, 1H), 7.47-7.42 
               
               
                   
                 5-yl]-8-thiophen-2-yl-1,3- 
                   
                   
                   
                 (m, 1H), 7.31 (t, 1H), 7.08 (dd, 1H), 6.98 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (dd, 1H), 6.92 (d, 1H), 3.83 (s, 2H), 3.77 (s, 
               
               
                   
                   
                   
                   
                   
                 2H), 2.35-2.30 (m, 2H), 2.05 (s, 6H), 1.96 
               
               
                   
                   
                   
                   
                   
                 (t, 2H), 1.88 (s, 2H), 1.60-1.54 (m, 2H). 
               
               
                 SC_3332 
                 cis-8-Dimethylamino-3-[4-methyl- 
                 INT-976 
                 4-(5-bromo-4-methyl-pyridin-2-yl)- 
                 step 2 of SC_3097 
                 1H-NMR (DMSO-d6, 400 MHz at 100° C.), δ 
                 463.2 
               
               
                   
                 6-(3-oxo-piperazin-1-yl)-pyridin-3- 
                   
                 piperazin-2-one 
                   
                 (ppm) = 7.89 (s, 1H), 7.62 (bs, 1H), 7.35- 
               
               
                   
                 yl]-8-phenyl-1,3- 
                   
                   
                   
                 7.22 (m, 5H), 6.73 (s, 1H), 6.62 (s, 1H), 3.96 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (s, 2H), 3.68 (t, 2H, J = 5.2 Hz), 3.39 (s, 2H), 
               
               
                   
                   
                   
                   
                   
                 3.30 (bs, 2H), 2.35-2.30 (m, 2H), 2.15 (s, 
               
               
                   
                   
                   
                   
                   
                 3H), 2.03-1.86 (m, 10H), 1.56-1.51 (m, 2H). 
               
               
                 SC_3333 
                 cis-8-Dimethylamino-3-(4-methyl- 
                 INT-976 
                 5-bromo-2-chloro-4-methyl-pyridine 
                 SC_3103 (for step 1), 
                 1H-NMR (DMSO-d6, 400 MHz at 100 0 C.), 
                 442.3 
               
               
                   
                 6-pyridin-2-yl-pyridin-3-yl)-8- 
                   
                 (step 1), 
                 SC_3162 (for step 2) 
                 δ (ppm) = 8.64 (d, 1H, J = 4.0 Hz), 8.45 (s, 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                 2-tributylstannanyl-pyridine 
                   
                 1H), 8.31 (d, 1H, J = 8.68 Hz), 8.22 (s, 1H), 
               
               
                   
                 one 
                   
                 (step 2) 
                   
                 7.88 (t, 1H, J = 7.04 Hz), 7.39-7.35 (m, 5H), 
               
               
                   
                   
                   
                   
                   
                 7.26-7.23 (m, 1H), 7.03 (s, 1H), 3.57 (s, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.39-2.33 (m, 5H), 2.04 (s, 6H), 2.01-1.88 
               
               
                   
                   
                   
                   
                   
                 (m, 4H), 1.61-1.57 (m, 2H). 
               
               
                 SC_3334 
                 cis-8-Dimethylamino-3-(4- 
                 INT-976 
                 3-bromo-4-methylsulfanyl- 
                 SC_3103 (for step 1), 
                 1HNMR at 100° C. (DMSO-d6, 400 MHz), δ 
                 429.3 
               
               
                   
                 methylsulfonyl-pyridin-3-yl)-8- 
                   
                 pyridine (step 1) 
                 SC_3008 (for step 2) 
                 (ppm) = 8.77-8.72 (m, 2H), 7.85-7.84 (m, 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 1H), 7.35-7.23 (m, 6H), 3.60 (s, 2H), 3.31 
               
               
                   
                 one 
                   
                   
                   
                 (s, 3H), 2.36 (bs, 2H), 2.03-1.82 (m, 10H), 
               
               
                   
                   
                   
                   
                   
                 1.60-1.58 (m, 2H). 
               
               
                 SC_3335 
                 cis-3-(Benzothiazol-7-yl)-8- 
                 INT-976 
                 7-bromo-benzothiazole 
                 SC_3103 
                   
                 407.1 
               
               
                   
                 dimethylamino-8-phenyl-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3336 
                 cis-8-Dimethylamino-8-(4- 
                 INT-1025 
                 4-(5-bromo-4-methyl- 
                 SC_3319 
                 1H NMR (600 MHz, DMSO) δ 8.13 (s, 1H), 
                 469.3 
               
               
                   
                 fluorophenyl)-3-(4-methyl-2- 
                   
                 pyrimidin-2-yl)morpholine 
                   
                 7.41-7.35 (m, 2H), 7.22-7.13 (m, 3H), 
               
               
                   
                 morpholin-4-yl-pyrimidin-5-yl)- 
                   
                   
                   
                 3.69-3.60 (m, 8H), 2.35-2.31 (m, 2H), 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2.20 (s, 3H), 1.94 (s, 6H), 1.93-1.74 (m, 
               
               
                   
                   
                   
                   
                   
                 4H), 1.53-1.43 (m, 2H). 
               
               
                 SC_3337 
                 cis-2-[8-Dimethylamino-3-[4- 
                 SC_3122 
                 2-chloro-N,N-dimethyl-acetamide 
                 INT-988 (step 1) 
                 1H NMR (600 MHz, DMSO) δ 8.59 (s, 1H), 
                 518.3 
               
               
                   
                 methyl-6-(trifluoromethyl)-pyridin- 
                   
                   
                   
                 7.82 (s, 1H), 7.37-7.32 (m, 4H), 7.25 (ddd, 
               
               
                   
                 3-yl]-2-oxo-8-phenyl-1,3- 
                   
                   
                   
                 1H), 4.00 (s, 2H), 3.80 (s, 2H), 3.07 (s, 3H), 
               
               
                   
                 diazaspiro[4.5]decan-1-yl]-N,N- 
                   
                   
                   
                 2.87 (s, 3H), 2.71-2.64 (m, 2H), 2.55 (s, 
               
               
                   
                 dimethyl-acetamide 
                   
                   
                   
                 3H), 2.34 (s, 3H), 2.03 (td, 2H), 1.98 (s, 6H), 
               
               
                   
                   
                   
                   
                   
                 1.67-1.58 (m, 2H), 1.49-1.40 (m, 2H). 
               
               
                 SC_3338 
                 cis-8-Dimethylamino-3-[2-(2- 
                 INT-989 
                 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2- 
                 SC_3208 
                 1H NMR (600 MHz, DMSO) δ 9.57 (s, 1H), 
                 497.3 
               
               
                   
                 methyl-1-oxo-2,3-dihydro-isoindol- 
                   
                 dioxaborolan-2-yl)isoindolin-1-one 
                   
                 9.08 (s, 2H), 8.52 (d, 1H), 8.43 (s, 1H), 7.77 
               
               
                   
                 4-yl)-pyrimidin-5-yl]-8-phenyl-1,3- 
                   
                   
                   
                 (d, 1H), 7.72 (d, 2H), 7.63 (t, 1H), 7.59 (t, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2H), 7.55 (t, 1H), 4.86 (s, 2H), 3.59 (s, 2H), 
               
               
                   
                   
                   
                   
                   
                 3.13 (s, 3H), 2.72 (d, 2H), 2.61 (s, 6H), 2.25 
               
               
                   
                   
                   
                   
                   
                 (td, 2H), 1.91 (d, 2H), 1.43-1.35 (m, 2H). 
               
               
                 SC_3339 
                 cis-2-[[5-(8-Dimethylamino-2-oxo- 
                 INT-976 
                 (5-bromo-2-methyl-pyrimidin-4- 
                 step 2 of SC_3242 (for step 1), 
                   1 HNMR at 100° C. (DMSO-d6, 400 MHz), δ 
                 438.4 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                 ylamino)-acetonitrile (step 1) 
                 SC_3016 (for step 2) 
                 (ppm) = 7.93 (s, 1H), 7.36-7.22 (m, 5H), 
               
               
                   
                 3-yl)-2-methyl-pyrimidin-4- 
                   
                   
                   
                 7.12 (s, 1H), 6.91 (bs, 2H), 6.58 (bs, 1H), 
               
               
                   
                 yl]amino]-acetamide 
                   
                   
                   
                 3.94 (d, 2H), 3.46 (s, 2H), 2.35-2.32 (m, 5H), 
               
               
                   
                   
                   
                   
                   
                 2.03-1.97 (m, 8H), 1.91-1.84 (m, 2H), 1.61- 
               
               
                   
                   
                   
                   
                   
                 1.56 (m, 2H). 
               
               
                 SC_3341 
                 cis-8-Dimethylamino-3-[4- 
                 INT-976 
                 3-bromo-4- 
                 step 2 of SC_3097 
                 1HNMR at 100° C. (DMSO-d6, 400 MHz), δ 
                 443.4 
               
               
                   
                 (methylsulfonyl-methyl)-pyridin-3- 
                   
                 methanesulfonylmethyl-pyridine 
                   
                 (ppm) = 8.53 (s, 1H), 8.43 (d, 1H, J = 4.88 
               
               
                   
                 yl]-8-phenyl-1,3- 
                   
                   
                   
                 Hz), 7.48 (d, 1H, J = 4.88 Hz), 7.36-7.23 (m, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 5H), 7.15 (s, 1H), 4.55 (s, 2H), 3.64 (s, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.95 (s, 3H), 2.38-2.33 (m, 2H), 2.04 (s, 6H), 
               
               
                   
                   
                   
                   
                   
                 1.99-1.83 (m, 4H), 1.62-1.57 (m, 2H). 
               
               
                 SC_3342 
                 cis-8-Dimethylamino-3-[6-(4- 
                 INT-976 
                 4-(5-bromo-2-pyridyl)-1-methyl- 
                 SC_3242 (step 2) 
                 1H NMR (600 MHz, CDCl3) δ 8.09 (d, 1H), 
                 463.3 
               
               
                   
                 methyl-3-oxo-piperazin-1-yl)- 
                   
                 piperazin-2-one 
                   
                 8.00 (dd, 1H), 7.45-7.39 (m, 2H), 7.37- 
               
               
                   
                 pyridin-3-yl]-8-phenyl-1,3- 
                   
                   
                   
                 7.28 (m, 3H), 6.61 (d, 1H), 5.71 (s, 1H), 4.04 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (s, 2H), 3.87-3.82 (m, 2H), 3.51 (s, 2H), 
               
               
                   
                   
                   
                   
                   
                 3.45 (t, 2H), 3.03 (s, 3H), 2.32-2.02 (m, 
               
               
                   
                   
                   
                   
                   
                 10H), 2.02-1.94 (m, 2H), 1.64-1.53 (m, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3343 
                 cis-8-Dimethylamino-3-(2,4- 
                 INT-976 
                 5-bromo-2,4-dimethyl-pyrimidine 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.46 (s, 1H), 
                 380.3 
               
               
                   
                 dimethyl-pyrimidin-5-yl)-8-phenyl- 
                   
                   
                   
                 7.45-7.33 (m, 5H), 7.28-7.24 (m, 1H), 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.51 (s, 2H), 2.54 (s, 3H), 2.41-2.28 (m, 
               
               
                   
                   
                   
                   
                   
                 5H), 2.03-1.77 (m, 10H), 1.56-1.49 (m, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3344 
                 cis-8-Dimethylamino-3-[2-(1-oxo- 
                 INT-989 
                 4-(4,4,5,5-tetramethyl-1,3,2- 
                 SC_3208 
                 1H NMR (600 MHz, DMSO) δ 9.06 (s, 2H), 
                 483.3 
               
               
                   
                 2,3-dihydro-isoindol-4-yl)- 
                   
                 dioxaborolan-2-yl)isoindolin-1-one 
                   
                 8.67 (s, 1H), 8.52 (d, 1H), 8.39 (s, 1H), 7.75 
               
               
                   
                 pyrimidin-5-yl]-8-phenyl-1,3- 
                   
                   
                   
                 (dd, 3H), 7.66-7.51 (m, 4H), 4.75 (s, 2H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one; 2,2,2- 
                   
                   
                   
                 3.58 (s, 2H), 3.18 (s, 2H), 2.75 (d, 2H), 2.60 
               
               
                   
                 trifluoro-acetic acid 
                   
                   
                   
                 (s, 6H), 2.27 (t, 2H), 1.91 (d, 2H), 1.39 (t, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3345 
                 cis-8-Dimethylamino-3-[6-[(2- 
                 INT-976 
                 2-[[5-bromo-3-(trifluoromethyl)-2- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.55-8.51 
                 492.3 
               
               
                   
                 hydroxy-ethyl)-methyl-amino]-5- 
                   
                 pyridyl]-methyl-amino]ethanol 
                   
                 (m, 1H), 8.35 (d, 1H), 7.62 (s, 1H), 7.37 (td, 
               
               
                   
                 (trifluoromethyl)-pyridin-3-yl]-8- 
                   
                   
                   
                 4H), 7.27 (td, 1H), 3.63 (s, 2H), 3.50 (td, 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 2H), 3.20 (t, 2H), 2.78 (s, 3H), 2.43-2.36 
               
               
                   
                 one 
                   
                   
                   
                 (m, 2H), 1.96 (s, 6H), 1.95-1.75 (m, 4H), 
               
               
                   
                   
                   
                   
                   
                 1.48 (t, 2H). 
               
               
                 SC_3346 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 3,3,3-trifluoroprop-1-yne, 
                 SC_3313 
                 1H NMR (600 MHz, DMSO) δ 9.56 (d, 1H), 
                 487.3 
               
               
                   
                 [2-[4-(trifluoromethyl)-1H- 
                   
                 2-azido-5-bromo-pyrimidine 
                   
                 9.16 (s, 2H), 7.99 (s, 1H), 7.42-7.35 (m, 
               
               
                   
                 [1,2,3]triazol-1-yl]-pyrimidin-5-yl]- 
                   
                   
                   
                 4H), 7.31-7.25 (m, 1H), 3.75 (s, 2H), 2.49- 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2.34 (m, 2H), 2.05-1.75 (m, 10H), 1.60- 
               
               
                   
                   
                   
                   
                   
                 1.47 (m, 2H). 
               
               
                 SC_3347 
                 cis-8-Dimethylamino-3-[2-(4- 
                 INT-976 
                 3-methylbut-1-yne, 
                 SC_3313 
                 1H NMR (600 MHz, DMSO) δ 9.10 (s, 2H), 
                 461.3 
               
               
                   
                 isopropyl-1H-[1,2,3]triazol-1-yl)- 
                   
                 2-azido-5-bromo-pyrimidine 
                   
                 8.50 (d, 1H), 7.91 (s, 1H), 7.42-7.35 (m, 
               
               
                   
                 pyrimidin-5-yl]-8-phenyl-1,3- 
                   
                   
                   
                 5H), 7.28 (td, 1H), 3.73 (s, 2H), 3.08 (hept, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 1H), 2.44 (s, 2H), 2.01-1.76 (m, 10H), 1.59- 
               
               
                   
                   
                   
                   
                   
                 1.48 (m, 2H), 1.30 (d, 6H). 
               
               
                 SC_3348 
                 cis-8-Dimethylamino-3-[6-(1,1- 
                 INT-976 
                 1,4-thiazinane 1,1-dioxide, 
                 SC_3242 
                 1H NMR (600 MHz, DMSO) δ 8.23 (d, 1H), 
                 484.2 
               
               
                   
                 dioxo-[1,4]thiazinan-4-yl)-pyridin- 
                   
                 5-bromo-2-chloro-pyridine (step 1) 
                   
                 7.93 (dd, 1H), 7.41-7.33 (m, 5H), 7.27 (t, 
               
               
                   
                 3-yl]-8-phenyl-1,3- 
                   
                   
                   
                 1H), 6.98 (d, 1H), 3.97 (t, 4H), 3.53 (s, 2H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.04 (t, 4H), 2.43-2.28 (m, 2H), 1.96 (s, 
               
               
                   
                   
                   
                   
                   
                 6H), 1.92-1.72 (m, 4H), 1.51-1.40 (m, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3349 
                 cis-5-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 5-bromo-2-chloropyridine-3- 
                 SC_3242 
                 1H NMR (600 MHz, DMSO-d6) δ 8.66 (d, 
                 461.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                 carbonitrile, morpholine 
                   
                 J = 2.9 Hz, 1H), 8.25 (d, J = 2.8 Hz, 1H), 7.60 
               
               
                   
                 yl)-2-morpholin-4-yl-nicotinonitrile 
                   
                   
                   
                 (s, 1H), 7.41-7.33 (m, 4H), 7.30-7.24 (m, 
               
               
                   
                   
                   
                   
                   
                 1H), 3.74-3.69 (m, 4H), 3.60 (s, 2H), 2.48- 
               
               
                   
                   
                   
                   
                   
                 2.29 (m, 2H), 1.96 (s, 6H), 1.94-1.68 (m, 
               
               
                   
                   
                   
                   
                   
                 4H), 1.52-1.41 (m, 2H). 
               
               
                 SC_3350 
                 cis-8-Dimethylamino-3-(1- 
                 INT-976 
                 5-bromo-1-methylsulfonyl- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.64 (d, 1H), 
                 468.2 
               
               
                   
                 methylsulfonyl-1H-pyrrolo[2,3- 
                   
                 pyrrolo[2,3-b]pyridine 
                   
                 8.28 (d, 1H), 7.65 (dd, 1H), 7.57 (s, 1H), 
               
               
                   
                 b]pyridin-5-yl)-8-phenyl-1,3- 
                   
                   
                   
                 7.38 (dd, 4H), 7.28 (dt, 1H), 6.72 (dd, 1H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.68 (s, 2H), 3.65 (s, 3H), 2.48-2.29 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 1.98 (s, 10H), 1.53-1.44 (m, 2H). 
               
               
                 SC_3351 
                 cis-8-Dimethylamino-3-(1H-indol- 
                 INT-976 
                 4-bromo-1-(toluene- 
                 SC_3357 
                 1H-NMR (DMSO-d6, 400 MHz at 100 0 C.), 
                 389.3 
               
               
                   
                 4-yl)-8-phenyl-1,3- 
                   
                 4-sulfonyl)-1H-indole (step 1) 
                   
                 δ (ppm) = 10.77 (bs, 1H), 7.37 (bs, 4H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 7.24-7.18 (m, 3H), 7.02-6.94 (m, 2H), 6.81 
               
               
                   
                   
                   
                   
                   
                 (bs, 1H), 6.41 (s, 1H), 3.66 (s, 2H), 2.36-2.33 
               
               
                   
                   
                   
                   
                   
                 (m, 2H), 2.05-1.96 (m, 10H), 1.60-156 (m, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3353 
                 cis-8-Dimethylamino-3-[2-fluoro- 
                 INT-976 
                 1-bromo-2-fluoro-4- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 7.62 (t, 1H), 
                 452.2 
               
               
                   
                 4-(trifluoromethyloxy)-phenyl]-8- 
                   
                 (trifluoromethoxy)-benzene 
                   
                 7.50-7.46 (m, 1H), 7.40 (dd, 1H), 7.38- 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 7.31 (m, 4H), 7.25 (t, 1H), 7.21 (d, 1H), 3.57 
               
               
                   
                 one 
                   
                   
                   
                 (s, 2H), 2.38 (d, 2H), 1.97-1.88 (m, 8H), 
               
               
                   
                   
                   
                   
                   
                 1.84-1.79 (m, 2H), 1.53-1.46 (m, 2H). 
               
               
                 SC_3355 
                 cis-8-Dimethylamino-3-(1-methyl- 
                 INT-976 
                 4-bromo-1-methyl-pyrrolo[2,3- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.04 (d, 1H), 
                 404.3 
               
               
                   
                 1H-pyrrolo[2,3-b]pyridin-4-yl)-8- 
                   
                 b]pyridine 
                   
                 7.70 (s, 1H), 7.47 (d, 1H), 7.41-7.33 (m, 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 4H), 7.31-7.24 (m, 2H), 6.65 (d, 1H), 3.91 
               
               
                   
                 one 
                   
                   
                   
                 (s, 2H), 3.74 (s, 3H), 2.44-2.25 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.08-1.74 (m, 10H), 1.52 (t, 2H). 
               
               
                 SC_3356 
                 cis-3-(1-Acetyl-1H-indol-4-yl)-8- 
                 SC_3351 
                 acetyl chloride 
                 SC_3379 
                 1H-NMR (DMSO-d6, 400 MHz at 100 0 C.), 
                 431.2 
               
               
                   
                 dimethylamino-8-phenyl-1,3- 
                   
                   
                   
                 δ (ppm) = 8.12 (d, 1H, J = 8.28 Hz), 7.68 (d, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 1H, J = 3.64 Hz), 7.36-7.22 (m, 6H), 7.16 (d, 
               
               
                   
                   
                   
                   
                   
                 1H, J = 7.80 Hz), 7.01 (s, 1H), 6.69 (d, 1H, 
               
               
                   
                   
                   
                   
                   
                 J = 3.8 Hz), 3.66 (s, 2H), 2.62 (s, 3H), 2.38- 
               
               
                   
                   
                   
                   
                   
                 2.33 (m, 2H), 2.05-1.92 (m, 10H), 1.61-1.56 
               
               
                   
                   
                   
                   
                   
                 (m, 2H). 
               
               
                 SC_3358 
                 cis-6-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 6-chloro-5-methyl-pyridine-3- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.64 (s, 1H), 
                 390.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                 carbonitrile 
                   
                 8.12 (s, 1H), 7.76 (s, 1H), 7.39-7.34 (m, 
               
               
                   
                 yl)-5-methyl-nicotinonitrile 
                   
                   
                   
                 4H), 7.27 (s, 1H), 3.71 (s, 2H), 2.43-2.15 
               
               
                   
                   
                   
                   
                   
                 (m, 5H), 2.11-1.70 (m, 10H), 1.52 (s, 2H). 
               
               
                 SC_3359 
                 cis-6-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 6-chloro-5-fluoro-pyridine-3- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.64 (d, 1H), 
                 394.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                 carbonitrile 
                   
                 8.30 (dd, 1H), 7.95 (s, 1H), 7.40-7.31 (m, 
               
               
                   
                 yl)-5-fluoro-nicotinonitrile 
                   
                   
                   
                 4H), 7.29-7.23 (m, 1H), 3.72 (s, 2H), 2.36- 
               
               
                   
                   
                   
                   
                   
                 2.33 (m, 2H), 1.96 (s, 6H), 1.94-1.79 (m, 
               
               
                   
                   
                   
                   
                   
                 4H), 1.52 (t, 2H). 
               
               
                 SC_3361 
                 cis-6-(8-Dimethylamino-2-oxo-8- 
                 SC_3358 
                   
                 SC_3016 
                 1H NMR (600 MHz, DMSO) δ 8.64 (d, 1H), 
                 408.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 8.06-8.02 (m, 2H), 7.54 (s, 1H), 7.44 (s, 
               
               
                   
                 yl)-5-methyl-pyridine-3-carboxylic 
                   
                   
                   
                 1H), 7.38-7.30 (m, 4H), 7.27-7.21 (m, 
               
               
                   
                 acid amide 
                   
                   
                   
                 1H), 3.67 (s, 2H), 2.37-2.26 (m, 5H), 2.05- 
               
               
                   
                   
                   
                   
                   
                 1.75 (m, 10H), 1.51 (t, 2H). 
               
               
                 SC_3362 
                 cis-6-(8-Dimethylamino-2-oxo-8- 
                 SC_3359 
                   
                 SC_3016 
                 1H NMR (600 MHz, DMSO) δ 8.65-8.61 
                 412.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 (m, 1H), 8.13 (s, 1H), 8.04 (dd, 1H), 7.76 (s, 
               
               
                   
                 yl)-5-fluoro-pyridine-3-carboxylic 
                   
                   
                   
                 1H), 7.59 (s, 1H), 7.39-7.30 (m, 4H), 7.28- 
               
               
                   
                 acid amide 
                   
                   
                   
                 7.21 (m, 1H), 3.70 (s, 2H), 2.41-2.23 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 1.96-1.76 (m, 10H), 1.50 (t, 2H). 
               
               
                 SC_3363 
                 cis-8-Dimethylamino-3-[4-methyl- 
                 INT-1038 
                 5-bromo-4-methyl-2- 
                 SC_3319 
                 1H NMR (600 MHz, DMSO) δ 8.56 (s, 1H), 
                 447.2 
               
               
                   
                 6-(trifluoromethyl)-pyridin-3-yl]-8- 
                   
                 (trifluoromethyl)pyridine 
                   
                 7.80 (s, 1H), 7.52 (s, 1H), 7.24 (t, 1H), 7.17- 
               
               
                   
                 m-tolyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 7.11 (m, 2H), 7.06 (d, 1H), 3.60 (s, 2H), 
               
               
                   
                 one 
                   
                   
                   
                 2.39-2.25 (m, 8H), 2.01-1.78 (m, 10H), 
               
               
                   
                   
                   
                   
                   
                 1.58-1.48 (m, 2H). 
               
               
                 SC_3364 
                 cis-3-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 3-bromopyridine-4-carbonitrile 
                 SC_3242 
                 1H NMR (600 MHz, DMSO) δ 8.79 (s, 1H), 
                 376.2 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                   
                   
                 8.50 (d, 1H), 7.84-7.80 (m, 1H), 7.37 (td, 
               
               
                   
                 yl)-isonicotinonitrile 
                   
                   
                   
                 4H), 7.26 (td, 1H), 3.79 (s, 2H), 2.43-2.36 
               
               
                   
                   
                   
                   
                   
                 (m, 2H), 1.97 (s, 7H), 1.96-1.91 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 1.88-1.81 (m, 2H), 1.61-1.45 (m, 2H). 
               
               
                 SC_3365 
                 cis-8-Dimethylamino-3-[3-fluoro- 
                 INT-1045 
                 4-(4,4,5,5-tetramethyl-1,3,2- 
                 SC_3354 
                 1H NMR (600 MHz, DMSO) δ 10.51 (s, 
                 500.2 
               
               
                   
                 5-(2-oxo-1,3-dihydro-indol-4-yl)- 
                   
                 dioxaborolan-2-yl)indolin-2-one 
                   
                 1H), 8.39 (d, 1H), 7.96 (dd, 1H), 7.41-7.32 
               
               
                   
                 pyridin-2-yl]-8-phenyl-1,3- 
                   
                 (step 2) 
                   
                 (m, 4H), 7.28 (dt, 2H), 7.08 (d, 1H), 6.88 (d, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 1H), 3.71 (s, 2H), 3.67 (s, 2H), 2.44-2.22 
               
               
                   
                   
                   
                   
                   
                 (m, 2H), 1.98-1.87 (m, 11H), 1.58-1.46 
               
               
                   
                   
                   
                   
                   
                 (m, 2H). 
               
               
                 SC_3366 
                 cis-8-Dimethylamino-3-[4-methyl- 
                 INT-1039 
                 5-bromo-4-methyl-2- 
                 SC_3319 
                 1H NMR (600 MHz, DMSO) δ 8.55 (s, 1H), 
                 517.2 
               
               
                   
                 6-(trifluoromethyl)-pyridin-3-yl]-8- 
                   
                 (trifluoromethyl)pyridine 
                   
                 7.79 (s, 1H), 7.51 (t, 2H), 7.38 (dd, 1H), 7.26 
               
               
                   
                 [3-(trifluoromethyloxy)-phenyl]- 
                   
                   
                   
                 (d, 2H), 3.62 (s, 2H), 2.40-2.34 (m, 2H), 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2.31 (s, 3H), 2.01-1.77 (m, 10H), 1.58- 
               
               
                   
                   
                   
                   
                   
                 1.49 (m, 2H). 
               
               
                 SC_3367 
                 cis-8-Dimethylamino-3-[4-methyl- 
                 INT-1040 
                 5-bromo-4-methyl-2- 
                 SC_3319 
                 1H NMR (600 MHz, DMSO) δ 8.55 (s, 1H), 
                 501.2 
               
               
                   
                 6-(trifluoromethyl)-pyridin-3-yl]-8- 
                   
                 (trifluoromethyl)pyridine 
                   
                 7.79 (s, 1H), 7.69-7.56 (m, 5H), 7.52 (s, 
               
               
                   
                 [3-(trifluoromethyl)phenyl]-1,3- 
                   
                   
                   
                 1H), 3.61 (s, 2H), 2.44-2.36 (m, 2H), 2.31 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (s, 3H), 2.02-1.80 (m, 10H), 1.60-1.47 
               
               
                   
                   
                   
                   
                   
                 (m, 2H). 
               
               
                 SC_3368 
                 cis-8-Dimethylamino-8-(3- 
                 INT-1041 
                 5-bromo-4-methyl-2- 
                 SC_3319 
                 1H NMR (600 MHz, DMSO) δ 8.56 (s, 1H), 
                 463.2 
               
               
                   
                 methoxyphenyl)-3-[4-methyl-6- 
                   
                 (trifluoromethyl)pyridine 
                   
                 7.80 (s, 1H), 7.51 (s, 1H), 7.31-7.25 (m, 
               
               
                   
                 (trifluoromethyl)-pyridin-3-yl]-1,3- 
                   
                   
                   
                 1H), 6.92 (dt, 1H), 6.87-6.82 (m, 2H), 3.75 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (s, 3H), 3.61 (s, 2H), 2.35-2.30 (m, 5H), 
               
               
                   
                   
                   
                   
                   
                 1.98 (s, 7H), 1.96-1.90 (m, 2H), 1.88- 
               
               
                   
                   
                   
                   
                   
                 1.80 (m, 2H), 1.60-1.49 (m, 2H). 
               
               
                 SC_3369 
                 cis-8-(5-Chloro-thiophen-2-yl)-8- 
                 INT-1042 
                 5-bromo-4-methyl-2- 
                 SC_3319 
                 1H NMR (600 MHz, DMSO) δ 8.56 (s, 1H), 
                 473.1 
               
               
                   
                 dimethylamino-3-[4-methyl-6- 
                   
                 (trifluoromethyl)pyridine 
                   
                 7.79 (s, 1H), 7.39 (s, 1H), 7.04-7.00 (m, 
               
               
                   
                 (trifluoromethyl)-pyridin-3-yl]-1,3- 
                   
                   
                   
                 1H), 6.80 (d, 1H), 3.64 (s, 2H), 2.31 (s, 3H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2.22-2.15 (m, 2H), 2.04 (s, 6H), 1.95- 
               
               
                   
                   
                   
                   
                   
                 1.87 (m, 2H), 1.83-1.77 (m, 2H), 1.63- 
               
               
                   
                   
                   
                   
                   
                 1.57 (m, 2H). 
               
               
                 SC_3370 
                 cis-8-Dimethylamino-8-(3- 
                 INT-1024 
                 5-bromo-4-methyl-2- 
                 SC_3319 
                 1H NMR (600 MHz, DMSO) δ 8.56 (s, 1H), 
                 451.2 
               
               
                   
                 fluorophenyl)-3-[4-methyl-6- 
                   
                 (trifluoromethyl)pyridine 
                   
                 7.80 (s, 1H), 7.51 (s, 1H), 7.41 (td, 1H), 7.21- 
               
               
                   
                 (trifluoromethyl)-pyridin-3-yl]-1,3- 
                   
                   
                   
                 7.12 (m, 2H), 7.12-7.06 (m, 1H), 3.61 (s, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2H), 2.38-2.30 (m, 5H), 1.97 (s, 6H), 1.96- 
               
               
                   
                   
                   
                   
                   
                 1.90 (m, 2H), 1.90-1.73 (m, 2H), 1.61- 
               
               
                   
                   
                   
                   
                   
                 1.45 (m, 2H). 
               
               
                 SC_3371 
                 cis-8-Dimethylamino-3-(2- 
                 INT-989 
                 methylamine 
                 SC_3239 
                 1H NMR (600 MHz, DMSO + TFA) δ 8.69 
                 381.2 
               
               
                   
                 methylamino-pyrimidin-5-yl)-8- 
                   
                   
                   
                 (s, 2H), 8.29 (s, 1H), 7.68 (d, 2H), 7.52 (dt, 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 3H), 2.90 (s, 3H), 2.68 (d, 2H), 2.59 (s, 6H), 
               
               
                   
                 one 
                   
                   
                   
                 2.24 (t, 2H), 1.86 (d, 2H), 1.39-1.31 (m, 
               
               
                   
                   
                   
                   
                   
                 2H) 
               
               
                 SC_3372 
                 cis-8-(5-Chloro-thiophen-2-yl)-8- 
                 INT-1042 
                 4-(5-bromo-4-methyl- 
                 SC_3242 
                 1H NMR (600 MHz, DMSO) δ 8.15 (d, 1H), 
                 491.2 
               
               
                   
                 dimethylamino-3-(4-methyl-2- 
                   
                 pyrimidin-2-yl)morpholine 
                   
                 7.15 (s, 1H), 7.05 (d, 1H), 6.82 (d, 1H), 3.70- 
               
               
                   
                 morpholin-4-yl-pyrimidin-5-yl)- 
                   
                   
                   
                 3.61 (m, 8H), 3.44 (s, 2H), 2.31-2.12 (m, 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 5H), 2.06 (s, 6H), 1.93-1.85 (m, 2H), 1.82- 
               
               
                   
                   
                   
                   
                   
                 1.69 (m, 2H), 1.64-1.49 (m, 2H). 
               
               
                 SC_3373 
                 cis-N-[5-(8-Dimethylamino-2-oxo- 
                 SC_3371 
                 Cyclopropancarbonyl chlorid 
                 SC_3240 
                 1H NMR (600 MHz, DMSO) δ 8.97 (s, 2H), 
                 449.3 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                   
                   
                 7.83-7.73 (m, 1H), 7.41-7.34 (m, 4H), 
               
               
                   
                 3-yl)-pyrimidin-2-yl]-N-methyl- 
                   
                   
                   
                 7.30-7.24 (m, 1H), 3.66 (s, 2H), 3.27 (s, 
               
               
                   
                 cyclopropanecarboxylic acid amide 
                   
                   
                   
                 3H), 2.47-2.29 (m, 2H), 1.99-1.87 (m, 
               
               
                   
                   
                   
                   
                   
                 10H), 1.49 (t, 2H), 0.88-0.80 (m, 2H), 0.70 
               
               
                   
                   
                   
                   
                   
                 (dt, 2H). 
               
               
                 SC_3374 
                 cis-N-[5-(8-Dimethylamino-2-oxo- 
                 SC_3371 
                 2,5-dimethylpyrazole-3-carbonyl 
                 SC_3240 
                 1H NMR (600 MHz, DMSO) δ 8.83 (s, 2H), 
                 503.3 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                 chloride 
                   
                 7.77 (s, 1H), 7.41-7.32 (m, 4H), 7.27 (td, 
               
               
                   
                 3-yl)-pyrimidin-2-yl]-N,2,5- 
                   
                   
                   
                 1H), 5.48 (s, 1H), 3.80 (s, 3H), 3.61 (s, 2H), 
               
               
                   
                 trimethyl-2H-pyrazole-3-carboxylic 
                   
                   
                   
                 3.40 (s, 3H), 2.46-2.31 (m, 2H), 1.96 (s, 
               
               
                   
                 acid amide 
                   
                   
                   
                 3H), 1.96 (s, 6H), 1.94-1.74 (m, 5H), 1.52- 
               
               
                   
                   
                   
                   
                   
                 1.42 (m, 2H). 
               
               
                 SC_3375 
                 cis-3-[4,6-Bis(trifluoromethyl)- 
                 INT-976 
                 5-bromo-2,4- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.98 (s, 1H), 
                 487.2 
               
               
                   
                 pyridin-3-yl]-8-dimethylamino-8- 
                   
                 bis(trifluoromethyl)pyridine 
                   
                 8.20 (s, 1H), 7.79 (s, 1H), 7.40-7.32 (m, 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 4H), 7.26 (td, 1H), 3.62 (s, 2H), 2.44-2.24 
               
               
                   
                 one 
                   
                   
                   
                 (m, 2H), 1.98-1.91 (m, 8H), 1.86 (s, 2H), 
               
               
                   
                   
                   
                   
                   
                 1.53 (t, 2H). 
               
               
                 SC_3376 
                 cis-8-Dimethylamino-3-[2-[(2- 
                 INT-976 
                 2-[(6-bromo-quinazolin-2-yl)- 
                 SC_3242 
                 1HNMR at 100° C. (DMSO-d6, 400 MHz), δ 
                 475.1 
               
               
                   
                 hydroxy-ethyl)-methyl-amino]- 
                   
                 methyl-amino]-ethanol 
                   
                 (ppm) = 8.99 (s, 1H), 8.28 (d, 1H, J = 9.24 
               
               
                   
                 quinazolin-6-yl]-8-phenyl-1,3- 
                   
                   
                   
                 Hz), 7.63 (s, 1H), 7.43-7.26 (m, 6H), 7.13 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (s, 1H), 4.31 (bs, 1H), 3.78-3.76 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 3.66 (bs, 4H), 3.24 (s, 3H), 2.43-2.38 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 2.05-1.90 (m, 10H), 1.56-1.54 (m, 2H). 
               
               
                 SC_3377 
                 cis-8-Dimethylamino-3-(2- 
                 INT-976 
                 6-bromo-2-morpholin-4-yl- 
                 SC_3242 
                 1HNMR at 100° C. (DMSO-d6, 400 MHz), δ 
                 487.2 
               
               
                   
                 morpholin-4-yl-quinazolin-6-yl)-8- 
                   
                 quinazoline 
                   
                 (ppm) = 9.05 (s, 1H), 8.34 (d, 1H), 7.68 (s, 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 1H), 7.48 (d, 1H, J = 9.4 Hz), 7.38-7.27 (m, 
               
               
                   
                 one 
                   
                   
                   
                 5H), 7.18 (s, 1H), 3.81-3.67 (m, 10H), 2.40- 
               
               
                   
                   
                   
                   
                   
                 2.38 (m, 2H), 2.05-1.90 (m, 10H), 1.57-1.54 
               
               
                   
                   
                   
                   
                   
                 (m, 2H). 
               
               
                 SC_3378 
                 cis-8-[Methyl-(oxetan-3-yl- 
                 INT-1047 
                 2-trifluoromethyl-5- 
                 SC_3103 
                 1H NMR (DMSO-d6): δ 9.21-9.15 (s, 2H), 
                 476.2 
               
               
                   
                 methyl)-amino]-8-phenyl-3-[2- 
                   
                 bromopyrimidine 
                   
                 8.19-8.18 (broad s, 1H), 7.41-7.34 (m, 4H), 
               
               
                   
                 (trifluoromethyl)-pyrimidin-5-yl]- 
                   
                   
                   
                 7.27-7.25 (m, 1H), 4.58-4.56 (m, 2H), 4.18 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (s, 1H), 3.69 (s, 2H), 3.05-2.99 (m, 1H), 
               
               
                   
                   
                   
                   
                   
                 2.41-2.36 (m, 4H), 1.91 (m, 7H), 1.47 (s, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3380 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 6-bromo-quinazoline 
                 SC_3103 
                 1HNMR at 100° C. (DMSO-d6, 400 MHz), δ 
                 402.2 
               
               
                   
                 quinazolin-6-yl-1,3- 
                   
                   
                   
                 (ppm) = 9.35 (s, 1H), 9.10 (s, 1H), 8.65 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (d, 1H, J = 9.04) 7.91-7.89 (m, 2H), 7.39- 
               
               
                   
                   
                   
                   
                   
                 7.27 (m, 5H), 3.75 (s, 2H), 2.42-2.32 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.05 (s, 6H), 2.00-1.92 (m, 4H), 1.56 (bs, 2H). 
               
               
                 SC_3381 
                 cis-5-(8-Dimethylamino-2-oxo-8- 
                 INT-976 
                 5-bromo-2-chloro- 
                 SC_3103 (for step 1), 
                 1H NMR (600 MHz, DMSO) δ 8.88 (s, 1H), 
                 507.3 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-3- 
                   
                 pyridine-4-carbonitrile (step 1), 
                 SC_3129 (for step 2) 
                 8.24 (s, 1H), 7.85 (s, 1H), 7.52-7.46 (m, 
               
               
                   
                 yl)-2-(2-oxo-1,3-dihydro-indol-4- 
                   
                 4-(4,4,5,5-tetramethyl-1,3,2- 
                   
                 1H), 7.41-7.29 (m, 6H), 7.27 (td, 1H), 6.92 
               
               
                   
                 yl)-isonicotinonitrile 
                   
                 dioxaborolan-2- 
                   
                 (d, 1H), 3.84 (s, 2H), 3.78 (s, 2H), 2.48- 
               
               
                   
                   
                   
                 yl)indolin-2-one (step 2) 
                   
                 2.30 (m, 2H), 1.99-1.93 (m, 8H), 1.92- 
               
               
                   
                   
                   
                   
                   
                 1.74 (m, 2H), 1.58-1.54 (m, 2H). 
               
               
                 SC_3382 
                 cis-N-[5-(8-Dimethylamino-2-oxo- 
                 SC_3371 
                 tetrahydropyran-4-carbonyl 
                 SC_3240 
                 1H NMR (600 MHz, DMSO) δ 8.97 (s, 2H), 
                 493.3 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                 chloride 
                   
                 7.80 (s, 1H), 7.42-7.34 (m, 4H), 7.31- 
               
               
                   
                 3-yl)-pyrimidin-2-yl]-N-methyl- 
                   
                   
                   
                 7.25 (m, 1H), 3.79 (ddd, 2H), 3.67 (s, 2H), 
               
               
                   
                 tetrahydro-pyran-4-carboxylic acid 
                   
                   
                   
                 3.25 (s, 2H), 3.17 (td, 2H), 3.04-2.96 (m, 
               
               
                   
                 amide 
                   
                   
                   
                 1H), 2.49-2.34 (m, 2H), 1.97 (s, 6H), 1.95- 
               
               
                   
                   
                   
                   
                   
                 1.74 (m, 4H), 1.68-1.53 (m, 4H), 1.54- 
               
               
                   
                   
                   
                   
                   
                 1.48 (m, 2H). 
               
               
                 SC_3383 
                 cis-N-[5-(8-Dimethylamino-2-oxo- 
                 SC_3371 
                 pivaloyl chloride 
                 SC_3240 
                 1H NMR (600 MHz, DMSO) δ 8.98 (s, 2H), 
                 465.3 
               
               
                   
                 8-phenyl-1,3-diazaspiro[4.5]decan- 
                   
                   
                   
                 7.42-7.34 (m, 4H), 7.30-7.26 (m, 1H), 
               
               
                   
                 3-yl)-pyrimidin-2-yl]-N,2,2- 
                   
                   
                   
                 3.69 (s, 2H), 3.14 (s, 3H), 2.46-2.41 (m, 
               
               
                   
                 trimethyl-propionamide 
                   
                   
                   
                 2H), 1.99-1.87 (m, 10H), 1.54-1.45 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 0.97 (s, 9H). 
               
               
                 SC_3384 
                 cis-8-Dimethylamino-3-[2-(1- 
                 INT-989 
                 1-methyl-4-(4,4,5,5- 
                 SC_3208 
                 1H NMR (600 MHz, CDCl3) δ 9.05 (s, 2H), 
                 497.3 
               
               
                   
                 methyl-2-oxo-1,3-dihydro-indol-4- 
                   
                 tetramethyl-1,3,2- 
                   
                 8.08 (d, 1H), 7.47-7.39 (m, 3H), 7.38- 
               
               
                   
                 yl)-pyrimidin-5-yl]-8-phenyl-1,3- 
                   
                 dioxaborolan-2- 
                   
                 7.31 (m, 3H), 6.91 (d, 1H), 5.46 (s, 1H), 4.04 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                 yl)indolin-2-one 
                   
                 (s, 2H), 3.64 (s, 2H), 3.27 (s, 3H), 2.35- 
               
               
                   
                   
                   
                   
                   
                 2.14 (m, 4H), 2.10 (s, 6H), 2.08-2.01 (m, 
               
               
                   
                   
                   
                   
                   
                 3H), 1.73-1.64 (m, 2H), 1.28 (s, 0H). 
               
               
                 SC_3385 
                 cis-8-Dimethylamino-3-(2- 
                 INT-976 
                 6-bromo-1-(tert-butylsilanyl- 
                 SC_3242 (for step 1), 
                 1HNMR at 100° C. (DMSO-d6, 400 MHz), δ 
                 475.2 
               
               
                   
                 morpholin-4-yl-1H-benzoimidazol- 
                   
                 methoxymethyl)-2- 
                 step 2 of SC_3352 (for step 2) 
                 (ppm) = 10.94 (bs, 1H), 7.50 (bs, 1H), 7.39- 
               
               
                   
                 5-yl)-8-phenyl-1,3- 
                   
                 morpholin-4-yl-1H- 
                   
                 7.27 (m, 5H), 7.06 (m, 2 H), 6.84 (bs, 1H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                 benzoimidazole (step 1) 
                   
                 3.72 (t, 4H, 4.56 Hz), 3.55 (s, 2H), 3.45 (t, 
               
               
                   
                   
                   
                   
                   
                 4H, 4.56 Hz), 2.372.24 (m, 2H), 1.95-1.81 
               
               
                   
                   
                   
                   
                   
                 (m, 10H), 1.52-1.50 (m, 2H) 
               
               
                 SC_3386 
                 cis-8-Dimethylamino-8-(3-fluoro- 
                 INT-1043 
                 5-bromo-4-methyl-2- 
                 SC_3319 
                 1H NMR (600 MHz, DMSO) δ 8.57 (s, 1H), 
                 465.2 
               
               
                   
                 5-methyl-phenyl)-3-[4-methyl-6- 
                   
                 (trifluoromethyl)pyridine 
                   
                 7.80 (s, 1H), 7.51 (s, 1H), 6.99 (s, 1H), 6.96- 
               
               
                   
                 (trifluoromethyl)-pyridin-3-yl]-1,3- 
                   
                   
                   
                 6.89 (m, 2H), 3.61 (s, 2H), 2.34 (s, 3H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2.32 (s, 3H), 2.07 (s, 1H), 1.97 (s, 6H), 1.96- 
               
               
                   
                   
                   
                   
                   
                 1.89 (m, 2H), 1.88-1.78 (m, 2H), 1.54 (d, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3387 
                 cis-8-Dimethylamino-3-[6-(2-oxo- 
                 INT-1048 
                 4-(4,4,5,5-tetramethyl-1,3,2- 
                 SC_3129 
                 1H NMR (600 MHz, DMSO) δ 8.83 (d, 1H), 
                 482.3 
               
               
                   
                 1,3-dihydro-indol-4-yl)-pyridin-3- 
                   
                 dioxaborolan-2-yl)indolin-2-one 
                   
                 8.11 (dd, 1H), 7.77 (d, 1H), 7.64 (s, 1H), 
               
               
                   
                 yl]-8-phenyl-1,3- 
                   
                   
                   
                 7.43-7.34 (m, 5H), 7.31-7.24 (m, 2H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 6.84 (d, 1H), 3.73 (s, 2H), 3.68 (s, 2H), 2.45- 
               
               
                   
                   
                   
                   
                   
                 2.31 (m, 2H), 1.99-1.79 (m, 10H), 1.51 
               
               
                   
                   
                   
                   
                   
                 (t, 2H). 
               
               
                 SC_3389 
                 cis-3-[6-(Azetidin-1-yl)-5- 
                 INT-976 
                 5-bromo-2-chloro-3- 
                 SC_3103 (for step 1), 
                 1H NMR (600 MHz, DMSO) δ 8.40 (d, 1H), 
                 453.2 
               
               
                   
                 (trifluoromethyl)-pyridin-3-yl]-8- 
                   
                 (trifluoromethyl)pyridine (step 1), 
                 SC_3120 (for step 2, 160° C.) 
                 8.21 (d, 1H), 7.47 (s, 1H), 7.41-7.33 (m, 
               
               
                   
                 dimethylamino-8-phenyl-1,3- 
                   
                 azetidine (step 2) 
                   
                 4H), 7.30-7.24 (m, 1H), 4.03 (t, 4H), 3.58 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 (s, 2H), 2.47-2.29 (m, 2H), 2.25 (p, 2H), 
               
               
                   
                   
                   
                   
                   
                 1.96 (s, 6H), 1.89 (s, 4H), 1.47 (t, 2H). 
               
               
                 SC_3390 
                 cis-3-[1-(Cyclopropyl-methyl)-8- 
                 SC_3364 
                 bromomethylcyclopropane 
                 INT-952 
                 1H NMR (600 MHz, DMSO) δ 8.82 (s, 1H), 
                 430.3 
               
               
                   
                 dimethylamino-2-oxo-8-phenyl- 
                   
                   
                   
                 8.51 (dd, 1H), 7.81 (d, 1H), 7.40-7.33 (m, 
               
               
                   
                 1,3-diazaspiro[4.5]decan-3-yl]- 
                   
                   
                   
                 4H), 7.29-7.23 (m, 1H), 3.93 (s, 2H), 3.10 
               
               
                   
                 isonicotinonitrile 
                   
                   
                   
                 (d, 2H), 2.76-2.70 (m, 2H), 2.29 (ddd, 2H), 
               
               
                   
                   
                   
                   
                   
                 2.02 (s, 6H), 1.58 (d, 2H), 1.52-1.44 (m, 
               
               
                   
                   
                   
                   
                   
                 2H), 1.01 (ddt, 1H), 0.55-0.49 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 0.37-0.31 (m, 2H). 
               
               
                 SC_3391 
                 cis-3-[3,5-Bis(trifluoromethyl)- 
                 INT-976 
                 2-chloro-3,5- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 9.04 (d, 1H), 
                 487.2 
               
               
                   
                 pyridin-2-yl]-8-dimethylamino-8- 
                   
                 bis(trifluoromethyl)pyridine 
                   
                 8.58 (d, 1H), 7.96 (s, 1H), 7.41-7.32 (m, 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 4H), 7.29-7.23 (m, 1H), 3.75 (s, 2H), 2.41- 
               
               
                   
                 one 
                   
                   
                   
                 2.25 (m, 2H), 1.98-1.89 (m, 10H), 1.52 
               
               
                   
                   
                   
                   
                   
                 (t, 2H). 
               
               
                 SC_3392 
                 cis-8-Dimethylamino-3-(5-fluoro- 
                 INT-976 
                 4-(5-bromo-3-fluoro- 
                 SC_3103 
                 1H NMR (600 MHz, CDCl3) δ 8.13 (dd, 
                 454.3 
               
               
                   
                 6-morpholin-4-yl-pyridin-3-yl)-8- 
                   
                 2-pyridyl)morpholine 
                   
                 1H), 7.76 (d, 1H), 7.42 (t, 2H), 7.33 (dd, 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 3H), 5.84 (s, 1H), 3.84 (t, 4H), 3.52 (s, 2H), 
               
               
                   
                 one 
                   
                   
                   
                 3.37 (t, 4H), 2.29-2.12 (m, 4H), 2.08 (s, 
               
               
                   
                   
                   
                   
                   
                 6H), 2.01-1.94 (m, 2H), 1.60 (t, 2H). 
               
               
                 SC_3393 
                 cis-8-(3-Chlorophenyl)-8- 
                 INT-1044 
                 5-bromo-4-methyl-2- 
                 SC_3319 
                 1H NMR (600 MHz, DMSO) δ 8.57 (s, 1H), 
                 467.2 
               
               
                   
                 dimethylamino-3-[4-methyl-6- 
                   
                 (trifluoromethyl)pyridine 
                   
                 7.80 (s, 1H), 7.55-7.49 (m, 1H), 7.43- 
               
               
                   
                 (trifluoromethyl)-pyridin-3-yl]-1,3- 
                   
                   
                   
                 7.37 (m, 1H), 7.38-7.29 (m, 3H), 3.61 (s, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2H), 2.40-2.24 (m, 5H), 1.99-1.90 (m, 
               
               
                   
                   
                   
                   
                   
                 8H), 1.90-1.76 (m, 2H), 1.60-1.47 (m, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3394 
                 cis-8-Dimethylamino-3-[5-(2-oxo- 
                 INT-1049 
                 4-(4,4,5,5-tetramethyl-1,3,2- 
                 SC_3354 
                 1H NMR (600 MHz, DMSO) δ 8.41 (d, 1H), 
                 482.3 
               
               
                   
                 1,3-dihydro-indol-4-yl)-pyridin-2- 
                   
                 dioxaborolan-2-yl)indolin-2-one 
                   
                 8.26 (d, 1H), 7.92 (dd, 1H), 7.75 (s, 1H), 
               
               
                   
                 yl]-8-phenyl-1,3- 
                   
                   
                   
                 7.41-7.32 (m, 5H), 7.30-7.23 (m, 2H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 7.01 (d, 1H), 6.83 (d, 1H), 3.75 (s, 2H), 3.61 
               
               
                   
                   
                   
                   
                   
                 (s, 2H), 2.46-2.30 (m, 2H), 1.96 (s, 6H), 
               
               
                   
                   
                   
                   
                   
                 1.94-1.88 (m, 2H), 1.86-1.82 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 1.48 (t, 2H). 
               
               
                 SC_3395 
                 cis-8-Dimethylamino-8-phenyl-3- 
                 INT-976 
                 2-bromo-5-(trifluoromethyl)- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.69 (s, 1H), 
                 426.2 
               
               
                   
                 [5-(trifluoromethyl)- 
                   
                 1,3,4-thiadiazole 
                   
                 7.42-7.34 (m, 4H), 7.28 (t, 1H), 3.89 (s, 
               
               
                   
                 [1,3,4]thiadiazol-2-yl]-1,3- 
                   
                   
                   
                 2H), 2.45-2.31 (m, 2H), 2.07-1.88 (m, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 8H), 1.88-1.84 (m, 2H), 1.60-1.53 (m, 
               
               
                   
                   
                   
                   
                   
                 2H). 
               
               
                 SC_3397 
                 cis-8-Dimethylamino-3-[2-[(2- 
                 INT-976 
                 2-{[6-bromo-1-(2-trimethylsilanyl- 
                 SC_3242 (for step 1), 
                 1HNMR (DMSO-d6, 400 MHz at 100° C.), δ 
                 463.3 
               
               
                   
                 hydroxy-ethyl)-methyl-amino]-1H- 
                   
                 ethoxymethyl)-1H-benzoimidazol-2-yl]- 
                 step 2 of SC_3352 (for step 2) 
                 (ppm) = 10.62 (bs, 1H), 7.48-7.24 (m, 6H), 
               
               
                   
                 benzoimidazol-5-yl]-8-phenyl-1,3- 
                   
                 methyl-amino}-ethanol (step 1) 
                   
                 7.01-6.91 (m, 2H,), 6.76 (s, 1H), 4.58 (bs, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 1H), 3.66 (t, 2H, J = 5.62 Hz), 3.54-3.50 (m, 
               
               
                   
                   
                   
                   
                   
                 4H), 3.09 (s, 3H), 2.37-2.32 (m, 2H), 2.04 (s, 
               
               
                   
                   
                   
                   
                   
                 6H), 1.96-1.91 (m, 4H), 1.52-1.40 (m, 2H). 
               
               
                 SC_3398 
                 cis-8-Dimethylamino-3-(5-methyl- 
                 INT-976 
                 4-(5-bromo-3-methyl- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.23 (s, 1H), 
                 450.3 
               
               
                   
                 6-morpholin-4-yl-pyridin-3-yl)-8- 
                   
                 2-pyridyl)morpholine 
                   
                 7.83 (s, 1H), 7.46-7.33 (m, 5H), 7.30- 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                   
                   
                 7.24 (m, 1H), 3.71 (t, 4H), 3.55 (s, 2H), 2.93 
               
               
                   
                 one 
                   
                   
                   
                 (t, 4H), 2.41-2.37 (m, 2H), 1.96 (s, 6H), 
               
               
                   
                   
                   
                   
                   
                 1.91-1.82 (m, 4H), 1.49-1.44 (m, 2H). 
               
               
                 SC_3399 
                 cis-1-(Cyclopropyl-methyl)-8- 
                 SC_3409 
                 bromomethylcyclopropane 
                 SC_3105 
                 1HNMR (DMSO-d6, 400 MHz), δ (ppm) = 
                 501.4 
               
               
                   
                 dimethylamino-8-(3-fluorophenyl)- 
                   
                   
                   
                 8.68-8.68 (d, 1H, J = 2.32 Hz), 8.42-8.40 (d, 
               
               
                   
                 3-(5-methylsulfonyl-pyridin-2-yl)- 
                   
                   
                   
                 1H, J = 9.04 Hz), 8.18-8.15 (m, 1H), 7.44- 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 7.38 (m, 1H), 7.20-7.08 (m, 3H), 3.90 (s, 
               
               
                   
                   
                   
                   
                   
                 2H), 3.22 (s, 3H), 3.11-3.10 (d, 2H, J = 6.68 
               
               
                   
                   
                   
                   
                   
                 Hz), 2.71-2.68 (d, 2H, J = 13.6 Hz), 2.27- 
               
               
                   
                   
                   
                   
                   
                 2.21(m, 2H), 2.00 (s, 6H), 1.53-1.44 (m, 
               
               
                   
                   
                   
                   
                   
                 4H), 1.02-0.99 (m, 1H), 0.54-0.50 (m, 2H), 
               
               
                   
                   
                   
                   
                   
                 0.36-0.35 (m, 2H). 
               
               
                 SC_3400 
                 cis-1-(Cyclopropyl-methyl)-8-(3- 
                 SC_3399 
                   
                 SC_3099 
                 1HNMR (DMSO-d6, 400 MHz), δ (ppm) = 
                 487.2 
               
               
                   
                 fluorophenyl)-8-methylamino-3-(5- 
                   
                   
                   
                 8.72-8.71 (d, 1H, J = 2.28 Hz), 8.42-8.40 (d, 
               
               
                   
                 methylsulfonyl-pyridin-2-yl)-1,3- 
                   
                   
                   
                 1H, J = 9.04 Hz), 8.18-8.15 (m, 1H), 7.40- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 7.31 (m, 3H), 7.05-7.01 (m, 1H), 3.93 (s, 
               
               
                   
                   
                   
                   
                   
                 2H), 3.23 (s, 3H), 3.14-3.13 (d, 2H, J = 6.76 
               
               
                   
                   
                   
                   
                   
                 Hz), 2.42 (bs, 1H), 2.28-2.23(m, 2H), 1.96- 
               
               
                   
                   
                   
                   
                   
                 1.88 (m, 5H), 1.79-1.73 (m, 2H), 1.44-1.41 
               
               
                   
                   
                   
                   
                   
                 (d, 2H, J = 12.2 Hz), 1.06-1.02 (m, 1H), 
               
               
                   
                   
                   
                   
                   
                 0.52-0.47 (m, 2H), 0.36-0.33 (m, 2H). 
               
               
                 SC_3401 
                 cis-1-(Cyclobutyl-methyl)-8-(3- 
                 SC_3404 
                 bromomethylcyclobutane (step 1) 
                 SC_3105 (for step 1), 
                 1HNMR at 100° C. (DMSO-d6, 400 MHz), δ 
                 492.1 
               
               
                   
                 fluorophenyl)-8-methylamino-3-[2- 
                   
                   
                 SC_3099 (for step 2) 
                 (ppm) = 9.23 (s, 2H), 7.38-7.26 (m, 3H), 
               
               
                   
                 (trifluoromethyl)-pyrimidin-5-yl]- 
                   
                   
                   
                 7.00 (t, 1H, J = 8.1 Hz), 3.86 (s, 2H), 3.30- 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.28 (d, 2H, J = 7.24 Hz), 2.68-2.65 (m, 1H), 
               
               
                   
                   
                   
                   
                   
                 2.27-2.16 (m, 3H), 2.06-1.78 (m, 13H), 1.46- 
               
               
                   
                   
                   
                   
                   
                 1.43 (m, 2H). 
               
               
                 SC_3402 
                 cis-1-(Cyclopropyl-methyl)-8- 
                 SC_3404 
                 bromomethylcyclopropane 
                 SC_3105 
                 1HNMR (DMSO-d6, 400 MHz), δ (ppm) = 
                 492.0 
               
               
                   
                 dimethylamino-8-(3-fluorophenyl)- 
                   
                   
                   
                 9.21 (s, 2H), 7.45-7.39 (m, 1H), 7.22-7.18 
               
               
                   
                 3-[2-(trifluoromethyl)-pyrimidin-5- 
                   
                   
                   
                 (m, 2H), 7.14-7.09 (m, 1H), 3.84 (s, 2H), 
               
               
                   
                 yl]-1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 3.09 (d, 2H, J = 6.4 Hz), 2.70 (d, 2H, J = 9.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 2.32-2.21 (m, 2H), 2.01 (s, 6H), 1.59- 
               
               
                   
                   
                   
                   
                   
                 1.46 (m, 4H), 1.01-1.00 (m, 1H), 0.54-0.49 
               
               
                   
                   
                   
                   
                   
                 (m, 2H), 0.35-0.33 (m, 2H). 
               
               
                 SC_3403 
                 cis-1-(Cyclopropyl-methyl)-8-(3- 
                 SC_3402 
                   
                 SC_3099 
                 1HNMR (DMSO-d6, 400 MHz), δ (ppm) = 
                 478.4 
               
               
                   
                 fluorophenyl)-8-methylamino-3-[2- 
                   
                   
                   
                 9.25 (s, 2H), 7.41-7.30 (m, 3H), 7.04 (t, 1H, 
               
               
                   
                 (trifluoromethyl)-pyrimidin-5-yl]- 
                   
                   
                   
                 J = 6.8 Hz), 3.89 (s, 2H), 3.12 (d, 2H, J = 6.8 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 Hz), 2.41 (bs, 1H), 2.27-2.22 (m, 2H), 1.93- 
               
               
                   
                   
                   
                   
                   
                 1.78 (m, 7H), 1.46-1.43 (m, 2H), 1.08-1.03 (m, 
               
               
                   
                   
                   
                   
                   
                 1H), 0.51-0.47 (m, 2H), 0.33-0.29 (m, 2H). 
               
               
                 SC_3404 
                 cis-8-Dimethylamino-8-(3- 
                 INT-1024 
                 2-trifluoromethyl-5- 
                 SC_3242 
                 1HNMR at 100° C. (DMSO-d6, 400 MHz), δ 
                 437.9 
               
               
                   
                 fluorophenyl)-3-[2- 
                   
                 bromopyrimidine 
                   
                 (ppm) = 9.15 (s, 2H), 7.75 (s, 1H), 7.44-7.38 
               
               
                   
                 (trifluoromethyl)-pyrimidin-5-yl]- 
                   
                   
                   
                 (m, 1H), 7.21-7.04 (m, 3H), 3.73 (s, 2H), 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 2.38-2.37 (m, 2H), 2.05 (s, 6H), 2.01-1.85 
               
               
                   
                   
                   
                   
                   
                 (m, 4H), 1.57-1.53 (m, 2H). 
               
               
                 SC_3405 
                 cis-1-(Cyclopropyl-methyl)-8- 
                 SC_3319 
                 bromomethylcyclopropane 
                 SC_3105 
                 1HNMR at 100° C. (DMSO-d6, 400 MHz), δ 
                 494.3 
               
               
                   
                 dimethylamino-8-(3-fluorophenyl)- 
                   
                   
                   
                 (ppm) = 7.39-7.36 (m, 1H), 7.19-7.05 (m, 
               
               
                   
                 3-[2-methyl-5-(trifluoromethyl)- 
                   
                   
                   
                 3H), 6.56 (s, 1H), 3.78-3.67 (m, 5H), 3.10- 
               
               
                   
                 2H-pyrazol-3-yl]-1,3- 
                   
                   
                   
                 3.08 (d, 2H, J = 6.12 Hz), 2.64-2.60 (d, 2H, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 J = 13.32 Hz), 2.37-2.26(m, 2H), 2.09 (s, 6H), 
               
               
                   
                   
                   
                   
                   
                 1.61-1.49 (m, 4H), 1.10-1.02 (m, 1H), 0.54- 
               
               
                   
                   
                   
                   
                   
                 0.52 (m, 2H), 0.36-0.33 (m, 2H). 
               
               
                 SC_3406 
                 cis-1-(Cyclopropyl-methyl)-8-(3- 
                 SC_3405 
                   
                 SC_3099 
                 1HNMR at 100° C. (DMSO-d6, 400 MHz), δ 
                 480.0 
               
               
                   
                 fluorophenyl)-8-methylamino-3-[2- 
                   
                   
                   
                 (ppm) = 7.39-7.24 (m, 3H), 6.99-6.96 (m, 
               
               
                   
                 methyl-5-(trifluoromethyl)-2H- 
                   
                   
                   
                 1H), 6.58 (s, 1H), 3.78-3.71 (m, 5H), 3.11- 
               
               
                   
                 pyrazol-3-yl]-1,3- 
                   
                   
                   
                 3.10 (d, 2H, J = 5.40 Hz), 2.30-2.23(m, 2H), 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 1.99-1.92 (m, 5H), 1.79-1.72 (m, 2H), 1.58- 
               
               
                   
                   
                   
                   
                   
                 1.56 (m, 2H), 1.10-1.00 (m, 1H), 0.54-0.52 
               
               
                   
                   
                   
                   
                   
                 (m, 2H), 0.36-0.33 (m, 2H). 
               
               
                 SC_3407 
                 cis-8-Methylamino-3-(4-methyl-2- 
                 SC_3148 
                   
                 SC_3099 
                   
                 437.3 
               
               
                   
                 morpholin-4-yl-pyrimidin-5-yl)-8- 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
               
               
                   
                 one 
               
               
                 SC_3408 
                 cis-3-[5-(Azetidin-1-yl)-3-methyl- 
                 INT-1024 
                 5-(azetidin-1-yl)-2-chloro-3-methyl- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 7.44-7.36 
                 438.3 
               
               
                   
                 pyridin-2-yl]-8-dimethylamino-8- 
                   
                 pyridine 
                   
                 (m, 2H), 7.20-7.05 (m, 4H), 6.69 (d, 1H), 
               
               
                   
                 (3-fluorophenyl)-1,3- 
                   
                   
                   
                 3.82 (t, 4H), 3.51 (s, 2H), 2.36-2.26 (m, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 4H), 2.15 (s, 3H), 1.96 (s, 6H), 1.94-1.76 
               
               
                   
                   
                   
                   
                   
                 (m, 4H), 1.49 (t, 2H). 
               
               
                 SC_3409 
                 cis-8-Dimethylamino-8-(3- 
                 INT-1024 
                 2-bromo-5-methylsulfonyl- 
                 SC_3103 
                 1H NMR (600 MHz, DMSO) δ 8.67 (dd, 
                 447.2 
               
               
                   
                 fluorophenyl)-3-(5-methylsulfonyl- 
                   
                 pyridine 
                   
                 1H), 8.39 (dd, 1H), 8.14 (dd, 1H), 8.04 (s, 
               
               
                   
                 pyridin-2-yl)-1,3- 
                   
                   
                   
                 1H), 7.42 (td, 1H), 7.19 (d, 1H), 7.15 (dt, 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
                   
                   
                   
                 1H), 7.11 (td, 1H), 3.78 (s, 2H), 3.21 (s, 3H), 
               
               
                   
                   
                   
                   
                   
                 2.41-2.37 (m, 2H), 1.97 (s, 6H), 1.94- 
               
               
                   
                   
                   
                   
                   
                 1.75 (m, 4H), 1.54-1.45 (m, 2H). 
               
               
                 SC_3410 
                 cis-3-(6-(azetidin--yl)-4- 
                 INT-976 
                 2-(azetidin-1-yl)-5-bromo-4- 
                 SC_3103 
               
               
                   
                 fluoropyridin-3-yl)-8- 
                   
                 fluoropyridine 
               
               
                   
                 (dimethylamino)-8-phenyl-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3411 
                 cis-3-(6-(azetidin-1-yl)pyridin-3- 
                 INT-1024 
                 2-(azetidin-1-yl)-5- 
                 SC_3103 
               
               
                   
                 yl)-8-(dimethylamino)-8-(3- 
                   
                 bromopyridine 
               
               
                   
                 fluorophenyl)-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3412 
                 cis-3-(1-(cyclopropanecarbonyl)-3- 
                 INT-1024 
                 (5-bromo-3-(trifluoromethyl)-1H- 
                 SC_3103 
               
               
                   
                 (trifluoromethyl)-1H-pyrazol-5-yl)- 
                   
                 pyrazol-1-yl)(cyclopropyl)methanone 
               
               
                   
                 8-(dimethylamino)-8-(3- 
               
               
                   
                 fluorophenyl)-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3413 
                 cis-8-(dimethylamino)-8-(3- 
                 INT-1024 
                 2-(5-bromo-3-(trifluoromethyl)-1H- 
                 SC_3242 
               
               
                   
                 fluorophenyl)-3-(1-(2- 
                   
                 pyrazol-1-yl)ethanol 
               
               
                   
                 hydroxyethyl)-3-(trifluoromethyl)- 
               
               
                   
                 1H-pyrazol-5-yl)-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3414 
                 cis-3-(1-(cyclopropylmethyl)-3- 
                 INT-1024 
                 5-bromo-1-(cyclopropylmethyl)- 
                 SC_3242 
                   
                 480.2 
               
               
                   
                 (trifluoromethyl)-1H-pyrazol-5-yl)- 
                   
                 3-(trifluoromethyl)-1H-pyrazole 
               
               
                   
                 8-(dimethylamino)-8-(3- 
               
               
                   
                 fluorophenyl)-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3415 
                 cis-8-(dimethylamino)-8-(3- 
                 INT-1024 
                 5-bromo-1-(methylsulfonyl)-3- 
                 SC_3242 
               
               
                   
                 fluorophenyl)-3-(1- 
                   
                 (trifluoromethyl)-1H-pyrazole 
               
               
                   
                 (methylsulfonyl)-3- 
               
               
                   
                 (trifluoromethyl)-1H-pyrazol-5-yl)- 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
               
               
                 SC_3416 
                 cis-1-(cyclopropylmethyl)-8- 
                 SC_3415 
                 bromomethylcyclopropane 
                 SC_3105 
               
               
                   
                 (dimethylamino)-8-(3- 
               
               
                   
                 fluorophenyl)-3-(1- 
               
               
                   
                 (methylsulfonyl)-3- 
               
               
                   
                 (trifluoromethyl)-1H-pyrazol-5-yl)- 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
               
               
                 SC_3417 
                 cis-2-(5-(8-(dimethylamino)-8-(3- 
                 INT-1024 
                 2-(5-bromo-3-(trifluoromethyl)-1H- 
                 SC_3242 
               
               
                   
                 fluorophenyl)-2-oxo-1,3- 
                   
                 pyrazol-1-yl)-N,N-dimethylacetamide 
               
               
                   
                 diazaspiro[4.5]decan-3-yl)-3- 
               
               
                   
                 (trifluoromethyl)-1H-pyrazol-1-yl)- 
               
               
                   
                 N,N-dimethylacetamide 
               
               
                 SC_3418 
                 cis-2-(5-(1-(cyclopropylmethyl)-8- 
                 SC_3417 
                 bromomethylcyclopropane 
                 SC_3105 
               
               
                   
                 (dimethylamino)-8-(3- 
               
               
                   
                 fluorophenyl)-2-oxo-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-3-yl)-3- 
               
               
                   
                 (trifluoromethyl)-1H-pyrazol-1-yl)- 
               
               
                   
                 N,N-dimethylacetamide 
               
               
                 SC_3419 
                 cis-8-(dimethylamino)-3-(1-methyl- 
                 INT-976 
                 5-bromo-1-methyl-1H-pyrrolo[2,3- 
                 SC_3103 
                   
                 404.3 
               
               
                   
                 1H-pyrrolo[2,3-b]pyridin-5-yl)-8- 
                   
                 b]pyridine 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
               
               
                   
                 one 
               
               
                 SC_3420 
                 cis-8-(dimethylamino)-3-(3-fluoro- 
                 INT-976 
                 5-bromo-3-fluoro-1-((2- 
                 SC_3352 
                   
                 408.2 
               
               
                   
                 1H-pyrrolo[2,3-b]pyridin-5-yl)-8- 
                   
                 (trimethylsilyl)ethoxy)methyl)- 
               
               
                   
                 phenyl-1,3-diazaspiro[4.5]decan-2- 
                   
                 1H-pyrrolo[2,3-b]pyridine (step 1) 
               
               
                   
                 one 
               
               
                 SC_3421 
                 cis-8-(dimethylamino)-8-phenyl-3- 
                 INT-976 
                 4-bromo-1-((2- 
                 SC_3352 
                   
                 390.2 
               
               
                   
                 (1H-pyrrolo[2,3-c]pyridin-4-yl)- 
                   
                 (trimethylsilyl)ethoxy)methyl)- 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
                   
                 1H-pyrrolo[2,3-c]pyridine 
               
               
                 SC_3422 
                 cis-8-(dimethylamino)-8-phenyl-3- 
                 INT-989 
                 4-(4,4,5,5-tetramethyl-1,3,2- 
                 SC_3354 
                   
                 430.2 
               
               
                   
                 (2-(pyridazin-4-yl)pyrimidin-5-yl)- 
                   
                 dioxaborolan-2-yl)pyridazine 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
               
               
                 SC_3423 
                 cis-8-(dimethylamino)-3-(2-(2-oxo- 
                 INT-989 
                 (2-oxo-1,2-dihydropyridin-4- 
                 SC_3354 
                   
                 445.2 
               
               
                   
                 1,2-dihydropyridin-4-yl)pyrimidin- 
                   
                 yl)boronic acid 
               
               
                   
                 5-yl)-8-phenyl-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3424 
                 cis-8-(dimethylamino)-8-(3- 
                 INT-1024 
                 3,5-dibromo-1-methyl-1H-pyrazole 
                 SC_3103 (for step 1), 
               
               
                   
                 fluorophenyl)-3-(1-methyl-3- 
                   
                 (step 1), thiophen-2-ylboronic acid 
                 SC_3354 (for step 2) 
               
               
                   
                 (thiophen-2-yl)-1H-pyrazol-5-yl)- 
                   
                 (step 2) 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
               
               
                 SC_3425 
                 cis-8-(dimethylamino)-8-(3- 
                 INT-1024 
                 3,5-dibromo-1-methyl-1H-pyrazole 
                 SC_3103 (for step 1), 
               
               
                   
                 fluorophenyl)-3-(1-methyl-3- 
                   
                 (step 1), morpholine (step 2) 
                 SC_3103 (for step 2) 
               
               
                   
                 morpholino-1H-pyrazol-5-yl)-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3426 
                 cis-8-(dimethylamino)-8-phenyl-1- 
                 INT-1068 
                 2-trifluoromethyl-5- 
                 SC_3103 
                   
                 502.2 
               
               
                   
                 (2,2,2-trifluoroethyl)-3-(2- 
                   
                 bromopyrimidine 
               
               
                   
                 (trifluoromethyl)pyrimidin-5-yl)- 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
               
               
                 SC_3427 
                 cis-8-(dimethylamino)-8-phenyl-3- 
                 INT-1070 
                 2-trifluoromethyl-5- 
                 SC_3103 
               
               
                   
                 (2-(trifluoromethyl)pyrimidin-5- 
                   
                 bromopyrimidine 
               
               
                   
                 yl)-1-(3,3,3-trifluoropropyl)-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3428 
                 cis-3-(4-methyl-6- 
                 SC_3122 
                   
                 SC_3099 
               
               
                   
                 (trifluoromethyl)pyridin-3-yl)-8- 
               
               
                   
                 (methylamino)-8-phenyl-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3429 
                 cis-3-(1-methyl-3- 
                 SC_3200 
                   
                 SC_3099 
               
               
                   
                 (trifluoromethyl)-1H-pyrazol-5-yl)- 
               
               
                   
                 8-(methylamino)-8-phenyl-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3430 
                 cis-8-(dimethylamino)-8-(3- 
                 INT-1024 
                 3-bromo-4- 
                 SC_3103 
               
               
                   
                 fluorophenyl)-3-(4- 
                   
                 (methylsulfonyl)pyridine 
               
               
                   
                 (methylsulfonyl)pyridin-3-yl)-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3431 
                 cis-8-(dimethylamino)-3-(1-ethyl- 
                 INT-1024 
                 5-bromo-1-ethyl-3- 
                 SC_3242 
               
               
                   
                 3-(trifluoromethyl)-1H-pyrazol-5- 
                   
                 (trifluoromethyl)-1H-pyrazole 
               
               
                   
                 yl)-8-(3-fluorophenyl)-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3432 
                 cis-3-(1-cyclopropyl-3- 
                 INT-1024 
                 5-bromo-1-cyclopropyl-3- 
                 SC_3242 
               
               
                   
                 (trifluoromethyl)-1H-pyrazol-5-yl)- 
                   
                 (trifluoromethyl)-1H-pyrazole 
               
               
                   
                 8-(dimethylamino)-8-(3- 
               
               
                   
                 fluorophenyl)-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3433 
                 cis-8-(dimethylamino)-8-(3- 
                 INT-1024 
                 5-bromo-1-(oxetan-3-ylmethyl)-3- 
                 SC_3242 
               
               
                   
                 fluorophenyl)-3-(1-(oxetan-3- 
                   
                 (trifluoromethyl)-1H-pyrazole 
               
               
                   
                 ylmethyl)-3-(trifluoromethyl)-1H- 
               
               
                   
                 pyrazol-5-yl)-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3434 
                 cis-8-(dimethylamino)-8-(3- 
                 INT-1024 
                 5-bromo-1-(2-(methylsulfonyl)ethyl)- 
                 SC_3242 
               
               
                   
                 fluorophenyl)-3-(1-(2- 
                   
                 3-(trifluoromethyl)-1H-pyrazole 
               
               
                   
                 (methylsulfonyl)ethyl)-3- 
               
               
                   
                 (trifluoromethyl)-1H-pyrazol-5-yl)- 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
               
               
                 SC_3435 
                 cis-8-(dimethylamino)-8-(3- 
                 INT-1076 
                 methylamine 
                 SC_3239 
               
               
                   
                 fluorophenyl)-3-(4-methyl-2- 
               
               
                   
                 (methylamino)pyrimidin-5-yl)-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3436 
                 cis-3-(2-cyclopropoxy-4- 
                 INT-1076 
                 cyclopropanol 
                 SC_3224 
                   
                 440.3 
               
               
                   
                 methylpyrimidin-5-yl)-8- 
               
               
                   
                 (dimethylamino)-8-(3- 
               
               
                   
                 fluorophenyl)-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3437 
                 cis-N-(5-(8-(dimethylamino)-8-(3- 
                 INT-1024 
                 N-(5-bromo-4-methylpyrimidin-2-yl)- 
                 SC_3103 
                   
                 481.3 
               
               
                   
                 fluorophenyl)-2-oxo-1,3- 
                   
                 N-methylcyclopropanecarboxamide 
               
               
                   
                 diazaspiro[4.5]decan-3-yl)-4- 
               
               
                   
                 methylpyrimidin-2-yl)-N- 
               
               
                   
                 methylcyclopropanecarboxamide 
               
               
                 SC_3438 
                 cis-N-(5-(8-(dimethylamino)-8-(3- 
                 INT-1024 
                 N-(5-bromo-4-methylpyrimidin-2-yl)- 
                 SC_3103 
                   
                 497.3 
               
               
                   
                 fluorophenyl)-2-oxo-1,3- 
                   
                 N-methylpivalamide 
               
               
                   
                 diazaspiro[4.5]decan-3-yl)-4- 
               
               
                   
                 methylpyrimidin-2-yl)-N- 
               
               
                   
                 methylpivalamide 
               
               
                 SC_3439 
                 cis-3-(4-(azetidin-1-yl)-2- 
                 INT-1077 
                 azetidine 
                 SC_3120 
                   
                 493.2 
               
               
                   
                 (trifluoromethyl)pyrimidin-5-yl)-8- 
               
               
                   
                 (dimethylamino)-8-(3- 
               
               
                   
                 fluorophenyl)-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3440 
                 cis-8-(dimethylamino)-8-(3- 
                 INT-1077 
                 oxetan-3-ylmethanol 
                 SC_3224 
                   
                 524.2 
               
               
                   
                 fluorophenyl)-3-(4-(oxetan-3- 
               
               
                   
                 ylmethoxy)-2- 
               
               
                   
                 (trifluoromethyl)pyrimidin-5-yl)- 
               
               
                   
                 1,3-diazaspiro[4.5]decan-2-one 
               
               
                 SC_3441 
                 cis-3-(2-cyclopropyl-4-(2,2,2- 
                 INT-1078 
                 2,2,2-trifluoroethanol 
                 SC_3224 
                   
                 508.2 
               
               
                   
                 trifluoroethoxy)pyrimidin-5-yl)-8- 
               
               
                   
                 (dimethylamino)-8-(3- 
               
               
                   
                 fluorophenyl)-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                 SC_3442 
                 cis-3-(2-cyclopropyl-4-((2-hy- 
                 INT-1078 
                 2-(methylamino)ethanol 
                 SC_3120 
                   
                 483.3 
               
               
                   
                 droxyethyl)(methyl)amino)pyrimidin- 
               
               
                   
                 5-yl)-8-(dimethylamino)-8-(3- 
               
               
                   
                 fluorophenyl)-1,3- 
               
               
                   
                 diazaspiro[4.5]decan-2-one 
               
               
                   
               
            
           
         
       
     
     Chemical Structures of all Examples 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Pharmacological Investigations 
     Functional investigation on the human mu-opioid receptor (hMOP), human kappa-opioid receptor (hKOP), human delta-opioid receptor (hDOP), and human nociceptin/orphanin FQ peptide receptor (hNOP) 
     Human Mu-Opioid Peptide (hMOP) Receptor Binding Assay 
     The hMOP receptor binding assay was performed as homogeneous SPA-assay (scintillation proximity assay) using the assay buffer 50 mM TRIS-HCl (pH 7.4) supplemented with 0.052 mg/ml bovine serum albumin (Sigma-Aldrich Co. St. Louis. Mo.). The final assay volume (250 μl/well) included 1 nM of [N-allyl-2.3- 3 H]naloxone as ligand (PerkinElmer Life Sciences. Inc. Boston. Mass. USA). and either test compound in dilution series or 25 μM unlabeled naloxone for determination of unspecific binding. The test compound was diluted with 25% DMSO in H 2 O to yield a final 0.5% DMSO concentration. which also served as a respective vehicle control. The assay was started by adding wheat germ agglutinin coated SPA beads (GE Healthcare UK Ltd. Buckinghamshire. UK) which had been preloaded with hMOP receptor membranes (PerkinElmer Life Sciences. Inc. Boston. Mass. USA). After incubation for 90 minutes at RT and centrifugation for 20 minutes at 500 rpm the signal rate was measured by means of a 1450 Microbeta Trilux ß-counter (PerkinElmer Life Sciences/Wallac. Turku. Finland). Half-maximal inhibitory concentration (TC50) values reflecting 50% displacement of [ 3 H]naloxone-specific receptor binding were calculated by nonlinear regression analysis and Ki values were calculated by using the Cheng-Prusoff equation. (Cheng and Prusoff. 1973). 
     Human Kappa-Opioid Peptide (hKOP) Receptor Binding Assay 
     The hKOP receptor binding assay is run as homogeneous SPA-assay (scintillation proximity assay) using the assay buffer 50 mM TRIS-HCl (pH 7.4) supplemented with 0.076 mg BSA/ml. The final assay volume of 250 μl per well includes 2 nM of [ 3 H]U69,593 as ligand, and either test compound in dilution series or 100 μM unlabeled naloxone for determination of unspecific binding. The test compound is diluted with 25% DMSO in H 2 O to yield a final 0.5% DMSO concentration which serves as respective vehicle control, as well. The assays are started by the addition of wheat germ agglutinin coated SPA beads (1 mg SPA beads/250 μl final assay volume per well) which has been preloaded for 15 minutes at room temperature with hKOP receptor membranes (14.8 μg/250 μl final assay volume per well). After short mixing on a mini-shaker, the microtiter plates are covered with a lid and the assay plates are incubated for 90 minutes at room temperature. After this incubation, the microtiter plates are sealed with a topseal and centrifuged for 20 minutes at 500 rpm. The signal rate is measured after a short delay of 5 minutes by means of a 1450 Microbeta Trilux ß-counter (PerkinElmer Life Sciences/Wallac, Turku, Finland). Half-maximal inhibitory concentration (IC50) values reflecting 50% displacement of [ 3 H]U69.593-specific receptor binding are calculated by nonlinear regression analysis and Ki values are calculated by using the Cheng-Prusoff equation, (Cheng and Prusoff, 1973). 
     Human Delta-Opioid Peptide (hDOP) Receptor Binding Assay 
     The hDOP receptor binding assay is performed as homogeneous SPA-assay using the assay buffer 50 mM TRIS-HCl, 5 mM MgCl 2  (pH 7.4). The final assay volume (250 μl/well) includes 1 nM of [Tyrosyl-3,5- 3 H]2-D-Ala-deltorphin II as ligand, and either test compound in dilution series or 10 μM unlabeled naloxone for determination of unspecific binding. The test compound is diluted with 25% DMSO in H 2 O to yield a final 0.5% DMSO concentration which serves as respective vehicle control, as well. The assays are started by the addition of wheat germ agglutinin coated SPA beads (1 mg SPA beads/250 μl final assay volume per well) which has been preloaded for 15 minutes at room temperature with hDOP receptor membranes (15.2 μg/250 μl final assay volume per well). After short mixing on a mini-shaker, the microtiter plates are covered with a lid and the assay plates are incubated for 120 minutes at room temperature and centrifuged for 20 minutes at 500 rpm. The signal rate is measured by means of a 1450 Microbeta Trilux ß-counter (PerkinElmer Life Sciences/Wallac, Turku, Finland). Half-maximal inhibitory concentration (IC50) values reflecting 50% displacement of [Tyrosyl-3,5- 3 H]2-D-Ala-deltorphin II-specific receptor binding are calculated by nonlinear regression analysis and Ki values are calculated by using the Cheng-Prusoff equation, (Cheng and Prusoff, 1973). 
     Human Nociceptin/Orphanin FQ Peptide (hNOP) Receptor Binding Assay 
     The hNOP receptor binding assay was performed as homogeneous SPA-assay (scintillation proximity assay) using the assay buffer 50 mM TRIS-HCl. 10 mM MgCl 2 . 1 mM EDTA (pH 7.4). The final assay volume (250 μl/well) included 0.5 nM of [leucyl- 3 H]nociceptin as ligand (PerkinElmer Life Sciences. Inc. Boston. Mass. USA). and either test compound in dilution series or 1 μM unlabeled nociceptin for determination of unspecific binding. The test compound was diluted with 25% DMSO in H 2 O to yield a final 0.5% DMSO concentration. which also served as a respective vehicle control. The assay was started by adding wheat germ agglutinin coated SPA beads (GE Healthcare UK Ltd. Buckinghamshire. UK) which had been preloaded with hMOP receptor membranes (PerkinElmer Life Sciences. Inc. Boston. Mass. USA). After incubation for 60 minutes at RT and centrifugation for 20 minutes at 500 rpm the signal rate was measured by means of a 1450 Microbeta Trilux ß-counter (PerkinElmer Life Sciences/Wallac. Turku. Finland). Half-maximal inhibitory concentration (IC50) values reflecting 50% displacement of [ 3 H]nociceptin-specific receptor binding were calculated by nonlinear regression analysis and Ki values were calculated by using the Cheng-Prusoff equation. (Cheng and Prusoff. 1973). 
     
       
         
           
               
               
               
               
             
               
                   
                   
               
               
                   
                   
                 hNOP Ki [nM] 
                 hMOP Ki [nM] 
               
               
                   
                   
                 or % inhibition 
                 or % inhibition 
               
               
                   
                 Example 
                 at 1 μM 
                 at 1 μM 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 SC_3001 
                 0.3 
                 120 
               
               
                   
                 SC_3002 
                 1.3 
                 250 
               
               
                   
                 SC_3003 
                 0.4 
                 350 
               
               
                   
                 SC_3004 
                 19.5 
                 515 
               
               
                   
                 SC_3005 
                 0.7 
                 12 
               
               
                   
                 SC_3006 
                 1.1 
                 46 
               
               
                   
                 SC_3007 
                 85.8 
                 705 
               
               
                   
                 SC_3008 
                 0.6 
                 23 
               
               
                   
                 SC_3009 
                 1.1 
                 41 
               
               
                   
                 SC_3010 
                 2.7 
                 18 
               
               
                   
                 SC_3011 
                 4.4 
                 4.4 
               
               
                   
                 SC_3012 
                 2.2 
                 120 
               
               
                   
                 SC_3013 
                 1.4 
                 39 
               
               
                   
                 SC_3014 
                 0.8 
                 29.5 
               
               
                   
                 SC_3015 
                 2.6 
                 32.5 
               
               
                   
                 SC_3016 
                 4.2 
                 45 
               
               
                   
                 SC_3017 
                 2 
                 30 
               
               
                   
                 SC_3018 
                 5.2 
                 101.5 
               
               
                   
                 SC_3019 
                 10.2 
                 135 
               
               
                   
                 SC_3020 
                 10.8 
                 290 
               
               
                   
                 SC_3021 
                 1.8 
                 14.5 
               
               
                   
                 SC_3022 
                 0.4 
                 37.2 
               
               
                   
                 SC_3023 
                 7.7 
                 36 
               
               
                   
                 SC_3024 
                 1 
                 145 
               
               
                   
                 SC_3025 
                 236.7 
                 1530 
               
               
                   
                 SC_3026 
                 4.6 
                 300 
               
               
                   
                 SC_3027 
                 5 
                 136 
               
               
                   
                 SC_3028 
                 0.6 
                 10.4 
               
               
                   
                 SC_3029 
                 1.8 
                 7.3 
               
               
                   
                 SC_3030 
                 2.2 
                 59 
               
               
                   
                 SC_3031 
                 4.1 
                 45.5 
               
               
                   
                 SC_3032 
                 11 
                 245 
               
               
                   
                 SC_3033 
                 107 
                 38%@10 μM 
               
               
                   
                 SC_3034 
                 12.2 
                 730 
               
               
                   
                 SC_3035 
                 6.6 
                 1055 
               
               
                   
                 SC_3036 
                 1.4 
                 220 
               
               
                   
                 SC_3037 
                 33.5 
                 775 
               
               
                   
                 SC_3038 
                 1 
                 76 
               
               
                   
                 SC_3039 
                 13 
                 380 
               
               
                   
                 SC_3040 
                 4 
                 335 
               
               
                   
                 SC_3041 
                 0.9 
                 79.5 
               
               
                   
                 SC_3042 
                 4.1 
                 136.5 
               
               
                   
                 SC_3043 
                 70 
                 655 
               
               
                   
                 SC_3044 
                 230 
                 10920 
               
               
                   
                 SC_3045 
                 55.5 
                 520 
               
               
                   
                 SC_3046 
                 13.9 
                 63 
               
               
                   
                 SC_3047 
                 10.1 
                 2105 
               
               
                   
                 SC_3048 
                 1 
                 38.5 
               
               
                   
                 SC_3049 
                 25 
                 940 
               
               
                   
                 SC_3050 
                 85 
                 28 
               
               
                   
                 SC_3051 
                 3.6 
                 170 
               
               
                   
                 SC_3052 
                 160 
                 355 
               
               
                   
                 SC_3053 
                 73.5 
                 1200 
               
               
                   
                 SC_3054 
                 16.5 
                 29.5 
               
               
                   
                 SC_3055 
                 94.5 
                 215 
               
               
                   
                 SC_3056 
                 9.8 
                 49.5 
               
               
                   
                 SC_3057 
                 955 
                 245 
               
               
                   
                 SC_3058 
                 5 
                 7.8 
               
               
                   
                 SC_3059 
                 11.4 
                 320 
               
               
                   
                 SC_3060 
                 3 
                 65 
               
               
                   
                 SC_3061 
                 4.7 
                 54.5 
               
               
                   
                 SC_3063 
                 0.7 
                 38 
               
               
                   
                 SC_3064 
                 119 
                 365 
               
               
                   
                 SC_3065 
                 6.2 
                 1990 
               
               
                   
                 SC_3066 
                 2.2 
                 96 
               
               
                   
                 SC_3067 
                 41.5 
                 99.5 
               
               
                   
                 SC_3068 
                 5.9 
                 50.5 
               
               
                   
                 SC_3069 
                 2.6 
                 49 
               
               
                   
                 SC_3070 
                 2.8 
                 12.5 
               
               
                   
                 SC_3071 
                 8.2 
                 170 
               
               
                   
                 SC_3072 
                 5.9 
                 235 
               
               
                   
                 SC_3073 
                 1 
                 110 
               
               
                   
                 SC_3074 
                 1.6 
                 55 
               
               
                   
                 SC_3075 
                 8.1 
                 260 
               
               
                   
                 SC_3076 
                 0.6 
                 35.3 
               
               
                   
                 SC_3077 
                 3.2 
                 325 
               
               
                   
                 SC_3078 
                 0.6 
                 77.5 
               
               
                   
                 SC_3079 
                 1.6 
                 38.5 
               
               
                   
                 SC_3080 
                 1.6 
                 90.5 
               
               
                   
                 SC_3081 
                 8 
                 1320 
               
               
                   
                 SC_3082 
                 39 
                 1110 
               
               
                   
                 SC_3083 
                 12 
                 117.3 
               
               
                   
                 SC_3084 
                 1.8 
                 22 
               
               
                   
                 SC_3085 
                 1.6 
                 107 
               
               
                   
                 SC_3086 
                 1.1 
                 43.5 
               
               
                   
                 SC_3087 
                 2.8 
                 99 
               
               
                   
                 SC_3088 
                 3.1 
                 770 
               
               
                   
                 SC_3089 
                 3.3 
                 235 
               
               
                   
                 SC_3090 
                 1.3 
                 67 
               
               
                   
                 SC_3091 
                 2.3 
                 24 
               
               
                   
                 SC_3092 
                 2.2 
                 330 
               
               
                   
                 SC_3093 
                 1.1 
                 47 
               
               
                   
                 SC_3094 
                 5.4 
                 45.5 
               
               
                   
                 SC_3096 
                 14 
                 250 
               
               
                   
                 SC_3097 
                 17 
                 18 
               
               
                   
                 SC_3098 
                 2 
                 6 
               
               
                   
                 SC_3099 
                 13 
                 19 
               
               
                   
                 SC_3100 
                 1 
                 1 
               
               
                   
                 SC_3101 
                 1 
                 3 
               
               
                   
                 SC_3102 
                 2 
                 1 
               
               
                   
                 SC_3103 
                 7 
                 1 
               
               
                   
                 SC_3104 
                 — 
                 — 
               
               
                   
                 SC_3105 
                 2 
                 97 
               
               
                   
                 SC_3106 
                 8 
                 165 
               
               
                   
                 SC_3107 
                 2 
                 115 
               
               
                   
                 SC_3108 
                 5 
                 26 
               
               
                   
                 SC_3109 
                 8 
                 19 
               
               
                   
                 SC_3110 
                 6 
                 20 
               
               
                   
                 SC_3111 
                 8 
                 37 
               
               
                   
                 SC_3112 
                 36 
                 120 
               
               
                   
                 SC_3113 
                 24 
                 26 
               
               
                   
                 SC_3114 
                 245 
                 460 
               
               
                   
                 SC_3115 
                 265 
                 915 
               
               
                   
                 SC_3116 
                 6 
                 170 
               
               
                   
                 SC_3117 
                 92 
                 1380 
               
               
                   
                 SC_3118 
                 80 
                  5% 
               
               
                   
                 SC_3119 
                 22%  
                 10% 
               
               
                   
                 SC_3120 
                 26 
                 4950 
               
               
                   
                 SC_3121 
                 44 
                 30% 
               
               
                   
                 SC_3122 
                 21 
                 32% 
               
               
                   
                 SC_3123 
                 82 
                 2260 
               
               
                   
                 SC_3124 
                 5 
                 1090 
               
               
                   
                 SC_3125 
                 3%@10 μM 
                 52%@10 μM 
               
               
                   
                 SC_3126 
                 0% 
                  0% 
               
               
                   
                 SC_3127 
                 0% 
                 3945 
               
               
                   
                 SC_3128 
                 0% 
                  1% 
               
               
                   
                 SC_3129 
                 6 
                 2180 
               
               
                   
                 SC_3130 
                 13 
                 4530 
               
               
                   
                 SC_3131 
                 4 
                 3090 
               
               
                   
                 SC_3132 
                 540 
                  6% 
               
               
                   
                 SC_3133 
                 19 
                 6515 
               
               
                   
                 SC_3134 
                 3%@10 μM 
                 40%@10 μM 
               
               
                   
                 SC_3135 
                 1% 
                  1% 
               
               
                   
                 SC_3136 
                 16 
                 5840 
               
               
                   
                 SC_3137 
                 5 
                 4235 
               
               
                   
                 SC_3138 
                 28 
                  7% 
               
               
                   
                 SC_3139 
                 59 
                 1690 
               
               
                   
                 SC_3140 
                 119 
                 2355 
               
               
                   
                 SC_3141 
                 34 
                 7855 
               
               
                   
                 SC_3142 
                 9 
                 3750 
               
               
                   
                 SC_3143 
                 0% 
                  4% 
               
               
                   
                 SC_3144 
                 0% 
                 3590 
               
               
                   
                 SC_3145 
                 46 
                 1635 
               
               
                   
                 SC_3146 
                 18 
                 7675 
               
               
                   
                 SC_3147 
                 27 
                 3325 
               
               
                   
                 SC_3148 
                 14 
                 4575 
               
               
                   
                 SC_3149 
                 18 
                 6900 
               
               
                   
                 SC_3150 
                 105 
                 16% 
               
               
                   
                 SC_3151 
                 115 
                 3490 
               
               
                   
                 SC_3152 
                 24 
                 4775 
               
               
                   
                 SC_3153 
                 77 
                 2220 
               
               
                   
                 SC_3154 
                 17 
                 3575 
               
               
                   
                 SC_3155 
                 34 
                 3495 
               
               
                   
                 SC_3156 
                 45 
                 6375 
               
               
                   
                 SC_3157 
                 35 
                 5690 
               
               
                   
                 SC_3158 
                 19 
                 2540 
               
               
                   
                 SC_3159 
                 13 
                 19% 
               
               
                   
                 SC_3160 
                 4% 
                 5730 
               
               
                   
                 SC_3161 
                 2% 
                 13% 
               
               
                   
                 SC_3162 
                 5 
                 1325 
               
               
                   
                 SC_3163 
                 28 
                 2095 
               
               
                   
                 SC_3164 
                 30 
                 880 
               
               
                   
                 SC_3165 
                 4% 
                 17% 
               
               
                   
                 SC_3166 
                 3% 
                 1640 
               
               
                   
                 SC_3167 
                 18 
                 3745 
               
               
                   
                 SC_3168 
                 11 
                 5 
               
               
                   
                 SC_3169 
                 635 
                 3445 
               
               
                   
                 SC_3170 
                 7 
                 3610 
               
               
                   
                 SC_3171 
                 15 
                 2010 
               
               
                   
                 SC_3172 
                 130 
                  7% 
               
               
                   
                 SC_3173 
                 10 
                 2525 
               
               
                   
                 SC_3174 
                 3% 
                 1265 
               
               
                   
                 SC_3175 
                 — 
                 — 
               
               
                   
                 SC_3176 
                 13 
                 3740 
               
               
                   
                 SC_3177 
                 8 
                 4630 
               
               
                   
                 SC_3178 
                 6 
                 6700 
               
               
                   
                 SC_3179 
                 15 
                 3950 
               
               
                   
                 SC_3180 
                 125 
                 2250 
               
               
                   
                 SC_3181 
                 22 
                 5490 
               
               
                   
                 SC_3182 
                 11 
                 2990 
               
               
                   
                 SC_3183 
                 165 
                 1415 
               
               
                   
                 SC_3184 
                 19 
                 7645 
               
               
                   
                 SC_3185 
                 335 
                 15% 
               
               
                   
                 SC_3186 
                 33 
                 2210 
               
               
                   
                 SC_3187 
                 87 
                 2240 
               
               
                   
                 SC_3188 
                 25 
                 1060 
               
               
                   
                 SC_3189 
                 57 
                 3470 
               
               
                   
                 SC_3190 
                 42 
                 28% 
               
               
                   
                 SC_3191 
                 27 
                 20% 
               
               
                   
                 SC_3192 
                 140 
                 4270 
               
               
                   
                 SC_3193 
                 100 
                 2480 
               
               
                   
                 SC_3194 
                 28 
                 5120 
               
               
                   
                 SC_3195 
                 15 
                 1240 
               
               
                   
                 SC_3196 
                 22 
                 1595 
               
               
                   
                 SC_3197 
                 44 
                 1680 
               
               
                   
                 SC_3198 
                 22 
                 5885 
               
               
                   
                 SC_3199 
                 19 
                 4020 
               
               
                   
                 SC_3200 
                 7 
                 13% 
               
               
                   
                 SC_3201 
                 115 
                 3885 
               
               
                   
                 SC_3202 
                 25 
                 3210 
               
               
                   
                 SC_3203 
                 68 
                 1225 
               
               
                   
                 SC_3204 
                 110 
                 14% 
               
               
                   
                 SC_3205 
                 20 
                 2465 
               
               
                   
                 SC_3206 
                 27 
                 2445 
               
               
                   
                 SC_3207 
                 39 
                 1505 
               
               
                   
                 SC_3208 
                 2 
                 3285 
               
               
                   
                 SC_3209 
                 — 
                 — 
               
               
                   
                 SC_3210 
                 — 
                 — 
               
               
                   
                 SC_3211 
                 — 
                 — 
               
               
                   
                 SC_3212 
                 9 
                 2005 
               
               
                   
                 SC_3213 
                 52 
                 18% 
               
               
                   
                 SC_3214 
                 7 
                 19% 
               
               
                   
                 SC_3215 
                 0% 
                 14% 
               
               
                   
                 SC_3216 
                 11 
                 14 
               
               
                   
                 SC_3217 
                 23 
                 2155 
               
               
                   
                 SC_3218 
                 83 
                 15% 
               
               
                   
                 SC_3219 
                 0% 
                  1% 
               
               
                   
                 SC_3220 
                 10%@10 μM 
                 24%@10 μM 
               
               
                   
                 SC_3221 
                 33 
                 1935 
               
               
                   
                 SC_3222 
                 6 
                 1910 
               
               
                   
                 SC_3223 
                 155 
                 6150 
               
               
                   
                 SC_3224 
                 10 
                 1695 
               
               
                   
                 SC_3225 
                 13 
                 2520 
               
               
                   
                 SC_3226 
                 — 
                 — 
               
               
                   
                 SC_3227 
                 16 
                 3785 
               
               
                   
                 SC_3228 
                 67 
                 3135 
               
               
                   
                 SC_3229 
                 105 
                 3625 
               
               
                   
                 SC_3230 
                 145 
                 2485 
               
               
                   
                 SC_3231 
                 120 
                 2420 
               
               
                   
                 SC_3232 
                 15 
                 3475 
               
               
                   
                 SC_3233 
                 38 
                 1390 
               
               
                   
                 SC_3234 
                 4 
                 1350 
               
               
                   
                 SC_3235 
                 30 
                 1095 
               
               
                   
                 SC_3236 
                 285 
                 18% 
               
               
                   
                 SC_3237 
                 20 
                 17% 
               
               
                   
                 SC_3238 
                 4 
                 25% 
               
               
                   
                 SC_3239 
                 35 
                 2410 
               
               
                   
                 SC_3240 
                 28 
                 17% 
               
               
                   
                 SC_3241 
                 8 
                 4610 
               
               
                   
                 SC_3242 
                 5 
                 675 
               
               
                   
                 SC_3243 
                 6 
                 695 
               
               
                   
                 SC_3244 
                 27 
                 4265 
               
               
                   
                 SC_3245 
                 67 
                 — 
               
               
                   
                 SC_3246 
                 11 
                 1025 
               
               
                   
                 SC_3247 
                 16 
                 1220 
               
               
                   
                 SC_3248 
                 4 
                 41 
               
               
                   
                 SC_3249 
                 740 
                 855 
               
               
                   
                 SC_3250 
                 52 
                 — 
               
               
                   
                 SC_3251 
                 185 
                 4550 
               
               
                   
                 SC_3252 
                 30 
                 — 
               
               
                   
                 SC_3253 
                 205 
                 — 
               
               
                   
                 SC_3254 
                 22 
                 240 
               
               
                   
                 SC_3255 
                 23 
                 150 
               
               
                   
                 SC_3256 
                 12 
                 61 
               
               
                   
                 SC_3257 
                 150 
                 240 
               
               
                   
                 SC_3258 
                 58 
                 7125 
               
               
                   
                 SC_3259 
                 45 
                 180 
               
               
                   
                 SC_3260 
                 570 
                 nd 
               
               
                   
                 SC_3261 
                 10 
                 63 
               
               
                   
                 SC_3262 
                 540 
                 3060 
               
               
                   
                 SC_3263 
                 66 
                 800 
               
               
                   
                 SC_3264 
                 145 
                 130 
               
               
                   
                 SC_3265 
                 38 
                 2405 
               
               
                   
                 SC_3266 
                 245 
                 1055 
               
               
                   
                 SC_3267 
                 460 
                 — 
               
               
                   
                 SC_3268 
                 41 
                 1625 
               
               
                   
                 SC_3269 
                 13 
                 5580 
               
               
                   
                 SC_3270 
                 305 
                 31 
               
               
                   
                 SC_3271 
                 34 
                 245 
               
               
                   
                 SC_3272 
                 115 
                 4175 
               
               
                   
                 SC_3273 
                 — 
                 — 
               
               
                   
                 SC_3274 
                 63 
                 1880 
               
               
                   
                 SC_3275 
                 155 
                 124 
               
               
                   
                 SC_3276 
                 24 
                 130 
               
               
                   
                 SC_3277 
                 37 
                 13% 
               
               
                   
                 SC_3278 
                 12 
                 7035 
               
               
                   
                 SC_3279 
                 17 
                 78 
               
               
                   
                 SC_3280 
                 6 
                 300 
               
               
                   
                 SC_3281 
                 19 
                 2580 
               
               
                   
                 SC_3282 
                 37 
                 3510 
               
               
                   
                 SC_3283 
                 12 
                 1030 
               
               
                   
                 SC_3284 
                 5 
                 305 
               
               
                   
                 SC_3285 
                 15 
                 20% 
               
               
                   
                 SC_3286 
                 18 
                 5895 
               
               
                   
                 SC_3287 
                 119 
                 18% 
               
               
                   
                 SC_3288 
                 15 
                 115 
               
               
                   
                 SC_3289 
                 84 
                 430 
               
               
                   
                 SC_3290 
                 16 
                 6605 
               
               
                   
                 SC_3291 
                 350 
                 15% 
               
               
                   
                 SC_3292 
                 4% 
                  0% 
               
               
                   
                 SC_3293 
                 3% 
                  0% 
               
               
                   
                 SC_3294 
                 9 
                 12% 
               
               
                   
                 SC_3295 
                 28 
                 2975 
               
               
                   
                 SC_3296 
                 10 
                 4530 
               
               
                   
                 SC_3297 
                 8 
                 4270 
               
               
                   
                 SC_3298 
                 20 
                 17% 
               
               
                   
                 SC_3299 
                 23 
                 5705 
               
               
                   
                 SC_3300 
                 22 
                 565 
               
               
                   
                 SC_3301 
                 33 
                 2320 
               
               
                   
                 SC_3302 
                 31 
                 1025 
               
               
                   
                 SC_3303 
                 450 
                 21% 
               
               
                   
                 SC_3304 
                 9% 
                  4% 
               
               
                   
                 SC_3305 
                 10%  
                  0% 
               
               
                   
                 SC_3306 
                 9 
                 4555 
               
               
                   
                 SC_3307 
                 13 
                 5345 
               
               
                   
                 SC_3308 
                 2 
                 2575 
               
               
                   
                 SC_3309 
                 17 
                 6910 
               
               
                   
                 SC_3310 
                 7 
                 23% 
               
               
                   
                 SC_3311 
                 14 
                 27% 
               
               
                   
                 SC_3312 
                 23 
                 1830 
               
               
                   
                 SC_3313 
                 10 
                 2400 
               
               
                   
                 SC_3314 
                 9 
                 4090 
               
               
                   
                 SC_3315 
                 14 
                 5325 
               
               
                   
                 SC_3316 
                 255 
                 5430 
               
               
                   
                 SC_3317 
                 56 
                 6045 
               
               
                   
                 SC_3318 
                 35 
                 1235 
               
               
                   
                 SC_3319 
                 4 
                 15% 
               
               
                   
                 SC_3320 
                 11 
                 1955 
               
               
                   
                 SC_3321 
                 13 
                 5715 
               
               
                   
                 SC_3322 
                 12 
                 1150 
               
               
                   
                 SC_3323 
                 27 
                 5530 
               
               
                   
                 SC_3324 
                 12%  
                  5% 
               
               
                   
                 SC_3325 
                 53%@10 μM 
                 20%@10 μM 
               
               
                   
                 SC_3326 
                 — 
                 — 
               
               
                   
                 SC_3327 
                 17 
                 3360 
               
               
                   
                 SC_3328 
                 31 
                 3295 
               
               
                   
                 SC_3329 
                 13 
                 4285 
               
               
                   
                 SC_3330 
                 14 
                 1505 
               
               
                   
                 SC_3331 
                 2 
                 5265 
               
               
                   
                 SC_3332 
                 19 
                 2055 
               
               
                   
                 SC_3333 
                 5 
                 1580 
               
               
                   
                 SC_3334 
                 17 
                 4005 
               
               
                   
                 SC_3335 
                 30 
                 2305 
               
               
                   
                 SC_3336 
                 240 
                 13% 
               
               
                   
                 SC_3337 
                 10 
                 1970 
               
               
                   
                 SC_3338 
                 36 
                  7% 
               
               
                   
                 SC_3339 
                 10 
                 6830 
               
               
                   
                 SC_3340 
                 150 
                 5750 
               
               
                   
                 SC_3341 
                 15 
                 3460 
               
               
                   
                 SC_3342 
                 21 
                 3845 
               
               
                   
                 SC_3343 
                 27 
                 16% 
               
               
                   
                 SC_3344 
                 1 
                 13% 
               
               
                   
                 SC_3345 
                 4 
                 1800 
               
               
                   
                 SC_3346 
                 12 
                 2580 
               
               
                   
                 SC_3347 
                 15 
                 4845 
               
               
                   
                 SC_3348 
                 25 
                 4090 
               
               
                   
                 SC_3349 
                 8 
                 3980 
               
               
                   
                 SC_3350 
                 7 
                 1485 
               
               
                   
                 SC_3351 
                 20 
                 2205 
               
               
                   
                 SC_3352 
                 37 
                 2160 
               
               
                   
                 SC_3353 
                 53 
                 15% 
               
               
                   
                 SC_3354 
                 2 
                 23% 
               
               
                   
                 SC_3355 
                 52 
                 4785 
               
               
                   
                 SC_3356 
                 9 
                 4805 
               
               
                   
                 SC_3357 
                 13 
                 555 
               
               
                   
                 SC_3358 
                 51 
                 7020 
               
               
                   
                 SC_3359 
                 66 
                 3520 
               
               
                   
                 SC_3360 
                 7 
                 2870 
               
               
                   
                 SC_3361 
                 27 
                 5095 
               
               
                   
                 SC_3362 
                 28 
                 29% 
               
               
                   
                 SC_3363 
                 33 
                  8% 
               
               
                   
                 SC_3364 
                 32 
                 4685 
               
               
                   
                 SC_3365 
                 2 
                 1655 
               
               
                   
                 SC_3366 
                 1285 
                 14% 
               
               
                   
                 SC_3367 
                 1220 
                  8% 
               
               
                   
                 SC_3368 
                 195 
                 11% 
               
               
                   
                 SC_3369 
                 51 
                 3105 
               
               
                   
                 SC_3370 
                 4 
                 14% 
               
               
                   
                 SC_3371 
                 350 
                  9% 
               
               
                   
                 SC_3372 
                 125 
                 3535 
               
               
                   
                 SC_3373 
                 19 
                 18% 
               
               
                   
                 SC_3374 
                 55 
                 10% 
               
               
                   
                 SC_3375 
                 13 
                 12% 
               
               
                   
                 SC_3376 
                 37 
                 1720 
               
               
                   
                 SC_3377 
                 22 
                 980 
               
               
                   
                 SC_3379 
                 11 
                 635 
               
               
                   
                 SC_3380 
                 102 
                 5415 
               
               
                   
                 SC_3381 
                 3 
                 1235 
               
               
                   
                 SC_3382 
                 29 
                 13% 
               
               
                   
                 SC_3383 
                 10 
                 17% 
               
               
                   
                 SC_3384 
                 6 
                 11% 
               
               
                   
                 SC_3385 
                 33 
                 925 
               
               
                   
                 SC_3386 
                 14 
                  0% 
               
               
                   
                 SC_3387 
                 2 
                 1245 
               
               
                   
                 SC_3388 
                 29 
                 185 
               
               
                   
                 SC_3389 
                 2 
                 1970 
               
               
                   
                 SC_3390 
                 18 
                 465 
               
               
                   
                 SC_3391 
                 53 
                 10% 
               
               
                   
                 SC_3392 
                 7 
                 4490 
               
               
                   
                 SC_3393 
                 88 
                 13% 
               
               
                   
                 SC_3394 
                 6 
                 735 
               
               
                   
                 SC_3395 
                 14 
                 4990 
               
               
                   
                 SC_3396 
                 44 
                 1730 
               
               
                   
                 SC_3397 
                 48 
                 560 
               
               
                   
                 SC_3398 
                 9 
                 5640 
               
               
                   
                 SC_3399 
                 5 
                 45% 
               
               
                   
                 SC_3400 
                 8 
                 635 
               
               
                   
                 SC_3401 
                 1 
                 455 
               
               
                   
                 SC_3402 
                 7 
                 3630 
               
               
                   
                 SC_3403 
                 9 
                 1440 
               
               
                   
                 SC_3404 
                 10 
                  5% 
               
               
                   
                 SC_3405 
                 12 
                 925 
               
               
                   
                 SC_3406 
                 24 
                 805 
               
               
                   
                 SC_3407 
                 77 
                 13% 
               
               
                   
                 SC_3408 
                 7 
                 18% 
               
               
                   
                 SC_3409 
                 11 
                 25% 
               
               
                   
                   
               
            
           
         
       
     
     Protocol for [ 35 S]GTPγS Functional NOP/MOP/KOP/DOP Assays 
     Cell membrane preparations of CHO-K1 cells transfected with the human MOP receptor (Art.-No. RBHOMM) or the human DOP receptor (Art.-No. RBHODM), and HEK293 cells transfected with the human NOP receptor (Art.-No. RBHORLM) or the human KOP receptor (Art.-No. 6110558) are available from PerkinElmer (Waltham, Mass.). Membranes from CHO-K1 cells transfected with the human nociceptin/orphanin FQ peptide (hNOP) receptor (Art.-No. 93-0264C2, DiscoveRx Corporation, Freemont, Calif.) are also used. [ 5 S]GTPγS (Art.-No. NEG030H; Lot-No. #0112, #0913, #1113 calibrated to 46.25 TBq/mmol) is available from PerkinElmer (Waltham, Mass.). 
     The [ 35 S]GTPγS assays are carried out essentially as described by Gillen et al (2000). They are run as homogeneous scintillation proximity (SPA) assays in microtiter luminescence plates, where each well contains 1.5 mg of WGA-coated SPA-beads. To test the agonistic activity of test compounds on recombinant hNOP, hMOP, hDOP, and hKOP receptor expressing cell membranes from CHO-K1 or HEK293 cells, 10 or 5 μg membrane protein per assay are incubated with 0.4 nM [ 35 S]GTPγS and serial concentrations of receptor-specific agonists in buffer containing 20 mM HEPES pH 7.4, 100 mM NaCl, 10 mM MgCl2, 1 mM EDTA, 1 mM dithiothreitol, 1.28 mM NaN 3 , and 10 μM GDP for 45 min at room temperature. The microtiter plates are then centrifuged for 10 min at 830 to sediment the SPA beads. The microtiter plates are sealed and the bound radioactivity [cpm] is determined after a delay of 15 min by means of a 1450 Microbeta Trilux (PerkinElmer, Waltham, Mass.). 
     The unstimulated basal binding activity (UBS obs  [cpm]) is determined from 12 unstimulated incubates and is set as 100% basal binding. For determination of the potency and the efficacy, the arithmetic mean of the observed total [ 35 S]GTPγS binding (TB obs  [cpm]) of all incubates (duplicates) stimulated by the receptor-specific agonists (i.e. N/OFQ, SNC80, DAMGO, or U69,593) are transformed in percent total binding (TB obs  [%]) relative to the basal binding activity (i.e. 100% binding). The potency (EC 50 ) of the respective agonist and its maximal achievable total [ 35 S]GTPγS binding (TB calc  [%]) above its calculated basal binding (UBS calc  [%]) are determined from its transformed data (TB obs  [%]) by means of nonlinear regression analysis with XLfit for each individual concentration series. Then the difference between the calculated unstimulated [ 35 S]GTPγS binding (UBS calc  [%]) and the maximal achievable total [ 35 S]GTPγS binding (TB calc  [%]) by each tested agonist is determined (i.e. B1 calc  [%]). This difference (B1 calc  [%]) as a measure of the maximal achievable enhancement of [ 35 S]GTPγS binding by a given agonist is used to calculate the relative efficacy of test compounds versus the maximal achievable enhancement by a receptor-specific full agonist, e.g. N/OFQ (B1 calc-N/OFQ  [%]) which is set as 100% relative efficacy for the hNOP receptor. Likewise, the percentage efficacies of test compounds at the hDOP, hMOP, or hKOP receptor are determined versus the calculated maximal enhancement of [ 35 S]GTPγS binding by the full agonists SNC80 (B1 calc-SNC80  [%]), DAMGO (B1 calc-DAMGO  [%]) and U69,593 (B1 calc-U69,593  [%]) which are set as 100% relative efficacy at each receptor, respectively. 
     The foregoing description and examples have been set forth merely to illustrate the invention and are not intended to be limiting. Since modifications of the described embodiments incorporating the spirit and substance of the invention may occur to persons skilled in the art, the invention should be construed broadly to include all variations within the scope of the appended claims and equivalents thereof.