Substituted 3-aminoindazole derivatives as kinase inhibitors

Abstract

The present invention relates to substituted 3-aminoindazole derivatives as kinase inhibitors, in particular as inhibitors of the CDK11 family. Due to the important role of protein kinases, in particular CDK11, in regulating cell proliferation, such compounds are useful for treating diseases caused by altered CDK11 activity, in particular in the treatment of cancer, as well as in the treatment of various cell proliferation and immune-related disorders. The present invention also provides methods for the preparation of these compounds, pharmaceutical compositions comprising these compounds, and methods for the treatment of diseases using pharmaceutical compositions comprising these compounds.

Description

[Technical Field]

[0001] The present invention relates to substituted 3-aminoindazole derivatives, processes for their preparation, pharmaceutical compositions containing them, and their use as therapeutic agents, particularly in the treatment of diseases caused by dysregulated protein kinase activity, such as cancer, cell proliferative disorders, viral infections, immune disorders, neurodegenerative disorders, and cardiovascular diseases. [Background technology]

[0002] Dysfunction of PKs is a hallmark of numerous diseases. The majority of oncogenes and proto-oncogenes involved in human cancers encode PKs. Enhanced PK activity has also been implicated in many non-malignant diseases, including benign prostatic hyperplasia, familial adenomatous polyposis, polyposis, neurofibromatosis, psoriasis, atherosclerosis-associated vascular smooth cell proliferation, pulmonary fibrosis, arthritis, glomerulonephritis, and postoperative stenosis and restenosis.

[0003] PKs have also been implicated in inflammatory conditions and viral and parasitic proliferation, and may also play an important role in the development and progression of neurodegenerative disorders.

[0004] For general references regarding PK dysfunction and dysregulation, see, e.g., Current Opinion in Chemical Biology, 1999, 3, 459-465; Nature Rev. Drug Discov. 2002; and Carcinogenesis, 2008, 29, 1087-1091.

[0005] Cyclin-dependent kinase 11 (CDK11) is a serine / threonine kinase encoded by two nearly identical genes, CDC2L1 and CDC2L2. Two major CDK11 protein isoforms are produced from the mammalian CDK11 gene: CDK11p110, which is detected in mammalian tissues and cell lines throughout the cell cycle, and CDK11p58, which is produced at the G2 / M cell cycle transition using an internal ribosome entry site within the CDK11 mRNA transcript (Trembley et al., 2004). CDK11 acts in a complex with cyclins L1 and L2 (CYCL1 and CYCL2; Loyer et al., 2008). CDK11 has been reported to be involved in regulating various cellular processes, including the cell cycle, transcription, splicing, and chromosome segregation. CDK11 has been shown to play a role in the survival and proliferation of various types of human cancers, including breast cancer, colorectal cancer, and cervical cancer, osteosarcoma, melanoma, multiple myeloma, and acute myeloid leukemia. Furthermore, CDK11 inhibition by gene knockout or knockdown has been shown to exert antitumor effects in various cancer models, suggesting that targeting CDK11 may have therapeutic potential (Zhou et al., 2016; Loyer and Trembley, 2020). [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] Current Opinion in Chemical Biology, 1999, 3, 459-465. [Non-patent document 2] Nature Rev. Drug Discov. 2002. [Non-patent document 3] Carcinogenesis, 2008, 29,1087-1091. Summary of the Invention [Problem to be solved by the invention]

[0007] Indazole derivatives are known in the art as protein kinase inhibitors. For example, WO2008 / 154241 in the name of Abbvie reports 5-heteroaryl-substituted indazoles useful for the treatment of diseases associated with dysregulated protein kinase activity, and WO2003 / 028720 discloses aminoindazole derivatives that are also active as kinase inhibitors. However, none of the aforementioned applications reports activity data against cyclin-dependent kinase 11 (CDK11).

[0008] In view of the above, there is a strong need for the development of CDK11 inhibitors for the treatment of cancer and other diseases.The present inventors have identified novel 3-aminoindazole derivatives that have inhibitory activity against the CDK11 protein kinase. [Means for solving the problem]

[0009] The present inventors have discovered that compounds of general formula (I) as defined below are kinase inhibitors, in particular inhibitors of the CDK11 family. Due to the important role of protein kinases, in particular CDK11, in regulating cell proliferation, such compounds are useful for treating diseases caused by altered CDK11 activity, in particular in the treatment of cancer, and various cell proliferative and immune-related disorders.

[0010] Therefore, a first object of the present invention is to provide a substituted 3-aminoindazole derivative of the following formula (I) or a pharmaceutically acceptable salt thereof:

[0011] [ka] During the ceremony, R1 is Optionally substituted straight-chain or branched (C1-C6) alkyl; optionally substituted (C3-C7)cycloalkyl; an optionally substituted 5- to 7-membered heterocycle; optionally substituted aryl; a 5- or 6-membered heteroaryl selected from the group consisting of pyridyl, pyrimidinyl, pyrrolyl, and pyrazolyl; or A group of formula (II):

[0012] [ka] and Here, R4 is Optionally substituted straight or branched (C2-C6) alkyl; optionally substituted (C3-C7)cycloalkyl; or Optionally substituted 5- to 7-membered heterocycle and; R2 is Straight or branched (C2-C6) alkyl; optionally substituted (C3-C7)cycloalkyl; optionally substituted heterocycles; a 5- to 6-membered heterocyclic methyl group [—CH2-Het], wherein the heterocyclic ring is selected from the group consisting of pyrrolidinyl, methylpiperazinyl, and piperidinyl; or A group of formula (III):

[0013] [ka] and; Here, R5 is hydrogen; Optionally substituted straight-chain or branched (C1-C6) alkyl; optionally substituted (C3-C7)cycloalkyl; optionally substituted aryl; an optionally substituted heterocycle; or Optionally substituted heteroaryl and; R6 is Optionally substituted straight-chain or branched (C1-C6) alkyl; optionally substituted (C3-C7)cycloalkyl; optionally substituted aryl; an optionally substituted heterocycle; or Optionally substituted heteroaryl and; R3 is hydrogen or a group of formula (IV):

[0014] [ka] and Here, R7 is Optionally substituted straight-chain or branched (C1-C6) alkyl; optionally substituted (C3-C7)cycloalkyl; optionally substituted aryl; an optionally substituted heterocycle; or Optionally substituted heteroaryl and; however, R1 is

[0015] [ka] isn't it.

[0016] Preferred compounds of formula (I) are R1, mono-, di- or tri-substituted phenyl; an optionally substituted 5- or 6-membered heteroaryl selected from the group consisting of pyridyl, pyrrolyl, and pyrazolyl, wherein the substituents are each independently selected from the group consisting of halogen, linear or branched (C-C) alkyl, alkoxy, hydroxyalkyl, polyfluorinated alkyl, polyfluorinated alkoxy, cyano, amino, alkylsulfonyl, aminosulfonyl, phenyl, hydroxy, aminocarbonyl, alkylaminocarbonyl, hydroxyalkylaminocarbonyl, formyl, formylamino, nitro, alkylcarbonyl, alkyloxycarbonyl, and oxadiazolyl; or A group of formula (II):

[0017] [ka] and Here, R4 is linear or branched (C2-C6) alkyl, C3-C7) cycloalkyl optionally substituted with halogen or alkoxy; R2, (C3-C7)cycloalkyl optionally substituted with hydroxy, aminoalkyl, alkylamino, dialkylamino, alkylaminoalkyl, heterocycle, C3-C7 cycloalkylamino, haloalkylamino; a 5- to 7-membered heterocycle optionally substituted with 1 to 2 heteroatoms selected from N and O; 1-Azabicyclo[2.2.2]octanyl; 2-Azabicyclo[2.2.2]octanyl; or A group of formula (III):

[0018] [ka] and; Here, R5 is hydrogen; Optionally substituted straight or branched (C1-C6) alkyl; or Optionally substituted (C3-C7)cycloalkyl and; R6, Optionally substituted straight-chain or branched (C1-C6) alkyl; optionally substituted (C3-C7)cycloalkyl; optionally substituted phenyl; an optionally substituted heterocycle; or 5- or 6-membered heteroaryl optionally substituted with 1 or 2 nitrogen atoms and; R3, hydrogen, or Group of formula (IV) and Here, R7 is a straight or branched (C1-C6) alkyl optionally substituted with (C3-C7) cycloalkyl, alkylthio, alkoxy, or alkoxy(C1-C6) alkoxy; or (C3-C7)cycloalkyl and; However, R1 is

[0019] [ka] or a pharmaceutically acceptable salt thereof.

[0020] More preferred compounds of formula (I) are R1, disubstituted phenyl; an optionally substituted 5- or 6-membered heteroaryl selected from the group consisting of pyridyl and pyrazolyl, wherein the substituents are each independently selected from the group consisting of halogen, linear or branched (C1-C6) alkylalkoxy, hydroxyalkyl, polyfluorinated alkyl, polyfluorinated alkoxy, cyano, amino, alkylsulfonyl, aminosulfonyl, phenyl, hydroxy, aminocarbonyl, alkylaminocarbonyl, hydroxyalkylaminocarbonyl, formyl, formylamino, nitro, alkylcarbonyl, alkyloxycarbonyl, and oxadiazolyl; or The group of formula (II) above and; R2, (C3-C7)cycloalkyl selected from the group consisting of cyclopropyl, cyclobutyl, and cyclohexyl, wherein said cycloalkyl is optionally substituted with hydroxy, aminoalkyl, alkylamino, dialkylamino, haloalkylamino, alkylaminoalkyl, morpholinyl, or (C3-C7)cycloalkylamino; a heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, morpholinyl, tetrahydropyranyl, and azepanyl, wherein the heterocycle is optionally substituted with linear or branched (C-C) alkyl, (C-C) cycloalkyl, spiro (C-C) cycloalkyl, aminoalkyl, alkoxyalkyl, hydroxyalkyl, phenyl, polyfluorinated alkyl, C-C cycloalkylamino, and hydroxy; or The group of formula (III) defined above and; R3 and R4 are as defined above, or a pharmaceutically acceptable salt thereof.

[0021] Preferred specific compounds of formula (I) (cpd) or salts thereof are the compounds listed below: N-[5-(4-amino-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide dihydrochloride (Compound 1); N-[5-(2,4-dichlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-3-carboxamide hydrochloride (Compound 2); N-[5-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 3); N-[5-(2,5-dichlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 4); (3R)-N-[5-(4-amino-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide dihydrochloride (Compound 5); (3R)-N-[5-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 6); (3S)-N-[5-(4-amino-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide dihydrochloride (Compound 7); (3R)-N-[5-(2-chloro-4-methylphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 8); N-[5-(5-carbamoyl-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 9); (3S)-N-[5-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 10); N-[5-(3-amino-2-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 11); (3S)-N-[5-(2-chloro-4-methylphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 12); (3R)-N-[5-(2,5-dichlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 13); (3R)-N-[5-(2,4-dichlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 14); N-{5-[5-chloro-2-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide trifluoroacetate (Compound 15); N-[5-(5-acetyl-2-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 16); N-[5-(2-chloro-5-methoxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 17); (3R)-N-[5-(2-chloro-5-methoxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 18); (3R)-N-[5-(5-acetyl-2-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 19); (3R)-N-[5-(2-fluoro-5-methoxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 20); (3R)-N-[5-(5-chloro-2-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 21); (3R)-N-[5-(5-ethoxy-2-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 22); (3R)-N-{5-[2-fluoro-5-(trifluoromethoxy)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (Compound 23); (3R)-N-[5-(5-cyano-2-methylphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 24); (3R)-N-[5-(5-cyano-2-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 25); (3R)-N-[5-(2-chloro-5-nitrophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 26); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-6-oxopiperidine-3-carboxamide (compound 27); N-[5-(5-acetyl-2-fluorophenyl)-1H-indazol-3-yl]-6-oxopiperidine-3-carboxamide (compound 28); Methyl 4-chloro-3-(3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (compound 29); (3R)-N-[5-(2,4-difluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 30); (3R)-N-{5-[4-methoxy-2-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (Compound 31); (3R)-N-[5-(2-fluoro-5-methylphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 32); (3R)-N-[5-(5-acetyl-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 33); (3R)-N-[5-(5-amino-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide dihydrochloride (compound 34); (3R)-N-[5-(2,5-difluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 35); (3R)-N-{5-[4-methyl-2-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (Compound 36); Methyl 4-chloro-3-(3-{[(3R)-pyrrolidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (compound 37); (3R)-N-[5-(5-acetyl-2-chlorophenyl)-1H-indazol-3-yl]pyrrolidine-3-carboxamide hydrochloride (compound 38); (3R)-N-{5-[2-chloro-5-(methylcarbamoyl)phenyl]-1H-indazol-3-yl}pyrrolidine-3-carboxamide hydrochloride (compound 39); Methyl 4-cyano-3-(3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (compound 40); (3R)-N-[5-(2-chloro-5-hydroxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 41); Methyl 2,4-dichloro-5-(3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (compound 42); (3R)-N-[5-(2-chloro-5-propanoylphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 43); (3R)-N-{5-[2-chloro-4-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (compound 44); (3R)-N-{5-[4-chloro-2-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (Compound 45); (3R)-N-{5-[5-fluoro-2-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (compound 46); (3R)-N-[5-(2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 47); (3R)-N-{5-[2-chloro-5-(propan-2-yl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (compound 48); (3R)-N-(5-phenyl-1H-indazol-3-yl)piperidine-3-carboxamide hydrochloride (compound 49); Methyl 2,4-difluoro-5-(3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (compound 50); (3R)-N-[5-(5-tert-butyl-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 51); (3R)-N-[5-(2-chloro-5-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 52); (3R)-N-[5-(2,5-dicyanophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 53); Methyl 2-amino-4-chloro-5-(3-{[(3R)-pyrrolidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate dihydrochloride (compound 54); (3R)-N-{5-[2-cyano-5-(methylcarbamoyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (Compound 55); Propan-2-yl 4-chloro-3-(3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (compound 56); Methyl 2,4-dichloro-3-(3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (compound 57); (3R)-N-{5-[2-chloro-5-(1,2,4-oxadiazol-3-yl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide dihydrochloride (compound 58); (3R)-N-{5-[2-chloro-5-(1,3,4-oxadiazol-2-yl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide trifluoroacetate (compound 59); (3R)-N-{5-[2-chloro-5-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide dihydrochloride (compound 60); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 61); N-[5-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]-3-(dimethylamino)cyclobutanecarboxamide hydrochloride (Compound 62); N-[5-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]-3-(methylamino)cyclobutanecarboxamide hydrochloride (Compound 63); N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 64); 1-Butyl-N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 65); 1-(3-aminopropyl)-N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide dihydrochloride (compound 66); N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]-1-(1-methoxypropan-2-yl)piperidine-4-carboxamide hydrochloride (compound 67); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide (compound 68); 1-Butyl-N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide (compound 69); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-1-(2-methylpropyl)piperidine-4-carboxamide (compound 70); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-1-(3-hydroxy-2,2-dimethylpropyl)piperidine-4-carboxamide (compound 71); N-[5-(6-chloro-2-fluoro-3-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 72); N-[5-(2-chloro-6-fluoro-3-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (compound 73); N-[5-(5-chloro-2-fluoro-3-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (compound 74); N-{5-[2-methoxy-5-(propan-2-yl)phenyl]-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide hydrochloride (Compound 75); 1-Methyl-N-{5-[3-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-4-carboxamide hydrochloride (Compound 76); N-{5-[2-chloro-5-(hydroxymethyl)phenyl]-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide p-toluenesulfonate (compound 77); N-[5-(2-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (compound 78); N-[5-(2-cyanophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide p-toluenesulfonate (compound 79); N-[5-(2,5-dichlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 80); N-[5-(3-carbamoylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 81); N-{5-[4-(hydroxymethyl)phenyl]-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide p-toluenesulfonate (compound 82); N-{5-[3-(hydroxymethyl)phenyl]-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide p-toluenesulfonate (compound 83); 1-Methyl-N-[5-(pyridin-3-yl)-1H-indazol-3-yl]piperidine-4-carboxamide dihydrochloride (compound 84); N-[5-(2-chlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 85); N-[5-(2-chloro-5-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 86); N-[5-(4-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 87); N-[5-(2-ethylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (compound 88); N-[5-(3-cyanophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (compound 89); N-[5-(4-aminophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide dihydrochloride (compound 90); N-[5-(2-aminophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide dihydrochloride (Compound 91); 1-Methyl-N-[5-(4-sulfamoylphenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 92); 1-Methyl-N-(5-phenyl-1H-indazol-3-yl)piperidine-4-carboxamide hydrochloride (compound 93); N-{5-[2-chloro-5-(trifluoromethyl)phenyl]-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide hydrochloride (Compound 94); N-[5-(2-fluoropyridin-3-yl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide dihydrochloride (compound 95); N-[5-(2-methoxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (compound 96); N-[5-(2,3-dichlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 97); N-[5-(2-chloro-6-methoxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (compound 98); N-[5-(2,3-difluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 99); 1-Methyl-N-{5-[3-(methylsulfonyl)phenyl]-1H-indazol-3-yl}piperidine-4-carboxamide hydrochloride (Compound 100); N-[5-(3-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 101); N-[5-(2-hydroxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 102); N-[5-(biphenyl-2-yl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 103); 1-Methyl-N-{5-[2-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-4-carboxamide hydrochloride (Compound 104); N-[5-(2,6-difluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 105); N-[5-(2,4-dichlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 106); N-[5-(4-amino-2-chlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide dihydrochloride (Compound 107); 1-Methyl-N-[5-(2,4,6-trichlorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 108); N-[5-(4-carbamoylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 109); N-[5-(4-cyanophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 110); N-[5-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 111); N-[5-(4-amino-3-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 112); N-[5-(4-cyano-2-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 113); N-[5-(2,6-dimethylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide trifluoroacetate (Compound 114); N-[5-(2-fluoro-5-nitrophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 115); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide trifluoroacetate (Compound 116); N-[5-(5-carbamoyl-2-chlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide trifluoroacetate (Compound 117); N-[5-(2-fluoro-4-formylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 118); N-[5-(2-fluoro-4-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 119); N-[5-(2,6-difluoro-4-methoxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 120); 1-Methyl-N-[5-(1H-pyrazol-4-yl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 121); 1-Methyl-N-[5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 122); 1-Methyl-N-[5-(2,4,6-trifluorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 123); N-[5-(2,4-difluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 124); 1-Methyl-N-[5-(1H-pyrazol-3-yl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 125); 1-Methyl-N-[5-(2,4,5-trifluorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 126); 1-Methyl-N-{5-[2,4,6-trifluoro-3-(propan-2-yloxy)phenyl]-1H-indazol-3-yl}piperidine-4-carboxamide hydrochloride (Compound 127); 1-Methyl-N-[5-(2,3,4-trifluorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 128); N-[5-(4-fluoro-2-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide trifluoroacetate (Compound 129); N-[5-(4-amino-2-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide dihydrochloride (Compound 130); 1-Methyl-N-[5-(2,4,6-trifluoro-3-methoxyphenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 131); N-[5-(2,3-difluoro-4-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 132); N-[5-(2-chloro-4-fluoro-3-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 133); N-[5-(3-cyano-2,6-difluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide (compound 134); N-[5-(3-cyano-4-hydroxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 135); N-[5-(2-cyano-5-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 136); N-[5-(2-chloro-5-nitrophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide trifluoroacetate (Compound 137); N-[5-(2,6-difluoro-4-hydroxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide trifluoroacetate (Compound 138); 1-methyl-N-[5-(2,4,6-trifluoro-3-hydroxyphenyl)-1H-indazol-3-yl]piperidine-4-carboxamide (compound 139); 1-Butyl-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 140); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-1-propylpiperidine-4-carboxamide hydrochloride (Compound 141); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-1-pentylpiperidine-4-carboxamide hydrochloride (Compound 142); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-1-(propan-2-yl)piperidine-4-carboxamide hydrochloride (compound 143); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-4-(methylamino)cyclohexanecarboxamide hydrochloride (Compound 144); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-3-(methylamino)cyclobutanecarboxamide hydrochloride (Compound 145); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-(methylamino)cyclobutanecarboxamide hydrochloride (Compound 146); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-(dimethylamino)cyclobutanecarboxamide hydrochloride (Compound 147); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-(propan-2-ylamino)cyclobutanecarboxamide hydrochloride (compound 148); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-(morpholin-4-yl)cyclobutanecarboxamide hydrochloride (Compound 149); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-[(2,2,2-trifluoroethyl)amino]cyclobutanecarboxamide hydrochloride (Compound 150); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-[(2-fluoroethyl)amino]cyclobutanecarboxamide hydrochloride (Compound 151); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-(ethylamino)cyclobutanecarboxamide hydrochloride (Compound 152); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-(cyclobutylamino)cyclobutanecarboxamide hydrochloride (Compound 153); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-(cyclopentylamino)cyclobutanecarboxamide hydrochloride (Compound 154); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-(cyclopropylamino)cyclobutanecarboxamide hydrochloride (Compound 155); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]tetrahydro-2H-pyran-4-carboxamide (compound 156); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 157); 1-Cyclopropyl-N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 158); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-1-phenylpiperidine-4-carboxamide hydrochloride (Compound 159); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-1-azabicyclo[2.2.2]octane-4-carboxamide (compound 160); N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-3-carboxamide hydrochloride (Compound 161); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-2-[(2S)-pyrrolidin-2-yl]acetamide hydrochloride (Compound 162); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-2-(piperidin-4-yl)acetamide hydrochloride (Compound 163); trans-4-(aminomethyl)-N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]cyclohexanecarboxamide hydrochloride (compound 164); N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 165); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-4-(dimethylamino)cyclohexanecarboxamide hydrochloride (Compound 166); (3R)-N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]pyrrolidine-3-carboxamide hydrochloride (compound 167); (3S)-N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]pyrrolidine-3-carboxamide hydrochloride (compound 168); (3R)-N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 169); (3S)-N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 170); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 171); (3R)-N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 172); (3S)-N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 173); (3R)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 174); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-b-alaninamide hydrochloride (Compound 175); (3R)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]pyrrolidine-3-carboxamide hydrochloride (Compound 176); (3R,6S)-N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-6-methylpiperidine-3-carboxamide trifluoroacetate (compound 177); (3R,6R)-N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-6-methylpiperidine-3-carboxamide trifluoroacetate (compound 178); (3R,6R)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-6-methylpiperidine-3-carboxamide trifluoroacetate (compound 179); (3R,6S)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-6-(trifluoromethyl)piperidine-3-carboxamide (compound 180); (3S)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 181); (2R)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]morpholine-2-carboxamide hydrochloride (Compound 182); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]azepane-3-carboxamide hydrochloride (compound 183); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-6,6-dimethylpiperidine-3-carboxamide hydrochloride (Compound 184); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-6-azaspiro[4.5]decane-8-carboxamide hydrochloride (compound 185); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-1-azaspiro[5.5]undecane-3-carboxamide hydrochloride (compound 186); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-2-azabicyclo[2.2.2]octane-4-carboxamide hydrochloride (compound 187); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-1-azabicyclo[2.2.2]octane-3-carboxamide hydrochloride (compound 188); 1-[(2,2-dimethylpentanoyl)oxy]ethyl (3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate (compound 189); 1-[(2-methylpropanoyl)oxy]ethyl (3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate (compound 190); (Acetyloxy)methyl (3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate (compound 191); [(2-methylpropanoyl)oxy]methyl (3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate (compound 192); [(2,2-dimethylpropanoyl)oxy]methyl (3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate (compound 193); 1-(Acetyloxy)ethyl (3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate (compound 194); 1-[(2,2-dimethylpropanoyl)oxy]ethyl (3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate (compound 195); 2-methyl-1-[(2-methylpropanoyl)oxy]propyl(3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate (compound 196); 1-[(2,2-dimethylpropanoyl)oxy]-2-methylpropyl(3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate (compound 197); 1-{[(1-methylcyclohexyl)carbonyl]oxy}ethyl (3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate (compound 198); 1-[(tetrahydro-2H-pyran-4-ylcarbonyl)oxy]ethyl (3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate (compound 199); 1-[(2,2-dimethylpropanoyl)oxy]propyl(3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate (compound 200); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-4-hydroxycyclohexanecarboxamide (compound 201); (+)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-6,6-dimethylpiperidine-3-carboxamide (compound 202); (-)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-6,6-dimethylpiperidine-3-carboxamide (compound 203); (8+)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-6-azaspiro[4.5]decane-8-carboxamide hydrochloride (compound 204); (8-)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-6-azaspiro[4.5]decane-8-carboxamide hydrochloride (compound 205); (3+)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-1-azaspiro[5.5]undecane-3-carboxamide (compound 206); (3-)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-1-azaspiro[5.5]undecane-3-carboxamide (compound 207); Butyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (compound 208); Ethyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (compound 209); propan-2-yl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (compound 210); Hexyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (compound 211); 2,2-Dimethylpropyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (compound 212); 2-Methylpropyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (compound 213); Pentyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (compound 214); 2-Methoxyethyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (compound 215); Cyclobutyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (compound 216); Pentan-3-yl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (compound 217); Cyclohexylmethyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (compound 218); Cyclopropylmethyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate formate (compound 219); 2-(Ethylsulfanyl)ethyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate formate (compound 220); 3-(3-Methoxypropoxy)propyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate formate (compound 221); 4-Methylpentyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate formate (compound 222); Cyclopentyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate formate (compound 223); 2,2-Dimethylpropyl 5-(2-chloro-5-cyanophenyl)-3-({[(3+)-6,6-dimethylpiperidin-3-yl]carbonyl}amino)-1H-indazole-1-carboxylate hydrochloride (compound 224); Hexyl 5-(2-chloro-5-cyanophenyl)-3-({[(3R)-6,6-dimethylpiperidin-3-yl]carbonyl}amino)-1H-indazole-1-carboxylate hydrochloride (compound 225); propan-2-yl 5-(2-chloro-5-cyanophenyl)-3-({[(3R)-6,6-dimethylpiperidin-3-yl]carbonyl}amino)-1H-indazole-1-carboxylate hydrochloride (compound 226); (3R)-N-[5-(2-fluoroethoxy)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 227); (3R)-N-[5-(2-methoxyethoxy)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 228); (3R)-N-(5-ethoxy-1H-indazol-3-yl)piperidine-3-carboxamide hydrochloride (compound 229); (3R)-N-[5-(propan-2-yloxy)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 230); (3R)-N-(5-butoxy-1H-indazol-3-yl)piperidine-3-carboxamide hydrochloride (Compound 231) is. DETAILED DESCRIPTION OF THE INVENTION

[0022] For specific compounds of formula (I) of the present invention, optionally in the form of a pharmaceutically acceptable salt, reference is made to the experimental section and claims.

[0023] Where a compound of formula (I) contains one or more chiral centers and can exist in two or more optically isomeric forms, a reference to a compound of formula (I) includes all its optical isomeric forms (e.g., enantiomers, epimers and diastereomers), either as individual optical isomers or as mixtures (e.g., racemic mixtures) or as two or more optical isomers, unless the context requires otherwise.

[0024] Optical isomers can be characterized and differentiated by optical activity (i.e., + and - isomers, or d and I isomers), or by absolute stereochemistry using the "R and S" nomenclature developed by Cahn, Ingold, and Prelog. See Advanced Organic Chemistry by Jerry March, 4th Edition, John Wiley & Sons, New York, 1992, pages 109-114; see also Cahn, Ingold, and Prelog, Angew. Chem. Int. Ed. Engl., 1966, 5, 385-415.

[0025] Optical isomers can be separated by a number of techniques, such as chiral chromatography (chromatography on a chiral support), and such techniques are well known to those skilled in the art.

[0026] When a compound of Formula (I) exists in two or more optical isomeric forms, one enantiomer in a pair of enantiomers may exhibit advantages over the other enantiomer, e.g., with respect to biological activity. Thus, in some situations, it may be desirable to use only one of a pair of enantiomers, or only one of multiple diastereomers, as a therapeutic agent. Accordingly, the present invention provides compositions comprising a compound of Formula (I) having one or more asymmetric centers, wherein at least 55% (e.g., at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%) of the compound of Formula (I) exists as a single optical isomer (e.g., enantiomer or diastereomer).

[0027] In cases in which compounds have unsaturated carbon-carbon double bonds, both the cis (Z) and trans (E) isomers are within the scope of this invention.

[0028] Where compounds exist as tautomers, such as keto-enol tautomers, each tautomer is considered to be included in the present invention, whether it exists in equilibrium or exists predominantly in one form. Thus, unless otherwise provided, if R3 is hydrogen in a compound of formula (I) and only one of the tautomers of formula (Ia) or (Ib) below is shown, the other should also be considered to be within the scope of the present invention.

[0029] [ka]

[0030] Pharmaceutically acceptable salts of the compounds of formula (I) include salts with inorganic or organic acids such as nitric acid, hydrochloric acid, hydrobromic acid, sulfuric acid, perchloric acid, phosphoric acid, acetic acid, trifluoroacetic acid, formic acid, propionic acid, glycolic acid, lactic acid, oxalic acid, fumaric acid, malonic acid, malic acid, maleic acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, isethionic acid and salicylic acid.

[0031] Pharmaceutically acceptable salts of the compounds of formula (I) also include salts with inorganic or organic bases, such as hydroxides, carbonates or bicarbonates of alkali or alkaline earth metals, in particular sodium, potassium, calcium, ammonium or magnesium, acyclic or cyclic amines.

[0032] Further objects of the present invention are the compounds of formula (I) as defined above, as well as their isomers, tautomers, hydrates, solvates, complexes, metabolites, prodrugs, carriers and N-oxides.

[0033] A metabolite of a compound of Formula (I) is a compound to which the same compound of Formula (I) is converted in vivo, for example, when administered to a mammal in need thereof. Typically, but not by way of limitation, upon administration of a compound of Formula (I), the same derivative may be converted to a variety of compounds, including more soluble derivatives, such as hydroxylated derivatives, which are readily excreted. Thus, depending on the metabolic pathway followed, any of these hydroxylated derivatives may be considered a metabolite of the compound of Formula (I).

[0034] Prodrugs are covalently bonded compounds that release the active parent drug according to formula (I) in vivo. N-oxides are compounds of formula (I) where the nitrogen and oxygen are joined by a dative bond.

[0035] A further object of the present invention are compounds of formula (I) in which one or more hydrogen atoms have been replaced by one or more deuterium atoms.

[0036] The term "linear or branched (C1-C6) alkyl" (and thus encompassing (C1-C4) alkyl) intends any of the groups, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, n-hexyl, etc.

[0037] The terms "carbocycle", "carbocyclic ring", and "cycloalkyl" refer to a monovalent non-aromatic, saturated or partially unsaturated ring having three to seven carbon atoms (C3-C7) as a monocyclic ring or seven to twelve carbon atoms (C7-C12) as a bicyclic ring.

[0038] Bicyclic carbocycles having 7 to 12 atoms can be arranged, for example, as bicyclo[4,5], [5,5], [5,6] or [6,6] systems, and bicyclic carbocycles having 9 or 10 ring atoms can be arranged as bicyclo[5,6] or [6,6] systems, or as bridged systems such as bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, and bicyclo[3.2.2]nonane. Examples of monocyclic carbocycles having 3 to 7 atoms include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopent-1-enyl, 1-cyclopent-2-enyl, 1-cyclopent-3-enyl, cyclohexyl, 1-cyclohex-1-enyl, 1-cyclohex-2-enyl, 1-cyclohex-3-enyl, cyclohexadienyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, and the like.

[0039] The term "aryl" refers to a monocyclic, bicyclic, or polycyclic carbocyclic hydrocarbon ring system having one to four rings, optionally further fused or connected together by a single bond, in which at least one carbocyclic ring is "aromatic," the term "aromatic" referring to a completely conjugated π-electron bonding system. Non-limiting examples of such aryl groups include phenyl, α- or β-naphthyl, α- or β-tetrahydronaphthalenyl, biphenyl, and indanyl groups.

[0040] The term "heteroaryl" refers to an aromatic heterocycle, typically a 5- to 7-membered heterocycle having 1 to 3 heteroatoms selected from N, O, or S; heteroaryl rings may be further fused to or linked to aromatic and non-aromatic carbocyclic and heterocyclic rings. Non-limiting examples of such heteroaryl groups include, for example, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, imidazolyl, thiazolyl, isothiazolyl, pyrrolyl, furanyl, oxazolyl, isoxazolyl, pyrazolyl, thiophenyl, thiadiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, indazolyl, cinnolinyl, benzo[1,3]dioxolyl, benzo[1,4]dioxinyl, benzo[1,5]dioxinyl, benzo[1,6]dioxinyl, benzo[1,7]dioxinyl, benzo[1,8]dioxinyl, benzo[1,9]dioxinyl, benzo[2,3]dioxinyl, benzo[2,4]dioxinyl, benzo[3,5]dioxinyl, benzo[3,6]dioxinyl, benzo[2,3]dioxinyl, benzo[3,4]dioxinyl, benzo[1,5]dioxinyl, benzo[2,3]dioxinyl, benzo[2,4]dioxinyl, benzo[2,4]dioxinyl, benzo[2,5 ... Examples include benzothiazolyl, benzothiophenyl, benzofuranyl, isoindolinyl, benzimidazolyl, benzoxazolyl, quinolinyl, isoquinolinyl, 1,2,3-triazolyl, 1-phenyl-1,2,3-triazolyl, 2,3-dihydroindolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothiophenyl, benzopyranyl, 2,3-dihydrobenzoxazinyl, and 2,3-dihydroquinoxalinyl.

[0041] The terms "heterocyclyl" and "heterocyclyle" intend a 3- to 7-membered saturated or partially unsaturated carbocyclic ring in which one or more carbon atoms are replaced by a heteroatom such as nitrogen, oxygen, or sulfur. Non-limiting examples of heterocyclic groups include, for example, pyranyl, tetrahydropyranyl, pyrrolidinyl, pyrrolinyl, imidazolinyl, imidazolidinyl, pyrazolidinyl, pyrazolinyl, thiazolinyl, thiazolidinyl, dihydrofuranyl, tetrahydrofuranyl, tetrahydropyridinyl, 1,3-dioxolanyl, piperidinyl, piperazinyl, morpholinyl, dihydroazepinyl, tetrahydroazepinyl, azepanyl, oxadiazole, and the like. A heterocycle can also be a bicyclic ring system having 7 to 10 ring members (4 to 9 carbon atoms and 1 to 6 heteroatoms selected from N, O, P, and S), such as a bicyclo[4,5], [5,5], [5,6], or [6,6] system. Non-limiting examples of such heterocyclic groups include 3-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[4.1.0]heptanyl, azabicyclo[2.2.2]hexanyl, 1-azabicyclo[2.2.2]octanyl, and 2-azabicyclo[2.2.2]octanyl. Spiro moieties are also included within this definition.

[0042] According to the present invention, unless otherwise specified, the above R1, R2, R3, R4, R5, R6 and R7 groups can all be selected in any of their free positions from halogen, nitro, oxo group (=0), cyano, (C1-C6) alkyl, polyfluorinated alkyl, polyfluorinated alkoxy, haloalkyl, haloalkylamino, alkenyl, alkynyl, hydroxyalkyl, aryl, arylalkyl, heterocycle, (C3-C7) cycloalkyl, hydroxy, alkoxy, alkoxyalkyl, alkoxy(C1-C6)alkoxy, aryloxy, heteroaryl, heterocycleoxy, methylenedioxy, alkylcarbonyloxy, arylcarbonyloxy, cycloalkenyloxy, C3-C7 cycloalkylamino, heterocyclecarbonyloxy, alkylideneaminooxy, carboxy, alkoxycarbonyl, aryloxycarbonyl, cycloalkyloxycarbonyl, heterocycleoxycarbonyl, amino, ureido, aminoalkyl, alkylamino, dialkylamino and alkylsulfonylamino, arylsulfonylamino, heterocyclic amino, formylamino, alkylcarbonylamino, arylcarbonylamino, heterocyclic carbonylamino, aminocarbonyl, alkylaminocarbonyl, alkylaminoalkyl, dialkylaminocarbonyl, arylaminocarbonyl, heterocyclic aminocarbonyl, alkoxycarbonylamino, hydroxyalkylaminocarbonyl, hydroxyaminocarbonylalkoxyimino, alkylsulfonylamino, arylsulfonylamino, heterocyclic sulfonylamino, formyl, alkylcarbonyl, arylcarbonyl, cycloalkylcarbonyl, heterocyclic carbonyl, alkylsulfonyl, arylsulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylaminosulfonyl, heterocyclic aminosulfonyl, arylthio, alkylthio, phosphonate, and alkylphosphonate.

[0043] In turn, whenever appropriate, each of the above substituents may be further substituted with one or more of the aforementioned groups.

[0044] In this respect, the term "halogen" intends a fluorine, chlorine, bromine, or iodine atom.

[0045] The term "cyano" intends the radical --CN.

[0046] The term "nitro" intends the group --NO.sub.2.

[0047] The term "alkenyl" or "alkynyl" contemplates any of the aforementioned straight chain or branched (C2-C6) alkyl groups further containing a double or triple bond. Non-limiting examples of alkenyl or alkynyl groups of the present invention include, for example, vinyl, allyl, 1-propenyl, isopropenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-pentenyl, 1-hexenyl, ethynyl, 2-propynyl, 4-pentynyl, and the like.

[0048] The term "polyfluoroalkyl or alkoxy" intends a straight or branched (C1-C6) alkyl or alkoxy group as defined above substituted with more than one fluorine atom, for example, trifluoromethyl, trifluoroethyl, 1,1,1,3,3,3-hexafluoropropyl, trifluoromethoxy, and the like.

[0049] The terms "alkoxy, aryloxy, heterocycleoxy" and derivatives thereof intend any of the above (C1-C6) alkyl, aryl or heterocycle groups linked to the remainder of the molecule via an oxygen atom (-O-).

[0050] From all of the above, it will be clear to one skilled in the art that groups that are compound names, such as arylamino, are intended to be conventionally interpreted according to the moiety from which they are derived, e.g., an amino group further substituted with an aryl, where aryl is as defined above.

[0051] Similarly, terms such as alkylthio, alkylamino, dialkylamino, alkoxycarbonyl, alkoxycarbonylamino, heterocyclecarbonyl, heterocyclecarbonylamino, cycloalkyloxycarbonyl, etc. all include groups in which the alkyl, alkoxy, aryl, (C-C)cycloalkyl, and heterocycle moieties are as defined above.

[0052] The present invention also provides methods for preparing compounds of formula (I) as defined above, using the following reaction pathways and synthetic schemes, and by using techniques available in the art and readily available starting materials. The preparation of specific embodiments of the present invention is described in the following examples, but those skilled in the art will recognize that the described preparations can be readily adapted to prepare other embodiments of the present invention. For example, the synthesis of unexemplified compounds according to the present invention can be carried out by modifications obvious to those skilled in the art, such as appropriate protection of blocking groups, substitution with other suitable reagents known in the art, or routine modification of reaction conditions. Alternatively, it will be recognized that other reactions mentioned herein or known in the art have applicability for preparing other compounds of the present invention.

[0053] The compounds of the present invention can be prepared from readily available starting materials using the following general methods and procedures. Unless otherwise specified, starting materials are known compounds or can be prepared from known compounds according to known procedures. Where typical or preferred process conditions (i.e., reaction temperatures, times, molar ratios of reactants, solvents, pressures) are described, it is understood that different process conditions can also be used unless otherwise specified. Optimum reaction conditions may vary with the particular reactants or solvents used, although such conditions can be determined by one skilled in the art by routine optimization procedures.

[0054] Compounds of formula (I) can be prepared according to the method reported in Scheme 1 below.

[0055] Diagram 1

[0056] [ka]

[0057] Thus, the method of the present invention comprises the following steps:

[0058] Step 1a) Compound of formula (V):

[0059] [ka] wherein R8 is bromine or 4,4,5,5-tetramethyl-[1,3,2]dioxaborolane and R9 is a suitable protecting group such as 1,1′,1″-methanetriyltribenzene, tert-butyloxycarbonyl, p-metossitritile, 1-(diphenylmethyl)-4-methoxybenzene or tetrahydro-2H-pyranyl (THP), to a compound of formula (VI):

[0060] [ka] [R2 is an optionally substituted linear or branched (C2-C6) alkyl, (C3-C7) cycloalkyl, heterocycle, or 5- to 6-membered heterocycle methyl, and the heterocycle is selected from the group consisting of pyrrolidinyl, methylpiperazinyl, and piperidinyl; Step 1b') Obtaining intermediate of formula (VII):

[0061] [ka] [R2 and R9 are as defined above in step 1a, and R8 is bromine], to a compound of formula (VIII) or (IX):

[0062] [ka] [R1 is optionally substituted linear or branched (C1-C6) alkyl, (C3-C7) cycloalkyl, heterocycle, aryl, and 5- or 6-membered heteroaryl.] mixing with; or Step 1b″) The intermediate of formula (VII), wherein R8 is 4,4,5,5-tetramethyl-[1,3,2]dioxaborolane, and R2 and R9 are as defined above in Step 1a, is converted into a compound of formula (X):

[0063] [ka] wherein R1 is as defined above in step 1b' and X is a halogen; Step 1c) Obtaining intermediate (XI):

[0064] [ka] [R1, R2 and R9 are defined as above in steps 1b' and 1b"] with a suitable deprotecting agent to give a compound of formula (I):

[0065] [ka] wherein R3 is hydrogen, and R1 and R2 are as defined above; or Step 1d) Compound of formula (V):

[0066] [ka] wherein R8 is bromine and R9 is as defined above in step 1a, with a compound of formula (VIII) or (IX):

[0067] [ka] [R1 is as defined above in step 1b']; Step 1e) Obtained intermediate (XII):

[0068] [ka] [R1 and R9 are as defined above in step 1c.] to a compound of formula (VI):

[0069] [ka] [R2 is as defined above in step 1a]; Step 1f) Obtained intermediate (XIII):

[0070] [ka] [R1, R2 and R9 are as defined above] is reacted with a suitable deprotecting agent to give a compound of formula (I):

[0071] [ka] wherein R3 is hydrogen and R1 and R2 are as defined above in step 1c.

[0072] Alternatively, if desired, a first compound of formula (VII) or (XII) can be converted to a second compound of formula (VII) or (XII), respectively, by operating according to known synthetic conditions.

[0073] Examples of possible transformations are shown below.

[0074] Conversion A) Compound of formula (VIIa):

[0075] [ka] [R2 is an optionally substituted heterocycle, and R9 is as defined above in step 1a] is first converted to a compound of formula (VIIb) by removing the protecting group, and then the resulting derivative is reacted with a compound of formula R10R11CO (XIV) [R10 and R11 are optionally substituted groups selected from hydrogen, linear or branched (C1-C6) alkyl, (C3-C7) cycloalkyl, or R10 and R11 can together form an optionally substituted (C3-C7) cycloalkyl and heterocycle group] in the presence of a suitable reducing agent under reductive amination conditions; Conversion B) Compounds of formula (VIId):

[0076] [ka] [R2 is (C4-C6)cycloalkyloxo] by reacting with a compound of formula R10R11NH (XV) [R10 and R11 are as defined above in Transformation A] under reductive amination conditions in the presence of a suitable reducing agent to convert to a compound of formula (VIIe); Conversion C) Compounds of formula (XIIIa):

[0077] [ka] wherein R2 is an optionally substituted heterocycle and R9 is as defined above in step 1a, is first converted to a compound of formula (XIIIb) by removing the protecting group, and then the resulting derivative is reacted with a compound of formula R10R11CO (XIV), wherein R10 and R11 are as defined above in transformation A, under reductive amination conditions in the presence of a suitable reducing agent; Conversion D) Compounds of formula (XIIId):

[0078] [ka] [R2 is (C4-C6)cycloalkyloxo] with a compound of formula R10R11NH (XV) [R10 and R11 are as defined above in Transformation A] under reductive amination conditions in the presence of a suitable reducing agent to convert to a compound of formula (XIIIe); Conversion E) Compounds of formula (XIIIf):

[0079] [ka] first by reacting with a compound of formula R5CHClOCOCl (XVI) [R5 is hydrogen, optionally substituted linear or branched (C1-C6) alkyl, (C3-C7) cycloalkyl, aryl, heterocycle, and heteroaryl] to convert to a compound of formula (XIIIg), and then by reacting with a compound of formula R6COOH (XVII) [R6 is optionally substituted linear or branched (C1-C6) alkyl, (C3-C7) cycloalkyl, aryl, heterocycle, or heteroaryl] under basic conditions to convert to a compound of formula (XIIIh).

[0080] The compound of the first general formula (I) can be conveniently converted to the compound of the second formula (I) by operating according to known synthetic conditions.

[0081] Examples of possible transformations are shown below.

[0082] Conversion 1) Compounds of formula (I):

[0083] [ka] converting the compound of formula (I) into a compound of formula (I), wherein R1 is as defined above in step 1b', and R2 is an optionally substituted linear or branched (C2-C6) alkyl, (C3-C7) cycloalkyl, heterocycle, or 5- to 6-membered heterocycle-methyl, wherein the heterocycle is selected from the group consisting of pyrrolidinyl and piperidinyl, with a compound of formula ROCOCl (XIX), wherein R7 is an optionally substituted linear or branched (C1-C6) alkyl, (C3-C7) cycloalkyl, aryl, heterocycle, or heteroaryl, under basic conditions; or Compounds of formula (I), wherein R1 is a group of formula (II) and R4 is an optionally substituted linear or branched (C2-C6) alkyl, (C3-C7) cycloalkyl or heterocycle, can be prepared according to the method reported in Scheme 2 below.

[0084] Diagram 2

[0085] [ka]

[0086] The method of the present invention therefore comprises the following steps:

[0087] Step 2a) Compound of formula (XX):

[0088] [ka] [R9 is as defined above in step 1a] to a compound of formula (XXI):

[0089] [ka] wherein R4 is an optionally substituted linear or branched (C2-C6) alkyl, (C3-C7) cycloalkyl, or heterocycle, and Y is halogen or hydroxy; Step 2b) Obtaining intermediate (XXII):

[0090] [ka] with a suitable deprotecting agent; Step 2c) Obtaining intermediate (XXIII):

[0091] [ka] with a compound of formula (VI):

[0092] [ka] [R2 is as defined above in step 1a]; Step 2d) Obtained intermediate (XXIV):

[0093] [ka] with a suitable deprotecting agent to give a compound of formula (I):

[0094] [ka] wherein R3 is hydrogen and R2 and R4 are as defined above.

[0095] According to step 1a, the coupling reaction of a compound of formula (V) with a suitable carboxylic acid of formula (VI) is carried out under basic conditions, preferably using DIPEA or TEA, in a suitable solvent such as DCM, DMF, THF, 1,4-dioxane or DMA, in the presence of a suitable condensing agent, such as dicyclohexylcarbodiimide (DCC), 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide (EDC), 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazolidinedione (DCM), The reaction is carried out in the presence of benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (DHBT), O-benzotriazolyltetramethylisouronium tetrafluoroborate (TBTU), benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (PyBOP), or 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) at a temperature ranging from about −10° C. to reflux for a suitable time, for example, from about 30 minutes to about 96 hours. The reaction may be carried out in the presence of a suitable catalyst, such as DMAP, or in the presence of an additional coupling reagent, such as N-hydroxybenzotriazole (HOBT); Alternatively, the conversion can be carried out by the mixed anhydride method using alkyl chloroformate such as ethyl, isopropyl, benzyl chloroformate in the presence of a tertiary amine such as TEA, DIPEA or pyridine in a suitable solvent such as DCM, DMF, THF at room temperature; Alternatively, the carboxylic acid of formula (VI) is first converted to the corresponding acyl chloride by reaction with an activating agent such as thionyl chloride, oxalyl chloride, cyanuric chloride, or 1-chloro-N,N,2-trimethylpropenylamine (Ghosez reagent) in a suitable solvent such as DCM or toluene, optionally in the presence of a catalytic amount of DMF, at a temperature ranging from about −10° C. to reflux for a suitable time, for example, from about 30 minutes to about 5 hours. The acyl chloride is then reacted with a suitable amine of formula (V) in the presence of a suitable base such as TEA, DIPEA, or pyridine in a suitable solvent such as DCM, THF, diethyl ether, 1,4-dioxane, ACN, toluene, or DMF, at a temperature ranging from about −10° C. to reflux for a suitable time, for example, from about 30 minutes to about 96 hours.

[0096] According to steps 1b' and 1b", the reaction of compound of formula (VII) with compound of formula (VIII), (IX) or (X) is carried out under standard Suzuki coupling conditions using a Pd-based catalyst such as dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct, [1,1'-bis(diphenylphosphine)ferrocene]-dichloropalladium, tetrakis(triphenylphosphine)-palladium, tris(dibenzylideneacetone)dipalladium, with a suitable base such as NaCO, CsCO, KPO, in a suitable solvent such as 1,4-dioxane, 1,4-dioxane / water, THF, DMF, toluene, at a temperature ranging from room temperature to 130°C, under conventional thermal conditions or in a microwave apparatus for a period ranging from 1 hour to 48 hours.

[0097] According to step 1c, removal of the R protecting group on the compound of formula (XI) can be carried out according to procedures known in the art. Depending on the protecting group selected, the following conditions can be used: For example, trityl or tert-butoxycarbonyl (Boc) groups can be removed under acidic conditions, such as TFA, HCl, in a solvent such as DCM or 1,4-dioxane, at a temperature ranging from room temperature to reflux for a suitable time, such as about 1 hour to 48 hours; methoxy or ethoxycarbonyl groups can be removed under basic conditions, such as TEA, DIPEA, NaCO, KCO, in a solvent such as MeOH or EtOH, at a temperature ranging from room temperature to reflux for a suitable time, such as 30 minutes to 24 hours.

[0098] According to step 1d, the Suzuki reaction of a compound of formula (V) with a compound of formula (VIII) or (IX) is carried out according to the method described for step 1b.

[0099] According to step 1e, the amidation of a compound of formula (XII) with a carboxylic acid of formula (VI) can be carried out according to the method described for step 1a.

[0100] According to step 1f, the deprotection of the compound of formula (XIII) is carried out according to the method described for step 1c.

[0101] According to transformation A of the process, a compound of formula (VIIa) is first deprotected under acidic, basic, or hydrogenation conditions, depending on the protecting group selected, to provide the free amine of formula (VIIb). This intermediate is then further reacted under reductive amination conditions with a reagent of formula (XIV) in the presence of a reducing agent such as NaBH, NaCNBH, or NaBH(OAc) in a solvent such as MeOH, EtOH, or DMF at a temperature ranging from room temperature to 40° C. for a time ranging from about 1 hour to 12 hours. The reduction reaction may be carried out in the presence of a suitable catalyst such as AcOH or TFA.

[0102] According to transformation B, the reductive amination of a compound of formula (VIId) with an amine of formula (XV) is carried out according to the methods described for transformation A.

[0103] According to transformation C, the reaction of a compound of formula (XIIIa) to give a compound of formula (XIIc) is carried out according to the method described for transformation A.

[0104] According to transformation D, the reductive amination of a compound of formula (XIIId) with an amine of formula (XV) is carried out according to the methods described for transformation B.

[0105] According to transformation E of the process, first, the piperidine ring of compound of formula (XIIIf) is reacted with a chloroformate of formula (XVI) under basic conditions, preferably with DIPEA, TEA, and pyridine, in a suitable solvent such as DCM, DMF, THF, 1,4-dioxane, or DMA, at a temperature ranging from about −10° C. to 50° C. for a suitable time, such as about 30 minutes to about 24 hours. Next, intermediate (XIIIg) is further reacted with a carboxylic acid of formula (XVII) using a suitable base, such as NaCO, KCO, or CsCO, in a suitable solvent such as 1,4-dioxane, 1,4-dioxane / water, THF, DMF, or toluene, at a temperature ranging from room temperature to 60° C. for a suitable time, such as about 2 hours to about 96 hours. The reaction may be carried out in the presence of a suitable catalyst, such as NaI or KI.

[0106] According to Transformation 1, the reaction of a compound of formula (I) with a compound of formula (XIX) is carried out under basic conditions, preferably with DIPEA, TEA and pyridine, in a suitable solvent such as DCM, DMF, THF, 1,4-dioxane or DMA, at a temperature ranging from about −10° C. to 50° C. for a suitable time, for example, from about 30 minutes to about 24 hours.

[0107] According to step 2a, alkylation of the intermediate of formula (XX) with an intermediate of formula (XXI) [Y is bromine or iodine] can be carried out in the presence of a suitable base such as Na2CO3, K2CO3, Cs2CO3, NaH, KH, in a suitable solvent such as DMF, DMA, ACN, acetone, THF, at a temperature ranging from 0°C to reflux, for a period varying from 1 hour to 24 hours. The intermediate of formula (XXI) [Y is hydroxy] can be carried out in the presence of a suitable base such as Na2CO3, K2CO3, Cs2CO3, NaH, KH, in a suitable solvent such as DMF, DMA, ACN, acetone, THF, at a temperature ranging from 0°C to reflux, for a period varying from 1 hour to 24 hours. ], the reaction is preferentially carried out under Mitsunobu alkylation conditions in the presence of a suitable reagent such as diethyl azodicarboxylate (DEAD), diisopropyl azodicarboxylate (DIAD), di-tert-butyl azodicarboxylate (DBAD), 1,1'-(azodicarbonyl)dipiperidine (ADDP) and a phosphine reagent such as trimethylphosphine, tri-tert-butylphosphine, in a suitable solvent such as THF, DMF, DCM, toluene, benzene, at a temperature ranging from 0°C to 65°C.

[0108] According to step 2b, the deprotection of the compound of formula (XXII) is carried out with hydrazine in a suitable solvent such as MeOH, EtOH, etc., at a temperature ranging from room temperature to reflux, for a period varying from about 1 hour to 96 hours.

[0109] According to step 2c, the amidation of a compound of formula (XXIII) with a carboxylic acid of formula (VI) can be carried out according to the method described for step 1a.

[0110] According to step 2d, the deprotection of the compound of formula (XXIV) is carried out according to the method described for step 1c.

[0111] From the above, it will be apparent to one skilled in the art that the conversion of a compound of formula (I) into a pharmaceutically acceptable salt thereof, or the conversion of a corresponding salt into the free compound (I), according to procedures known in the art, still falls within the scope of the present invention. When preparing a compound of formula (I) according to any variation of the process, all of which are intended to be within the scope of the present invention, any functional groups in the starting materials, reagents, or intermediates thereof, and any functional groups that may cause undesired side reactions, should be appropriately protected according to conventional techniques.

[0112] Such protection of reactive centers, and subsequent deprotection after completion of synthetic transformations, can be achieved according to standard procedures as described, for example, in Green, Theodora W. and Wuts, Peter GM - Protective Groups in Organic Synthesis, Third Edition, John Wiley & Sons Inc., New York (NY), 1999.

[0113] For any variation of the process for preparing the compounds of formula (I), the starting materials and other reactants are known, readily prepared according to known methods, or commercially available.

[0114] The final compounds can be isolated and purified using conventional procedures, such as chromatography and / or crystallization and salt formation.

[0115] The compounds of general formula (I) defined above can be converted into pharmaceutically acceptable salts.

[0116] The synthesis of compounds of general formula (I) can be carried out stepwise according to the synthetic methods described above, with each intermediate being isolated and purified, as necessary, by standard purification techniques, such as column chromatography, before carrying out the next reaction. Alternatively, two or more steps of the synthetic procedure can be carried out in a so-called "one-pot" procedure, as is known in the art, in which case only the compound resulting from the two or more steps is isolated and purified.

[0117] When the compound of formula (I) contains one or more asymmetric centers, the compound can be separated into single stereoisomers by procedures known to those skilled in the art. Such procedures include standard chromatographic techniques, such as chromatography using chiral stationary phases, or crystallization. A general method for separating compounds containing one or more asymmetric centers is reported, for example, in Jacques, Jean; Collet, Andre; Wilen, Samuel H., Enantiomers, Racemates, and Resolutions, John Wiley & Sons Inc., New York (NY), 1981.

[0118] The present invention also provides a method for treating diseases caused by and / or associated with dysregulated protein kinase activity, in particular CDK1 / CYCB, CDK2 / CYCA, CDK4 / CYCD1, CDK7 / CYCH / MAT1, CDK9 / CYCT, CDK11A, CDK11B, particularly CDK11 family kinases, which method comprises administering to a mammal, particularly a human in need of treatment, an effective amount of a compound of formula (I) as defined above.

[0119] The present invention further provides a compound of formula (I) as defined above, or a pharmaceutically acceptable salt thereof, for use in a method for the treatment of diseases caused by and / or associated with the above-reported dysregulated protein kinase activity, in particular CDK11 kinase activity, which method comprises administering to a mammal, preferably a human, in need of treatment an effective amount of a compound of formula (I) as defined above, or a pharmaceutically acceptable salt thereof.

[0120] A preferred method of the present invention is treating a disease caused by and / or associated with dysregulated protein kinase activity selected from the group consisting of cancer, cell proliferative disorders, viral infections, immune disorders, neurodegenerative disorders, and cardiovascular diseases. More preferably, the disease is cancer.

[0121] According to the most preferred embodiment of the present invention, the cancer is selected from the group consisting of carcinomas such as bladder cancer, breast cancer, kidney cancer, liver cancer, colon cancer, lung cancer including small cell lung cancer, esophageal cancer, gallbladder cancer, ovarian cancer, pancreatic cancer, gastric cancer, cervical cancer, prostate cancer, and skin cancer including squamous cell carcinoma; lymphoid hematopoietic tumors including leukemia, acute lymphocytic leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, B-cell lymphoma, angioimmunoblastic T-cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, hairy cell lymphoma, and Burkitt's lymphoma B; acute and chronic Hematopoietic tumors of the myeloid lineage, such as myeloid leukemia, myelodysplastic syndrome, and promyelocytic leukemia; tumors of mesenchymal origin, including fibrosarcoma and rhabdomyosarcoma; tumors of the central and peripheral nervous system, including glioma, glioblastoma, glioblastoma multiforme, astrocytoma, oligodendroglioma, paraglioma, neuroblastoma, and schwannoma; and other tumors, including melanoma, seminoma, teratocarcinoma, osteosarcoma, xeroderma pigmentosum, keratoxanthoma, thyroid carcinoma, such as papillary and medullary thyroid carcinoma, Kaposi's sarcoma, chondrosarcoma, and cholangiocarcinoma.

[0122] Another preferred method of the invention is to treat certain cell proliferative disorders such as, for example, benign prostatic hyperplasia, familial adenomatous polyposis, neurofibromatosis, psoriasis, atherosclerosis-associated vascular smooth cell proliferation, pulmonary fibrosis, arthritis, glomerulonephritis, and post-surgical stenosis and restenosis.

[0123] Another preferred method of the present invention is to treat viral infections, particularly to prevent the onset of AIDS in HIV-infected individuals.

[0124] Another preferred method of the present invention is treating immune disorders such as inflammatory and autoimmune diseases, e.g., multiple sclerosis, rheumatoid arthritis (RA), systemic lupus erythematosus, inflammatory bowel disease (IBD), Crohn's disease, irritable bowel syndrome, pancreatitis, ulcerative colitis, diverticulosis, myasthenia gravis, vasculitis, psoriasis, scleroderma, asthma, allergies, systemic sclerosis, vitiligo, arthritis such as osteoarthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, and the like.

[0125] Another preferred method of the present invention is treating neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease.

[0126] Another preferred method of the present invention is to treat certain cardiovascular diseases such as coronary heart disease, cardiomyopathy, ischemic heart disease, heart failure, hypertensive heart disease, inflammatory heart disease, and valvular heart disease.

[0127] Additionally, the methods of the present invention provide for the inhibition of tumor angiogenesis and metastasis, as well as the treatment of organ transplant rejection and host-versus-graft disease.

[0128] The present invention further provides pharmaceutical compositions comprising a compound of formula (I) in combination with one or more chemotherapeutic agents, such as cytostatic or cytotoxic agents. Cytostatic or cytotoxic agents include, but are not limited to, antibiotic-type agents, alkylating agents, antimetabolite agents, hormonal agents, immunological agents, interferon-type agents, cyclooxygenase inhibitors (e.g., COX-2 inhibitors), matrix metalloproteinase inhibitors, telomerase inhibitors, tyrosine kinase inhibitors, anti-growth factor receptor agents, anti-HER agents, anti-EGFR agents, anti-angiogenic agents (e.g., angiogenesis inhibitors), farnesyltransferase inhibitors, ras-raf signaling pathway inhibitors, cell cycle inhibitors, inhibitors of other cdks, tubulin binding agents, topoisomerase I inhibitors, topoisomerase II inhibitors, aromatase inhibitors, inhibitors of kinesin, therapeutic monoclonal antibodies, inhibitors of mTOR, histone deacetylase inhibitors, hypoxia response inhibitors, PD-1 antagonists, or antigen-binding fragments thereof that specifically bind to PD-1 or PD-L1.

[0129] If formulated as a fixed dose, such combination products utilize the compounds of this invention within the dosage range described below and the other pharmaceutically active agent within its approved dosage range.

[0130] The present invention further provides an in vitro method of inhibiting CDK11 protein kinase activity, which method comprises contacting CDK11 kinase with an effective amount of a compound of formula (I) as defined above.

[0131] Furthermore, the present invention provides a product comprising a compound of formula (I) as defined above or a pharmaceutically acceptable salt thereof and one or more chemotherapeutic agents as a combined preparation for simultaneous, separate or sequential use in anti-cancer therapy.

[0132] The compounds of formula (I) of the present invention are suitable for administration to mammals, for example humans, and can be administered by conventional routes, with the dosage level depending on the age, weight, condition of the patient and the administration route.

[0133] For example, a suitable dosage adopted for oral administration of a compound of formula (I) may be in the range of about 10 to about 1000 mg per dose, 1 to 5 times per day. The compounds of the present invention can be administered in various dosage forms, for example, orally in the form of tablets, capsules, sugar-coated tablets or film-coated tablets, liquids or suspensions; rectally in the form of suppositories; or parenterally, for example, intramuscularly, or by intravenous and / or intrathecal and / or intraspinal injection or infusion.

[0134] The pharmaceutical compositions containing the compounds of the present invention are usually prepared following conventional methods and are administered in a suitable pharmaceutical form.

[0135] For example, solid oral preparations may contain, together with the active compound, diluents such as lactose, dextrose, saccharose, sucrose, cellulose, corn starch, or potato starch; lubricants such as silica, talc, stearic acid, magnesium or calcium stearate, and / or polyethylene glycol; binders such as starch, gum arabic, gelatin methylcellulose, carboxymethylcellulose, or polyvinylpyrrolidone; disintegrants such as starch, alginic acid, alginates, or sodium starch glycolate; effervescent mixtures; dyes; sweeteners; wetting agents such as lecithin, polysorbates, and lauryl sulfate; and non-toxic, pharmacologically inactive substances generally used in pharmaceutical preparations. These pharmaceutical preparations can be produced by known methods, for example, by mixing, granulating, tableting, sugar-coating, or film-coating processes.

[0136] The suspensions and the emulsions may contain, as examples of carriers, natural gum, agar, sodium alginate, pectin, methylcellulose, carboxymethylcellulose, or polyvinyl alcohol.

[0137] Suspensions or solutions for intramuscular injection may contain the active compound together with a pharmaceutically acceptable carrier, such as sterile water, olive oil, ethyl oleate, glycols such as propylene glycol, and, if desired, an appropriate amount of lidocaine hydrochloride.

[0138] The solutions for intravenous injections or infusions may contain, as a carrier, sterile water or preferably they may be in the form of sterile aqueous isotonic saline solutions or they may contain propylene glycol as a carrier.

[0139] The suppositories may contain, together with the active compound, a pharmaceutically acceptable carrier, for example, cocoa butter, polyethylene glycol, a polyoxyethylene sorbitan fatty acid ester surfactant, or lecithin.

[0140] In another aspect, the present invention provides a compound of formula (I) as defined above or a pharmaceutically acceptable salt thereof for use as a medicament.

[0141] Finally, the present invention provides the use of a compound of formula (I) as defined above, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament having anti-cancer activity. [Example]

[0142] Experimental section Contractions and abbreviations used throughout this specification and description have the following meanings:

[0143] [Table 1]

[0144] Preparation of Compounds of Formula (I) For specific compounds of formula (I) of the present invention (optionally in the form of a pharmaceutically acceptable salt), see the experimental section and claims. With respect to the following examples, compounds of the present invention were synthesized using methods described herein or other methods known in the art.

[0145] The following examples are provided for the purpose of better illustrating the present invention, without imposing any limitations thereon.

[0146] As used herein, the symbols and conventions used in the processes, schemes and examples are consistent with those used in the contemporary scientific literature, e.g., the Journal of the American Chemical Society or the Journal of Biological Chemistry.

[0147] Compound names are IUPAC names and were generated using ACD Names (produced by Advanced Chemistry Development, Inc.).

[0148] Unless otherwise noted, all materials, including non-aqueous solvents such as DMF, THF, and DCM, were obtained from commercial suppliers, were of the highest grade, and were used without further purification. All reactions involving air- or moisture-sensitive compounds were performed under a nitrogen or argon atmosphere.

[0149] General Purification and Analytical Methods The synthesis of some of the compounds of formula (I) is described in the Examples below.

[0150] Compounds of the present invention prepared according to the following examples were: 1 They were also characterized by H NMR and / or HPLC / MS analytical data, which were collected according to either LCQ or LCT methods. Flash chromatography was performed on silica gel (Merck grade 9395, 60A).

[0151] HPLC LCQ method HPLC-MS / UV analysis was performed on an LCQ DecaXP (Thermo, San Jose, US) ion trap instrument equipped with an electrospray (ESI) ion source. The mass spectrometer was connected to a Surveyor HPLC system (Thermo, San Jose, US) equipped with a UV photodiode array detector (UV detection 215–400 nm). A Waters XSelect CSH C18 column, 50 × 4.6 mm, with a particle size of 3.5 μm was used. Mobile phase A was 5 mM ammonium acetate buffer (pH 4.5 with acetic acid): acetonitrile 95:5, and mobile phase B was 5 mM ammonium acetate buffer (pH 4.5 with acetic acid): acetonitrile 5:95. The gradient was 0% to 100% B in 7 min, with a 2-min hold at 100% B. The flow rate was 1 mL / min. The injection volume was 10 μL. Retention times (HPLC rt) are provided in minutes. The full scan mass range was 50–1200 amu. The heated capillary temperature was 200° C. and the spray voltage value was set at 4 kV. Masses are provided as m / z ratios.

[0152] Instrument control, data acquisition, and processing were performed using Xcalibur 1.4 SR1 software (Thermo).

[0153] HPLC LCT method HPLC-MS / UV analysis and high-resolution mass spectrometry (HRMS) were performed on a Waters Alliance LC2795 equipped with a Waters PDA UV detector 2996 and a TOF Waters LCT Premier XE mass detector (ESI interface) supported by a Waters Reagent Manager liquid pump. The assay is based on general-purpose gradient reversed-phase chromatography, which complements the identity-purity assay by measuring and confirming the predicted accurate mass of the compounds in the same run. Compound identification was performed by online serial ESI(+) full-scan MS detection, and sample purity was obtained as the relative "area percent" of the integrated LC / UV trace from 216 to 400 nm. The liquid chromatography system was equipped with a Waters XBridge CSH C18 column (3.0 x 30 mm, 3.5 μm particle size) thermostated at 50 °C. Alternatively, a Supelco column, Ascentis Express C18 (2.7 x 30 mm x 3 μm), was used.

[0154] Mobile phase A was 0.05% wt / v formic acid in highly purified water, and mobile phase B was a 70 / 25 / 5 (v / v / v) mixture of MeOH / iPrOH / HO containing 0.035% wt / v formic acid. The gradient was 0% to 100% B in 17.5 min, with a 5-min hold at 100% B. The flow rate was 0.8 mL / min, and the injection volume was 4 μL. The ESI source was operated at 100 °C, 2.5 kV capillary voltage, 60 V cone, 600 L / h nitrogen desolvation flow at 350 °C, and 10 L / h nitrogen cone flow. The "Normal" Z focus was set to 140. The analyzer was typically optimized with a 7200 V flight tube.

[0155] To obtain high-resolution mass spectra, the eluate from the HPLC column was split and mixed at 25 μL / min with a 100 μL / min flow of a 30 / 10 / 60 (vol / vol / vol) mixture of MeOH / iPrOH / HO containing 0.01 wt / vol% formic acid and 80 nM trimethoprim from a Waters Reagent Manager pump before entering the MS source. Trimethoprim was selected as a suitable, stable, and highly soluble reference compound for real-time single-point mass correction. ES(+) full-scan 80-1200 amu centroid data acquisition was performed in "W" mode with a 2 Hz sampling rate. A PC incorporating an LCT provided both real-time data centroiding and real-time mass correction based on the trimethoprim.H+ reference mass of 291.1452 Da. MS spectra of appropriate intensity (40-2000 analyte counts) were averaged to obtain the final results.

[0156] 1 H-NMR spectra were obtained at a constant temperature of 28°C for 5 mm 1 H{ 15 N- 31 P} a Varian INOVA 400 spectrometer operating at 400.5 MHz equipped with a z-axis PFG Indirect Detection probe, and a 5 mm 1 H{ 13 C- 15 Chemical shifts were recorded on a Varian INOVA 500 spectrometer equipped with a {N} triple resonance Indirect Detection probe. Chemical shifts were recorded relative to the non-deuterated residual solvent signal (DMSO-d5: 1 The reference was 2.50 ppm for H. Data are reported as follows: chemical shift (δ), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, qt = quintet, br.s = broad singlet, dd = doublet of doublets, ddd = doublet of doublets of doublets, m = multiplet), coupling constant (J, Hz) and number of protons.

[0157] Example 1 Step 1a (Scheme 1)

[0158] [ka]

[0159] tert-Butyl 3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate [(VII), R2 = tert-butylpiperidine-1-carboxylate, R8 = Br, R9 = 1,1′,1″-methanetriyltribenzene]

[0160] [ka]

[0161] To a solution of 1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (0.093 g, 0.405 mmol) in anhydrous DCM (5 mL) cooled to 0-5°C was added 1-chloro-N,N,2-trimethyl-1-propenylamine (Ghosez reagent) (0.080 mL, 0.608 mmol). The mixture was stirred at room temperature for 2 hours and then added dropwise to a solution of 5-bromo-1-trityl-1H-indazol-3-ylamine (0.153 g, 0.338 mmol) and pyridine (0.098 mL, 1.215 mmol) in anhydrous THF (10 mL) cooled to 0-5°C. The reaction was stirred at room temperature for 2 hours, diluted with DCM (20 mL), and washed with 10% aqueous citric acid (20 mL), water (20 mL), and brine (20 mL). The organic phase was dried over anhydrous NaSO, filtered, and evaporated to dryness. The crude material was purified by flash chromatography (hexane / EtOAc 70:30) to give tert-butyl 3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate (0.215 g, 96% yield) as a white solid.

[0162] 1H NMR (500MHz, DMSO-d6) δppm1.27-1.47(m, 9H), 1.60-1.76(m, 2H), 1.95(d, J=1 1.90Hz, 1H), 2.54-2.61(m, 1H), 2.82(m, 1H), 2.88-3.19(m, 1H), 3.80(d, J=12) .35Hz, 1H), 4.03(q, J=7.17Hz, 2H), 6.33(d, J=9.15Hz, 1H), 7.17-71.18(m, 7H ), 7.26-7.30(m, 3H), 7.30-7.36(m, 6H), 7.93(d, J=1.53Hz, 1H), 10.67(s, 1H). HRMS(ESI);C37H38BrN4O3Na[M+H+Na] + Calculated value: 687.1941, measured value: 687.1938.

[0163] Following this same method, but using the appropriate intermediates and reagents, the following compounds were prepared:

[0164] (R)-tert-butyl 3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate [(VII), R2 = tert-butylpiperidine-1-carboxylate, R8 = Br, R9 = 1,1′,1″-methanetriyltribenzene]

[0165] [ka]

[0166] Starting from 5-bromo-1-trityl-1H-indazol-3-ylamine and (3R)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid, flash column chromatography (hexane / EtOAc 70:30) gave 0.150 g (90% yield). 1H NMR (500MHz, DMSO-d6) δppm1.27-1.47(m, 9H), 1.60-1.76(m, 2H), 1.95(d, J=1 1.90Hz, 1H), 2.54-2.61(m, 1H), 2.82(m, 1H), 2.88-3.19(m, 1H), 3.80(d, J=12) .35Hz, 1H), 4.03(q, J=7.17Hz, 2H), 6.33(d, J=9.15Hz, 1H), 7.17-71.18(m, 7H ), 7.26-7.30(m, 3H), 7.30-7.36(m, 6H), 7.93(d, J=1.53Hz, 1H), 10.67(s, 1H). HRMS(ESI);C37H38BrN4O3Na[M+H+Na] + Calculated value: 687.1941, measured value: 687.1935.

[0167] (S)-tert-butyl 3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate [(VII), R2 = tert-butylpiperidine-1-carboxylate, R8 = Br, R9 = 1,1′,1″-methanetriyltribenzene]

[0168] [ka]

[0169] Starting from 5-bromo-1-trityl-1H-indazol-3-ylamine and (3S)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid, flash column chromatography (hexane / EtOAc 70:30) gave 0.110 g (93% yield). 1H NMR (500MHz, DMSO-d6) δppm1.27-1.47(m, 9H), 1.60-1.76(m, 2H), 1.95(d, J=1 1.90Hz, 1H), 2.54-2.61(m, 1H), 2.82(m, 1H), 2.88-3.19(m, 1H), 3.80(d, J=12) .35Hz, 1H), 4.03(q, J=7.17Hz, 2H), 6.33(d, J=9.15Hz, 1H), 7.17-71.18(m, 7H ), 7.26-7.30(m, 3H), 7.30-7.36(m, 6H), 7.93(d, J=1.53Hz, 1H), 10.67(s, 1H). HRMS(ESI);C37H38BrN4O3Na[M+H+Na] + Calculated value: 687.1941, measured value: 687.1943.

[0170] N-(5-Bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-3-carboxamide [(VII), R2 = methylpiperidine, R8 = Br, R9 = 1,1',1"-methanetriyltribenzene]

[0171] [ka]

[0172] Starting from 5-bromo-1-trityl-1H-indazol-3-ylamine and 1-methylpiperidine-3-carboxylic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 95:5:0.5) gave 0.293 g (67% yield). 1H NMR (500MHz, DMSO-d6) δppm1.34-1.55(m, 2H), 1.66(d, J=12.35Hz, 1H), 1.84(d, J=10.68Hz, 2H), 1.98-2.07(m, 1H), 2.17(s, 3H), 2.66-2.75(m, 2H) ), 2.86(d, J=10.68Hz, 1H), 6.32(d, J=9.15Hz, 1H), 7.14-7.21(m, 7H), 7. 25-7.30(m, 3H), 7.31-7.36(m, 6H), 7.89(d, J=1.22Hz, 1H), 10.58(s, 1H). HRMS(ESI);C33H32BrNO[M+H] + Calculated value: 579.1754, measured value: 579.1766.

[0173] tert-Butyl 4-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate [(VII), R2 = tert-butylpiperidine-1-carboxylate, R8 = Br, R9 = 1,1′,1″-methanetriyltribenzene]

[0174] [ka]

[0175] 5-Bromo-1-trityl-1H-indazol-3-ylamine and 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid. Starting from flash column chromatography (hexane / EtOAc 70:30). Obtained 0.100 g (90% yield). LCMS (ESI) m / z 666 (M+H). + .

[0176] tert-Butyl (3R)-3-{[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(VII), R2 = tert-butylpiperidine-1-carboxylate, R8 = 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl, R9 = 1,1′,1″-methanetriyltribenzene]

[0177] [ka]

[0178] Starting from 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-trityl-1H-indazol-3-amine and (3R)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid, flash column chromatography (hexane / EtOAc 70:30) gave 0.077 g (92% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.26(s, 12H), 1.31-1.39(m, 10H), 1.59-1.78(m, 2H), 1.96-2.00(m, 1H), 2.61(m, 1H), 2.73-2.82(m, 2H), 3.87(d, J=12) .96Hz, 1H), 3.96-4.05(m, 1H), 6.39(d, J=8.69Hz, 1H), 7.17(d, J=7.47Hz , 6H), 7.24-7.28(m, 4H), 7.30-7.33(m, 6H), 8.16(s, 1H), 10.59(brs, 1H). HRMS(ESI);C43H50BN4O5[M+H] + Calculated value: 712.3905, measured value: 712.3895.

[0179] tert-Butyl (3R)-3-{[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-trityl-1H-indazol-3-yl]carbamoyl}-pyrrolidine-1-carboxylate [(XXIX), R2 = tert-butylpyrrolidine-1-carboxylate, R8 = 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl, R9 = 1,1′,1″-methanetriyltribenzene]

[0180] [ka]

[0181] Starting from 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-trityl-1H-indazol-3-amine and (3R)-1-(tert-butoxycarbonyl)pyrrolidine-3-carboxylic acid, flash column chromatography (hexane / EtOAc 70:30) gave 0.127 g (89% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.26(s, 12H), 1.41(s, 9H), 2.00-2.20(m, 2H), 3.15-3.30(m, 2H), 3.38-3.45(m, 2H), 3.55(m, 1H), 6.40(d, J=8.85Hz, 1H), 7.17(d, J=7.63Hz, 6H), 7.25-7.29(m, 4H), 7.30-7.33(m, 6H), 8.15(brs, 1H), 10.66(d, J=6.41Hz, 1H). HRMS(ESI);C42H48BN4O5[M+H] + Calculated value: 698.3749, measured value: 698.3740.

[0182] N-(5-Bromo-1-trityl-1H-indazol-3-yl)-6-oxopiperidine-3-carboxamide [(VII), R2 = piperidin-2-one, R8 = Br, R9 = 1,1',1"-methanetriyltribenzene]

[0183] [ka]

[0184] Starting from 5-bromo-1-trityl-1H-indazol-3-ylamine and 6-oxopiperidine-3-carboxylic acid, flash column chromatography (DCM / MeOH 95:5) gave 0.157 g (96% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.85-1.96(m, 1H), 1.99-2.08(m, 1H), 2.13-2.30(m, 2H), 2.51-2.54(m, 2H), 2.89(m, 1H), 6.33(d, J=9.15Hz, 1H), 7.13-7.23(m, 7H), 7.26-7.30(m, 3H), 7.31-7.36(m, 6H), 7.52(brs, 1H), 7.93(d, J=1.22Hz, 1H), 10.73(s, 1H). HRMS(ESI);C32H28BrN4O2Na[M+H+Na] + Calculated value: 601.1209, measured value: 601.1234.

[0185] tert-Butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]pyrrolidine-1-carboxylate [(VII), R2 = tert-butylpyrrolidine-1-carboxylate, R8 = Br, R9 = 1,1′,1″-methanetriyltribenzene]

[0186] [ka]

[0187] Starting from 5-bromo-1-trityl-1H-indazol-3-ylamine and (3R)-1-(tert-butoxycarbonyl)pyrrolidine-3-carboxylic acid, flash column chromatography (hexane / EtOAc 70:30) gave 0.162 g (97% yield). 1H NMR (500MHz, DMSO-d6) δppm1.40(s, 9H), 2.00-2.18(m, 2H), 3.16-3.29(m, 2H), 3.38-3.45(m, 2H), 3.52(m, 1H), 6 .34(d, J=9.15Hz, 1H), 7.17-7.19(m, 7H), 7.25-7.31(m, 3H), 7.31-7.38(m, 6H), 7.94(brs, 1H), 10.73(brs, 1H). HRMS(ESI);C36H36BrN4O3Na[M+H+Na] + Calculated value: 673.1785, measured value: 673.1804.

[0188] 9H-Fluoren-9-ylmethyl 4-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate [(VII), R2 = piperidine-1,4-dicarboxylic acid mono-(9H-fluoren-9-ylmethyl) ester, R8 = Br, R9 = 1,1′,1″-methanetriyltribenzene]

[0189] [ka]

[0190] Starting from 5-bromo-1-trityl-1H-indazol-3-ylamine and piperidine-1,4-dicarboxylic acid mono-(9H-fluoren-9-ylmethyl) ester, flash column chromatography (hexane / EtOAc 60:40) gave 6.53 g (75% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.40-1.52(m, 2H), 1.72-1.85(m, 2H), 2.77-2.82(m, 1H), 3.46-3.56(m, 2H), 4.28-4.43(m, 4H), 6.33(d, J=8. 69Hz, 1H), 7.16-7.21(m, J=7.17Hz, 7H), 7.25-7.37(m, 11H), 7.40-7.44(m, 2H), 7.64(d, J=7.17Hz, 2H), 7.87-7.95(m, 3H), 10.59(s, 1H). HRMS(ESI);C47H40BrN4O3[M+H] +Calculated value: 809.2098, measured value: 809.2077.

[0191] N-(5-bromo-1-trityl-1H-indazol-3-yl)-3-oxocyclobutanecarboxamide [(VII), R2 = 3-oxocyclobutane, R8 = Br, R9 = 1,1′,1″-methanetriyltribenzene]

[0192] [ka]

[0193] Starting from 5-bromo-1-trityl-1H-indazol-3-ylamine and 3-oxocyclobutanecarboxylic acid, flash column chromatography (hexane / EtOAc 70:30) gave 0.55 g (91% yield). 1 H NMR (500MHz, DMSO-d6) δppm3.26-3.31(m, 2H), 3.44(m, 1H), 6.34(d, J=9.15Hz, 1H), 7.19(d, J=7.32Hz, 7H), 7.27-7.30(m, 3H), 7.32-7.36(m, 6H), 8.05(d, J=1.22Hz, 1H), 10.90(s, 1H). HRMS(ESI);C31H25BrN3O2Na[M+H+Na] + Calculated value: 572.0944, measured value: 572.0957.

[0194] Steps 1b' and 1b" (Scheme 1)

[0195] [ka]

[0196] tert-Butyl 3-{[5-(4-amino-2-chlorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 4-amino-2-chlorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0197] [ka]

[0198] A mixture of tert-butyl 3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate (0.060 g, 0.090 mmol) in 1,4-dioxane / water (3:1) (4 mL) was purged with argon for 5 min. 3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.068 g, 0.271 mmol), 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) x DCM (10% mol, 0.0074 g, 0.009 mmol), and CsCO (0.059 g, 0.180 mmol) were added. The mixture was heated at 80 °C for 1 h under argon, then cooled, diluted with EtOAc (20 mL), and washed with aqueous NaHCO (20 mL), water (20 mL), and brine (20 mL). The organic phase was separated, dried over anhydrous NaSO, filtered, and evaporated to dryness. The crude material was purified by flash column chromatography (hexane / EtOAc 60:40) to afford tert-butyl 3-{[5-(4-amino-2-chlorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate (0.050 g, 78% yield) as a white solid. 1H NMR (500MHz, DMSO-d6) δppm1.37(s, 9H), 1.51-1.76(m, 2H), 1.92-1.99(m, 2H), 2.57(m, 1H) ), 2.73-2.79(m, 2H), 3.81-3.84(m, 2H), 5.44(s, 2H), 6.37(d, J=9.00Hz, 1H), 6.54(dd, J= 8.39, 2.29Hz, 1H), 6.66(d, J=2.29Hz, 1H), 6.98(d, J=8.39Hz, 1H), 7.04(d, J=9.91Hz, 1H) , 7.23(d, J=7.63Hz, 6H), 7.26-7.30(m, 3H), 7.31-7.38(m, 6H), 7.63(s, 1H), 10.56(s, 1H). HRMS(ESI);C43H43ClN5O3[M+H] + Calculated value: 712.3049, measured value: 712.3026.

[0199] Following this same method, but using the appropriate intermediates and reagents, the following compounds were prepared:

[0200] N-[5-(2,4-dichlorophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-3-carboxamide [(XI), R1 = 2,4-dichlorophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0201] [ka]

[0202] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-3-carboxamide and (2,4-dichlorophenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.035 g (73% yield). LCMS (ESI) m / z 645 (M+H). + .

[0203] tert-Butyl 3-{[5-(2-chloro-4-hydroxyphenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2-chloro-4-hydroxyphenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0204] [ka]

[0205] Starting from tert-butyl 3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2-chloro-4-hydroxyphenyl)boronic acid, flash column chromatography (hexane / EtOAc 60:40) yielded 0.058 g (74% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.37(s, 9H), 1.60-1.69(m, 2H), 1.88-1.97(m, 2H), 2.57(m, 1H) ), 2.73-2.79(m, 2H), 3.80-3.83(m, 2H), 6.40(d, J=8.85Hz, 1H), 6.78(dd, J=8.39, 2.44Hz , 1H), 6.89(d, J=2.44Hz, 1H), 7.06(d, J=9.30Hz, 1H), 7.15(d, J=8.24Hz, 1H), 7.24(d, J=7 .63Hz, 6H), 7.27-7.31(m, 3H), 7.32-7.38(m, 6H), 7.68(s, 1H), 9.96(s, 1H), 10.59(s, 1H). HRMS(ESI);C43H42ClN4O4Na[M+H+Na] + Calculated value: 735.2708, measured value: 735.2701.

[0206] tert-Butyl 4-{[5-(2-chloro-5-cyanophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2-chloro-5-cyanophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0207] [ka]

[0208] Starting from tert-butyl 4-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2-chloro-5-cyanophenyl)boronic acid. Flash column chromatography (hexane / EtOAc 80:20). Obtained 0.055 g (78% yield). LCMS (ESI) m / z 722 (M+H). + .

[0209] tert-Butyl 3-{[5-(2,5-dichlorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2,5-dichlorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0210] [ka]

[0211] Starting from tert-butyl 3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2,5-dichlorophenyl)boronic acid, flash column chromatography (hexane / EtOAc 80:20) gave 0.067 g (76% yield). 1H NMR (500MHz, DMSO-d6) δppm1.30-1.36 (m, 10H), 1.56-1.76 (m, 2H), 1.94 (d, J=11.59Hz, 1H), 2. 58(m, 1H), 2.77-2.81(m, 2H), 3.79(d, J=12.51Hz, 1H), 3.93-3.96(m, 2H), 6.45(d, J=9.00Hz, 1H ), 7.14(dd, J=8.92, 1.30Hz, 1H), 7.24(d, J=7.47Hz, 6H), 7.27-7.32(m, 3H), 7.32-7.39(m, 6H) , 7.41-7.45(m, 1H), 7.46(d, J=2.59Hz, 1H), 7.57(d, J=8.39Hz, 1H), 7.82(s, 1H), 10.64(s, 1H). HRMS(ESI);C43H41Cl2N4O3Na[M+H+Na] + Calculated value: 753.2369, measured value: 753.2368.

[0212] tert-Butyl (3R)-3-{[5-(4-amino-2-chlorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 4-amino-2-chlorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0213] [ka]

[0214] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and 3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline, flash column chromatography (hexane / EtOAc 60:40) yielded 0.063 g (84% yield). 1H NMR (500MHz, DMSO-d6) δppm1.37(s, 9H), 1.51-1.76(m, 2H), 1.92-1.99(m, 2H), 2.57(m, 1H) ), 2.73-2.79(m, 2H), 3.81-3.84(m, 2H), 5.44(s, 2H), 6.37(d, J=9.00Hz, 1H), 6.54(dd, J= 8.39, 2.29Hz, 1H), 6.66(d, J=2.29Hz, 1H), 6.98(d, J=8.39Hz, 1H), 7.04(d, J=9.91Hz, 1H) , 7.23(d, J=7.63Hz, 6H), 7.26-7.30(m, 3H), 7.31-7.38(m, 6H), 7.63(s, 1H), 10.56(s, 1H). HRMS(ESI);C43H43ClN5O3[M+H] + Calculated value: 712.3049, measured value: 712.3030.

[0215] tert-Butyl (3R)-3-{[5-(2-chloro-4-hydroxyphenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2-chloro-4-hydroxyphenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0216] [ka]

[0217] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2-chloro-4-hydroxyphenyl)boronic acid, flash column chromatography (hexane / EtOAc 60:40) was performed to obtain 0.060 g (80% yield). 1H NMR (500MHz, DMSO-d6) δppm1.37(s, 9H), 1.60-1.69(m, 2H), 1.88-1.97(m, 2H), 2.57(m, 1H) ), 2.73-2.79(m, 2H), 3.80-3.83(m, 2H), 6.40(d, J=8.85Hz, 1H), 6.78(dd, J=8.39, 2.44Hz , 1H), 6.89(d, J=2.44Hz, 1H), 7.06(d, J=9.30Hz, 1H), 7.15(d, J=8.24Hz, 1H), 7.24(d, J=7 .63Hz, 6H), 7.27-7.31(m, 3H), 7.32-7.38(m, 6H), 7.68(s, 1H), 9.96(s, 1H), 10.59(s, 1H). HRMS(ESI);C43H42ClN4O[M+H] + Calculated value: 713.2889, measured value: 713.2870.

[0218] tert-Butyl (3S)-3-{[5-(4-amino-2-chlorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 4-amino-2-chlorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0219] [ka]

[0220] Starting from tert-butyl (3S)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and 3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline, flash column chromatography (hexane / EtOAc 60:40) yielded 0.059 g (79% yield). 1H NMR (500MHz, DMSO-d6) δppm1.37(s, 9H), 1.51-1.76(m, 2H), 1.92-1.99(m, 2H), 2.57(m, 1H) ), 2.73-2.79(m, 2H), 3.81-3.84(m, 2H), 5.44(s, 2H), 6.37(d, J=9.00Hz, 1H), 6.54(dd, J= 8.39, 2.29Hz, 1H), 6.66(d, J=2.29Hz, 1H), 6.98(d, J=8.39Hz, 1H), 7.04(d, J=9.91Hz, 1H) , 7.23(d, J=7.63Hz, 6H), 7.26-7.30(m, 3H), 7.31-7.38(m, 6H), 7.63(s, 1H), 10.56(s, 1H). HRMS(ESI);C43H43ClN5O3[M+H] + Calculated value: 712.3049, measured value: 712.3031.

[0221] tert-Butyl (3R)-3-{[5-(2-chloro-4-methylphenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2-chloro-4-methylphenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0222] [ka]

[0223] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2-chloro-5-methylphenyl)boronic acid, flash column chromatography (hexane / EtOAc 80:20) yielded 0.060 g (75% yield). LCMS (ESI) m / z 711 (M+H) + .

[0224] tert-Butyl 3-{[5-(5-carbamoyl-2-chlorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 5-carbamoyl-2-chlorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0225] [ka]

[0226] Starting from tert-butyl 3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (5-carbamoyl-2-chlorophenyl)boronic acid. Flash column chromatography (hexane / EtOAc 70:30). Obtained 0.077 g (83% yield). LCMS (ESI) m / z 740 (M+H). + .

[0227] tert-Butyl (3S)-3-{[5-(2-chloro-4-hydroxyphenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2-chloro-4-hydroxyphenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0228] [ka]

[0229] Starting from tert-butyl (3S)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2-chloro-4-hydroxyphenyl)boronic acid, flash column chromatography (hexane / EtOAc 60:40) yielded 0.064 g (85% yield). 1H NMR (500MHz, DMSO-d6) δppm1.37(s, 9H), 1.60-1.69(m, 2H), 1.88-1.97(m, 2H), 2.57(m, 1H) ), 2.73-2.79(m, 2H), 3.80-3.83(m, 2H), 6.40(d, J=8.85Hz, 1H), 6.78(dd, J=8.39, 2.44Hz , 1H), 6.89(d, J=2.44Hz, 1H), 7.06(d, J=9.30Hz, 1H), 7.15(d, J=8.24Hz, 1H), 7.24(d, J=7 .63Hz, 6H), 7.27-7.31(m, 3H), 7.32-7.38(m, 6H), 7.68(s, 1H), 9.96(s, 1H), 10.59(s, 1H). HRMS(ESI);C43H42ClN4ONa[M+H+Na] + Calculated value: 735.2708, measured value: 735.2687.

[0230] tert-Butyl 3-{[5-(3-amino-2-fluorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 3-amino-2-fluorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0231] [ka]

[0232] Starting from tert-butyl 3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (3-amino-2-fluorophenyl)boronic acid. Flash column chromatography (hexane / EtOAc 80:20). Obtained 0.048 g (72% yield). LCMS (ESI) m / z 696 (M+H). + .

[0233] tert-Butyl (3S)-3-{[5-(2-chloro-4-methylphenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2-chloro-4-methylphenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0234] [ka]

[0235] Starting from tert-butyl (3S)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2-chloro-5-methylphenyl)boronic acid, flash column chromatography (hexane / EtOAc 80:20) yielded 0.052 g (76% yield). LCMS (ESI) m / z 711 (M+H) + .

[0236] tert-Butyl (3R)-3-{[5-(2,5-dichlorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2,5-dichlorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0237] [ka]

[0238] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2,5-dichlorophenyl)boronic acid, flash column chromatography (hexane / EtOAc 80:20) yielded 0.064 g (77% yield). 1H NMR (500MHz, DMSO-d6) δppm1.30-1.36 (m, 10H), 1.56-1.76 (m, 2H), 1.94 (d, J=11.59Hz, 1H), 2. 58(m, 1H), 2.77-2.81(m, 2H), 3.79(d, J=12.51Hz, 1H), 3.93-3.96(m, 2H), 6.45(d, J=9.00Hz, 1H ), 7.14(dd, J=8.92, 1.30Hz, 1H), 7.24(d, J=7.47Hz, 6H), 7.27-7.32(m, 3H), 7.32-7.39(m, 6H) , 7.41-7.45(m, 1H), 7.46(d, J=2.59Hz, 1H), 7.57(d, J=8.39Hz, 1H), 7.82(s, 1H), 10.64(s, 1H). HRMS(ESI);C43H41Cl2N4O3Na[M+H+Na] + Calculated value: 753.2369, measured value: 753.2366.

[0239] tert-Butyl (3R)-3-{[5-(2,4-dichlorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2,4-dichlorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0240] [ka]

[0241] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2,4-dichlorophenyl)boronic acid, flash column chromatography (hexane / EtOAc 80:20) was performed to obtain 0.056 g (64% yield). 1H NMR (500MHz, DMSO-d6) δppm1.26-1.36(m, 10H), 1.57-1.79(m, 2H), 1.94(d, J=13.57Hz, 1H), 2.5 8(m, 1H), 2.73-2.82(m, 1H), 3.80(d, J=13.12Hz, 1H), 3.85-4.09(m, 2H), 6.44(d, J=9.00Hz, 1H), 7.12(d, J=8.85Hz, 1H), 7.24(d, J=7.63Hz, 6H), 7.27-7.31(m, 3H), 7.32-7.37(m, 6H), 7.39(d, J =8.39Hz, 1H), 7.47(dd, J=8.39, 2.14Hz, 1H), 7.70(d, J=2.13Hz, 1H), 7.79(s, 1H), 10.64(s, 1H). HRMS(ESI);C43H41Cl2N4O3Na[M+H+Na] + Calculated value: 753.2369, measured value: 753.2379.

[0242] tert-Butyl 3-({5-[5-chloro-2-(trifluoromethyl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)piperidine-1-carboxylate [(XI), R1 = 5-chloro-2-(trifluoromethyl)phenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0243] [ka]

[0244] Starting from tert-butyl 3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and [5-chloro-2-(trifluoromethyl)phenyl]boronic acid, flash column chromatography (hexane / EtOAc 80:20) yielded 0.055 g (68% yield). 1H NMR (500MHz, DMSO-d6) δppm1.35-1.39(m, 10H), 1.57-1.71(m, 2H), 1.92(m, 1H), 2.57(m, 1H), 2.7 6-2.84(m, 1H), 3.76-3.80(m, 2H), 3.90-3.97(m, 1H), 6.32(d, J=9.15Hz, 1H), 6.41(d, J=9.00Hz, 1H), 7.03(d, J=8.69Hz, 1H), 7.17-7.18(m, 4H), 7.23-7.24(m, 3H), 7.27-7.36(m, 6H), 7.45(s, 1H) ), 7.67(dd, J=8.69, 1.68Hz, 1H), 7.72(s, 1H), 7.82(d, J=8.54Hz, 1H), 7.93(s, 1H), 10.63(s, 1H). HRMS(ESI);C44H41ClF3N4O3Na[M+H+Na] + Calculated value: 787.2633, measured value: 787.2622.

[0245] tert-Butyl 3-{[5-(5-acetyl-2-fluorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 5-acetyl-2-fluorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0246] [ka]

[0247] Starting from tert-butyl 3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (5-acetyl-2-fluorophenyl)boronic acid, flash column chromatography (hexane / EtOAc 80:20) yielded 0.089 g (96% yield). 1H NMR (500MHz, DMSO-d6) δppm1.33-1.36(m, 10H), 1.56-1.76(m, 2H), 1.96(d, J=12.81Hz, 1H), 2.60(m, 1H), 2.78-2.81(m, 1H), 2.89(s, 3H), 3 .79(d, J=12.96Hz, 1H), 3.92-4.03(m, 2H), 6.48(d, J=9.00Hz, 1H), 7.23-7.37(m, 16H), 7.41-7.48(m, 1H), 7.93-7.99(m, 3H), 10.65(s, 1H). HRMS(ESI);C45H44FN4O4Na[M+H+Na] + Calculated value: 745.3160, measured value: 745.3149.

[0248] tert-Butyl 3-{[5-(2-chloro-5-methoxyphenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2-chloro-5-methoxyphenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0249] [ka]

[0250] Starting from tert-butyl 3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2-chloro-5-methoxyphenyl)boronic acid, flash column chromatography (hexane / EtOAc 80:20) yielded 0.072 g (94% yield). 1H NMR (500MHz, DMSO-d6) δppm1.30-1.36(m, 10H), 1.59-1.69(m, 2H), 1.93(d, J=14.03Hz, 1H), 2.58(m , 1H), 2.74-2.81(m, 1H), 3.76(s, 3H), 3.79(d, J=12.81Hz, 1H), 3.90-3.98(m, 2H), 6.44(d, J=9.00H z, 1H), 6.88(d, J=2.90Hz, 1H), 6.95(dd, J=8.85, 3.05Hz, 1H), 7.13(d, J=8.69Hz, 1H), 7.24(d, J=7. 63Hz, 6H), 7.28-7.30(m, 3H), 7.33-7.36(m, 6H), 7.42(d, J=8.85Hz, 1H), 7.78(s, 1H), 10.62(s, 1H). HRMS(ESI);C44H44ClN4O4[M+H] + Calculated value: 727.3046, measured value: 727.3045.

[0251] tert-Butyl (3R)-3-{[5-(2-chloro-5-methoxyphenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2-chloro-5-methoxyphenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0252] [ka]

[0253] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2-chloro-5-methoxyphenyl)boronic acid, flash column chromatography (hexane / EtOAc 80:20) yielded 0.063 g (95% yield). 1H NMR (500MHz, DMSO-d6) δppm1.30-1.36(m, 10H), 1.59-1.69(m, 2H), 1.93(d, J=14.03Hz, 1H), 2.58(m , 1H), 2.74-2.81(m, 1H), 3.76(s, 3H), 3.79(d, J=12.81Hz, 1H), 3.90-3.98(m, 2H), 6.44(d, J=9.00H z, 1H), 6.88(d, J=2.90Hz, 1H), 6.95(dd, J=8.85, 3.05Hz, 1H), 7.13(d, J=8.69Hz, 1H), 7.24(d, J=7. 63Hz, 6H), 7.28-7.30(m, 3H), 7.33-7.36(m, 6H), 7.42(d, J=8.85Hz, 1H), 7.78(s, 1H), 10.62(s, 1H). HRMS(ESI);C44H44ClN4O4[M+H] + Calculated value: 727.3046, measured value: 727.3042.

[0254] tert-Butyl (3R)-3-{[5-(5-acetyl-2-fluorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 5-acetyl-2-fluorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0255] [ka]

[0256] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (5-acetyl-2-fluorophenyl)boronic acid, flash column chromatography (hexane / EtOAc 80:20) yielded 0.110 g (91% yield). 1H NMR (500MHz, DMSO-d6) δppm1.33-1.36(m, 10H), 1.56-1.76(m, 2H), 1.96(d, J=12.81Hz, 1H), 2.60(m, 1H), 2.78-2.81(m, 1H), 2.89(s, 3H), 3 .79(d, J=12.96Hz, 1H), 3.92-4.03(m, 2H), 6.48(d, J=9.00Hz, 1H), 7.23-7.37(m, 16H), 7.41-7.48(m, 1H), 7.93-7.99(m, 3H), 10.65(s, 1H). HRMS(ESI);C45H44FN4O4Na[M+H+Na] + Calculated value: 745.3160, measured value: 745.3155.

[0257] tert-Butyl (3R)-3-{[5-(2-fluoro-5-methoxyphenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2-fluoro-5-methoxyphenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0258] [ka]

[0259] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2-fluoro-5-methoxyphenyl)boronic acid, flash column chromatography (hexane / EtOAc 80:20) was performed to obtain 0.099 g (93% yield). 1H NMR (500MHz, DMSO-d6) δppm1.27-1.40(m, 10H), 1.61-1.71(m, 2H), 1.95(d, J =12.66Hz, 1H), 2.59(m, 1H), 2.74-2.80(m, 1H), 3.76(s, 3H), 3.80(d, J=12.81 Hz, 1H), 3.95-4.00(m, 2H), 6.45(d, J=9.15Hz, 1H), 6.86-6.97(m, 2H), 7.15-7 .26(m, 8H), 7.27-7.32(m, 3H), 7.32-7.40(m, 6H), 7.87(s, 1H), 10.63(s, 1H). HRMS(ESI);C44H44FN4O4Na[M+H+Na] + Calculated value: 745.3160, measured value: 745.3163.

[0260] tert-Butyl (3R)-3-{[5-(5-chloro-2-fluorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 5-chloro-2-fluorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0261] [ka]

[0262] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (5-chloro-2-fluorophenyl)boronic acid, flash column chromatography (hexane / EtOAc 80:20) was performed to obtain 0.055 g (87% yield). 1H NMR (500MHz, DMSO-d6) δppm1.29-1.40(m, 10H), 1.64-1.71(m, 2H), 1.92-1.9 7(m, 1H), 2.59(m, 1H), 2.75-2.81(m, 1H), 3.80(d, J=11.59Hz, 1H), 3.96-3.99 (m, 2H), 6.46 (d, J=9.00Hz, 1H), 7.19-7.27 (m, 7H), 7.27-7.31 (m, 3H), 7.33-7 .37(m, 7H), 7.42-7.47(m, 1H), 7.49-7.54(m, 1H), 7.92(s, 1H), 10.65(s, 1H). HRMS(ESI);C43H41ClFN4O3Na[M+H+Na] + Calculated value: 737.2665, measured value: 737.2661.

[0263] tert-Butyl (3R)-3-{[5-(5-ethoxy-2-fluorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 5-ethoxy-2-fluorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0264] [ka]

[0265] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (5-ethoxy-2-fluorophenyl)boronic acid, flash column chromatography (hexane / EtOAc 80:20) yielded 0.066 g (83% yield). 1H NMR (500MHz, DMSO-d6) δppm1.28-1.33(m, 4H), 1.37(s, 9H), 1.61-1.70(m, 2H), 1.94-1.9 8(m, 1H), 2.59(m, 1H), 2.76-2.81(m, 1H), 3.81(d, J=11.44Hz, 1H), 3.95-4.00(m, 2H), 4. 02(q, J=6.91Hz, 2H), 6.44(d, J=9.00Hz, 1H), 6.84-6.94(m, 2H), 7.18(t, J=9.61Hz, 1H), 7.22(d, J=7.78Hz, 6H), 7.28-7.30(m, 4H), 7.33-7.36(m, 6H), 7.87(s, 1H), 10.62(s, 1H). HRMS(ESI);C45H46FN4O4Na[M+H+Na] + Calculated value: 747.3317, measured value: 747.3312.

[0266] tert-Butyl (3R)-3-({5-[2-fluoro-5-(trifluoromethoxy)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)piperidine-1-carboxylate [(XI), R1 = 2-fluoro-5-(trifluoromethoxy)phenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0267] [ka]

[0268] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and [2-fluoro-5-(trifluoromethoxy)phenyl]boronic acid, flash column chromatography (hexane / EtOAc 80:20) yielded 0.110 g (89% yield). 1H NMR (500MHz, DMSO-d6) δppm1.31-1.36(m, 10H), 1.59-1.74(m, 2H), 1.92-1.97( m, 1H), 2.59(m, 1H), 2.76-2.84(m, 1H), 3.79(d, J=13.42Hz, 1H), 3.89-3.97(m, 2 H), 6.47(d, J=9.00Hz, 1H), 7.17(d, J=7.47Hz, 1H), 7.22(d, J=7.78Hz, 6H), 7.28 -7.31(m, 3H), 7.33-7.36(m, 6H), 7.40-7.51(m, 3H), 7.93(s, 1H), 10.66(s, 1H). HRMS(ESI);C44H41F4N4O4Na[M+H+Na] + Calculated value: 787.2878, measured value: 787.2872.

[0269] tert-Butyl (3R)-3-{[5-(5-cyano-2-methylphenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 5-cyano-2-methylphenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0270] [ka]

[0271] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (5-cyano-2-methylphenyl)boronic acid, flash column chromatography (hexane / EtOAc 70:30) yielded 0.060 g (87% yield). 1H NMR (500MHz, DMSO-d6) δppm1.30-1.35(m, 10H), 1.55-1.78(m, 2H), 1.92-1.95(m, 1H), 2.24(s, 3H), 2.58(m, 1H), 2.76-2.81(m, 1H), 3.76(d, J=12.66Hz, 1H), 3.91-3.97(m, 2 H), 6.44(d, J=9.00Hz, 1H), 7.09(d, J=9.15Hz, 1H), 7.24(d, J=7.63Hz, 6H), 7.28-7.31 (m, 3H), 7.33-7.36(m, 6H), 7.49(m, 1H), 7.59(s, 1H), 7.70-7.71(m, 2H), 10.62(s, 1H). HRMS(ESI);C45H44N5O3Na[M+H+Na] + Calculated value: 724.3258, measured value: 724.3259.

[0272] tert-Butyl (3R)-3-{[5-(5-cyano-2-fluorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 5-cyano-2-fluorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0273] [ka]

[0274] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (5-cyano-2-fluorophenyl)boronic acid, flash column chromatography (hexane / EtOAc 70:30) yielded 0.037 g (54% yield). LCMS (ESI) m / z 706 (M+H) + .

[0275] tert-Butyl (3R)-3-{[5-(2-chloro-5-nitrophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2-chloro-5-nitrophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0276] [ka]

[0277] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2-chloro-5-nitrophenyl)boronic acid, flash column chromatography (hexane / EtOAc 70:30) yielded 0.060 g (83% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.23-1.43(m, 10H), 1.57-1.73(m, 2H), 1.89-1.98(m, 1H), 2.59(m, 1H), 2.76-2.84(m, 1H), 3.77(d, J=13.42Hz, 1H), 3.93-3.98(m, 2H), 6.49(d, J=9.00Hz, 1H), 7. 20(d, J=9.00Hz, 1H), 7.24(d, J=7.63Hz, 6H), 7.28-7.31(m, 3H), 7.34-7.37(m, 6H), 7.86(d, J= 8.85Hz, 1H), 7.91(s, 1H), 8.11(d, J=2.44Hz, 1H), 8.21(dd, J=8.85, 2.75Hz, 1H), 10.67(s, 1H). HRMS(ESI);C43H41ClN5O5Na[M+H+Na] + Calculated value: 764.2610, measured value: 764.2593.

[0278] N-[5-(2,6-dichlorophenyl)-1-trityl-1H-indazol-3-yl]-6-oxopiperidine-3-carboxamide [(XI), R1 = 2,6-dichlorophenyl, R2 = piperidin-2-one, R9 = 1,1′,1″-methanetriyltribenzene]

[0279] [ka]

[0280] N-(5-Bromo-1-trityl-1H-indazol-3-yl)-6-oxopiperidine-3-carboxamide and (2,6-dichlorophenyl)boronic acid. Starting from flash column chromatography (DCM / MeOH 95:5). Obtained 0.050 g (75% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.81-1.92(m, 1H), 1.94-2.02(m, 1H), 2.08-2.28(m , 2H), 2.88(m, 1H), 3.23-3.31(m, 2H), 6.47(d, J=8.85Hz, 1H), 6.94(d, J=8.39H) z, 1H), 7.25(d, J=7.63Hz, 6H), 7.27-7.30(m, 3H), 7.34-7.37(m, 6H), 7.41(t, J =8.08Hz, 1H), 7.48(m, 1H), 7.55(d, J=8.08Hz, 2H), 7.67(s, 1H), 10.68(s, 1H). HRMS(ESI);C38H31Cl2N4O2Na[M+H+Na] + Calculated value: 667.1638, measured value: 667.1664.

[0281] N-[5-(5-acetyl-2-fluorophenyl)-1-trityl-1H-indazol-3-yl]-6-oxopiperidine-3-carboxamide [(XI), R1 = 5-acetyl-2-fluorophenyl, R2 = piperidin-2-one, R9 = 1,1′,1″-methanetriyltribenzene]

[0282] [ka]

[0283] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-6-oxopiperidine-3-carboxamide and (5-acetyl-2-fluorophenyl)boronic acid, flash column chromatography (DCM / MeOH 95:5) gave 0.080 g (82% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.87-1.94(m, 1H), 1.99-2.05(m, 1H), 2.13-2.26(m, 2H), 2.60(s, 3H), 2.91(m, 1H), 3.29-3.31(m, 2H), 6.49(d, J=9.0 0Hz, 1H), 7.25(d, J=7.63Hz, 6H), 7.28-7.31(m, 4H), 7.34-7.37(m, 6H), 7.44(m, 1H), 7.50(m, 1H), 7.93(s, 1H), 7.95-8.04(m, 2H), 10.71(s, 1H). HRMS(ESI);C40H34FN4O3Na[M+H+Na] + Calculated value: 659.2429, measured value: 659.2455.

[0284] tert-Butyl (3R)-3-({5-[2-chloro-5-(methoxycarbonyl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)piperidine-1-carboxylate [(XI), R1 = 2-chloro-5-(methoxycarbonyl)phenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0285] [ka]

[0286] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and [2-chloro-5-(methoxycarbonyl)phenyl]boronic acid, flash column chromatography (hexane / EtOAc 70:30) was performed to obtain 0.055 g (74% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.30-1.35(m, 10H), 1.59-1.69(m, 2H), 1.92-1.94(m, 1H), 2.59(m , 1H), 2.77-2.85(m, 1H), 3.77(d, J=13.42Hz, 1H), 3.85(s, 3H), 3.92-4.00(m, 2H), 6.47(d, J= 8.85Hz, 1H), 7.15(d, J=9.91Hz, 1H), 7.24(d, J=7.63Hz, 6H), 7.28-7.31(m, 3H), 7.34-7.37(m , 6H), 7.71(d, J=8.24Hz, 1H), 7.83-7.84(m, 2H), 7.92(dd, J=8.39, 2.14Hz, 1H), 10.65(s, 1H). HRMS(ESI);C45H44ClN4O5Na[M+H+Na] + Calculated value: 777.2814, measured value: 777.2816.

[0287] tert-Butyl (3R)-3-{[5-(2,4-difluorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2,4-difluorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0288] [ka]

[0289] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2,4-difluorophenyl)boronic acid, flash column chromatography (hexane / EtOAc 70:30) yielded 0.098 g (51% yield). LCMS (ESI) m / z 699 (M+H) + .

[0290] tert-Butyl (3R)-3-({5-[4-methoxy-2-(trifluoromethyl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)piperidine-1-carboxylate [(XI), R1 = 4-methoxy-2-(trifluoromethyl)phenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0291] [ka]

[0292] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and [4-methoxy-2-(trifluoromethyl)phenyl]boronic acid, flash column chromatography (hexane / EtOAc 70:30) yielded 0.062 g (83% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.30-1.35(m, 10H), 1.59-1.68(m, 2H), 1.90-1.93(m, 1H), 2.56(m, 1H), 2.74-2.80(m, 1H), 3.77(d, J=13.27) Hz, 1H), 3.85(s, 3H), 3.92-3.97(m, 2H), 6.39(d, J=8.85Hz, 1H), 6.97(d, J=8.69Hz, 1H), 7.23-7.36(m, 18H), 7.62(s, 1H), 10.59(s, 1H). HRMS(ESI);C45H44F3N4O4Na[M+H+Na] + Calculated value: 783.3128, measured value: 783.3122.

[0293] tert-Butyl (3R)-3-{[5-(2-fluoro-5-methylphenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2-fluoro-5-methylphenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0294] [ka]

[0295] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2-fluoro-5-methylphenyl)boronic acid, flash column chromatography (hexane / EtOAc 70:30) was performed to obtain 0.048 g (88% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.31-1.37(m, 10H), 1.62-1.71(m, 2H), 1.94-1.9 7(m, 1H), 2.30(s, 3H), 2.59(m, 1H), 2.74-2.81(m, 1H), 3.81(d, J=13.27Hz, 1H ), 3.93-4.03(m, 2H), 6.44(d, J=9.00Hz, 1H), 7.14-7.20(m, 4H), 7.22(d, J=7 .63Hz, 6H), 7.28-7.30(m, 3H), 7.33-7.36(m, 6H), 7.86(s, 1H), 10.62(s, 1H). HRMS(ESI);C44H44FN4O3[M+H] + Calculated value: 695.3392, Measured value: 695.3387.

[0296] tert-Butyl (3R)-3-{[5-(5-acetyl-2-chlorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 5-acetyl-2-chlorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0297] [ka]

[0298] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (5-acetyl-2-chlorophenyl)boronic acid, flash column chromatography (hexane / EtOAc 80:20) yielded 0.061 g (84% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.29-1.35(m, 10H), 1.51-1.75(m, 2H), 1.86-1.98(m, 1H), 2.56-2 .60(m, 4H), 2.74-2.82(m, 1H), 3.77(d, J=12.81Hz, 1H), 3.88-3.97(m, 2H), 6.47(d, J=9.00Hz , 1H), 7.16(d, J=9.00Hz, 1H), 7.24(d, J=7.63Hz, 6H), 7.28-7.31(m, 3H), 7.34-7.37(m, 6H), 7 .70(d, J=8.39Hz, 1H), 7.83(s, 1H), 7.87(s, 1H), 7.91(dd, J=8.39, 2.14Hz, 1H), 10.64(s, 1H). HRMS(ESI);C45H44ClN4O4Na[M+H+Na] + Calculated value: 761.2865, measured value: 761.2868.

[0299] tert-Butyl (3R)-3-{[5-(5-amino-2-chlorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 5-amino-2-chlorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0300] [ka]

[0301] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (5-amino-2-chlorophenyl)boronic acid, flash column chromatography (hexane / EtOAc 70:30) yielded 0.045 g (74% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.30-1.37(m, 10H), 1.59-1.69(m, 2H), 1.94-1.96(m, 1H), 2. 57(m, 1H), 2.72-2.78(m, 1H), 3.82(d, J=13.73Hz, 1H), 3.91-3.98(m, 2H), 5.28(s, 2H), 6. 40(d, J=9.00Hz, 1H), 6.48-6.56(m, 2H), 7.05(d, J=9.00Hz, 1H), 7.09(d, J=8.24Hz, 1H), 7.23(d, J=7.63Hz, 6H), 7.27-7.30(m, 3H), 7.33-7.36(m, 6H), 7.71(s, 1H), 10.60(s, 1H). HRMS(ESI);C43H43ClN5O3Na[M+H+Na] + Calculated value: 734.2868, measured value: 734.2874.

[0302] tert-Butyl (3R)-3-{[5-(2,5-difluorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2,5-difluorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0303] [ka]

[0304] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2,5-difluorophenyl)boronic acid, flash column chromatography (hexane / EtOAc 80:20) was performed to obtain 0.071 g (59% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.31-1.37(m, 10H), 1.61-1.71(m, 2H), 1.94-1.99(m, 1H), 2.59(m, 1H), 2.75-2.82(m, 1H) , 3.80(d, J=12.81Hz, 1H), 3.93-4.00(m, 2H), 6.46(d, J=8.85Hz, 1H), 7.18-7.36(m, 19H), 7.92(s, 1H), 10.65(s, 1H). HRMS(ESI);C43H41F2N4O3[M+H] + Calculated value: 699.3141, measured value: 699.3129.

[0305] tert-Butyl (3R)-3-({5-[4-methyl-2-(trifluoromethyl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)piperidine-1-carboxylate [(XI), R1 = 4-methyl-2-(trifluoromethyl)phenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0306] [ka]

[0307] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and [4-methyl-2-(trifluoromethyl)phenyl]boronic acid, flash column chromatography (hexane / EtOAc 80:20) yielded 0.047 g (65% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.29-1.35(m, 10H), 1.55-1.68(m, 2H), 1.89-1.93(m, 1H), 2.41(s , 3H), 2.56(m, 1H), 2.70-2.79(m, 1H), 3.78(d, J=14.03Hz, 1H), 3.87-3.98(m, 1H), 6.40(d, J= 8.85Hz, 1H), 6.98(d, J=9.30Hz, 1H), 7.23(d, J=7.63Hz, 6H), 7.27-7.30(m, 3H), 7.33-7.36(m , 6H), 7.40(d, J=0.91Hz, 1H), 7.46(d, J=7.93Hz, 1H), 7.58(s, 1H), 7.66(s, 1H), 10.60(s, 1H). HRMS(ESI);C45H44F3N4O3Na[M+H+Na] + Calculated value: 767.3179, measured value: 767.3188.

[0308] tert-Butyl (3R)-3-({5-[2-chloro-5-(methoxycarbonyl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)pyrrolidine-1-carboxylate [(XI), R1 = 2-chloro-5-(methoxycarbonyl)phenyl, R2 = tert-butylpyrrolidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0309] [ka]

[0310] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]pyrrolidine-1-carboxylate and [2-chloro-5-(methoxycarbonyl)phenyl]boronic acid, flash column chromatography (hexane / EtOAc 70:30) yielded 0.054 g (73% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.36(s, 9H), 2.05-2.17(m, 2H), 3.12-3.28(m, 2H), 3.37-3 .41(m, 2H), 3.51(d, J=8.54Hz, 1H), 3.85(s, 3H), 6.48(d, J=9.00Hz, 1H), 7.15(d, J=8. 54Hz, 1H), 7.24(d, J=7.63Hz, 6H), 7.28-7.31(m, 3H), 7.34-7.37(m, 6H), 7.71(d, J=8. 39Hz, 1H), 7.80-7.87(m, 2H), 7.92(dd, J=8.24, 2.14Hz, 1H), 10.71(d, J=6.71Hz, 1H). HRMS(ESI);C44H42ClN4O5Na[M+H+Na] + Calculated value: 763.2657, measured value: 763.2645.

[0311] tert-Butyl (3R)-3-{[5-(5-acetyl-2-chlorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}pyrrolidine-1-carboxylate [(XI), R1 = 5-acetyl-2-chlorophenyl, R2 = tert-butylpyrrolidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0312] [ka]

[0313] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]pyrrolidine-1-carboxylate and (5-acetyl-2-chlorophenyl)boronic acid, flash column chromatography (hexane / EtOAc 70:30) was performed to obtain 0.047 g (65% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.36(s, 9H), 2.01-2.15(m, 2H), 2.59(s, 3H), 3.15-3.29( m, 2H), 3.36-3.43(m, 2H), 3.48-3.52(m, 1H), 6.48(d, J=8.85Hz, 1H), 7.17(d, J=9.00 Hz, 1H), 7.24(d, J=7.63Hz, 6H), 7.28-7.31(m, 3H), 7.34-7.37(m, 6H), 7.70(d, J=8.3 9Hz, 1H), 7.79-7.88(m, 2H), 7.91(dd, J=8.39, 2.14Hz, 1H), 10.71(d, J=5.64Hz, 1H). HRMS(ESI);C44H42ClN4O4Na[M+H+Na] + Calculated value: 747.2708, measured value: 747.2712.

[0314] tert-Butyl (3R)-3-({5-[2-chloro-5-(methylcarbamoyl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)pyrrolidine-1-carboxylate [(XI), R1 = 2-chloro-5-(methylcarbamoyl)phenyl, R2 = tert-butylpyrrolidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0315] [ka]

[0316] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]pyrrolidine-1-carboxylate and [2-chloro-5-(methylcarbamoyl)phenyl]boronic acid, flash column chromatography (hexane / EtOAc 30:70) was performed to obtain 0.045 g (61% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.36(s, 9H), 2.03-2.13(m, 2H), 2.75(d, J=4.58Hz, 3H), 3 .13-3.29(m, 2H), 3.37-3.40(m, 1H), 3.43-3.57(m, 1H), 6.48(d, J=8.85Hz, 1H), 7.16( d, J=8.85Hz, 1H), 7.24(d, J=7.78Hz, 6H), 7.28-7.31(m, 3H), 7.34-7.37(m, 6H), 7.63( d, J=8.85Hz, 1H), 7.80-7.81(m, 3H), 8.55(d, J=4.57Hz, 1H), 10.70(d, J=6.86Hz, 1H). HRMS(ESI);C44H43ClN5O4Na[M+H+Na] + Calculated value: 762.2817, measured value: 762.2827.

[0317] tert-Butyl (3R)-3-({5-[2-cyano-5-(methoxycarbonyl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)piperidine-1-carboxylate [(XI), R1 = 2-cyano-5-(methoxycarbonyl)phenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0318] [ka]

[0319] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and methyl 4-cyano-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate. Flash column chromatography (hexane / EtOAc 80:20). Obtained 0.160 g (84% yield). LCMS (ESI) m / z 746 (M+H). + .

[0320] tert-Butyl (3R)-3-{[5-(2-chloro-5-hydroxyphenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2-chloro-5-hydroxyphenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0321] [ka]

[0322] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2-chloro-5-hydroxyphenyl)boronic acid, flash column chromatography (hexane / EtOAc 70:30) yielded 0.045 g (58% yield). 1H NMR (500MHz, DMSO-d6) δppm1.30-1.37(m, 10H), 1.57-1.72(m, 2H), 1.95(d, J=12.81Hz, 1H), 2 .58(m, 1H), 2.72-2.80(m, 1H), 3.82(d, J=13.12Hz, 1H), 3.97-4.02(m, 2H), 6.42(d, J=9.00Hz , 1H), 6.71(d, J=2.75Hz, 1H), 6.75(dd, J=8.62, 2.97Hz, 1H), 7.10(d, J=8.85Hz, 1H), 7.23(d, J=7.47Hz, 6H), 7.27-7.30(m, 4H), 7.33-7.36(m, 6H), 7.74(s, 1H), 9.77(s, 1H), 10.63(s, 1H). HRMS(ESI);C43H42ClN4O4[M+H] + Calculated value: 713.2889, measured value: 713.2894.

[0323] tert-Butyl (3R)-3-({5-[2,4-dichloro-5-(methoxycarbonyl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)piperidine-1-carboxylate [(XI), R1 = 2,4-dichloro-5-(methoxycarbonyl)phenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0324] [ka]

[0325] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and methyl 2,4-dichloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate. Flash column chromatography (hexane / EtOAc 70:30). Obtained 0.030 g (55% yield). LCMS (ESI) m / z 789 (M+H). + .

[0326] tert-Butyl (3R)-3-{[5-(2-chloro-5-propanoylphenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2-chloro-5-propanoylphenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0327] [ka]

[0328] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2-chloro-5-propanoylphenyl)boronic acid. Flash column chromatography (hexane / EtOAc 70:30). Obtained 0.023 g (50% yield). LCMS (ESI) m / z 753 (M+H). + .

[0329] tert-Butyl (3R)-3-({5-[2-chloro-4-(trifluoromethyl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)piperidine-1-carboxylate [(XI), R1 = 2-chloro-4-(trifluoromethyl)phenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0330] [ka]

[0331] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and [2-chloro-4-(trifluoromethyl)phenyl]boronic acid, flash column chromatography (hexane / EtOAc 80:20) was performed to obtain 0.058 g (85% yield). 1H NMR (500MHz, DMSO-d6) δppm1.29-1.38(m, 10H), 1.56-1.73(m, 2H), 1.93(d, J=10.98Hz, 1H) , 2.59(m, 1H), 2.75-2.84(m, 1H), 3.77(d, J=12.20Hz, 1H), 3.90-4.00(m, 2H), 6.47(d, J=8.8 5Hz, 1H), 7.18(d, J=8.85Hz, 1H), 7.24(d, J=7.47Hz, 6H), 7.28-7.31(m, 3H), 7.34-7.37(m, 6 H), 7.60(d, J=8.08Hz, 1H), 7.76(d, J=8.08Hz, 1H), 7.85(s, 1H), 7.95(s, 1H), 10.66(s, 1H). HRMS(ESI);C44H41ClF3N4O3Na[M+H+Na] + Calculated value: 787.2633, measured value: 787.2635.

[0332] tert-Butyl (3R)-3-({5-[4-chloro-2-(trifluoromethyl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)piperidine-1-carboxylate [(XI), R1 = 4-chloro-2-(trifluoromethyl)phenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0333] [ka]

[0334] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and [4-chloro-2-(trifluoromethyl)phenyl]boronic acid, flash column chromatography (hexane / EtOAc 80:20) was performed to obtain 0.062 g (90% yield). 1H NMR (500MHz, DMSO-d6) δppm1.26-1.35(m, 10H), 1.57-1.69(m, 2H), 1.92(d, J=10.52Hz, 1H), 2.5 7(m, 1H), 2.72-2.82(m, 1H), 3.77(d, J=13.12Hz, 1H), 3.87-3.98(m, 2H), 6.42(d, J=9.00Hz, 1H), 7.01(d, J=8.85Hz, 1H), 7.23(d, J=7.63Hz, 6H), 7.27-7.30(m, 3H), 7.33-7.36(m, 6H), 7.40(d, J =8.39Hz, 1H), 7.69(s, 1H), 7.76(dd, J=8.24, 1.98Hz, 1H), 7.86(d, J=1.98Hz, 1H), 10.63(s, 1H). HRMS(ESI);C44H41ClF3N4O3Na[M+H+Na] + Calculated value: 787.2633, measured value: 787.2650.

[0335] tert-Butyl (3R)-3-({5-[5-fluoro-2-(trifluoromethyl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)piperidine-1-carboxylate [(XI), R1 = 5-fluoro-2-(trifluoromethyl)phenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0336] [ka]

[0337] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and [5-fluoro-2-(trifluoromethyl)phenyl]boronic acid, flash column chromatography (hexane / EtOAc 80:20) yielded 0.060 g (89% yield). 1H NMR (500MHz, DMSO-d6) δppm1.29-1.38(m, 10H), 1.57-1.69(d, 2H), 1.90(d, J=13.27Hz, 1H), 2 .57(m, 1H), 2.73-2.80(m, 1H), 3.77(d, J=11.59Hz, 1H), 3.89-3.99(m, 2H), 6.42(d, J=9.00Hz , 1H), 7.04(d, J=9.00Hz, 1H), 7.18(d, J=7.02Hz, 1H), 7.23(d, J=7.47Hz, 6H), 7.28-7.31(m, 3 H), 7.33-7.46(m, 6H), 7.43(m, 1H), 7.72(s, 1H), 7.88(dd, J=8.85, 5.49Hz, 1H), 10.63(s, 1H). HRMS(ESI);C44H41F4N4O3[M+H] + Calculated value: 749.3110, measured value: 749.3121.

[0338] tert-Butyl (3R)-3-{[5-(2-chlorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2-chlorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0339] [ka]

[0340] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2-chlorophenyl)boronic acid, flash column chromatography (hexane / EtOAc 70:30) yielded 0.037 g (76% yield). LCMS (ESI) m / z 697 (M+H) + .

[0341] tert-Butyl (3R)-3-({5-[2-chloro-5-(propan-2-yl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)piperidine-1-carboxylate [(XI), R1 = 2-chloro-5-(propan-2-yl)phenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0342] [ka]

[0343] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and [2-chloro-5-(propan-2-yl)phenyl]boronic acid, flash column chromatography (hexane / EtOAc 75:25) yielded 0.042 g (81% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.18 (d, J=7.02Hz, 6H), 1.30-1.37 (m, 10H), 1.60-1.70 (m, 2H), 1.90-1.97(m, 1H), 2.58(m, 1H), 2.76-2.83(m, 1H), 2.91(m, 1H), 3.77(d, J= 13.42Hz, 1H), 3.90-4.00(m, 1H), 6.44(d, J=8.85Hz, 1H), 7.11(d, J=9.00Hz, 1H), 7 .19(s, 1H), 7.22-7.36(m, 16H), 7.43(d, J=8.24Hz, 1H), 7.75(s, 1H), 10.61(s, 1H). HRMS(ESI);C46H48ClN4O3[M+H] + Calculated value: 739.3410, measured value: 739.3405.

[0344] tert-Butyl (3R)-3-[(5-phenyl-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate [(XI), R1 = phenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0345] [ka]

[0346] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and phenylboronic acid, flash column chromatography (hexane / EtOAc 75:25) gave 0.041 g (89% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.32-1.38(m, 10H), 1.63-1.72(m, 2H), 1.95-2. 04(m, 1H), 2.60(m, 1H), 2.75-2.82(m, 1H), 3.83(d, J=12.96Hz, 1H), 3.92-4 .05(m, 2H), 6.44(d, J=9.00Hz, 1H), 7.22(d, J=7.63Hz, 6H), 7.27-7.37(m, 1 1H), 7.43(t, J=7.70Hz, 2H), 7.55-7.56(m, 2H), 7.94(s, 1H), 10.62(s, 1H). HRMS(ESI);C43H43N4O3[M+H] + Calculated value: 663.3330, measured value: 663.3345.

[0347] tert-Butyl (3R)-3-({5-[2,4-difluoro-5-(methoxycarbonyl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)piperidine-1-carboxylate [(XI), R1 = 2,4-difluoro-5-(methoxycarbonyl)phenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0348] [ka]

[0349] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and methyl 2,4-difluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate, flash column chromatography (hexane / EtOAc 70:30) yielded 0.036 g (68% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.31-1.39(m, 10H), 1.61-1.71(m, 2H), 1.94-1.98(m , 1H), 2.60(m, 1H), 2.75-2.84(m, 1H), 3.79(d, J=12.05Hz, 1H), 3.85(s, 3H), 3.9 2-4.04(m, 2H), 6.48(d, J=9.15Hz, 1H), 7.22(d, J=7.63Hz, 6H), 7.28-7.31(m, 4H ), 7.33-7.36(m, 6H), 7.55(t, J=10.68Hz, 1H), 7.86-7.96(m, 2H), 10.66(s, 1H). HRMS(ESI);C45H43F2N4O5[M+H] + Calculated value: 757.3196, measured value: 757.3211.

[0350] tert-Butyl (3R)-3-{[5-(5-tert-butyl-2-chlorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 5-tert-butyl-2-chlorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0351] [ka]

[0352] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (5-tert-butyl-2-chlorophenyl)boronic acid, flash column chromatography (hexane / EtOAc 75:25) yielded 0.047 g (80% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.27(s, 9H), 1.32-1.37(m, 10H), 1.59-1.70(m, 2H) , 1.91-1.96(m, 1H), 2.58(m, 1H), 2.74-2.83(m, 1H), 3.76(d, J=12.81Hz, 1H), 3. 91-4.00(m, 2H), 6.43(d, J=9.00Hz, 1H), 7.11(d, J=8.24Hz, 1H), 7.22-7.38(m, 1 6H), 7.39(d, J=2.29Hz, 1H), 7.43(d, J=8.39Hz, 1H), 7.74(s, 1H), 10.61(s, 1H). HRMS(ESI);C47H50ClN4O3[M+H] + Calculated value: 753.3566, measured value: 753.3578.

[0353] tert-Butyl (3R)-3-{[5-(2-chloro-5-fluorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2-chloro-5-fluorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0354] [ka]

[0355] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and (2-chloro-5-fluorophenyl)boronic acid, flash column chromatography (hexane / EtOAc 85:15) yielded 0.048 g (96% yield). 1H NMR (500MHz, DMSO-d6) δppm1.30-1.36(m, 10H), 1.60-1.70(m, 2H), 1.93-1.96(m, 1 H), 2.58(m, 1H), 2.75-2.84(m, 1H), 3.78(d, J=13.12Hz, 1H), 3.89-3.99(m, 2H), 6. 45(d, J=8.85Hz, 1H), 7.15(d, J=8.69Hz, 1H), 7.24(d, J=8.24Hz, 6H), 7.27-7.31(m , 5H), 7.33-7.36(m, 6H), 7.58(dd, J=8.62, 5.26Hz, 1H), 7.82(s, 1H), 10.64(s, 1H). HRMS(ESI);C43H41ClFN4O3[M+H] + Calculated value: 715.2846, measured value: 715.2831.

[0356] tert-Butyl (3R)-3-{[5-(2,5-dicyanophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XI), R1 = 2,5-dicyanophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0357] [ka]

[0358] Starting from tert-butyl (3R)-3-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidine-1-carboxylate and 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzene-1,4-dicarbonitrile. Flash column chromatography (hexane / EtOAc 70:30). Obtained 0.013 g (22% yield). LCMS (ESI) m / z 713 (M+H). + .

[0359] N-[5-(2-chloro-6-fluorophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-chloro-6-fluorophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0360] [ka]

[0361] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-chloro-6-fluorophenyl)boronic acid, flash column chromatography (DCM / MeOH 80:20) gave 0.053 g (56% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.64-1.75(m, 2H), 1.82-1.89(m, 2H), 2.33-2.44(m, 4H), 2.98-3.09(m, 2H), 6.48(d, J=8.85 Hz, 1H), 7.03(d, J=8.69Hz, 1H), 7.19-7.32(m, 10H), 7.32-7.39(m, 6H), 7.40-7.47(m, 2H), 7.74(s, 1H), 10.57(brs, 1H). HRMS(ESI);C39H35ClFN4O[M+H] + Calculated value: 629.2478, measured value: 629.2497.

[0362] 1-Butyl-N-[5-(2-chloro-6-fluorophenyl)-1-trityl-1H-indazol-3-yl]piperidine-4-carboxamide [(XI), R1 = 2-chloro-6-fluorophenyl, R2 = 1-butylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0363] [ka]

[0364] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-butylpiperidine-4-carboxamide and (2-chloro-6-fluorophenyl)boronic acid, flash column chromatography (DCM / MeOH 92:8) gave 0.056 g (48% yield). 1 H NMR (500MHz, DMSO-d6) δppm0.87(t, J=7.32Hz, 3H), 1.27(m, 2H), 1.40(m, 2H), 1.74-1.97(m, 6H), 2.18-2.29(m, 2H), 2.52-2.54(m, 1H), 2.84-2.94(m, 2H), 6.48(d, J=9.00Hz, 1H), 7.03(d, J=8.69Hz, 1H), 7.20-7.38(m, 16H), 7.40-7.47(m, 2H), 7.73(s, 1H), 10.51(brs, 1H). HRMS(ESI);C42H41ClFN4O[M+H] + Calculated value: 671.2948, measured value: 671.2935.

[0365] tert-Butyl [3-(4-{[5-(2-chloro-6-fluorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidin-1-yl)propyl]-carbamate [(XI), R1 = 2-chloro-6-fluorophenyl, R2 = tert-butyl [3-(piperidin-1-yl)propyl]carbamate, R9 = 1,1′,1″-methanetriyltribenzene]

[0366] [ka]

[0367] Starting from tert-butyl (3-{4-[(5-bromo-1-trityl-1H-indazol-3-yl)carbamoyl]piperidin-1-yl}propyl)carbamate and (2-chloro-6-fluorophenyl)boronic acid. Flash column chromatography (DCM / MeOH 94:6). Obtained 0.061 g (54% yield). 1H NMR (500MHz, DMSO-d6) δppm1.35(s, 9H), 1.44-1.68(m, 5H), 1.70-1.93(m, 5H), 2.23(m, 2H), 2.44(m, 1H), 2.76-2.98(m, 3H), 6.4 7(d, J=9.15Hz, 1H), 6.81(brs, 1H), 7.03(d, J=8.54Hz, 1H), 7.24-7.36(m, 16H), 7.42-7.44(m, 2H), 7.72(s, 1H), 10.49(brs, 1H). HRMS(ESI);C46H48ClFN5O3[M+H] + Calculated value: 772.3424, measured value: 772.3416.

[0368] N-[5-(2-chloro-6-fluorophenyl)-1-trityl-1H-indazol-3-yl]-1-(1-methoxypropan-2-yl)piperidine-4-carboxamide [(XI), R1 = 2-chloro-6-fluorophenyl, R2 = 1-(1-methoxypropan-2-yl)piperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0369] [ka]

[0370] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-(1-methoxypropan-2-yl)piperidine-4-carboxamide and (2-chloro-6-fluorophenyl)boronic acid, flash column chromatography (DCM / MeOH 92:8) gave 0.032 g (52% yield). LCMS (ESI) m / z 687 (M+H). + .

[0371] N-[5-(2,6-dichlorophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2,6-dichlorophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0372] [ka]

[0373] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2,6-dichlorophenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.106 g (64% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.60-1.68(m, 2H), 1.77(d, J=10.68Hz, 2H), 1.8 1-2.04(m, 2H), 2.19(brs, 3H), 2.42(m, 1H), 2.80-2.86(m, 2H), 6.46(d, J=9 .00Hz, 1H), 6.94(d, J=8.54Hz, 1H), 7.21-7.31(m, 9H), 7.32-7.37(m, 6H), 7 .41(t, J=8.24Hz, 1H), 7.56(d, J=8.08Hz, 2H), 7.67(s, 1H)10.49(brs, 1H). HRMS (ESI); C39H35Cl2N4O [M+H] + Calculated value: 645.2183, measured value: 645.2186.

[0374] 1-Butyl-N-[5-(2,6-dichlorophenyl)-1-trityl-1H-indazol-3-yl]piperidine-4-carboxamide [(XI), R1 = 2,6-dichlorophenyl, R2 = 1-butylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0375] [ka]

[0376] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-butylpiperidine-4-carboxamide and (2,6-dichlorophenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 95:5:0.5) yielded 0.144 g (79% yield). 1H NMR (500MHz, DMSO-d6) δppm0.89(t, J=7.32Hz, 3H), 1.28(m, 2H), 1.41(m, 2H), 1.5 9-1.68(m, 2H), 1.76-1.88(m, 4H), 2.25(m, 2H), 2.45(m, 1H), 2.89(d, J=9.00Hz, 2H ), 6.49(d, J=9.00Hz, 1H), 6.97(d, J=8.69Hz, 1H), 7.28-7.33(m, 9H), 7.35-7.41( m, 6H), 7.44(t, J=8.39Hz, 1H), 7.59(d, J=8.08Hz, 2H), 7.69(s, 1H), 10.49(s, 1H). HRMS(ESI);C42H41Cl2N4O[M+H] + Calculated value: 687.2652, measured value: 687.2680.

[0377] N-[5-(2,6-dichlorophenyl)-1-trityl-1H-indazol-3-yl]-1-(2-methylpropyl)piperidine-4-carboxamide [(XI), R1 = 2,6-dichlorophenyl, R2 = 1-(2-methylpropyl)piperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0378] [ka]

[0379] Starting from 1N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-(2-methylpropyl)piperidine-4-carboxamide and (2,6-dichlorophenyl)boronic acid. Flash column chromatography (DCM / MeOH 95:5). Obtained 0.105 g (70% yield). LCMS (ESI) m / z 687 (M+H). + .

[0380] N-[5-(2,6-dichlorophenyl)-1-trityl-1H-indazol-3-yl]-1-(3-hydroxy-2,2-dimethylpropyl)piperidine-4-carboxamide [(XI), R1 = 2,6-dichlorophenyl, R2 = 1-(3-hydroxy-2,2-dimethylpropyl)piperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0381] [ka]

[0382] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-(3-hydroxy-2,2-dimethylpropyl)piperidine-4-carboxamide and (2,6-dichlorophenyl)boronic acid, flash column chromatography (DCM / MeOH 92:8) gave 0.077 g (62% yield). 1 H NMR (401MHz, DMSO-d6) δppm0.76(s, 6H), 1.54-1.77(m, 4H), 2.07-2.22(m, 3H) ), 2.40(m, 1H), 2.81(d, J=9.64Hz, 2H), 3.13(s, 2H), 4.45(m, 1H), 6.45(d, J= 8.79Hz, 1H), 6.93(d, J=9.03Hz, 1H), 7.16-7.31(m, 9H), 7.32-7.38(m, 6H), 7 .41(t, J=8.67Hz, 1H), 7.54(d, J=8.18Hz, 2H), 7.66(s, 1H), 10.43(brs, 1H). HRMS(ESI);C43H43Cl2N4O2[M+H] + Calculated value: 717.2758, measured value: 717.2746.

[0383] N-[5-(6-chloro-2-fluoro-3-methylphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 6-chloro-2-fluoro-3-methylphenyl, R2 = 1-methylpiperidine, R9 = 1,1',1"-methanetriyltribenzene]

[0384] [ka]

[0385] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (6-chloro-2-fluoro-3-methylphenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 94:6:0.5) yielded 0.060 g (64% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.60-1.65(m, 2H), 1.73-1.75(m, 2H), 1.81-1.84(m, 2H), 2.13(s, 3H), 2.23(d, J=1.98Hz, 3H), 2.40(m, 1H), 2.78(d, J= 10.68Hz, 2H), 6.46(d, J=8.85Hz, 1H), 7.00(d, J=8.85Hz, 1H), 7.21-7.28 (m, 6H), 7.28-7.32(m, 5H), 7.32-7.39(m, 6H), 7.72(s, 1H), 10.47(s, 1H). HRMS(ESI);C40H37ClFNO[M+H] + Calculated value: 643.2635, measured value: 643.2640.

[0386] N-[5-(2-chloro-6-fluoro-3-methylphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-chloro-6-fluoro-3-methylphenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0387] [ka]

[0388] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-chloro-6-fluoro-3-methylphenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.5) yielded 0.065 g (76% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.53-1.67(m, 2H), 1.73-1.74(m, 2H), 1.79-1.85(m, 2H), 2.13(s, 3H), 2.39(m, 1H), 2.77(d, J=11.13Hz, 2H), 6.47(d , J=9.00Hz, 1H), 6.99(d, J=9.30Hz, 1H), 7.21(t, J=8.69Hz, 1H), 7.23-7 .31(m, 9H), 7.33-7.36(m, 6H), 7.41(m, 1H), 7.71(s, 1H), 10.47(s, 1H). HRMS(ESI);C40H37ClFNO[M+H] + Calculated value: 643.2635, measured value: 643.2643.

[0389] N-[5-(5-chloro-2-fluoro-3-methylphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 5-chloro-2-fluoro-3-methylphenyl, R2 = 1-methylpiperidine, R9 = 1,1',1"-methanetriyltribenzene]

[0390] [ka]

[0391] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (5-chloro-2-fluoro-3-methylphenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 92:8:0.5) yielded 0.071 g (80% yield). 1H NMR (500MHz, DMSO-d6) δppm1.60-1.72(m, 2H), 1.76-1.79(m, 2H), 1.82-1.87(m, 2H), 2.14(s, 3H), 2.26(d, J=1.53Hz, 3H), 2.41(m, 1H) , 2.79(d, J=10.52Hz, 2H), 6.44(d, J=8.85Hz, 1H), 7.17-7.25(m, 6H), 7.26-7.31(m, 5H), 7.32-7.40(m, 7H), 7.88(s, 1H), 10.47(s, 1H). HRMS(ESI);C40H37ClFN4O[M+H] + Calculated value: 643.2635, measured value: 643.2640.

[0392] N-{5-[2-methoxy-5-(propan-2-yl)phenyl]-1-trityl-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-methoxy-5-(propan-2-yl)phenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0393] [ka]

[0394] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and [2-methoxy-5-(propan-2-yl)phenyl]boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.074 g (88% yield). 1H NMR (500MHz, DMSO-d6) δppm1.18(d, J=6.86Hz, 6H), 1.63-1.69(m, 2H), 1.76-1.78(m, 2H), 1.86-1 .92(m, 2H), 2.15(brs, 3H), 2.41(m, 1H), 2.79(d, J=9.00Hz, 2H), 2.85(m, 1H), 3.68(s, 3H), 6.36( d, J=8.85Hz, 1H), 6.98(d, J=8.54Hz, 1H), 7.05(s, 1H), 7.13(d, J=9.30Hz, 1H), 7.16(dd, J=8.54, 2.29Hz, 1H), 7.23-7.25(m, 6H), 7.27-7.31(m, 3H), 7.31-7.38(m, 6H), 7.70(s, 1H), 10.39(s, 1H). HRMS(ESI);C43H45N4O2[M+H] + Calculated value: 649.3537, measured value: 649.3548.

[0395] 1-Methyl-N-{5-[3-(trifluoromethyl)phenyl]-1-trityl-1H-indazol-3-yl}piperidine-4-carboxamide [(XI), R1 = 3-(trifluoromethyl)phenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0396] [ka]

[0397] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and [3-(trifluoromethyl)phenyl]boronic acid. Flash column chromatography (DCM / MeOH 90:10). Obtained 0.033 g (40% yield). LCMS (ESI) m / z 645 (M+H). + .

[0398] N-{5-[2-chloro-5-(hydroxymethyl)phenyl]-1-trityl-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-chloro-5-(hydroxymethyl)phenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0399] [ka]

[0400] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and [2-chloro-5-(hydroxymethyl)phenyl]boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 92:8:0.5) yielded 0.069 g (78% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.56-1.70(m, 2H), 1.76-1.78(m, 2H), 1.82-1.89(m, 2H), 2 .14(brs, 3H), 2.41(m, 1H), 2.79(d, J=10.68Hz, 2H), 4.50(d, J=5.80Hz, 2H), 5.28(t, J= 5.80Hz, 1H), 6.44(d, J=9.00Hz, 1H), 7.10(d, J=8.85Hz, 1H), 7.24(d, J=7.78Hz, 6H), 7. 26-7.32(m, 5H), 7.32-7.38(m, 6H), 7.47(d, J=8.24Hz, 1H), 7.76(s, 1H), 10.46(s, 1H). HRMS(ESI);C40H38ClN4O2[M+H] + Calculated value: 641.2678, measured value: 641.2698.

[0401] N-[5-(2-fluorophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-fluorophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0402] [ka]

[0403] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-fluorophenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.5) yielded 0.071 g (87% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.58-1.72(m, 2H), 1.77-1.86(m, 4H), 2.14(s, 3H), 2.41(m, 1H), 2. 79(d, J=10.52Hz, 2H), 6.45(d, J=8.85Hz, 1H), 7.17-7.45(m, 20H), 7.86(s, 1H), 10.47(s, 1H). HRMS(ESI);C39H36FN4O[M+H] + Calculated value: 595.2868, measured value: 595.2884.

[0404] N-[5-(2-cyanophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-cyanophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0405] [ka]

[0406] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-cyanophenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.5) yielded 0.059 g (71% yield). 1H NMR (500MHz, DMSO-d6) δppm1.60-1.71(m, 2H), 1.75-1.78(m, 2H), 1.82-1.87(m, 2H) , 2.14(s, 3H), 2.42(m, 1H), 2.79(d, J=10.37Hz, 2H), 6.48(d, J=8.85Hz, 1H), 7.22-7. 27(m, 6H), 7.28-7.32(m, 4H), 7.33-7.38(m, 6H), 7.54(td, J=7.63, 1.07Hz, 1H), 7.5 8(d, J=7.93Hz, 1H), 7.75(m, 1H), 7.91(d, J=7.93Hz, 1H), 7.95(s, 1H), 10.53(s, 1H). HRMS(ESI);C40H36N5O[M+H] + Calculated value: 602.2915, measured value: 602.2935.

[0407] N-[5-(2,5-dichlorophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2,5-dichlorophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0408] [ka]

[0409] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2,5-dichlorophenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.5) yielded 0.074 g (83% yield). 1H NMR (500MHz, DMSO-d6) δppm1.56-1.70(m, 2H), 1.73-1.77(m, 2H), 1.81-1.86(m , 2H), 2.13(s, 3H), 2.40(m, 1H), 2.78(d, J=10.52Hz, 2H), 6.45(d, J=9.00Hz, 1H ), 7.14(d, J=8.54Hz, 1H), 7.24(d, J=7.63Hz, 6H), 7.26-7.31(m, 3H), 7.32-7.3 9(m, 6H), 7.42-7.47(m, 2H), 7.57(d, J=8.69Hz, 1H), 7.81(s, 1H), 10.48(s, 1H). HRMS(ESI);C39H35Cl2N4O[M+H] + Calculated value: 645.2183, measured value: 645.2198.

[0410] N-[5-(3-carbamoylphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 3-carbamoylphenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0411] [ka]

[0412] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (3-carbamoylphenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:1) gave 0.077 g (91% yield). 1H NMR (500MHz, DMSO-d6) δppm1.62-1.74(m, 2H), 1.76-1.92(m, 4H), 2.15(brs, 3H), 2.4 3(m, 1H), 2.81(d, J=9.61Hz, 2H), 6.44(d, J=9.00Hz, 1H), 7.23(d, J=7.63Hz, 6H), 7.27 -7.31(m, 4H), 7.32-7.37(m, 3H), 7.39-7.43(m, 2H), 7.49(t, J=7.78Hz, 1H), 7.70(d, J=7.02Hz, 1H), 7.81(d, J=7.78Hz, 1H), 7.96(s, 1H), 8.03-8.06(m, 2H), 10.45(s, 1H). HRMS(ESI);C40H38N5O2[M+H] + Calculated value: 620.3020, measured value: 620.3038.

[0413] N-{5-[4-(hydroxymethyl)phenyl]-1-trityl-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide [(XI), R1 = 4-(hydroxymethyl)phenyl, R2 = 1-methylpiperidine, R9 = 1,1',1"-methanetriyltribenzene]

[0414] [ka]

[0415] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and [4-(hydroxymethyl)phenyl]boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.5) yielded 0.073 g (87% yield). 1H NMR (500MHz, DMSO-d6) δppm1.60-1.75(m, 2H), 1.76-1.94(m, 4H), 2.15(s, 3 H), 2.42(m, 1H), 2.80(d, J=10.83Hz, 2H), 4.51(d, J=5.80Hz, 2H), 5.19(t, J= 5.72Hz, 1H), 6.42(d, J=8.85Hz, 1H), 7.22(d, J=7.47Hz, 6H), 7.27-7.31(m, 3H), 7.32-7.38(m, 10H), 7.50(d, J=7.78Hz, 1H), 7.90(s, 1H), 10.43(s, 1H). HRMS(ESI);C40H39N4O2[M+H] + Calculated value: 607.3068, measured value: 607.3079.

[0416] N-{5-[3-(hydroxymethyl)phenyl]-1-trityl-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide [(XI), R1 = 3-(hydroxymethyl)phenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0417] [ka]

[0418] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and [3-(hydroxymethyl)phenyl]boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.5) yielded 0.068 g (81% yield). 1H NMR (500MHz, DMSO-d6) δppm1.62-1.74(m, 2H), 1.79-1.91(m, 4H), 2.16(brs, 2H), 2.43(m, 1H), 2.81(d, J=9.46Hz, 2H), 4.53(d , J=5.64Hz, 2H), 5.22(t, J=5.72Hz, 1H), 6.43(d, J=9.00Hz, 1H), 7.18-7.43(m, 19H), 7.48(m, 1H), 7.90(s, 1H), 10.44(s, 1H). HRMS(ESI);C40H39N4O2[M+H] + Calculated value: 607.3068, measured value: 607.3085.

[0419] 1-Methyl-N-[5-(pyridin-3-yl)-1-trityl-1H-indazol-3-yl]piperidine-4-carboxamide [(XI), R1 = pyridin-3-yl, R2 = 1-methylpiperidine, R9 = 1,1',1"-methanetriyltribenzene]

[0420] [ka]

[0421] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and pyridin-3-ylboronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.055 g (73% yield). 1H NMR (500MHz, DMSO-d6) δppm1.76-1.86(m, 2H), 1.92-1.99(m, 2H), 2.20(brs, 2H), 2.45 (m, 1H), 3.13(m, 2H), 6.48(d, J=8.85Hz, 1H), 7.22(d, J=7.63Hz, 6H), 7.26-7.32(m, 3H) , 7.32-7.39(m, 6H), 7.42(d, J=8.85Hz, 1H), 7.45(dd, J=7.93, 4.88Hz, 1H), 7.97(d, J= 7.78Hz, 1H), 7.99(s, 1H), 8.53(dd, J=4.73, 1.37Hz, 1H), 8.79(s, 1H), 10.61(brs, 1H). HRMS(ESI);C38H36N5O[M+H] + Calculated value: 578.2915, measured value: 578.2916.

[0422] N-[5-(2-chlorophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-chlorophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0423] [ka]

[0424] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-chlorophenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.041 g (51% yield). LCMS (ESI) m / z 612 (M+H). + .

[0425] N-[5-(2-chloro-5-methylphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-chloro-5-methylphenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0426] [ka]

[0427] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-chloro-5-methylphenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.5) yielded 0.057 g (66% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.58-1.70(m, 2H), 1.74-1.77(m, 2H), 1.81-1.85(m , 2H), 2.13(s, 3H), 2.40(m, 1H), 2.78(d, J=10.98Hz, 2H), 6.43(d, J=8.85Hz, 1H ), 7.09(d, J=8.85Hz, 1H), 7.17-7.18(m, 2H), 7.24(d, J=7.63Hz, 6H), 7.27-7.3 2(m, 3H), 7.33-7.37(m, 6H), 7.38(d, J=8.69Hz, 1H), 7.75(s, 1H), 10.45(s, 1H). HRMS(ESI);C40H38ClN4O[M+H] + Calculated value: 625.2729, measured value: 625.2744.

[0428] N-[5-(4-fluorophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 4-fluorophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0429] [ka]

[0430] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (4-fluorophenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 92:8:0.5) yielded 0.078 g (95% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.65-1.71(m, 2H), 1.75-1.93(m, 4H), 2.15(s, 3H), 2.42(m, 1H), 2.81(d, J=10.83Hz, 2H), 6. 43(d, J=8.85Hz, 1H), 7.19-7.25(m, 6H), 7.25-7.31(m, 6H), 7.32-7.37(m, 6H), 7.59(m, 2H), 7.89(s, 1H), 10.44(s, 1H). HRMS(ESI);C39H36FN4O[M+H] + Calculated value: 595.2868, measured value: 595.2878.

[0431] N-[5-(2-ethylphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-ethylphenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0432] [ka]

[0433] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-ethylphenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.5) yielded 0.067 g (81% yield). 1H NMR (500MHz, DMSO-d6) δppm1.01(t, J=7.47Hz, 3H), 1.58-1.68(m, 2H), 1.73-1.76(m, 2H), 1.80-1.84(m, 2H), 2.12(s, 3H), 2.39(m, 1H), 2.47(m, 2H)2.77(d, J=10.83Hz, 2H) , 6.43(d, J=9.00Hz, 1H), 7.00(d, J=8.69Hz, 1H), 7.10(d, J=7.32Hz, 1H), 7.20(td, J= 7.09, 1.98Hz, 1H), 7.23-7.31(m, 11H), 7.32-7.38(m, 6H), 7.60(s, 1H), 10.43(s, 1H). HRMS(ESI);C41H41N4O[M+H] + Calculated value: 605.3275, measured value: 605.3289.

[0434] N-[5-(3-cyanophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 3-cyanophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0435] [ka]

[0436] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (3-cyanophenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.5) yielded 0.070 g (85% yield). 1H NMR (500MHz, DMSO-d6) δppm1.62-1.74(m, 2H), 1.77-1.92(m, 4H), 2.15(s, 3H), 2. 42(m, 1H), 2.81(d, J=10.52Hz, 2H), 6.45(d, J=8.85Hz, 1H), 7.22(d, J=7.63Hz, 6H) , 7.27-7.31(m, 3H), 7.33-7.38(m, 6H), 7.42(d, J=8.54Hz, 1H), 7.64(t, J=7.78Hz , 1H), 7.77-7.80(m, 1H), 7.91(d, J=7.93Hz, 1H), 8.00-8.02(m, 2H), 10.47(s, 1H). HRMS(ESI);C40H36N5O[M+H] + Calculated value: 602.2915, measured value: 602.2935.

[0437] N-[5-(4-aminophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 4-aminophenyl, R2 = 1-methylpiperidine, R9 = 1,1',1"-methanetriyltribenzene]

[0438] [ka]

[0439] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (4-aminophenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.059 g (77% yield). 1H NMR (500MHz, DMSO-d6) δppm1.67-1.76(m, 4H), 1.81-1.86(m, 2H), 2.26(brs, 3H), 2.46(m, 1H), 2.91(m, 2H), 5.15(s, 2H), 6.35(d , J=9.00Hz, 1H), 6.60(d, J=8.54Hz, 2H), 7.21-7.25(m, 8H), 7.26-7.30(m, 4H), 7.31-7.36(m, 6H), 7.72(s, 1H), 10.39(brs, 1H). HRMS(ESI);C39H38N5O[M+H] + Calculated value: 592.3071, measured value: 592.3098.

[0440] N-[5-(2-aminophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-aminophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0441] [ka]

[0442] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-aminophenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.044 g (57% yield). 1H NMR (500MHz, DMSO-d6) δppm1.63-1.68(m, 2H), 1.74-1.77(m, 2H), 1.79-1.90(m, 2H), 2.13(s, 3 H), 2.39(m, 1H), 2.78(m, J=10.83Hz, 2H), 4.68(s, 2H), 6.42(d, J=8.85Hz, 1H), 6.60(td, J=7.4 0, 1.07Hz, 1H), 6.72(d, J=8.08Hz, 1H), 6.91(d, J=7.02Hz, 1H), 7.01(m, 1H), 7.06(d, J=8.54Hz) , 1H), 7.24(d, J=7.63Hz, 6H), 7.27-7.32(m, 3H), 7.32-7.39(m, 6H), 7.70(s, 1H), 10.41(s, 1H). HRMS(ESI);C39H38N5O[M+H] + Calculated value: 592.3071, measured value: 592.3093.

[0443] 1-Methyl-N-[5-(4-sulfamoylphenyl)-1-trityl-1H-indazol-3-yl]piperidine-4-carboxamide [(XI), R1 = 4-sulfamoylphenyl, R2 = 1-methylpiperidine, R9 = 1,1',1"-methanetriyltribenzene]

[0444] [ka]

[0445] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (4-sulfamoylphenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.5) yielded 0.065 g (72% yield). 1H NMR (500MHz, DMSO-d6) δppm1.65-1.72(m, 2H), 1.77-1.93(m, 4H), 2.16(brs , 3H), 2.43(m, 1H), 2.81(m, J=9.30Hz, 2H), 6.46(d, J=9.00Hz, 1H), 7.22(d, J =7.47Hz, 6H), 7.26-7.31(m, 3H), 7.32-7.38(m, 8H), 7.42(d, J=8.85Hz, 1H) , 7.75(d, J=8.08Hz, 2H), 7.85(d, J=8.54Hz, 2H), 8.01(s, 1H), 10.48(s, 1H). HRMS(ESI);C39H38N5O3S[M+H] + Calculated value: 656.2690, measured value: 656.2707.

[0446] 1-Methyl-N-(5-phenyl-1-trityl-1H-indazol-3-yl)piperidine-4-carboxamide [(XI), R1 = phenyl, R2 = 1-methylpiperidine, R9 = 1,1',1"-methanetriyltribenzene]

[0447] [ka]

[0448] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and phenylboronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.062 g (83% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.62-1.74(m, 2H), 1.79-1.87(m, 4H), 2.15(s, 3H), 2.42(m, 1H), 2.80(d, J=10.52Hz, 2H), 6.44(d, J=9 .00Hz, 1H), 7.23(d, J=7.63Hz, 6H), 7.27-7.36.38(m, 10H), 7.41-7.44(m, 3H), 7.55(d, J=7.47Hz, 2H), 7.92(s, 1H), 10.44(s, 1H). HRMS(ESI);C39H37N4O[M+H] +Calculated value: 577.2962, measured value: 577.2974.

[0449] N-{5-[2-chloro-5-(trifluoromethyl)phenyl]-1-trityl-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-chloro-5-(trifluoromethyl)phenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0450] [ka]

[0451] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and [2-chloro-5-(trifluoromethyl)phenyl]boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.055 g (62% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.62-1.66(m, 2H), 1.74-1.77(m, 2H), 1.81-1.85(m, 2H), 2.13(s, 3H), 2.40(m, 1H), 2.77(d, J=10.52Hz, 2H), 6.46(d, J=8.69Hz, 1H), 7.17(d, J= 9.00Hz, 1H), 7.24(d, J=7.63Hz, 6H), 7.27-7.32(m, 3H), 7.32-7.38(m, 6H), 7.68(s, 1 H), 7.73(dd, J=8.39, 2.14Hz, 1H), 7.79(d, J=8.39Hz, 1H), 7.84(s, 1H), 10.49(s, 1H). HRMS(ESI);C40H35ClF3N4O[M+H] + Calculated value: 679.2446, measured value: 679.2467.

[0452] N-[5-(2-fluoropyridin-3-yl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-fluoropyridin-3-yl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0453] [ka]

[0454] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-fluoropyridin-3-yl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.068 g (87% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.57-1.72(m, 2H), 1.77-1.80(m, 2H), 1.82-1.96(m, 2H) , 2.15(brs, 3H), 2.42(m, 1H), 2.80(d, J=10.07Hz, 2H), 6.47(d, J=8.85Hz, 1H), 7.23( d, J=7.63Hz, 6H), 7.26-7.31(m, 4H), 7.31-7.40(m, 6H), 7.44(ddd, J=7.17, 5.11, 1.7 5Hz, 1H), 7.94(s, 1H), 8.04(t, J=9.30Hz, 1H), 8.19(d, J=4.88Hz, 1H), 10.50(s, 1H). HRMS(ESI);C38H35FN5O[M+H] + Calculated value: 596.2820, measured value: 596.2834.

[0455] N-[5-(2-Methoxyphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-methoxyphenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0456] [ka]

[0457] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-methoxyphenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.056 g (71% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.69-1.77(m, 2H), 1.86-1.89(m, 2H), 2.39(m, 1H), 3.04(m, 2H), 3.71(s, 3H), 6.37(d, J=9.00Hz, 1H), 6.99(td, J=7.43, 0.69Hz, 1H), 7.08(d, J=8.24Hz, 1H), 7.16(d, J=9.00Hz, 1H), 7.20-7.26(m , 7H), 7.26-7.32(m, 3H), 7.32-7.41(m, 7H), 7.73(s, 1H), 10.49(brs, 1H). HRMS(ESI);C40H39N4O2[M+H] + Calculated value: 607.3068, measured value: 607.3087.

[0458] N-[5-(2,3-dichlorophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2,3-dichlorophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0459] [ka]

[0460] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2,3-dichlorophenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.043 g (56% yield). LCMS (ESI) m / z 646 (M+H). + .

[0461] N-[5-(2-chloro-6-methoxyphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-chloro-6-methoxyphenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0462] [ka]

[0463] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-chloro-6-methoxyphenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.048 g (57% yield). LCMS (ESI) m / z 641 (M+H). + .

[0464] N-[5-(2,3-difluorophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2,3-difluorophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0465] [ka]

[0466] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2,3-difluorophenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.5) yielded 0.064 g (76% yield). 1H NMR (500MHz, DMSO-d6) δppm1.59-1.71(m, 2H), 1.78(d, J=11.44Hz, 2H), 1.85(t, J=10.68Hz, 2H), 2.15(s, 3H), 2.42(brs, 1H), 2.80(d, J=10 .37Hz, 2H), 6.47(d, J=8.85Hz, 1H), 7.23(d, J=7.63Hz, 6H), 7.26-7.32(m, 6H), 7.32-7.38(m, 6H), 7.41(m, 1H), 7.91(s, 1H), 10.50(s, 1H). HRMS(ESI);C39H35F2N4O[M+H] + Calculated value: 613.2774, measured value: 613.2791.

[0467] 1-Methyl-N-{5-[3-(methylsulfonyl)phenyl]-1-trityl-1H-indazol-3-yl}piperidine-4-carboxamide [(XI), R1 = 3-(methylsulfonyl)phenyl, R2 = 1-methylpiperidine, R9 = 1,1',1"-methanetriyltribenzene]

[0468] [ka]

[0469] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and [3-(methylsulsonyl)phenyl]boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.036 g (43% yield). 1H NMR (500MHz, DMSO-d6) δppm1.65-1.70(m, 2H), 1.80-1.83(m, J=11.74Hz, 2H), 1.89-1.92(m, 1H), 2. 02-2.16(m, 1H), 2.18(brs, 3H), 2.39-2.47(m, 1H), 2.80-2.86(m, 2H), 3.25(s, 3H), 6.47(d, J=9.00H z, 1H), 7.23(d, J=7.47Hz, 6H), 7.27-7.32(m, 3H), 7.32-7.38(m, 6H), 7.44(d, J=8.54Hz, 1H), 7.71( t, J=7.78Hz, 1H), 7.87(m, 1H), 7.92(d, J=7.63Hz, 1H), 8.00(s, 1H), 8.04(brs, 1H), 10.50(brs, 1H). HRMS(ESI);C40H39N4O3S[M+H] + Calculated value: 655.2738, measured value: 655.2762.

[0470] N-[5-(3-fluorophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 3-fluorophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0471] [ka]

[0472] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (3-fluorophenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.054 g (70% yield). 1H NMR (500MHz, DMSO-d6) δppm1.63-1.75(m, 2H), 1.80-1.82(m, 2H), 1.85-1.90 (m, 2H), 2.16 (brs, 3H), 2.42 (m, 1H), 2.82 (m, J=8.39Hz, 2H), 6.43 (d, J=8.85H) z, 1H), 7.15(td, J=8.92, 2.59Hz, 1H), 7.20-7.25(m, 6H), 7.27-7.31(m, 3H), 7 .32-7.36(m, 7H), 7.37-7.43(m, 2H), 7.45(m, 1H), 7.97(s, 1H), 10.47(s, 1H). HRMS(ESI);C39H36FN4O[M+H] + Calculated value: 595.2868, measured value: 595.2891.

[0473] N-[5-(2-hydroxyphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-hydroxyphenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0474] [ka]

[0475] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-hydroxyphenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.061 g (78% yield). LCMS (ESI) m / z 593 (M+H). + .

[0476] N-[5-(biphenyl-2-yl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = biphenyl-2-yl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0477] [ka]

[0478] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and biphenyl-2-ylboronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.064 g (74% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.61-1.66(m, J=9.76Hz, 2H), 1.71-1.73(m, 2H) , 1.80-1.87(m, 2H), 2.15(brs, 3H), 2.36(m, 1H), 2.80(m, J=10.22Hz, 2H), 6 .04(d, J=8.85Hz, 1H), 6.53(d, J=8.54Hz, 1H), 6.89-6.98(m, 2H), 7.08-7.2 1(m, 8H), 7.24-7.34(m, 11H), 7.35-7.46(m, 3H), 7.57(s, 1H), 10.35(s, 1H). HRMS(ESI);C45H41N4O[M+H] + Calculated value: 653.3275, measured value: 653.3276.

[0479] 1-Methyl-N-{5-[2-(trifluoromethyl)phenyl]-1-trityl-1H-indazol-3-yl}piperidine-4-carboxamide [(XI), R1 = 2-(trifluoromethyl)phenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0480] [ka]

[0481] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and [2-(trifluoromethyl)-phenyl]boronic acid. Flash column chromatography (DCM / MeOH 90:10). Obtained 0.038 g (99% yield). LCMS (ESI) m / z 645 (M+H).+ .

[0482] N-[5-(2,6-difluorophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2,6-difluorophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0483] [ka]

[0484] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2,6-difluorophenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.037 g (34% yield). LCMS (ESI) m / z 613 (M+H). + .

[0485] N-[5-(2,4-dichlorophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2,4-dichlorophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0486] [ka]

[0487] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2,4-dichlorophenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 95:5:0.5) yielded 0.080 g (61% yield). 1H NMR (500MHz, DMSO-d6) δppm1.62-1.66(m, 2H), 1.74-1.76(m, 2H), 1.81-1.86(m, 2H) , 2.14(s, 3H), 2.41(m, 1H), 2.78(d, J=10.37Hz, 2H), 6.44(d, J=9.00Hz, 1H), 7.12(d , J=8.85Hz, 1H), 7.24(d, J=7.63Hz, 6H), 7.27-7.31(m, 3H), 7.32-7.37(m, 6H), 7.39 (d, J=8.39Hz, 1H), 7.46(m, 1H), 7.70(d, J=2.13Hz, 1H), 7.78(s, 1H), 10.48(s, 1H). HRMS(ESI);C39H35Cl2N4O[M+H] + Calculated value: 645.2183, measured value: 645.2186.

[0488] N-[5-(4-amino-2-chlorophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 4-amino-2-chlorophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0489] [ka]

[0490] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and 3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline, flash column chromatography (DCM / MeOH 90:10) gave 0.081 g (76% yield). 1H NMR (500MHz, DMSO-d6) δppm1.67-1.73(d, J=10.37Hz, 3H), 1.82-1.85(m, 2H), 2.27-2.33( m, 2H), 2.57(m, 1H), 2.89-3.01(m, 2H), 5.45(s, 2H), 6.37(d, J=8.85Hz, 1H), 6.54(dd, J=8. 31, 2.21Hz, 1H), 6.66(d, J=2.29Hz, 1H), 6.98(d, J=8.24Hz, 1H), 7.03(d, J=9.15Hz, 1H), 7 .23(d, J=7.63Hz, 6H), 7.27-7.30(m, 3H), 7.32-7.39(m, 6H), 7.63(s, 1H), 10.45(brs, 1H). HRMS(ESI);C39H37ClN5O[M+H] + Calculated value: 626.2681, measured value: 626.2695.

[0491] 1-Methyl-N-[5-(2,4,6-trichlorophenyl)-1-trityl-1H-indazol-3-yl]piperidine-4-carboxamide [(XI), R1 = 2,4,6-trichlorophenyl, R2 = 1-methylpiperidine, R9 = 1,1',1"-methanetriyltribenzene]

[0492] [ka]

[0493] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2,4,6-trichlorophenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 95:5:0.5) yielded 0.038 g (56% yield). LCMS (ESI) m / z 679 (M+H) + .

[0494] N-[5-(4-carbamoylphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 4-carbamoylphenyl, R2 = 1-methylpiperidine, R9 = 1,1',1"-methanetriyltribenzene]

[0495] [ka]

[0496] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (4-carbamoylphenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:1) gave 0.056 g (87% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.61-1.74(m, 2H), 1.78-1.93(m, 4H), 2.17(brs, 3H), 2.44(m, 1H), 2.81-2.83(m, 2H), 6.45(d, J=8.85Hz, 1H) , 7.18-7.25(m, 6H), 7.26-7.31(m, 3H), 7.32-7.38(m, 8H), 7.64(d, J=8.08Hz, 2H), 7.92(d, J=8.39Hz, 2H), 7.99(brs, 2H), 10.47(s, 1H). HRMS(ESI);C40H38N5O2[M+H] + Calculated value: 620.3020, measured value: 620.3024.

[0497] N-[5-(4-cyanophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 4-cyanophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0498] [ka]

[0499] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (4-cyanophenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:1) gave 0.059 g (97% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.63-1.76(m, 2H), 1.76-1.85(m, 2H), 1.89-1.94(m , 2H), 2.18(brs, 3H), 2.44(m, 1H), 2.82-2.85(m, 2H), 6.46(d, J=9.00Hz, 1H), 7. 22(d, J=7.47Hz, 6H), 7.26-7.31(m, 3H), 7.32-7.38(m, 6H), 7.44(d, J=8.54Hz, 1H), 7.77(d, J=8.24Hz, 2H), 7.89(d, J=8.54Hz, 2H), 8.06(s, 1H), 10.52(s, 1H). HRMS(ESI);C40H36N5O[M+H] + Calculated value: 602.2915, measured value: 602.2923.

[0500] N-[5-(2-chloro-4-hydroxyphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-chloro-4-hydroxyphenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0501] [ka]

[0502] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-chloro-4-hydroxyphenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.046 g (73% yield). LCMS (ESI) m / z 627 (M+H). + .

[0503] N-[5-(4-amino-3-fluorophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 4-amino-3-fluorophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0504] [ka]

[0505] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline, flash column chromatography (DCM / MeOH 90:10) gave 0.050 g (81% yield). LCMS (ESI) m / z 610 (M+H) + .

[0506] N-[5-(4-cyano-2-methylphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 4-cyano-2-methylphenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0507] [ka]

[0508] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (4-cyano-2-methylphenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.5) yielded 0.053 g (75% yield). 1H NMR (500MHz, DMSO-d6) δppm1.61-1.67(m, 2H), 1.74-1.78(m, 2H), 1.82-2.00(m, 2 H), 2.17(brs, 3H), 2.22(s, 3H), 2.41(m, 1H), 2.78-2.82(m, 2H), 6.44(d, J=9.00Hz) , 1H), 7.10(d, J=8.85Hz, 1H), 7.24(d, J=7.63Hz, 6H), 7.27-7.31(m, 3H), 7.32-7. 38(m, 7H), 7.68(dd, J=7.93, 1.22Hz, 1H), 7.71(s, 1H), 7.77(s, 1H), 10.50(s, 1H). HRMS(ESI);C41H38N5O[M+H] + Calculated value: 616.3071, measured value: 616.3083.

[0509] N-[5-(2,6-dimethylphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2,6-dimethylphenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0510] [ka]

[0511] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2,6-dimethylphenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 95:5:0.5) gave 0.040 g (58% yield). LCMS (ESI) m / z 605 (M+H). + .

[0512] N-[5-(2-fluoro-5-nitrophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-fluoro-5-nitrophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0513] [ka]

[0514] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-fluoro-5-nitrophenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.074 g (67% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.68-1.71(m, 2H), 1.79-1.82(m, 2H), 1.89-1.96(m, 2H), 2.19(brs, 3H), 2.45(m, 1H), 2.82-2.87(m, 2H), 6.50(d, J=9. 15Hz, 1H), 7.23(d, J=7.63Hz, 6H), 7.27-7.32(m, 4H), 7.33-7.39(m, 6H), 7.61(t, J=9.68Hz, 1H), 8.00(s, 1H), 8.23-8.30(m, 2H), 10.55(brs, 1H). HRMS(ESI);C39H35FN5O3[M+H] + Calculated value: 640.2719, measured value: 640.2732.

[0515] N-[5-(2-chloro-5-cyanophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-chloro-5-cyanophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0516] [ka]

[0517] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-chloro-5-cyanophenyl)boronic acid. Flash column chromatography (DCM / MeOH 90:10). Obtained 0.047 g (46% yield). LCMS (ESI) m / z 636 (M+H). + .

[0518] N-[5-(5-carbamoyl-2-chlorophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 5-carbamoyl-2-chlorophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0519] [ka]

[0520] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (5-carbamoyl-2-chlorophenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.085 g (49% yield). LCMS (ESI) m / z 654 (M+H). + .

[0521] N-[5-(2-fluoro-4-formylphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-fluoro-4-formylphenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0522] [ka]

[0523] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-fluoro-4-formylphenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.040 g (39% yield). LCMS (ESI) m / z 623 (M+H). + .

[0524] N-[5-(2-fluoro-4-methylphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-fluoro-4-methylphenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0525] [ka]

[0526] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-fluoro-4-methylphenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.052 g (85% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.58-1.72(m, 2H), 1.77-1.80(m, 2H), 1.86-1.92(m, 2H), 2.17(brs, 3H), 2.33(s, 3H), 2.41(m, 1H), 2.81(d, J=8.54Hz, 2H), 6.43(d, J=8.85Hz, 1H), 7.08(d, J=8.24Hz, 1H), 7.10(d, J=12.51Hz, 1H), 7.18-7.36(m, 17H), 7.82(s, 1H), 10.45(s, 1H). HRMS(ESI);C40H38FN4O[M+H] + Calculated value: 609.3024, measured value: 609.3027.

[0527] N-[5-(2,6-difluoro-4-methoxyphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2,6-difluoro-4-methoxyphenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0528] [ka]

[0529] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2,6-difluoro-4-methoxyphenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.104 g (80% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.55-1.71(m, 2H), 1.75-1.77(m, 2H), 1.82-1.89( m, 2H), 2.15(brs, 3H), 2.40(m, 1H), 2.79(d, J=8.54Hz, 2H), 3.80(s, 3H), 6.45 (d, J=8.85Hz, 1H), 6.83(d, J=9.91Hz, 2H), 7.06(d, J=8.69Hz, 1H), 7.23(d, J= 7.63Hz, 6H), 7.27-7.30(m, 3H), 7.33-7.36(m, 6H), 7.75(s, 1H), 10.47(s, 1H). HRMS(ESI);C40H39FN4O[M+H] + Calculated value: 643.2879, measured value: 643.2887.

[0530] tert-Butyl 4-(3-{[(1-methylpiperidin-4-yl)carbonyl]amino}-1-trityl-1H-indazol-5-yl)-1H-pyrazole-1-carboxylate [(XI), R1 = tert-butyl 1H-pyrazole-1-carboxylate, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0531] [ka]

[0532] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and [1-(tert-butoxycarbonyl)-1H-pyrazol-4-yl]boronic acid. Flash column chromatography (DCM / MeOH 80:20). Obtained 0.056 g (81% yield). LCMS (ESI) m / z 667 (M+H). + .

[0533] N-[5-(2-chloro-4-hydroxyphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-chloro-4-hydroxyphenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0534] [ka]

[0535] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-chloro-4-hydroxyphenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.5) yielded 0.059 g (78% yield). 1H NMR (500MHz, DMSO-d6) δppm1.63-1.72(m, 2H), 1.75-1.82(m, 2H), 1.83-1.88(m, 2H), 2.15(s , 3H), 2.41(m, 1H), 2.80(d, J=11.13Hz, 2H), 6.40(s, 1H), 6.72(dd, J=8.39, 2.44Hz, 1H), 6.8 0(d, J=2.44Hz, 1H), 6.90(d, J=8.39Hz, 1H), 7.00(d, J=8.85Hz, 1H), 7.19(d, J=7.47Hz, 6H), 7.24-7.28(m, 3H), 7.29-7.34(m, 6H), 7.68(d, J=8.39Hz, 1H), 9.98(brs, 1H), 10.42(s, 1H). HRMS(ESI);C39H36ClN4O2[M+H] + Calculated value: 627.2522, measured value: 627.2529.

[0536] 1-Methyl-N-[5-(1-methyl-1H-pyrazol-4-yl)-1-trityl-1H-indazol-3-yl]piperidine-4-carboxamide [(XI), R1 = 1-methyl-1H-pyrazol-4-yl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0537] [ka]

[0538] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. Flash column chromatography (DCM / MeOH 85:15). Obtained 0.060 g (95% yield). LCMS (ESI) m / z 581 (M+H). + .

[0539] 1-Methyl-N-[5-(2,4,6-trifluorophenyl)-1-trityl-1H-indazol-3-yl]piperidine-4-carboxamide [(XI), R1 = 2,4,6-trifluorophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0540] [ka]

[0541] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2,4,6-trifluorophenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.011 g (17% yield). LCMS (ESI) m / z 631 (M+H). + .

[0542] N-[5-(2,4-difluorophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2,4-difluorophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0543] [ka]

[0544] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2,4-difluorophenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.044 g (72% yield). 1H NMR (500MHz, DMSO-d6) δppm1.62-1.68(m, 2H), 1.77-1.79(m, 2H), 1.84-1.94(m, 1H), 2.17(brs, 3H), 2.43(m, 1H), 2.82(d, J=8.85Hz, 2H), 6.4 5(d, J=8.85Hz, 1H), 7.14-7.19(m, 2H), 7.22(d, J=7.63Hz, 6H), 7.27-7 .30(m, 4H), 7.33-7.36(m, 6H), 7.49(m, 1H), 7.84(s, 1H), 10.48(s, 1H). HRMS(ESI);C39H35F2N4O[M+H] + Calculated value: 613.2774, measured value: 613.2773.

[0545] 1-Methyl-N-[5-(1H-pyrazol-3-yl)-1-trityl-1H-indazol-3-yl]piperidine-4-carboxamide [(XI), R1 = 1H-pyrazol-3-yl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0546] [ka]

[0547] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and 1H-pyrazol-3-ylboronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:1) yielded 0.040 g (69% yield). LCMS (ESI) m / z 567 (M+H) + .

[0548] 1-Methyl-N-[5-(2,4,5-trifluorophenyl)-1-trityl-1H-indazol-3-yl]piperidine-4-carboxamide [(XI), R1 = 2,4,5-trifluorophenyl, R2 = 1-methylpiperidine, R9 = 1,1',1"-methanetriyltribenzene]

[0549] [ka]

[0550] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2,4,5-trifluorophenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.039 g (62% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.67-1.72(m, 2H), 1.80-1.85(m, 2H), 1.93-2.02(m, 2H), 2.24(brs, 3H), 2.45(m, 1H), 2.85-2.94(m, 2H), 6 .45(d, J=9.00Hz, 1H), 7.21(d, J=7.63Hz, 6H), 7.28-7.30(m, 4H), 7.33-7.36(m, 6H), 7.60-7.67(m, 2H), 7.88(s, 1H), 10.52(brs, 1H). HRMS(ESI);C39H34F3N4O[M+H] + Calculated value: 631.2679, measured value: 631.2680.

[0551] 1-Methyl-N-{5-[2,4,6-trifluoro-3-(propan-2-yloxy)phenyl]-1-trityl-1H-indazol-3-yl}piperidine-4-carboxamide [(XI), R1 = 2,4,6-trifluoro-3-(propan-2-yloxy)phenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0552] [ka]

[0553] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and [2,4,6-trifluoro-3-(propan-2-yloxy)phenyl]boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.034 g (50% yield).1 H NMR (500MHz, DMSO-d6) δppm1.26 (d, J=6.10Hz, 6H), 1.65-1.70 (m, 2H), 1.79-1.8 2(m, 2H), 1.99-2.07(m, 2H), 2.24(brs, 3H), 2.46(m, 1H), 2.86-2.93(m, 2H), 4.30 (spt, J=6.13Hz, 1H), 6.47(d, J=9.00Hz, 1H), 7.10(d, J=8.85Hz, 1H), 7.23(d, J= 7.78Hz, 6H), 7.28-7.30(m, 4H), 7.33-7.36(m, 6H), 7.81(s, 1H), 10.53(brs, 1H). HRMS(ESI);C42H40F3N4O2[M+H] + Calculated value: 689.3098, measured value: 689.3083.

[0554] 1-Methyl-N-[5-(2,3,4-trifluorophenyl)-1-trityl-1H-indazol-3-yl]piperidine-4-carboxamide [(XI), R1 = 2,3,4-trifluorophenyl, R2 = 1-methylpiperidine, R9 = 1,1',1"-methanetriyltribenzene]

[0555] [ka]

[0556] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2,3,4-trifluorophenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.091 g (35% yield). 1H NMR (500MHz, DMSO-d6) δppm1.59-1.70(m, 2H), 1.76-1.79(m, 2H), 1.82-1.89(m, 2H), 2.15(brs, 3H), 2.42(m, 1H), 2.80(d, J=1 0.07Hz, 2H), 6.47(d, J=9.00Hz, 1H), 7.22(d, J=7.63Hz, 6H), 7.27-7.30(m, 4H), 7.33-7.36(m, 8H), 7.89(s, 1H), 10.50(s, 1H). HRMS(ESI);C39H34F3N4O[M+H] + Calculated value: 631.2679, measured value: 631.2680.

[0557] N-[5-(4-fluoro-2-methylphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 4-fluoro-2-methylphenyl, R2 = 1-methylpiperidine, R9 = 1,1',1"-methanetriyltribenzene]

[0558] [ka]

[0559] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (4-fluoro-2-methylphenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.077 g (71% yield). 1H NMR (500MHz, DMSO-d6) δppm1.63-1.67(m, 2H), 1.76-1.78(m, 2H), 1.87-1.93(m, 2H) ), 2.16-2.19(m, 6H), 2.41(m, 1H), 2.81-2.84(m, 2H), 6.41(d, J=9.00Hz, 1H), 7.01- 7.07(m, 2H), 7.13(dd, J=10.14, 2.67Hz, 1H), 7.17(dd, J=8.39, 6.25Hz, 1H), 7.24( d, J=7.63Hz, 6H), 7.27-7.31(m, 3H), 7.32-7.37(m, 6H), 7.61(s, 1H), 10.45(s, 1H). HRMS(ESI);C40H38FN4O[M+H] + Calculated value: 609.3024, measured value: 609.3029.

[0560] N-[5-(4-amino-2-methylphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 4-amino-2-methylphenyl, R2 = 1-methylpiperidine, R9 = 1,1',1"-methanetriyltribenzene]

[0561] [ka]

[0562] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (4-amino-2-methylphenyl)boronic acid, flash column chromatography (DCM / MeOH 85:15) gave 0.046 g (61% yield). 1H NMR (500MHz, DMSO-d6) δppm1.58-1.70(m, 2H), 1.74-1.79(m, 2H), 1.85-1.89(m, 2H), 2.04(s, 3H), 2.16(brs, 3H), 2.41(m, 1H), 2.79-2.81(m, 2H), 5.01(s, 2H), 6.35(d, J=8.85Hz, 1H), 6.41 (dd, J=8.16, 2.21Hz, 1H), 6.44(d, J=2.14Hz, 1H), 6.79(d, J=8.24Hz, 1H), 6.95(d, J=8.69Hz, 1H), 7.24(d, J=7.63Hz, 6H), 7.25-7.30(m, 3H), 7.31-7.37(m, 6H), 7.49(s, 1H), 10.36(s, 1H). HRMS(ESI);C40H40N5O[M+H] + Calculated value: 606.3228, measured value: 606.3224.

[0563] 1-Methyl-N-[5-(2,4,6-trifluoro-3-methoxyphenyl)-1-trityl-1H-indazol-3-yl]piperidine-4-carboxamide [(XI), R1 = 2,4,6-trifluoro-3-methoxyphenyl, R2 = 1-methylpiperidine, R9 = 1,1',1"-methanetriyltribenzene]

[0564] [ka]

[0565] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2,4,6-trifluoro-3-methoxyphenyl)boronic acid, flash column chromatography (DCM / MeOH 95:5) gave 0.055 g (61% yield). 1H NMR (500MHz, DMSO-d6) δppm1.59-1.71(m, 2H), 1.76-1.79(m, 2H), 1.87-1.96(m, 2H), 2.18(brs, 3H), 2.43(m, 1H), 2.83(d, J=2.90Hz, 2H), 3.89( s, 3H), 6.47(d, J=8.85Hz, 1H), 7.09(d, J=8.69Hz, 1H), 7.23(d, J=7.78H) z, 6H), 7.26-7.31(m, 4H), 7.32-7.42(m, 7H), 7.80(s, 1H), 10.51(s, 1H). HRMS(ESI);C40H36F3N4O2[M+H] + Calculated value: 661.2785, measured value: 661.2786.

[0566] N-[5-(2,3-difluoro-4-methylphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2,3-difluoro-4-methylphenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0567] [ka]

[0568] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2,3-difluoro-4-methylphenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.050 g (77% yield). LCMS (ESI) m / z 627 (M+H). + .

[0569] N-[5-(2-chloro-4-fluoro-3-methylphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-chloro-4-fluoro-3-methylphenyl, R2 = 1-methylpiperidine, R9 = 1,1',1"-methanetriyltribenzene]

[0570] [ka]

[0571] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-chloro-4-fluoro-3-methylphenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.058 g (48% yield). LCMS (ESI) m / z 643 (M+H). + .

[0572] N-[5-(3-cyano-2,6-difluorophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 3-cyano-2,6-difluorophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0573] [ka]

[0574] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (3-cyano-2,6-difluorophenyl)boronic acid, flash column chromatography (DCM / MeOH 95:5) gave 0.030 g (45% yield). LCMS (ESI) m / z 638 (M+H). + .

[0575] N-[5-(3-cyano-4-hydroxyphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 3-cyano-4-hydroxyphenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0576] [ka]

[0577] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and 2-hydroxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile, purified by flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.5). Obtained 0.047 g (87% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.66-1.89(m, 6H), 2.16(s, 3H), 2.42(m, 1H), 2.82(d, J=10.98Hz, 2H), 6.39(d, J=8.85Hz, 1H), 7.05(d, J=8.85 Hz, 1H), 7.21(d, J=7.63Hz, 6H), 7.26-7.31(m, 4H), 7.31-7.39(m, 6H), 7.68(d, J=8.24Hz, 1H), 7.75(brs, 1H), 7.85(s, 1H), 10.41(s, 1H). HRMS(ESI);C40H37F3N4O2[M+H] + Calculated value: 618.2864, measured value: 618.2874.

[0578] N-[5-(2-cyano-5-fluorophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-cyano-5-fluorophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0579] [ka]

[0580] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-cyano-5-fluorophenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.053 g (93% yield). 1H NMR (500MHz, DMSO-d6) δppm1.66-1.72(m, 2H), 1.78-1.81(m, 2H), 1.91-2. 01(m, 2H), 2.20(brs, 3H), 2.44(m, 1H), 2.82-2.87(m, 2H), 6.49(d, J=9.00 Hz, 1H), 7.24(d, J=7.63Hz, 6H), 7.28-7.32(m, 4H), 7.33-7.38(m, 6H), 7.4 3(td, J=8.39, 2.59Hz, 1H), 7.49(m, 1H), 7.98-8.05(m, 2H), 10.57(s, 1H). HRMS(ESI); CHFNO[M+H] + Calculated value: 620.2820, measured value: 620.2830.

[0581] N-[5-(2-chloro-5-nitrophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide [(XI), R1 = 2-chloro-5-nitrophenyl, R2 = 1-methylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[0582] [ka]

[0583] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-1-methylpiperidine-4-carboxamide and (2-chloro-5-nitrophenyl)boronic acid, flash column chromatography (DCM / MeOH 90:10) gave 0.040 g (61% yield). LCMS (ESI) m / z 656 (M+H). + .

[0584] N-[5-(2-chloro-4-hydroxyphenyl)-1-trityl-1H-indazol-3-yl]-3-(dimethylamino)cyclobutanecarboxamide [(XI), R1 = 2-chloro-4-hydroxyphenyl, R2 = (dimethylamino)cyclobutane, R9 = 1,1′,1″-methanetriyltribenzene]

[0585] [ka]

[0586] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-3-(dimethylamino)cyclobutanecarboxamide and (2-chloro-4-hydroxyphenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 95:10:0.5) yielded 0.050 g (54% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.94-2.01(m, 8H), 2.19(m, 2H), 2.54(m, 1H), 2.92( m, 1H), 6.40(d, J=8.85Hz, 1H), 6.78(dd, J=8.46, 2.52Hz, 1H), 6.89(d, J=2.44H) z, 1H), 7.06(d, J=8.85Hz, 1H), 7.16(d, J=8.39Hz, 1H), 7.24(d, J=7.63Hz, 6H), 7.26-7.30(m, 3H), 7.32-7.38(m, 6H), 7.70(s, 1H), 9.96(s, 1H), 10.43(s, 1H). HRMS(ESI);C39H36ClN4O2[M+H] + Calculated value: 627.2522, measured value: 627.2520.

[0587] N-[5-(2-chloro-4-hydroxyphenyl)-1-trityl-1H-indazol-3-yl]-3-(methylamino)cyclobutanecarboxamide [(XI), R1 = 2-chloro-4-hydroxyphenyl, R2 = (methylamino)cyclobutane, R9 = 1,1′,1″-methanetriyltribenzene]

[0588] [ka]

[0589] Starting from N-(5-bromo-1-trityl-1H-indazol-3-yl)-3-(methylamino)cyclobutanecarboxamide and (2-chloro-4-hydroxyphenyl)boronic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.5) yielded 0.059 g (60% yield). LCMS (ESI) m / z 613 (M+H) + .

[0590] tert-Butyl (3R)-3-({5-[4-amino-2-chloro-5-(methoxycarbonyl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)-pyrrolidine-1-carboxylate [(XI), R1 = 4-amino-2-chloro-5-(methoxycarbonyl)phenyl, R2 = tert-butylpyrrolidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0591] [ka]

[0592] A mixture of tert-butyl (3R)-3-{[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-trityl-1H-indazol-3-yl]carbamoyl}-pyrrolidine-1-carboxylate (0.070 g, 0.10 mmol) in 1,4-dioxane / water (3:1, 4 mL) was purged with argon for 5 min. Methyl 2-amino-5-bromo-4-chlorobenzoate (0.053 g, 0.20 mmol), 1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) x DCM (10% mol, 0.0082 g, 0.01 mmol), and CsCO (0.064 g, 0.20 mmol) were added. The mixture was heated at 80 °C for 1 h under argon, then cooled, diluted with EtOAc (20 mL), and washed with aqueous NaHCO (20 mL), water (20 mL), and brine (20 mL). The organic phase was separated, dried over anhydrous NaSO, filtered, and evaporated to dryness. The crude material was purified by flash column chromatography (hexane / EtOAc 65:35) to afford tert-butyl (3R)-3-({5-[4-amino-2-chloro-5-(methoxycarbonyl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)pyrrolidine-1-carboxylate (0.064 g, 85% yield) as a white solid. 1 H NMR (500MHz, DMSO-d6) δppm1.37(s, 9H), 1.98-2.19(m, 2H), 3.13-3.30(m, 2H), 3.36-3.43(m, 2H), 3.46-3.57(m, 1H), 3.76(s, 3H), 6.40(d, J=9.00Hz, 1H), 6.85 (s, 2H), 6.96(s, 1H), 7.03(d, J=9.15Hz, 1H), 7.22(d, J=7.63Hz, 6H), 7.27-7.3 0(m, 3H), 7.33-7.36(m, 6H), 7.59(s, 1H), 7.67(s, 1H), 10.65(d, J=8.24Hz, 1H). HRMS(ESI);C44H43ClN5O5Na[M+H+Na] + Calculated value: 778.2766, measured value: 778.2772.

[0593] Following this same method, but using the appropriate intermediates and reagents, the following compounds were prepared:

[0594] tert-Butyl (3R)-3-({5-[2-cyano-5-(methylcarbamoyl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)piperidine-1-carboxylate [(XI), R1 = 2-cyano-5-(methylcarbamoyl)phenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0595] [ka]

[0596] Starting from tert-butyl (3R)-3-{[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-trityl-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate and 3-bromo-4-cyano-N-methyl-benzamide. Flash column chromatography (hexane / EtOAc 50:50). Obtained 0.035 g (56% yield). LCMS (ESI) m / z 745 (M+H). + .

[0597] tert-Butyl (3R)-3-[(5-{2-chloro-5-[(propan-2-yloxy)carbonyl]phenyl}-1-trityl-1H-indazol-3-yl)carbamoyl]-piperidine-1-carboxylate [(XI), R1 = 2-chloro-5-[(propan-2-yloxy)carbonyl]phenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0598] [ka]

[0599] Starting from tert-butyl (3R)-3-{[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-trityl-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate and propan-2-yl 3-bromo-4-chlorobenzoate, flash column chromatography (hexane / EtOAc 75:25) yielded 0.050 g (77% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.30(d, J=6.25Hz, 6H), 1.33-1.34(m, 10H), 1.56-1.72(m, 2H), 1.90-1.97( m, 1H), 2.59(m, 1H), 2.76-2.85(m, 1H), 3.77(d, J=13.12Hz, 1H), 3.88-3.98(m, 2H), 5.13(quin, J=6.25 Hz, 1H), 6.47(d, J=9.00Hz, 1H), 7.15(d, J=9.30Hz, 1H), 7.24(d, J=7.47Hz, 6H), 7.28-7.31(m, 3H), 7.3 4-7.37(m, 6H), 7.70(d, J=8.39Hz, 1H), 7.80-7.73(m, 2H), 7.90(dd, J=8.24, 2.14Hz, 1H), 10.65(s, 1H). HRMS(ESI);C47H48ClN4O5[M+H] + Calculated value: 783.3308, measured value: 783.3306.

[0600] tert-Butyl (3R)-3-({5-[2,6-dichloro-3-(methoxycarbonyl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)piperidine-1-carboxylate [(XI), R1 = 2,6-dichloro-3-(methoxycarbonyl)phenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0601] [ka]

[0602] Starting from tert-butyl (3R)-3-{[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-trityl-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate and methyl 3-bromo-2,4-dichlorobenzoate, flash column chromatography (hexane / EtOAc 80:20) yielded 0.056 g (72% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.29-1.35(m, 10H), 1.56-1.74(m, 2H), 1.90-1.93(m , 1H), 2.57(m, 1H), 2.73-2.80(m, 1H), 3.74(d, J=14.03Hz, 1H), 3.86(s, 3H), 3.9 1-3.97(m, 2H), 6.48(d, J=9.00Hz, 1H), 6.94(d, J=10.07Hz, 1H), 7.25-7.30(m, 9 H), 7.33-7.36(m, 6H), 7.65-7.70(m, 2H), 7.75(d, J=8.39Hz, 1H), 10.63(s, 1H). HRMS(ESI);C45H43Cl2N4O5[M+H] + Calculated value: 789.2605, measured value: 789.2589.

[0603] tert-Butyl (3R)-3-({5-[2-chloro-5-(1,2,4-oxadiazol-3-yl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)piperidine-1-carboxylate [(XI), R1 = 2-chloro-5-(1,2,4-oxadiazol-3-yl)phenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0604] [ka]

[0605] Starting from tert-butyl (3R)-3-{[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-trityl-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate and 3-(4-chloro-3-iodophenyl)-1,2,4-oxadiazole. Flash column chromatography (hexane / EtOAc 70:30). Obtained 0.023 g (39% yield). LCMS (ESI) m / z 765 (M+H). + .

[0606] tert-Butyl (3R)-3-({5-[2-chloro-5-(1,3,4-oxadiazol-2-yl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)piperidine-1-carboxylate [(XI), R1 = 2-chloro-5-(1,3,4-oxadiazol-2-yl)phenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0607] [ka]

[0608] Starting from tert-butyl (3R)-3-{[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-trityl-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate and 2-(3-bromo-4-chlorophenyl)-1,3,4-oxadiazole, flash column chromatography (hexane / EtOAc 60:40) yielded 0.061 g (95% yield). 1H NMR (500MHz, DMSO-d6) δppm1.31-1.37(m, 10H), 1.55-1.75(m, 2H), 1.92-1.95(m, 1H), 2.59(m , 1H), 2.74-2.85(m, 1H), 3.77(d, J=13.12Hz, 1H), 3.90-3.99(m, 2H), 6.49(d, J=8.85Hz, 1H), 7.20(d, J=9.30Hz, 1H), 7.24(d, J=7.63Hz, 6H), 7.28-7.31(m, 3H), 7.34-7.37(m, 6H), 7.80(d , J=8.39Hz, 1H), 7.89-7.92(m, 2H), 8.00(dd, J=8.31, 2.21Hz, 1H), 9.38(s, 1H), 10.66(s, 1H). HRMS(ESI);C45H42ClN6O4Na[M+H+Na] + Calculated value: 787.2770, measured value: 787.2787.

[0609] tert-Butyl (3R)-3-({5-[2-chloro-5-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]-1-trityl-1H-indazol-3-yl}carbamoyl)-piperidine-1-carboxylate [(XI), R1 = 2-chloro-5-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[0610] [ka]

[0611] Starting from tert-butyl (3R)-3-{[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-trityl-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate and 2-(3-bromo-4-chlorophenyl)-5-methyl-1,3,4-oxadiazole, flash column chromatography (hexane / EtOAc 50:50) yielded 0.066 g (99% yield). 1H NMR (500MHz, DMSO-d6) δppm1.30-1.37(m, 10H), 1.59-1.70(m, 2H), 1.91-1.96(m, 1H), 2.57-2.6 0(m, 4H), 2.74-2.83(m, 1H), 3.77(d, J=12.05Hz, 1H), 3.86-3.98(m, 2H), 6.49(d, J=8.85Hz, 1H), 7.18(d, J=9.00Hz, 1H), 7.24(d, J=7.47Hz, 6H), 7.28-7.31(m, 3H), 7.34-7.37(m, 6H), 7.78(d, J =8.39Hz, 1H), 7.84(d, J=1.83Hz, 1H), 7.89(s, 1H), 7.95(dd, J=8.39, 2.14Hz, 1H), 10.66(s, 1H). HRMS(ESI);C46H44ClN6O4[M+H] + Calculated value: 779.3107, measured value: 779.3118.

[0612] Step 1c (Scheme 1)

[0613] [ka]

[0614] N-[5-(4-amino-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide dihydrochloride (Compound 1) [(I), R1 = 4-amino-2-chlorophenyl, R2 = piperidine, R3 = H]

[0615] [ka]

[0616] To a solution of tert-butyl 3-{[5-(4-amino-2-chlorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate (0.082 g, 0.115 mmol) in anhydrous DCM (5 mL) was added triethylsilane (0.055 mL, 0.345 mmol) and a 4 M solution of HCl in dioxane (0.29 mL, 1.15 mmol). The mixture was stirred at room temperature for 3 hours, and then the resulting suspension was evaporated to dryness. The crude material was treated with MTBE (10 mL), stirred for 10 minutes, and filtered. After drying under reduced pressure at 40 °C, N-[5-(4-amino-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide dihydrochloride (0.041 g, 87% yield) was obtained as a white solid. 1 H NMR (500MHz, DMSO-d6) δppm1.67-1.76(m, 2H), 1.81-1.85(m, 2H), 2.09(m, 1H), 2.87-3.15(m, 3H), 6.82(d, J=7.47Hz, 1H), 6.95(brs, 1H), 7.17(d, J=8 .24Hz, 1H), 7.34(dd, J=8.62, 1.30Hz, 1H), 7.47(d, J=8.69Hz, 1H), 7.70(s, 1H), 8.70(brs, 1H), 8.79(d, J=8.69Hz, 1H), 10.67(s, 1H), 12.80(brs, 1H). HRMS (ESI); C19H21ClNO[M+H] + Calculated value: 370.1429, measured value: 370.1438.

[0617] Following this same method, but substituting trifluoroacetic acid or p-toluenesulfonic acid for the appropriate intermediate and optionally 4M HCl in dioxane, the following compounds were prepared:

[0618] N-[5-(2,4-dichlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-3-carboxamide hydrochloride (Compound 2) [(I), R1 = 2,4-dichlorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0619] [ka]

[0620] 0.007 g (70% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.49-1.59(m, 1H), 1.73-1.95(m, 2H), 2.10-2.16(m, 1H) ), 2.76(d, J=4.73Hz, 3H), 2.86-2.94(m, 1H), 3.02-3.27(m, 2H), 3.53-3.59(m, 1H), 7.39(dd, J=8.54, 1.53Hz, 1H) 7.44(d, J=8.24Hz, 1H), 7.51-7.54(m, 2H), 7.74(d, J =2.14Hz, 1H), 7.68-7.76(m, 1H), 10.01(brs, 1H), 10.74(brs, 1H), 12.89(brs, 1H). HRMS(ESI);C20H21Cl2N4O[M+H] + Calculated value: 403.1087, measured value: 403.1095.

[0621] N-[5-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 3) [(I), R1 = 2-chloro-4-hydroxyphenyl, R2 = piperidine, R3 = H]

[0622] [ka]

[0623] 0.011 g (37% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.63-1.90 (m, 3H), 2.08 (d, J=7.02Hz, 1H), 2.87-3.2 1(m, 4H), 3.29-3.37(m, 2H), 6.83(dd, J=8.39, 2.44Hz, 1H), 6.94(d, J=2.44Hz, 1 H), 7.21(d, J=8.24Hz, 1H), 7.34(dd, J=8.77, 1.30Hz, 1H), 7.47(d, J=8.69Hz, 1H ), 7.71(s, 1H), 8.52-8.76(m, 2H), 9.99(brs, 1H), 10.67(s, 1H), 12.80(brs, 1H). HRMS(ESI);C19H20ClN4O2[M+H] + Calculated value: 371.1270, measured value: 371.1278.

[0624] N-[5-(2,5-dichlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 4) [(I), R1 = 2,5-dichlorophenyl, R2 = piperidine, R3 = H]

[0625] [ka]

[0626] 0.048 g (95% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.62-1.88(m, 3H), 2.04-2.16(m, 1H), 2.83-3.01(m, 2H), 3.04-3.20(m, 3H), 7.41(dd, J=8.69, 1.53Hz, 1H), 7 .46-7.51(m, 2H), 7.54(d, J=8.54Hz, 1H), 7.61(dd, J=7.32, 1.22Hz, 1H), 7.83(s, 1H), 8.52-8.76(m, 2H), 10.73(s, 1H), 12.90(brs, 1H). HRMS(ESI);C19H19Cl2N4O[M+H] + Calculated value: 389.0931, measured value: 389.0929.

[0627] (3R)-N-[5-(4-amino-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide dihydrochloride (Compound 5) [(I), R1 = 4-amino-2-chlorophenyl, R2 = piperidine, R3 = H]

[0628] [ka]

[0629] 0.029 g (83% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.63-1.90(m, 3H), 2.05-2.11(m, 1H), 2.88-2.93(m, 1H), 2 .95-3.04(m, 1H), 3.05-3.13(m, 1H), 3.16(d, J=11.59Hz, 1H), 6.81(d, J=7.93Hz, 1H), 6.95(brs, 1H), 7.17(d, J=8.24Hz, 1H), 7.34(dd, J=8.62, 1.45Hz, 1H), 7.45-7.51(m, 1 H), 7.70(s, 1H), 8.69(brs, 1H), 8.78(d, J=9.76Hz, 1H), 10.67(s, 1H), 12.79(brs, 1H). HRMS(ESI);C19H21ClN5O[M+H] + Calculated value: 370.1429, measured value: 370.1436.

[0630] (3R)-N-[5-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 6) [(I), R1 = 2-chloro-4-hydroxyphenyl, R2 = piperidine, R3 = H]

[0631] [ka]

[0632] 0.030 g (97% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.63-1.90 (m, 3H), 2.08 (d, J=7.02Hz, 1H), 2.87-3.2 1(m, 4H), 3.29-3.37(m, 2H), 6.83(dd, J=8.39, 2.44Hz, 1H), 6.94(d, J=2.44Hz, 1 H), 7.21(d, J=8.24Hz, 1H), 7.34(dd, J=8.77, 1.30Hz, 1H), 7.47(d, J=8.69Hz, 1H ), 7.71(s, 1H), 8.52-8.76(m, 2H), 9.99(brs, 1H), 10.67(s, 1H), 12.80(brs, 1H). HRMS(ESI);C19H20ClN4O2[M+H] + Calculated value: 371.1270, measured value: 371.1276.

[0633] (3S)-N-[5-(4-amino-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide dihydrochloride (Compound 7) [(I), R1 = 4-amino-2-chlorophenyl, R2 = piperidine, R3 = H]

[0634] [ka]

[0635] 0.026 g (76% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.63-1.90(m, 3H), 2.05-2.11(m, 1H), 2.88-2.93(m, 1H), 2 .95-3.04(m, 1H), 3.05-3.13(m, 1H), 3.16(d, J=11.59Hz, 1H), 6.81(d, J=7.93Hz, 1H), 6.95(brs, 1H), 7.17(d, J=8.24Hz, 1H), 7.34(dd, J=8.62, 1.45Hz, 1H), 7.45-7.51(m, 1 H), 7.70(s, 1H), 8.69(brs, 1H), 8.78(d, J=9.76Hz, 1H), 10.67(s, 1H), 12.79(brs, 1H). HRMS(ESI);C19H21ClN5O[M+H] +Calculated value: 370.1429, measured value: 370.1431.

[0636] (3R)-N-[5-(2-chloro-4-methylphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 8) [(I), R1 = 2-chloro-4-methylphenyl, R2 = piperidine, R3 = H]

[0637] [ka]

[0638] 0.043 g (99% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.65-1.88(m, 3H), 2.06-2.12(m, 1H), 2.36(s, 3H), 2.92- 3.02(m, 2H), 3.06-3.12(m, 1H), 3.16(d, J=12.05Hz, 1H), 3.31-3.36(m, 1H), 7.23(d, J=7.78Hz, 1H), 7.28(d, J=7.78Hz, 1H), 7.37(dd, J=8.69, 1.53Hz, 1H), 7.40(s, 1H), 7 .51(d, J=8.69Hz, 1H), 7.76(s, 1H), 8.54-8.84(m, 2H), 10.70(s, 1H), 12.84(brs, 1H). HRMS(ESI);C20H22ClN4O[M+H] + Calculated value: 369.1477, measured value: 369.1484.

[0639] N-[5-(5-carbamoyl-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 9) [(I), R1 = 5-carbamoyl-2-chlorophenyl, R2 = piperidine, R3 = H]

[0640] [ka]

[0641] 0.025 g (96% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.70-1.94(m, 3H), 2.10-2.19(m, 1H), 2.95(d, J=11.74Hz, 1H), 3.01( m, 1H), 3.07-3.15(m, 1H), 3.19(d, J=9.91Hz, 1H), 3.34-3.38(m, 1H), 7.46(dd, J=8.69, 1.53Hz, 1H ), 7.54(s, 1H), 7.58(d, J=8.69Hz, 1H), 7.69(d, J=8.24Hz, 1H), 7.87(s, 1H), 7.91(dd, J=8.31, 2. 21Hz, 1H), 7.95(d, J=2.14Hz, 1H), 8.16(s, 1H), 8.62-8.86(m, 2H), 10.76(s, 1H), 12.93(brs, 1H). HRMS(ESI);C20H21ClN5O2[M+H] + Calculated value: 398.1379, measured value: 398.1387.

[0642] (3S)-N-[5-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 10) [(I), R1 = 2-chloro-4-hydroxyphenyl, R2 = piperidine, R3 = H]

[0643] [ka]

[0644] 0.027 g (74% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.63-1.90 (m, 3H), 2.08 (d, J=7.02Hz, 1H), 2.87-3.2 1(m, 4H), 3.29-3.37(m, 2H), 6.83(dd, J=8.39, 2.44Hz, 1H), 6.94(d, J=2.44Hz, 1 H), 7.21(d, J=8.24Hz, 1H), 7.34(dd, J=8.77, 1.30Hz, 1H), 7.47(d, J=8.69Hz, 1H ), 7.71(s, 1H), 8.52-8.76(m, 2H), 9.99(brs, 1H), 10.67(s, 1H), 12.80(brs, 1H). HRMS(ESI);C19H20ClN4O2[M+H] + Calculated value: 371.1270, measured value: 371.1272.

[0645] N-[5-(3-amino-2-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 11) [(I), R1 = 3-amino-2-fluorophenyl, R2 = piperidine, R3 = H]

[0646] [ka]

[0647] 0.036 g (99% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.63-1.95(m, 3H), 2.07-2.17(m, 1H), 2.92(d, J=9.30Hz, 1H), 3.00(m, 1H), 3.08(m, 1H), 3.18(d, J=12.81Hz, 2H), 6.73 (m, 1H), 6.88 (m, 1H), 7.01 (m, 1H), 7.45 (d, J=8.69Hz, 1H), 7.51 (d, J=8.6 9Hz, 1H), 7.89(s, 1H), 8.61-8.90(m, 2H), 10.71(s, 1H), 12.83(brs, 1H). HRMS(ESI); CHFNO[M+H] + Calculated value: 354.1725, measured value: 354.1730.

[0648] (3S)-N-[5-(2-chloro-4-methylphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 12) [(I), R1 = 2-chloro-4-methylphenyl, R2 = piperidine, R3 = H]

[0649] [ka]

[0650] 0.037 g (98% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.65-1.88(m, 3H), 2.06-2.12(m, 1H), 2.36(s, 3H), 2.92- 3.02(m, 2H), 3.06-3.12(m, 1H), 3.16(d, J=12.05Hz, 1H), 3.31-3.36(m, 1H), 7.23(d, J=7.78Hz, 1H), 7.28(d, J=7.78Hz, 1H), 7.37(dd, J=8.69, 1.53Hz, 1H), 7.40(s, 1H), 7 .51(d, J=8.69Hz, 1H), 7.76(s, 1H), 8.54-8.84(m, 2H), 10.70(s, 1H), 12.84(brs, 1H). HRMS(ESI);C20H22ClN4O[M+H] + Calculated value: 369.1477, measured value: 369.1484.

[0651] (3R)-N-[5-(2,5-dichlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 13) [(I), R1 = 2,5-dichlorophenyl, R2 = piperidine, R3 = H]

[0652] [ka]

[0653] 0.016 g (47% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.62-1.88(m, 3H), 2.04-2.16(m, 1H), 2.83-3.01(m, 2H), 3.04-3.20(m, 3H), 7.41(dd, J=8.69, 1.53Hz, 1H), 7 .46-7.51(m, 2H), 7.54(d, J=8.54Hz, 1H), 7.61(dd, J=7.32, 1.22Hz, 1H), 7.83(s, 1H), 8.52-8.76(m, 2H), 10.73(s, 1H), 12.90(brs, 1H). HRMS(ESI);C19H19Cl2N4O[M+H] + Calculated value: 389.0931, measured value: 389.0937.

[0654] (3R)-N-[5-(2,4-dichlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 14) [(I), R1 = 2,4-dichlorophenyl, R2 = piperidine, R3 = H]

[0655] [ka]

[0656] 0.027 g (93% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.60-1.77(m, 3H), 1.83(brs, 1H), 2.04-2.14(m, 1H), 2.83-3.03(m, 2H), 3.04-3.13(m, 1H), 3.17(d, J=12.51Hz, 1H), 7.39(dd , J=8.69, 1.53Hz, 1H), 7.44(d, J=8.39Hz, 1H), 7.51-7.55(m, 2H), 7.74(d, J= 2.14Hz, 1H), 7.80(s, 1H), 8.58-8.77(m, 2H), 10.73(s, 1H), 12.89(brs, 1H). HRMS (ESI); C19H19Cl2N4O [M+H] + Calculated value: 389.0931, measured value: 389.0941.

[0657] N-{5-[5-chloro-2-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide trifluoroacetate (Compound 15) [(I), R1 = 5-chloro-2-(trifluoromethyl)phenyl, R2 = piperidine, R3 = H]

[0658] [ka]

[0659] 0.030 g (88% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.69-1.72(m, 3H) 1.77-1.86(m, 1H), 2.02-2.12(m, 1H), 2.93(m, 1H), 3.07-3.18(m, 1H), 3.33-3.36(m, 2H), 7.31(d, J= 8.85Hz, 1H), 7.46-7.55(m, 2H), 7.71(dd, J=8.54, 1.53Hz, 1H), 7.76(s, 1 H), 7.87(d, J=8.54Hz, 1H), 8.48(brs, 2H), 10.72(s, 1H), 12.90(brs, 1H). HRMS (ESI); C20H19ClF3N4O [M+H] + Calculated value: 423.1194, measured value: 423.1190.

[0660] N-[5-(5-acetyl-2-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 16) [(I), R1 = 5-acetyl-2-fluorophenyl, R2 = piperidine, R3 = H]

[0661] [ka]

[0662] 0.070 g (95% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.69-1.85(m, 3H), 2.11(m, 1H), 2.64(s, 3H), 2.90-3.03(m, 2H), 3.06-3.22(m, 1H) ), 3.35-3.38(m, 2H), 7.44-7.66(m, 3H), 7.94-8.14(m, 3H), 8.56-8.84(m, 2H), 10.75(s, 1H), 12.91(brs, 1H). HRMS(ESI);C21H22FN4O2[M+H] + Calculated value: 381.1722, measured value: 381.1718.

[0663] N-[5-(2-chloro-5-methoxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 17) [(I), R1 = 2-chloro-5-methoxyphenyl, R2 = piperidine, R3 = H]

[0664] [ka]

[0665] 0.030 g (91% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.66-1.90(m, 3H), 2.05-2.15(m, 1H), 2.86-3.02(m, 2 H), 3.04-3.21(m, 2H), 3.30-3.38(m, 1H), 3.79(s, 3H), 6.94(d, J=3.05Hz, 1H), 6.9 9(dd, J=8.77, 3.13Hz, 1H), 7.40(dd, J=8.69, 1.53Hz, 1H), 7.47-7.49(m, 1H), 7.52 (d, J=8.69Hz, 1H), 7.80(s, 1H), 8.55-8.81(m, 2H), 10.71(s, 1H), 12.86(brs, 1H). HRMS(ESI);C20H22ClN4O2[M+H] + Calculated value: 385.1426, measured value: 385.1432.

[0666] (3R)-N-[5-(2-chloro-5-methoxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 18) [(I), R1 = 2-chloro-5-methoxyphenyl, R2 = piperidine, R3 = H]

[0667] [ka]

[0668] 0.035 g (94% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.66-1.90(m, 3H), 2.05-2.15(m, 1H), 2.86-3.02(m, 2 H), 3.04-3.21(m, 2H), 3.30-3.38(m, 1H), 3.79(s, 3H), 6.94(d, J=3.05Hz, 1H), 6.9 9(dd, J=8.77, 3.13Hz, 1H), 7.40(dd, J=8.69, 1.53Hz, 1H), 7.47-7.49(m, 1H), 7.52 (d, J=8.69Hz, 1H), 7.80(s, 1H), 8.55-8.81(m, 2H), 10.71(s, 1H), 12.86(brs, 1H). HRMS(ESI);C20H22ClN4O2[M+H] + Calculated value: 385.1426, measured value: 385.1430.

[0669] (3R)-N-[5-(5-acetyl-2-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 19) [(I), R1 = 5-acetyl-2-fluorophenyl, R2 = piperidine, R3 = H]

[0670] [ka]

[0671] 0.033 g (99% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.69-1.85(m, 3H), 2.11(m, 1H), 2.64(s, 3H), 2.90-3.03(m, 2H), 3.06-3.22(m, 1H) ), 3.35-3.38(m, 2H), 7.44-7.66(m, 3H), 7.94-8.14(m, 3H), 8.56-8.84(m, 2H), 10.75(s, 1H), 12.91(brs, 1H). HRMS(ESI);C21H22FN4O2[M+H] + Calculated value: 381.1722, measured value: 381.1724.

[0672] (3R)-N-[5-(2-fluoro-5-methoxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 20) [(I), R1 = 2-fluoro-5-methoxyphenyl, R2 = piperidine, R3 = H]

[0673] [ka]

[0674] 0.029 g (90% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.64-1.92(m, 3H), 2.09(m, 1H), 2.87-3.03(m, 2H), 3.05-3.24(m, 2H), 3.79(s, 3H), 6.95(dt, J=8.85, 3.43Hz, 1H), 6.99(dd, J=6.41, 3.05Hz, 1H), 7.24(t, J=6.41, 9.30Hz, 1H), 7.50-7.57 (m, 2H), 7.92(s, 1H), 8.46-8.89(m, 2H), 10.71(s, 1H), 12.86(brs, 1H). HRMS(ESI);C20H22FN4O2[M+H] + Calculated value: 369.1722, measured value: 369.1725.

[0675] (3R)-N-[5-(5-chloro-2-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 21) [(I), R1 = 5-chloro-2-fluorophenyl, R2 = piperidine, R3 = H]

[0676] [ka]

[0677] 0.030 g (87% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.66-1.87(m, 3H), 1.85(brs, 1H), 2.09(m, 1H), 2.86-3.02(m, 2H), 3.07-3.23(m, 2H), 7.39(m, 1 H), 7.47(ddd, J=6.56, 4.27, 2.14Hz, 1H), 7.51-7.58(m, 3H), 7.96(s, 1H), 8.60-8.84(m, 2H), 10.74(s, 1H), 12.90(brs, 1H). HRMS(ESI);C19H19ClFN4O[M+H] + Calculated value: 373.1226, measured value: 373.1236.

[0678] (3R)-N-[5-(5-ethoxy-2-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 22) [(I), R1 = 5-ethoxy-2-fluorophenyl, R2 = piperidine, R3 = H]

[0679] [ka]

[0680] 0.028 g (84% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.34(t, J=7.02Hz, 3H), 1.65-1.88(m, 3H), 2.09(m, 1H), 2.87-3.04(m, 2H), 3.06-3.25(m, 2H), 4.06(q, J=7.02Hz) , 2H), 6.90-6.95(m, 1H), 6.96-7.00(m, 1H), 7.22(m, 1H), 7.49-7.56( m, 2H), 7.92(s, 1H), 8.54-8.84(m, 2H), 10.71(s, 1H), 12.86(brs, 1H). HRMS(ESI);C21H24FN4O2[M+H] + Calculated value: 383.1878, measured value: 383.1883.

[0681] (3R)-N-{5-[2-fluoro-5-(trifluoromethoxy)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (Compound 23) [(I), R1 = 2-fluoro-5-(trifluoromethoxy)phenyl, R2 = piperidine, R3 = H]

[0682] [ka]

[0683] 0.029 g (87% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.56-1.89(m, 3H), 2.11(m, 1H), 2.82-3.04(m, 2H), 3.07-3.27 (m, 2H), 7.37-7.61(m, 5H), 7.98(s, 1H), 8.57-8.84(m, 2H), 10.75(s, 1H), 12.92(brs, 1H). HRMS(ESI);C20H19F4N4O2[M+H] + Calculated value: 423.1439, measured value: 423.1443.

[0684] (3R)-N-[5-(5-cyano-2-methylphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 24) [(I), R1 = 5-cyano-2-methylphenyl, R2 = piperidine, R3 = H]

[0685] [ka]

[0686] 0.025 g (81% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.63-1.89(m, 3H), 2.02-2.14(m, 1H), 2.30(s, 3H), 2.83-3.02(m, 2H), 3.05-3.18(m, 2H), 7.36(dd, J=8 .54, 1.37Hz, 1H), 7.51-7.57(m, 2H), 7.65(d, J=1.37Hz, 1H), 7.72-7.77(m, 2H), 8.56-8.76(m, 2H), 10.71(s, 1H), 12.87(brs, 1H). HRMS(ESI);C21H22N5O[M+H] + Calculated value: 360.1819, measured value: 360.1830.

[0687] (3R)-N-[5-(5-cyano-2-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 25) [(I), R1 = 5-cyano-2-fluorophenyl, R2 = piperidine, R3 = H]

[0688] [ka]

[0689] 0.018 g (86% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.65-1.92(m, 3H), 2.11(m, 1H), 2.84-3.03(m, 2H), 3.09-3.21(m, 2H), 7.53-7.62(m, 3H), 7.94(d dd. HRMS(ESI);C20H18FN5O[M+H]+ Calculated value: 364.1568, measured value: 364.1568.

[0690] (3R)-N-[5-(2-chloro-5-nitrophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 26) [(I), R1 = 2-chloro-5-nitrophenyl, R2 = piperidine, R3 = H]

[0691] [ka]

[0692] 0.010 g (31% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.60-1.87(m, 3H), 2.09(m, 1H), 2.83-3.02(m, 2H), 3.04-3.13(m, 1H), 3.17(d, J=12.35Hz, 1H), 3.36(m, 1H), 7.46(dd, J=8.85, 1.5 3Hz, 1H), 7.58(d, J=8.69Hz, 1H), 7.86-7.96(m, 2H), 8.18(d, J=2.75Hz, 1H), 8. 25(dd, J=8.77, 2.82Hz, 1H), 8.57-8.78(m, 2H), 10.77(s, 1H), 12.96(brs, 1H). HRMS(ESI);C19H19ClN5O3[M+H] + Calculated value: 400.1171, measured value: 400.1174.

[0693] N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-6-oxopiperidine-3-carboxamide (Compound 27) [(I), R1 = 2,6-dichlorophenyl, R2 = piperidin-2-one, R3 = H]

[0694] [ka]

[0695] 0.021 g (62% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.79-1.95(m, 1H), 1.99-2.04(m, 1H), 2.13-2.29(m, 2H), 2.89(m, 1H), 3.24-3.37(m, 2H), 7.18(d d, J=8.54, 1.37Hz, 1H), 7.44(m, 1H), 7.48-7.55(m, 2H), 7.59(d, J=8.08Hz, 2H), 7.70(s, 1H), 10.58(s, 1H), 12.83(brs, 1H). HRMS(ESI);C19H17Cl2N4O2[M+H] + Calculated value: 403.0723, measured value: 403.0723.

[0696] N-[5-(5-acetyl-2-fluorophenyl)-1H-indazol-3-yl]-6-oxopiperidine-3-carboxamide (Compound 28) [(I), R1 = 5-acetyl-2-fluorophenyl, R2 = piperidin-2-one, R3 = H]

[0697] [ka]

[0698] 0.046 g (99% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.83-1.97(m, 1H), 2.02-2.07(m, 1H), 2.16-2.32(m, 2H), 2.63(s, 3H), 2.92(dt, J=9.65, 4.86Hz, 1H), 3.29-3.41(m, 2H) , 7.46(m, 1H), 7.52-7.59(m, 2H), 7.98(s, 1H), 8.02(ddd, J=8.50, 4.84, 2 .21Hz, 1H), 8.05(dd, J=7.78, 1.83Hz, 1H), 10.60(s, 1H), 12.86(brs, 1H). HRMS(ESI);C21H20FN4O3[M+H] + Calculated value: 395.1514, measured value: 395.1516.

[0699] Methyl 4-chloro-3-(3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (Compound 29) [(I), R1 = methyl 4-chlorobenzoate, R2 = piperidine, R3 = H]

[0700] [ka]

[0701] 0.020 g (69% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.65-1.91(m, 3H), 2.08(m, 1H), 2.84-3.02(m, 2H), 3. 05-3.13(m, 1H), 3.14-3.20(m, 1H), 3.87(s, 3H), 7.42(dd, J=8.62, 1.45Hz, 1H), 7. 55(d, J=8.69Hz, 1H), 7.75(d, J=8.39Hz, 1H), 7.86(s, 1H), 7.92(d, J=2.13Hz, 1H) , 7.96(dd, J=8.31, 2.21Hz, 1H), 8.56-8.76(m, 2H), 10.74(s, 1H), 12.91(brs, 1H). HRMS(ESI);C21H22ClN4O3[M+H] + Calculated value: 413.1375, measured value: 413.1378.

[0702] (3R)-N-[5-(2,4-difluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 30) [(I), R1 = 2,4-difluorophenyl, R2 = piperidine, R3 = H]

[0703] [ka]

[0704] 0.029 g (99% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.64-1.90(m, 3H), 2.10(m, 1H), 2.85-3.04(m, 2H), 3.05-3.14(m, 1H), 3.18(d, J=11.90Hz, 1H), 7.21( td. HRMS(ESI);C19H19F2N4O[M+H] + Calculated value: 357.1522, measured value: 357.1524.

[0705] (3R)-N-{5-[4-methoxy-2-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (Compound 31) [(I), R1 = 4-methoxy-2-(trifluoromethyl)phenyl, R2 = piperidine, R3 = H]

[0706] [ka]

[0707] 0.026 g (82% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.67-1.84(m, 3H), 2.07(m, 1H), 2.90(m, 1H), 2.93-3 .00(m, 2H), 3.07(q, J=10.01Hz, 1H), 3.16(d, J=11.90Hz, 1H), 3.32(d, J=11.44Hz , 1H), 3.88(s, 3H), 7.25(d, J=8.69Hz, 1H), 7.27-7.32(m, 2H), 7.33(m, 1H), 7.48( d, J=8.69Hz, 1H), 7.68(s, 1H), 8.51-8.77(m, 2H), 10.68(s, 1H), 12.84(brs, 1H). HRMS(ESI);C21H22F3N4O2[M+H] + Calculated value: 419.1690, measured value: 419.1703.

[0708] (3R)-N-[5-(2-fluoro-5-methylphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 32) [(I), R1 = 2-fluoro-5-methylphenyl, R2 = piperidine, R3 = H]

[0709] [ka]

[0710] 0.020 g (96% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.64-1.92(m, 3H), 2.11(m, 1H), 2.35(s, 3H), 2.83-3.02(m, 2H), 3.06-3.13(m, 1H), 3.18(d, J=12.20Hz) , 1H), 7.18-7.20(m, 2H), 7.29(d, J=7.78Hz, 1H), 7.45-7.56(m, 2H), 7.90(s, 1H), 8.59-8.79(m, 2H), 10.70(s, 1H), 12.85(brs, 1H). HRMS(ESI);C20H22FN4O[M+H] + Calculated value: 353.1772, measured value: 353.1777.

[0711] (3R)-N-[5-(5-acetyl-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 33) [(I), R1 = 5-acetyl-2-chlorophenyl, R2 = piperidine, R3 = H]

[0712] [ka]

[0713] 0.027 g (94% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.62-1.89(m, 3H), 2.05-2.14(m, 1H), 2.62(s, 3H), 2.88-3.00(m, 2H), 3.09(q, J=9.91Hz, 1H), 3.16(d, J=11.29Hz, 1H), 3.31-3.36(m, 1H), 7.43(dd, J=8.69, 1.5 3Hz, 1H), 7.56(d, J=8.69Hz, 1H), 7.75(d, J=8.24Hz, 1H), 7.85(s, 1H), 7.92(d, J=2.14Hz, 1H) , 7.97(dd, J=8.39, 2.29Hz, 1H), 8.64(brs, 1H), 8.71(brs, 1H), 10.74(s, 1H), 12.91(brs, 1H). HRMS(ESI);C21H22ClN4O2[M+H] + Calculated value: 397.1426, measured value: 397.1426.

[0714] (3R)-N-[5-(5-amino-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide dihydrochloride (Compound 34) [(I), R1 = 5-amino-2-chlorophenyl, R2 = piperidine, R3 = H]

[0715] [ka]

[0716] 0.021 g (81% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.67-1.86(m, 3H), 2.05-2.16(m, 1H), 2.87-2.95(m, 1H), 2.99(m, 1H), 3.05-3.12(m, 1H), 3.17(d, J=12.05Hz, 1H), 6.88-6.96(m, 2H), 7.32-7.42(m, 2H), 7.51(m, 1H), 7.77(s, 1H), 8.66-8.75(m, 1H), 8.77-8.88(m, 1H), 10.73(s, 1H), 12.87(brs, 1H). HRMS (ESI); C19H21ClNO[M+H] + Calculated value: 370.1429, measured value: 370.1439.

[0717] (3R)-N-[5-(2,5-difluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 35) [(I), R1 = 2,5-difluorophenyl, R2 = piperidine, R3 = H]

[0718] [ka]

[0719] 0.024 g (99% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.64-1.90(m, 3H), 2.09(m, 1H), 2.82-3.03(m, 2H), 3.07-3.15(m, 1H), 3.18(d, J=11.90Hz, 1 H), 7.20-7.29(m, 1H), 7.33-7.42(m, 2H), 7.51-7.58(m, 2H), 7.97(s, 1H), 8.67(brs, 2H), 10.73(s, 1H), 12.90(brs, 1H). HRMS(ESI);C19H19F2N4O[M+H] + Calculated value: 357.1522, measured value: 357.1525.

[0720] (3R)-N-{5-[4-methyl-2-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (Compound 36) [(I), R1 = 4-methyl-2-(trifluoromethyl)phenyl, R2 = piperidine, R3 = H]

[0721] [ka]

[0722] 0.009 g (90% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.64-1.89(m, 3H), 2.07(m, 1H), 2.44(s, 3H), 2.83-2.93(m , 1H), 2.94-3.00(m, 1H), 3.04-3.10(m, 1H), 3.15(d, J=12.81Hz, 1H), 3.30-3.34(m, 1H) , 7.26(d, J=8.69Hz, 1H), 7.30(d, J=7.63Hz, 1H), 7.43(d, J=8.54Hz, 1H), 7.52(d, J=7. 78Hz, 1H), 7.64(s, 1H), 7.69(s, 1H), 8.52-8.75(m, 2H), 10.68(s, 1H), 12.85(brs, 1H). HRMS(ESI);C21H22F3N4O[M+H] + Calculated value: 403.1740, measured value: 403.1743.

[0723] Methyl 4-chloro-3-(3-{[(3R)-pyrrolidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (Compound 37) [(I), R1 = methyl 4-chlorobenzoate, R2 = pyrrolidine, R3 = H]

[0724] [ka]

[0725] 0.026 g (88% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm2.05-2.35(m, 2H), 3.15-3.30(m, 2H), 3.87(s, 3H), 7.42(dd, J=8.62, 1.60Hz, 1H), 7.55(d, J=8.69Hz, 1H), 7.75(d, J=8.39Hz, 1H), 7.90-7.93(m, 2H), 7.96(dd, J=8.39, 2.14Hz, 1H), 8.85-9.08(m, 2H), 10.83(s, 1H), 12.93(brs, 1H). HRMS(ESI);C20H20ClN4O3[M+H] + Calculated value: 399.1219, measured value: 399.1219.

[0726] (3R)-N-[5-(5-acetyl-2-chlorophenyl)-1H-indazol-3-yl]pyrrolidine-3-carboxamide hydrochloride (Compound 38) [(I), R1 = 5-acetyl-2-chlorophenyl, R2 = pyrrolidine, R3 = H]

[0727] [ka]

[0728] 0.021 g (89% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm2.05-2.35(m, 2H), 2.62(s, 3H), 3.15-3.30(m, 2H), 7.43(dd, J=8.69, 1.68Hz, 1H), 7.56(d, J=8.69Hz, 1H), 7.75(d, J=8.39Hz, 1H), 7.89-7.93(m, 2H), 7.97(dd, J=8.31, 2.21Hz, 1H), 8.80-9.11(m, 2H), 10.82(s, 1H), 12.92(brs, 1H). HRMS(ESI);C20H20ClN4O2[M+H] + Calculated value: 383.1270, measured value: 383.1276.

[0729] (3R)-N-{5-[2-chloro-5-(methylcarbamoyl)phenyl]-1H-indazol-3-yl}pyrrolidine-3-carboxamide hydrochloride (Compound 39) [(I), R1 = 2-chloro-5-(methylcarbamoyl)phenyl, R2 = pyrrolidine, R3 = H]

[0730] [ka]

[0731] 0.018 g (75% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm2.04-2.18(m, 1H), 2.26-2.35(m, 1H), 2.78(d, J=4.58Hz, 3H) , 3.23(td, J=14.03, 6.56Hz, 2H), 7.43(dd, J=8.69, 1.53Hz, 1H), 7.55(d, J=8.54Hz, 1H), 7.67(d, J=8.24Hz, 1H), 7.84(dd, J=8.31, 2.21Hz, 1H), 7.88(d, J=2.14Hz, 1H), 7.90(d, J =0.76Hz, 1H), 8.62(q, J=4.17Hz, 1H), 8.82-9.12(m, 2H), 10.82(s, 1H), 12.91(brs, 1H). HRMS(ESI);C20H21ClN5O2[M+H] + Calculated value: 398.1379, measured value: 398.1386.

[0732] Methyl 4-cyano-3-(3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (Compound 40) [(I), R1 = methyl 4-cyanobenzoate, R2 = piperidine, R3 = H]

[0733] [ka]

[0734] 0.009 g (84% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.63-1.93(m, 3H), 2.04-2.16(m, 1H), 2.90-3.03(m, 2H), 3.10(q, J=9.81Hz, 1H), 3.17(d, J=11.74Hz, 1H), 3. 92(s, 3H), 7.57-7.68(m, 2H), 8.04(s, 1H), 8.07-8.09(m, 2H), 8.12(d, J=8.69Hz, 1H), 8.52-8.84(m, 2H), 10.80(s, 1H), 13.01(brs, 1H). HRMS(ESI);C22H22N5O3[M+H] + Calculated value: 404.1717, measured value: 404.1717.

[0735] (3R)-N-[5-(2-chloro-5-hydroxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 41) [(I), R1 = 2-chloro-5-hydroxyphenyl, R2 = piperidine, R3 = H]

[0736] [ka]

[0737] 0.017 g (85% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.65-1.92(m, 3H), 2.07-2.12(m, 1H), 2.88-2.94(m, 1H), 2. 95-3.03(m, 1H), 3.10(q, J=9.91Hz, 1H), 3.16(d, J=12.20Hz, 1H), 3.31-3.36(m, 1H), 6. 75-6.82(m, 2H), 7.32(d, J=7.47Hz, 1H), 7.37(dd, J=8.69, 1.53Hz, 1H), 7.49(d, J=9.15 Hz, 1H), 7.76(s, 1H), 8.57-8.85(m, 2H), 9.83(brs, 1H), 10.70(s, 1H), 12.84(brs, 1H). HRMS(ESI);C19H20ClN4O2[M+H] + Calculated value: 371.1270, measured value: 371.1279.

[0738] Methyl 2,4-dichloro-5-(3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (Compound 42) [(I), R1 = methyl 2,4-dichlorobenzoate, R2 = piperidine, R3 = H]

[0739] [ka]

[0740] 0.016 g (89% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.64-1.89(m, 3H), 2.06-2.14(m, 1H), 2.86-3.00(m, 2H), 3.03-3.14(m, 2H), 3.17(d, J=12.20Hz, 1H), 3.87(s, 3H) ), 7.41(dd, J=8.62, 1.30Hz, 1H), 7.55(d, J=8.69Hz, 1H), 7.81-7.86(m, 2H), 7.93(s, 1H), 8.51-8.81(m, 2H), 10.74(s, 1H), 12.93(brs, 1H). HRMS (ESI); C21H21Cl2N4O3 [M+H] + Calculated value: 447.0985, measured value: 447.0989.

[0741] (3R)-N-[5-(2-chloro-5-propanoylphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 43) [(I), R1 = 2-chloro-5-propanoylphenyl, R2 = piperidine, R3 = H]

[0742] [ka]

[0743] 0.007 g (93% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.09(m, 3H), 1.64-1.89(m, 3H), 2.08(d, J=12.35Hz, 1H), 2.91 -3.02(m, 2H), 3.09(m, 2H), 3.16(d, J=11.29Hz, 1H), 3.31-3.36(m, 2H), 7.43(dd, J=8.62, 1.45Hz, 1H), 7.55(d, J=8.54Hz, 1H), 7.74(d, J=8.24Hz, 1H), 7.85(s, 1H), 7.92(d, J=1.98 Hz, 1H), 7.98 (dd, J=8.31, 2.21Hz, 1H), 8.58-8.80 (m, 2H), 10.74 (s, 1H), 12.91 (brs, 1H). HRMS(ESI);C22H24ClN4O2[M+H] + Calculated value: 411.1583, measured value: 411.1591.

[0744] (3R)-N-{5-[2-chloro-4-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (Compound 44) ​​[(I), R1 = 2-chloro-4-(trifluoromethyl)phenyl, R2 = piperidine, R3 = H]

[0745] [ka]

[0746] 0.027 g (98% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.65-1.91(m, 3H), 2.02-2.16(m, 1H), 2.88-2.93(m, 1H), 2.99( m, 1H), 3.09(q, J=9.81Hz, 1H), 3.17(d, J=12.35Hz, 1H), 3.30-3.34(m, 2H), 7.45(dd, J=8.6 2, 1.60Hz, 1H), 7.57(d, J=8.69Hz, 1H), 7.66(d, J=7.93Hz, 1H), 7.82(dd, J=8.01, 1.14Hz, 1 H), 7.87(s, 1H), 8.00(d, J=1.07Hz, 1H), 8.42-8.79(m, 2H), 10.76(s, 1H), 12.93(brs, 1H). HRMS(ESI);C20H19ClF3N4O[M+H] + Calculated value: 423.1194, measured value: 423.1205.

[0747] (3R)-N-{5-[4-chloro-2-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (Compound 45) [(I), R1 = 4-chloro-2-(trifluoromethyl)phenyl, R2 = piperidine, R3 = H]

[0748] [ka]

[0749] 0.030 g (99% yield) was obtained.1 H NMR (500MHz, DMSO-d6) δppm1.63-1.89(m, 3H), 2.06-2.10(m, 1H), 2.86-2.92(m, 1H), 2.9 7(m, 1H), 3.07(q, J=10.17Hz, 1H), 3.16(d, J=11.59Hz, 1H), 3.31-3.34(m, 1H), 7.28(d, J= 8.85Hz, 1H), 7.46(d, J=8.24Hz, 1H), 7.51(d, J=8.69Hz, 1H), 7.73(s, 1H), 7.82(dd, J=8.2 4, 2.14Hz, 1H), 7.91 (d, J=2.14Hz, 1H), 8.55-8.77 (m, 2H), 10.72 (s, 1H), 12.90 (brs, 1H). HRMS(ESI);C20H19ClF3N4O[M+H] + Calculated value: 423.1194, measured value: 423.1201.

[0750] (3R)-N-{5-[5-fluoro-2-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (Compound 46) [(I), R1 = 5-fluoro-2-(trifluoromethyl)phenyl, R2 = piperidine, R3 = H]

[0751] [ka]

[0752] 0.028 g (98% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.62-1.91(m, 3H), 2.02-2.14(m, 1H), 2.87-2.92(m, 1H), 2.96(m, 1H), 3.07(q, J=9.76Hz, 1H), 3.16(d, J=12.20Hz, 1H), 3.31-3.36(m, 1H), 7.29-7.32(m, 2H), 7.45-7.50(m, 1H), 7.52(d, J=8.54Hz, 1H), 7.76(s, 1H), 7.92(dd, J=8.92, 5.41Hz, 1H), 8.49-8.78(m, 1H), 10.72(s, 1H), 12.90(brs, 1H). HRMS(ESI);C20H19F4N4O[M+H] + Calculated value: 407.1490, measured value: 407.1499.

[0753] (3R)-N-[5-(2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 47) [(I), R1 = 2-chlorophenyl, R2 = piperidine, R3 = H]

[0754] [ka]

[0755] 0.018 g (86% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.69-1.86(m, 3H), 2.10(d, J=8.24Hz, 1H), 2.87-3.02(m, 2H), 3.03-3.21(m, 2H), 3.32-3.34(m, 1H), 7 .37-7.46(m, 4H), 7.52(d, J=8.69Hz, 1H), 7.57(d, J=7.63Hz, 1H), 7.80(s, 1H), 8.51-8.80(m, 2H), 10.71(s, 1H), 12.86(brs, 1H). HRMS(ESI);C19H20ClN4O[M+H] + Calculated value: 355.1320, measured value: 355.1326.

[0756] (3R)-N-{5-[2-chloro-5-(propan-2-yl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (Compound 48) [(I), R1 = 2-chloro-5-(propan-2-yl)phenyl, R2 = piperidine, R3 = H]

[0757] [ka]

[0758] 0.020 g (91% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.22(d, J=7.02Hz, 6H), 1.56-1.95(m, 3H), 2.07-2.12( m, 1H), 2.84-3.02(m, 3H), 3.05-3.13(m, 1H), 3.16(d, J=12.96Hz, 1H), 3.32-3.36(m , 1H), 7.25-7.31(m, 2H), 7.37(dd, J=8.69, 1.37Hz, 1H), 7.47(d, J=8.24Hz, 1H), 7.5 2(d, J=8.69Hz, 1H), 7.78(s, 1H), 8.54-8.85(m, 2H), 10.70(s, 1H), 12.85(brs, 1H). HRMS(ESI);C22H26ClN4O[M+H] + Calculated value: 397.1790, measured value: 397.1798.

[0759] (3R)-N-(5-phenyl-1H-indazol-3-yl)piperidine-3-carboxamide hydrochloride (Compound 49) [(I), R1 = phenyl, R2 = piperidine, R3 = H]

[0760] [ka]

[0761] 0.018 g (90% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.69-1.91(m, 3H), 2.10-2.18(m, 1H), 2.90-3.02(m, 2H), 3.08-3.15(m, 1H), 3.19(d, J=11.74Hz, 1H), 7.35(t, J=7.47) Hz, 1H), 7.47(t, J=7.93Hz, 2H), 7.54(d, J=8.54Hz, 1H), 7.61-7.67(m, 3 H), 7.99(s, 1H), 8.71(d, J=19.98Hz, 2H), 10.70(s, 1H), 12.81(brs, 1H). HRMS(ESI); CHNO[M+H] + Calculated value: 321.1710, measured value: 321.1719.

[0762] Methyl 2,4-difluoro-5-(3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (Compound 50) [(I), R1 = methyl 2,4-difluorobenzoate, R2 = piperidine, R3 = H]

[0763] [ka]

[0764] 0.011 g (93% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.62-1.90(m, 3H), 2.03-2.18(m, 1H), 2.89-3.04(m, 2H), 3.10(q, J=9.61Hz, 1H), 3.18(d, J=11.59Hz, 1H), 3.33-3. 38(m, 2H), 3.88(s, 3H), 7.49(d, J=9.50Hz, 1H), 7.55-7.66(m, 2H), 7.9 3-8.04(m, 2H), 8.72(d, J=16.47Hz, 2H), 10.75(s, 1H), 12.92(brs, 1H). HRMS(ESI);C21H21F2N4O3[M+H] + Calculated value: 415.1576, measured value: 415.1584.

[0765] (3R)-N-[5-(5-tert-butyl-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 51) [(I), R1 = 5-tert-butyl-2-chlorophenyl, R2 = piperidine, R3 = H]

[0766] [ka]

[0767] 0.016 g (70% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.31(s, 9H), 1.65-1.92(m, 3H), 2.06-2.15(m, 1H), 2.89-3.01(m, 2H), 3.05-3.11(m, 1H), 3.16(d, J=12.35Hz, 1H), 3.3 2-3.35(m, 1H), 7.37-7.44(m, 3H), 7.47(d, J=8.39Hz, 1H), 7.52(d, J=8.6 9Hz, 1H), 7.79(s, 1H), 8.54-8.78(m, 2H), 10.70(s, 1H), 12.85(brs, 1H). HRMS (ESI); C23H28ClNO[M+H] + Calculated value: 411.1946, measured value: 411.1956.

[0768] (3R)-N-[5-(2-chloro-5-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 52) [(I), R1 = 2-chloro-5-fluorophenyl, R2 = piperidine, R3 = H]

[0769] [ka]

[0770] 0.021 g (99% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm 1.69-1.92 (m, 3H), 2.10-2.15 (m, 1H), 2.92-2.97 (m, 1H) ), 3.01(m, 1H), 3.09-3.14(m, 1H), 3.20(d, J=12.20Hz, 1H), 3.36-3.41(m, 1H), 7.2 9-7.37(m, 2H), 7.45(dd, J=8.69, 1.53Hz, 1H), 7.57(d, J=8.69Hz, 1H), 7.66(dd, J= 8.54, 5.19Hz, 1H), 7.87(s, 1H), 8.58-8.85(m, 2H), 10.76(s, 1H), 12.93(brs, 1H). HRMS(ESI);C19H19ClFN4O[M+H] + Calculated value: 373.1226, measured value: 373.1222.

[0771] (3R)-N-[5-(2,5-dicyanophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 53) [(I), R1 = 2,5-dicyanophenyl, R2 = piperidine, R3 = H]

[0772] [ka]

[0773] 0.008 g (80% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.62-1.91(m, 3H), 2.04-2.15(m, 1H), 2.86-3.04(m, 2H), 3.06-3.15(m, 1H), 3.18(d, J=12.66Hz, 1H), 7.57-7.66(m, 2 H), 8.04(s, 1H), 8.05(dd, J=8.08, 1.53Hz, 1H), 8.15(d, J=1.22Hz, 1H), 8 .19(d, J=8.08Hz, 1H), 8.54-8.77(m, 2H), 10.80(s, 1H), 13.03(brs, 1H). HRMS(ESI);C21H19N6O[M+H] + Calculated value: 371.1615, measured value: 371.1618.

[0774] Methyl 2-amino-4-chloro-5-(3-{[(3R)-pyrrolidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate dihydrochloride (Compound 54) [(I), R1 = methyl 2-amino-4-chlorobenzoate, R2 = pyrrolidine, R3 = H]

[0775] [ka]

[0776] 0.028 g (74% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm2.06-2.35(m, 2H), 3.14-3.33(m, 3H), 3.79(s, 3H), 7.01(s, 1H), 7.31(dd, J=8.62, 1.45Hz , 1H), 7.46(d, J=8.69Hz, 1H), 7.67(s, 1H), 7.75(d, J=0.76Hz, 1H), 8.88-9.14(m, 2H), 10.76(s, 1H), 12.82(brs, 1H). HRMS(ESI);C20H21ClN5O3[M+H] + Calculated value: 414.1328, measured value: 414.1339.

[0777] (3R)-N-{5-[2-cyano-5-(methylcarbamoyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (Compound 55) [(I), R1 = 2-cyano-5-(methylcarbamoyl)phenyl, R2 = piperidine, R3 = H]

[0778] [ka]

[0779] 0.016 g (88% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.60-1.91(m, 3H), 2.07-2.17(m, 1H), 2.82(d, J=4 .58Hz, 3H), 2.89-2.95(m, 1H), 3.00(m, 1H), 3.08-3.13(m, 1H), 3.14-3.22(m, 1 H), 7.58-7.66(m, 2H), 7.96(dd, J=8.08, 1.68Hz, 1H), 8.01-8.04(m, 2H), 8.06 (d, J=8.08Hz, 1H), 8.63(brs, 2H), 8.81(m, 1H), 10.79(s, 1H), 12.99(brs, 1H). HRMS(ESI);C22H23N6O2[M+H] + Calculated value: 403.1877, measured value: 403.1879.

[0780] Propan-2-yl 4-chloro-3-(3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (Compound 56) [(I), R1 = propan-2-yl 4-chlorobenzoate, R2 = piperidine, R3 = H]

[0781] [ka]

[0782] 0.018 g (67% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.32(d, J=6.25Hz, 6H), 1.66-1.89(m, 3H), 2.06-2.14(m, 1H), 2.87-3.0 0(m, 2H), 3.04-3.13(m, 1H), 3.16(d, J=11.90Hz, 1H), 3.34-3.36(m, 1H), 5.15(quin, J=6.25Hz, 1H) , 7.41(dd, J=8.69, 1.53Hz, 1H), 7.56(d, J=8.69Hz, 1H), 7.74(d, J=8.24Hz, 1H), 7.84(s, 1H), 7.89( d, J=2.14Hz, 1H), 7.94(dd, J=8.31, 2.21Hz, 1H), 8.59-8.78(m, 2H), 10.74(s, 1H), 12.91(brs, 1H). HRMS(ESI);C23H26ClN4O3[M+H] + Calculated value: 441.1688, measured value: 441.1693.

[0783] Methyl 2,4-dichloro-3-(3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (Compound 57) [(I), R1 = methyl 2,4-dichlorobenzoate, R2 = piperidine, R3 = H]

[0784] [ka]

[0785] 0.026 g (90% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.64-1.85(m, 3H), 2.04-2.12(m, 1H), 2.86-2.9 9(m, 2H), 3.04-3.12(m, 1H), 3.15(d, J=12.81Hz, 1H), 3.29-3.35(m, 1H), 3. 88(s, 3H), 7.20(d, J=9.30Hz, 1H), 7.56(d, J=8.69Hz, 1H), 7.70-7.73(m, 2H ), 7.78(d, J=8.85Hz, 1H), 8.55-8.78(m, 1H), 10.73(s, 1H), 12.92(brs, 1H). HRMS (ESI); C21H21Cl2N4O3 [M+H] + Calculated value: 447.0985, measured value: 447.0990.

[0786] (3R)-N-{5-[2-chloro-5-(1,2,4-oxadiazol-3-yl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide dihydrochloride (Compound 58) [(I), R1 = 3-(4-chlorophenyl)-1,2,4-oxadiazole, R2 = piperidine, R3 = H]

[0787] [ka]

[0788] 0.014 g (94% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.65-1.91(m, 3H), 2.01-2.16(m, 1H), 2.84-3.01(m, 2H ), 3.02-3.18(m, 2H), 3.33-3.36(m, 1H), 7.47(dd, J=8.69, 1.53Hz, 1H), 7.57(d, J=8 .69Hz, 1H), 7.82(d, J=8.39Hz, 1H), 7.90(s, 1H), 8.01(d, J=1.98Hz, 1H), 8.05(dd, J =8.39, 2.14Hz, 1H), 8.57-8.78(m, 2H), 9.78(s, 1H), 10.75(s, 1H), 12.93(brs, 1H). HRMS(ESI);C21H20ClN6O2[M+H] +Calculated value: 423.1331, measured value: 423.1340.

[0789] (3R)-N-{5-[2-chloro-5-(1,3,4-oxadiazol-2-yl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide trifluoroacetate (Compound 59) [(I), R1 = 2-(4-chlorophenyl)-1,3,4-oxadiazole, R2 = piperidine, R3 = H]

[0790] [ka]

[0791] 0.004 g (13% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.67-1.86(m, 3H), 2.08-2.11(m, 1H), 2.90-2.98(m, 2H), 3.08-3.20(m, 2H), 7.45(m , 1H), 7.57(m, 1H), 7.72(m, 1H), 7.84-7.93(m, 3H), 8.13(s, 1H), 8.51(brs, 2H), 10.74(s, 1H), 12.91(brs, 1H). ). HRMS(ESI);C21H20ClN6O2[M+H] + Calculated value: 423.1331, measured value: 423.1331.

[0792] (3R)-N-{5-[2-chloro-5-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide dihydrochloride (Compound 60) [(I), R1 = 3-(4-chlorophenyl)-5-methyl-1,2,4-oxadiazole, R2 = piperidine, R3 = H]

[0793] [ka]

[0794] 0.020 g (60% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.66-1.84(m, 3H)2.02-2.15(m, 1H)2.68(s, 3H), 2.84-2.93 (m, 1H), 2.98(m, 1H), 3.05-3.13(m, 1H), 3.14-3.22(m, 1H), 7.45(dd, J=8.08, 1.53Hz, 1 H), 7.57(d, J=8.69Hz, 1H), 7.79(d, J=8.39Hz, 1H), 7.89(s, 1H), 7.96(d, J=1.98Hz, 1H) , 8.00(dd, J=8.39, 2.14Hz, 1H), 8.63(d, J=16.01Hz, 2H), 10.75(s, 1H), 12.92(brs, 1H). ). HRMS(ESI);C22H22ClN6O2[M+H] + Calculated value: 437.1488, measured value: 437.1488.

[0795] N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 61) [(I), R1 = 2-chloro-5-cyanophenyl, R2 = piperidine, R3 = H]

[0796] [ka]

[0797] 0.029 g (85% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.73-1.92(m, 2H), 2.02(d, J=12.05Hz, 2H), 2.77(tt, J=10.98, 3 .51Hz, 1H), 2.85-3.01(m, 2H), 3.32-3.36(m, 2H), 7.43(dd, J=8.77, 1.30Hz, 1H), 7.55(d, J= 8.69Hz, 1H), 7.82(d, J=8.40Hz, 1H), 7.84(s, 1H), 7.89(dd, J=8.40, 2.00Hz, 1H), 7.93(d, J= 1.98Hz, 1H), 8.41(q, J=8.80Hz, 1H), 8.73(d, J=10.07Hz, 1H), 10.58(s, 1H), 12.90(brs, 1H). HRMS(ESI);C20H19ClN5O[M+H] + Calculated value: 380.1273, measured value: 380.1281.

[0798] N-[5-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]-3-(dimethylamino)cyclobutanecarboxamide hydrochloride (Compound 62) [(I), R1 = 2-chloro-4-hydroxyphenyl, R2 = (dimethylamino)cyclobutane, R3 = H]

[0799] [ka]

[0800] 0.028 g (90% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm2.37-2.44(m, 2H), 2.67(d, J=4.88Hz, 6H), 3.04(m, 1H), 3.65(m, 1H), 6.83(dd, J=8.39, 2.44Hz, 1H), 6.94(d, J=2.44Hz, 1H), 7.20(d, J=8.39Hz, 1H), 7.34(dd, J=8.62, 1.45Hz, 1H), 7.47(d, J=8.6 9Hz, 1H), 7.73(s, 1H), 9.71-10.16(m, 2H), 10.51(s, 1H), 12.77(brs, 1H). HRMS (ESI); C20H22ClN4O2 [M+H] +Calculated value: 385.1426, measured value: 385.1428.

[0801] N-[5-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]-3-(methylamino)cyclobutanecarboxamide hydrochloride (Compound 63) [(I), R1 = 2-chloro-4-hydroxyphenyl, R2 = (methylamino)cyclobutane, R3 = H]

[0802] [ka]

[0803] 0.039 g (75% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm2.26-2.36(m, 2H), 2.41-2.48(m, 4H), 3.12(m, 1H), 3 .60-3.69(m, 1H), 3.81(m, 1H), 6.83(dd, J=8.31, 2.52Hz, 1H), 6.94(d, J=2.44Hz, 1H), 7.22(d, J=8.40Hz, 1H), 7.33(dd, J=8.62, 1.30Hz, 1H), 7.47(d, J=8.54Hz, 1H ), 7.73(s, 1H), 8.67-8.93(m, 2H), 9.99(brs, 1H), 10.49(m, 1H), 12.76(brs, 1H). HRMS(ESI);C19H20ClN4O2[M+H] + Calculated value: 371.1270, measured value: 371.1273.

[0804] N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 64) [(XV), R1 = 2-chloro-6-fluorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0805] [ka]

[0806] 0.027 g (80% yield) was obtained.1 H NMR (500MHz, DMSO-d6) δppm1.79-1.92(m, 2H), 2.04-2.10(m, 2H), 2.70(t, J=11 .90Hz, 1H), 2.76(d, J=4.73Hz, 3H), 2.92-3.02(m, 2H), 3.47(m, J=11.59Hz, 2H) , 7.29(d, J=9.00Hz, 1H), 7.32-7.39(m, 1H), 7.42-7.50(m, 2H), 7.55(d, J=8.54 Hz, 1H), 7.77(s, 1H), 9.40-10.08(m, 1H), 10.45-10.76(m, 1H), 12.89(brs, 1H). HRMS(ESI);C20H21ClFN4O[M+H] + Calculated value: 387.1383, measured value: 387.1386.

[0807] 1-Butyl-N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 65) [(I), R1 = 2-chloro-6-fluorophenyl, R2 = 1-butylpiperidine, R3 = H]

[0808] [ka]

[0809] 0.031 g (89% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm0.88-0.95(m, 3H), 1.26-1.36(m, 2H), 1.58-1.71(m, 2H), 1.90( q, J=13.42Hz, 2H), 2.03-2.13(m, 2H), 2.73(t, J=12.12Hz, 1H), 2.93(q, J=10.88Hz, 2H), 2. 99-3.07(m, 2H), 3.51-3.57(m, 2H), 7.29(d, J=7.93Hz, 1H), 7.33-7.37(m, 1H), 7.45-7.50( m, 2H), 7.55 (d, J=8.54Hz, 1H), 7.77 (s, 1H), 9.43 (brs, 1H), 10.60 (s, 1H), 12.89 (brs, 1H). HRMS(ESI);C23H27ClFN4O[M+H]+ Calculated value: 429.1852, measured value: 429.1855.

[0810] 1-(3-aminopropyl)-N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide dihydrochloride (Compound 66) [(I), R1 = 2-chloro-6-fluorophenyl, R21-(3-aminopropyl)piperidine, R3 = H]

[0811] [ka]

[0812] 0.034 g (93% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.89-2.05(m, 3H), 2.09(d, J=12.66Hz, 3H), 2.75(m, J=12.28, 1H), 2.82-3.03(m, 4H), 3.10-3.23(m, 2H), 3.53(d, J=11.29Hz, 2H), 7. 29(d, J=9.00Hz, 1H), 7.32-7.40(m, 1H), 7.43-7.48(m, 2H), 7.55(d, J=8.69Hz, 1 H), 7.76(s, 1H), 8.00(brs, 3H), 10.11(brs, 1H), 10.61(s, 1H), 12.89(brs, 1H). HRMS(ESI);C22H26ClFN5O[M+H] + Calculated value: 430.1805, measured value: 430.1802.

[0813] N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]-1-(1-methoxypropan-2-yl)piperidine-4-carboxamide hydrochloride (Compound 67) [(I), R1 = 2-chloro-6-fluorophenyl, R2 = 1-(1-methoxypropan-2-yl)piperidine, R3 = H]

[0814] [ka]

[0815] 0.018 g (80% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.27(d, J=6.56Hz, 3H), 1.92-2.03(m, 2H), 2.05-2.14(m, 2H), 2.74(t, J=12.05Hz, 1H), 3.00-3.12(m, 2H), 3.32(s, 3H), 3.45-3.51(m, 2H), 3.54 -3.65(m, 3H), 7.27-7.31(m, 1H), 7.32-7.38(m, 1H), 7.43-7.50(m, 2H), 7.55(d, J=8.6 9Hz, 1H), 7.73-7.78(m, 1H), 9.14-9.59(m, 1H), 10.51-10.68(m, 1H), 12.89(brs, 1H). HRMS(ESI);C23H27ClFN4O2[M+H] + Calculated value: 445.1801, measured value: 445.1799.

[0816] N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide (Compound 68) [(I), R1 = 2,6-dichlorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0817] [ka]

[0818] After completion of the reaction, the suspension was diluted with DCM and washed with aqueous NaHCO and brine. The organic phase was dried over anhydrous NaSO, filtered, and evaporated to dryness. The crude material was purified by flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:1) to give 0.026 g (41% yield). 1H NMR (500MHz, DMSO-d6) δppm1.56-1.70(m, 2H), 1.77(d, J=12.35Hz, 2H), 1.87(brs, 2H), 2.15(s, 3H), 2.40(brs, 1H), 2.80(d, J=10.37H) z, 2H), 7.17(d, J=8.69Hz, 1H), 7.41-7.46(m, 1H), 7.48-7.54(m, 1H), 7.59(d, J=8.08Hz, 2H), 7.69(s, 1H), 10.36(s, 1H), 12.78(s, 1H). HRMS(ESI);C20H21Cl2N4O[M+H] + Calculated value: 403.1087, measured value: 403.1084.

[0819] 1-Butyl-N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide (Compound 69) [(I), R1 = 2,6-dichlorophenyl, R2 = 1-butylpiperidine, R3 = H]

[0820] [ka]

[0821] After completion of the reaction, the suspension was diluted with DCM and washed with aqueous NaHCO and brine. The organic phase was dried over anhydrous NaSO, filtered, and evaporated to dryness. The crude material was purified by flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.5) to give 0.048 g (53% yield). 1H NMR (401MHz, DMSO-d6) δppm0.87(t, J=7.26Hz, 3H), 1.22-1.33(m, 2H), 1.36-1.44(m, 2H), 1.5 7-1.70(m, 2H), 1.78(d, J=11.60Hz, 2H), 1.83-1.92(m, 2H), 2.25(t, J=6.96Hz, 2H), 2.37-2.47 (m, 1H), 2.88(d, J=11.23Hz, 2H), 7.17(dd, J=8.54, 1.59Hz, 1H), 7.43(dd, J=8.67, 7.57Hz, 1H ), 7.52(dd, J=8.67, 0.61Hz, 1H), 7.57-7.61(m, 2H), 7.69(s, 1H), 10.31(s, 1H), 12.75(s, 1H). HRMS(ESI);C23H27Cl2N4O[M+H] + Calculated value: 445.1557, measured value: 445.1560.

[0822] N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-1-(2-methylpropyl)piperidine-4-carboxamide (Compound 70) [(I), R1 = 2,6-dichlorophenyl, R2 = 1-(2-methylpropyl)piperidine, R3 = H]

[0823] [ka]

[0824] After completion of the reaction, the suspension was diluted with DCM and washed with aqueous NaHCO and brine. The organic phase was dried over anhydrous NaSO, filtered, and evaporated to dryness. The crude material was purified by flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.5) to give 0.041 g (63% yield). 1H NMR (401MHz, DMSO-d6) δppm0.84(d, J=6.59Hz, 6H), 1.56-1.81(m, 5H), 1.86(t, J=11.11Hz, 2H), 2.01(d, J=7.08Hz, 2H), 2.38-2.48(m, 1H), 2.85(d, J =10.86Hz, 2H), 7.17(d, J=8.67Hz, 1H), 7.40-7.46(m, 1H), 7.52(d, J=8.67 Hz, 1H), 7.59(d, J=8.06Hz, 2H), 7.69(s, 1H), 10.31(s, 1H), 12.75(s, 1H). HRMS (ESI); C23H27Cl2N4O [M+H] + Calculated value: 445.1557, measured value: 445.1559.

[0825] N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-1-(3-hydroxy-2,2-dimethylpropyl)piperidine-4-carboxamide (Compound 71) [(I), R1 = 2,6-dichlorophenyl, R2 = 1-(3-hydroxy-2,2-dimethylpropyl)piperidine, R3 = H]

[0826] [ka]

[0827] After completion of the reaction, the suspension was diluted with DCM and washed with aqueous NaHCO and brine. The organic phase was dried over anhydrous NaSO, filtered, and evaporated to dryness. The crude material was purified by flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.5) to give 0.017 g (35% yield). 1H NMR (401MHz, DMSO-d6) δppm0.77(s, 6H), 1.58-1.82(m, 4H), 2.01-2.29(m, 4H), 2.40(brs, 1H), 2.84(d, J=9.64Hz, 2H), 3.15(s, 2H), 4.55(brs, 1H), 7 .18(dd, J=8.61, 1.53Hz, 1H), 7.43(dd, J=8.67, 7.57Hz, 1H), 7.52(d, J=8. 79Hz, 1H), 7.56-7.62(m, 2H), 7.68(brs, 1H), 10.31(s, 1H), 12.75(s, 1H). HRMS (ESI); C24H29Cl2N4O2 [M+H] + Calculated value: 475.1662, measured value: 475.1639.

[0828] N-[5-(6-chloro-2-fluoro-3-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 72) [(I), R1 = 6-chloro-2-fluoro-3-methylphenyl, R2 = 1-methylpiperidine, R3 = H]

[0829] [ka]

[0830] 0.030 g (79% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.81-1.91(m, 2H), 2.03-2.10(m, 2H), 2.27(d, J =1.98Hz, 3H), 2.65-2.73(m, 1H), 2.76(d, J=4.58Hz, 3H), 2.92-3.02(m, 2H), 3.47(d, J=12.66Hz, 2H), 7.26(d, J=9.15Hz, 1H), 7.31-7.39(m, 2H), 7.54(d , J=8.69Hz, 1H), 7.75(s, 1H), 9.65(brs, 1H), 10.60(s, 1H), 12.86(brs, 1H). HRMS(ESI);C21H23ClFN4O[M+H] + Calculated value: 401.1539, measured value: 401.1546.

[0831] N-[5-(2-chloro-6-fluoro-3-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 73) [(I), R1 = 2-chloro-6-fluoro-3-methylphenyl, R2 = 1-methylpiperidine, R3 = H]

[0832] [ka]

[0833] 0.037 g (90% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.78-1.92(m, 2H), 2.04-2.11(m, 2H), 2.36-2.39(m , 3H), 2.70(t, J=11.90Hz, 1H), 2.76(d, J=4.73Hz, 3H), 2.92-3.04(m, 2H), 3.46( d, J=11.90Hz, 2H), 7.20-7.29(m, 2H), 7.44(dd, J=8.46, 6.02Hz, 1H), 7.54(d, J= 8.69Hz, 1H), 7.73(s, 1H), 9.65(brs, 1H), 10.53-10.65(m, 1H), 12.87(brs, 1H). HRMS(ESI);C21H23ClFN4O[M+H] + Calculated value: 401.1539, measured value: 401.1539.

[0834] N-[5-(5-chloro-2-fluoro-3-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 74) [(I), R1 = 5-chloro-2-fluoro-3-methylphenyl, R2 = 1-methylpiperidine, R3 = H]

[0835] [ka]

[0836] 0.032 g (71% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.83-1.97(m, 2H), 2.09(d, J=14.03Hz, 2H), 2.30(d, J=1.37H) z, 3H), 2.72(tt, J=12.12, 3.30Hz, 1H), 2.77(d, J=4.58Hz, 3H), 2.93-3.05(m, 2H), 3.49(d , J=10.37Hz, 2H), 7.35(dd, J=6.25, 2.44Hz, 1H), 7.40(dd, J=5.80, 2.44Hz, 1H), 7.47-7. 52(m, 2H), 7.52-7.57(m, 1H), 7.93(s, 1H), 9.66(brs, 1H), 10.61(s, 1H), 12.86(brs, 1H). HRMS(ESI);C21H23ClFN4O[M+H] + Calculated value: 401.1539, measured value: 401.1541.

[0837] N-{5-[2-methoxy-5-(propan-2-yl)phenyl]-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide hydrochloride (Compound 75) [(I), R1 = 2-methoxy-5-(propan-2-yl)phenyl, R2 = 1-methylpiperidine, R3 = H]

[0838] [ka]

[0839] 0.035 g (89% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.21 (d, J=6.86Hz, 6H), 1.89 (qd, J=13.30, 3.80Hz, 2H), 2.08 (d, J=14.18 Hz, 2H), 2.71(tt, J=12.10, 3.40Hz, 1H), 2.77(d, J=4.58Hz, 3H), 2.89(m, J=6.90Hz, 1H), 2.93-3.04(m , 2H), 3.47(t, J=11.20Hz, 2H), 3.71(s, 3H), 7.03(d, J=8.39Hz, 1H), 7.11(d, J=2.14Hz, 1H), 7.20(dd , J=8.46, 2.06Hz, 1H), 7.39-7.47(m, 2H), 7.72(s, 1H), 9.65(brs, 1H), 10.50(s, 1H), 12.71(brs, 1H). HRMS(ESI);C24H31N4O2[M+H] + Calculated value: 407.2442, measured value: 407.2443.

[0840] 1-Methyl-N-{5-[3-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-4-carboxamide hydrochloride (Compound 76) [(I), R1 = 3-(trifluoromethyl)phenyl, R2 = 1-methylpiperidine, R3 = H]

[0841] [ka]

[0842] 0.017 g (95% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.92(qd, J=13.00, 2.90Hz, 2H), 2.12(d, J=13.88Hz, 2H), 2.74(tt, J=12.10, 3.60Hz, 3H), 2.78(d, J=4.42Hz, 3H), 2.94 -3.06(m, 2H), 3.48(t, J=13.40Hz, 2H), 7.57(d, J=8.85Hz, 1H), 7.65-7.7 7(m, 3H), 791-7.98(m, 3H), 9.71(brs, 1H), 10.62(s, 1H), 12.85(brs, 1H). HRMS(ESI);C21H22F3N4O[M+H]+ Calculated value: 403.1740, measured value: 403.1742.

[0843] N-{5-[2-chloro-5-(hydroxymethyl)phenyl]-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide p-toluenesulfonate (Compound 77) [(I), R1 = 2-chloro-5-(hydroxymethyl)phenyl, R2 = 1-methylpiperidine, R3 = H]

[0844] [ka]

[0845] 0.055 g (96% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.76-1.91(m, 2H), 2.05-2.13(m, 2H), 2.28(s, 8H), 2.71(t, J=12.12Hz, 1H), 2.79(d, J=4.73Hz, 3H), 2.93- 3.05(m, 2H), 4.54(s, 2H), 7.26-7.41(m, 4H), 7.50-7.53(m, 2H), 7.79(d, J=0.76Hz, 1H), 9.14(brs, 1H), 10.59(s, 1H), 12.82(brs, 1H). HRMS(ESI);C21H24ClN4O2[M+H] + Calculated value: 399.1583, measured value: 399.1585.

[0846] N-[5-(2-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 78) [(I), R1 = 2-fluorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0847] [ka]

[0848] 0.038 g (86% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.82-1.96(m, 2H), 2.06-2.13(m, 2H), 2.66-2.74(m, 1H), 2.77(d, J=4.73Hz, 3H), 2.93-3.05(m, 2H), 3.48(d, J =12.20Hz, 2H), 7.27-7.35(m, 2H), 7.37-7.44(m, 1H), 7.47-7.58(m, 3H), 7.89-8.00(m, 1H), 9.68(brs, 1H), 10.60(s, 1H), 12.83(brs, 1H). HRMS(ESI);C20H22FN4O[M+H] + Calculated value: 353.1772, measured value: 353.1778.

[0849] N-[5-(2-cyanophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide p-toluenesulfonate (Compound 79) [(I), R1 = 2-cyanophenyl, R2 = 1-methylpiperidine, R3 = H]

[0850] [ka]

[0851] 0.044 g (90% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.79-1.89(m, 2H), 2.07-2.13(m, 2H), 2.28(s, 3H) , 2.68-2.76(m, 2H), 2.78-2.81(m, 3H), 2.94-3.05(m, 2H), 3.50(d, J=11.90Hz , 2H), 7.11(d, J=7.93Hz, 5H), 7.47(d, J=7.93Hz, 5H), 7.52-7.66(m, 4H), 7.80 (td, J=7.74, 1.30Hz, 1H), 7.93-7.99(m, 2H), 9.15(brs, 1H), 12.92(brs, 1H). ). HRMS(ESI);C21H22N5O[M+H] + Calculated value: 360.1819, measured value: 360.1821.

[0852] N-[5-(2,5-dichlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 80) [(I), R1 = 2,5-dichlorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0853] [ka]

[0854] 0.034 g (79% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.82-1.94(m, 2H), 2.05-2.12(m, 2H), 2.71(t, J=12.0 5Hz, 1H), 2.77(d, J=4.73Hz, 3H), 2.93-3.03(m, 2H), 3.48(d, J=10.83Hz, 2H), 7.4 1(dd, J=8.54, 1.37Hz, 1H), 7.47-7.50(m, 2H), 7.53(d, J=8.69Hz, 1H), 7.60-7.64 (m, 1H), 7.81-7.89(m, 1H), 9.62(brs, 1H), 10.58-10.64(m, 1H), 12.88(brs, 1H). HRMS(ESI);C20H21Cl2N4O[M+H] + Calculated value: 403.1087, measured value: 403.1091.

[0855] N-[5-(3-carbamoylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 81) [(I), R1 = 3-carbamoylphenyl, R2 = 1-methylpiperidine, R3 = H]

[0856] [ka]

[0857] 0.041 g (82% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.84-1.99(m, 2H), 2.12(d, J=13.57Hz, 2H), 2.71-2.75(m , 1H), 2.76-2.79(m, 3H), 2.95-3.05(m, 2H), 3.50(d, J=11.74Hz, 2H), 7.44(s, 1H), 7.5 6(d, J=7.93Hz, 1H), 7.70-7.74(m, 1H), 7.77(d, J=7.78Hz, 1H), 7.84(d, J=7.78Hz, 1H) , 8.01-8.07(m, 1H), 8.09-8.17(m, 3H), 9.66(brs, 1H), 10.62(s, 1H), 12.80(brs, 1H). HRMS(ESI);C21H24N5O2[M+H] + Calculated value: 378.1925, measured value: 378.1930.

[0858] N-{5-[4-(hydroxymethyl)phenyl]-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide p-toluenesulfonate (Compound 82) [(I), R1 = 4-(hydroxymethyl)phenyl, R2 = 1-methylpiperidine, R3 = H]

[0859] [ka]

[0860] 0.068 g (98% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.84-1.94(m, 2H), 2.11(d, J=13.42Hz, 2H), 2.28(s, 3H), 2.70-2.74(m, 1H), 2.79-2.84(m, 3H), 2.97-3.06( m, 2H), 3.50(d, J=11.44Hz, 2H), 4.54(s, 2H), 7.10(d, J=7.78Hz, 2H), 7.28-7.66(m, 9H), 9.16(brs, 1H), 10.56(s, 1H), 12.76(brs, 1H). HRMS(ESI);C21H25N4O2[M+H] + Calculated value: 365.1972, measured value: 365.1977.

[0861] N-{5-[3-(hydroxymethyl)phenyl]-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide p-toluenesulfonate (Compound 83) [(I), R1 = 3-(hydroxymethyl)phenyl, R2 = 1-methylpiperidine, R3 = H]

[0862] [ka]

[0863] 0.061 g (97% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.79-1.95(m, 2H), 2.09-2.16(m, 2H), 2.28(s, 3H), 2.68-2.76(m, 1H), 2.79-2.83(m, 3H), 2.96-3.10(m, 2H), 3. 51(d, J=11.29Hz, 2H), 4.58(s, 2H), 7.98(s, 1H), 7.10(d, J=7.78Hz, 2H), 7.28-7.65(m, 9H),9.15(brs, 1H), 10.57(s, 1H), 12.78(brs, 1H) HRMS(ESI);C21H25N4O2[M+H] + Calculated value: 365.1972, measured value: 365.1970.

[0864] 1-Methyl-N-[5-(pyridin-3-yl)-1H-indazol-3-yl]piperidine-4-carboxamide dihydrochloride (Compound 84) [(I), R1 = pyridin-3-yl, R2 = 1-methylpiperidine, R3 = H]

[0865] [ka]

[0866] 0.023 g (73% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.89-2.03(m, 2H), 2.11(d, J=13.27Hz, 2H), 2.69-2.80(m , 1H), 2.76(d, J=4.73Hz, 3H), 2.92-3.06(m, 2H), 7.63(d, J=8.69Hz, 1H), 7.79(dd, J=8 .77, 1.45Hz, 1H), 7.96(dd, J=7.55, 6.02Hz, 1H), 8.22(s, 1H), 8.62(d, J=7.47Hz, 1H) , 8.78(d, J=4.88Hz, 1H), 9.12(s, 1H), 10.06(brs, 1H), 10.71(s, 1H), 12.98(brs, 1H). HRMS(ESI);C19H22N5O[M+H] + Calculated value: 336.1819, measured value: 336.1817.

[0867] N-[5-(2-chlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 85) [(I), R1 = 2-chlorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0868] [ka]

[0869] 0.027 g (78% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.80-1.95(m, 2H), 2.08(d, J=13.73Hz, 2H), 2.71(tt, J =11.95, 3.60Hz, 1H), 2.76(d, J=4.73Hz, 3H), 2.92-3.05(m, 2H), 3.47(d, J=12.51H) z, 2H), 7.36-7.46(m, 4H), 7.52(d, J=8.69Hz, 1H), 7.57(ddd, J=7.45, 1.40, 0.70Hz , 1H), 7.79(dd, J=1.53, 0.91Hz, 1H), 9.65(brs, 1H), 10.59(s, 1H), 12.84(brs, 1H). HRMS(ESI);C20H22ClN4O[M+H] + Calculated value: 369.1477, measured value: 369.1483.

[0870] N-[5-(2-chloro-5-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 86) [(I), R1 = 2-chloro-5-methylphenyl, R2 = 1-methylpiperidine, R3 = H]

[0871] [ka]

[0872] 0.029 g (81% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.80-1.94(m, 2H), 2.04-2.13(m, 2H), 2.34(s, 3H), 2.6 6-2.75(m, 1H), 2.76(d, J=4.58Hz, 3H), 2.93-3.03(m, 2H), 3.47(d, J=11.90Hz, 2H) , 7.18-7.26(m, 2H), 7.37(dd, J=8.62, 1.30Hz, 1H), 7.44(d, J=8.08Hz, 1H), 7.49-7 .54(m, 1H), 7.77(d, J=0.61Hz, 1H), 9.66(brs, 1H), 10.58(s, 1H), 12.82(brs, 1H). HRMS(ESI);C21H24ClN4O[M+H] + Calculated value: 383.1633, measured value: 383.1642.

[0873] N-[5-(4-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 87) [(I), R1 = 4-fluorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0874] [ka]

[0875] 0.038 g (79% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.88-2.03(m, 2H), 2.14(d, J=13.42Hz, 2H), 2.70-2.79(m, 1H), 2.80-2.83(m, 3H), 2.98-3.09(m, 2H), 3.52(d, J=1 1.44Hz, 2H), 7.30-7.38(m, 2H), 7.56(d, J=8.69Hz, 1H), 7.62-7.74(m, 3H), 7.99(s, 1H), 9.75(brs, 1H), 10.52-10.66(m, 1H), 12.82(brs, 1H). HRMS(ESI); CHFNO[M+H] + Calculated value: 353.1772, measured value: 353.1773.

[0876] N-[5-(2-ethylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 88) [(I), R1 = 2-ethylphenyl, R2 = 1-methylpiperidine, R3 = H]

[0877] [ka]

[0878] 0.033 g (80% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm0.99-1.06(m, 3H), 1.76-1.94(m, 2H), 2.03-2.11(m, 2H) , 2.53-2.61(m, 2H), 2.66-2.73(m, 1H), 2.76(d, J=4.58Hz, 3H), 2.92-3.02(m, 2H), 3. 46(d, J=11.59Hz, 2H), 7.17(d, J=7.17Hz, 1H), 7.22-7.26(m, 1H), 7.27-7.36(m, 3H), 7.46-7.52(m, 1H), 7.62-7.75(m, 1H), 9.62(brs, 1H), 10.55(s, 1H), 12.77(brs, 1H). HRMS(ESI);C22H27N4O[M+H] + Calculated value: 363.2180, measured value: 363.2181.

[0879] N-[5-(3-cyanophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 89) [(I), R1 = 3-cyanophenyl, R2 = 1-methylpiperidine, R3 = H]

[0880] [ka]

[0881] 0.034 g (81% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.84-2.00(m, 2H), 2.06-2.16(m, 2H), 2.69-2.76(m, 1H), 2.77-2.82(m, 3H), 2.95-3.06(m, 2H), 3.50(d, J=11.74Hz, 2H), 7.56(d, J=8 .69Hz, 1H), 7.66-7.70(m, 1H), 7.71-7.74(m, 1H), 7.80-7.84(m, 1H), 7.95-8.02 (m, 1H), 8.06-8.13(m, 2H), 9.65(brs, 1H), 10.52-10.66(m, 1H), 12.87(brs, 1H). HRMS(ESI);C21H22N5O[M+H] + Calculated value: 360.1819, measured value: 360.1818.

[0882] N-[5-(4-aminophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide dihydrochloride (Compound 90) [(I), R1 = 4-aminophenyl, R2 = 1-methylpiperidine, R3 = H]

[0883] [ka]

[0884] 0.023 g (76% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.88-2.00 (m, 2H), 2.10 (d, J=13.73Hz, 2H), 2.70-2.75 (m, 1H), 2.77(d, J=4.73Hz, 3H), 2.94-3.05(m, 2H), 3.49(d, J=2.14Hz, 2H), 7.37(d , J=7.02Hz, 2H), 7.54(d, J=8.69Hz, 1H), 7.64(d, J=8.54Hz, 1H), 7.69(d, J=8.24Hz , 2H), 7.98-8.04(m, 1H), 9.82-10.23(m, 3H), 10.55-10.64(m, 1H), 12.81(brs, 1H). HRMS(ESI);C20H24N5O[M+H] + Calculated value: 350.1976, measured value: 350.1981.

[0885] N-[5-(2-aminophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide dihydrochloride (Compound 91) [(I), R1 = 2-aminophenyl, R2 = 1-methylpiperidine, R3 = H]

[0886] [ka]

[0887] 0.028 g (79% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.87-1.99(m, 2H), 2.07-2.15(m, 2H), 2.70-2.76(m, 1H), 2.78-2.81(m, 3H), 2.97-3.06(m, 2H), 7.12-7. 40(m, 6H), 7.46(d, J=7.63Hz, 1H), 7.57(d, J=8.54Hz, 1H), 7.77-7.96(m, 1H), 9.89(brs, 1H), 10.57-10.65(m, 1H), 12.87(brs, 1H). HRMS(ESI);C20H24N5O[M+H] + Calculated value: 350.1976, measured value: 350.1976.

[0888] 1-Methyl-N-[5-(4-sulfamoylphenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 92) [(I), R1 = 4-sulfamoylphenyl, R2 = 1-methylpiperidine, R3 = H]

[0889] [ka]

[0890] 0.036 g (86% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.83-2.00(m, 2H), 2.11(d, J=13.88Hz, 2H), 2.74(tt, J= 12.10, 3.20Hz, 1H), 2.78(d, J=4.73Hz, 3H), 2.89-3.06(m, 2H), 3.49(d, J=12.05Hz, 2 H), 7.40(s, 2H), 7.57(d, J=8.85Hz, 1H), 7.71(dd, J=8.92, 1.30Hz, 1H), 7.79-7.86(m , 2H), 7.88-7.93(m, 2H), 8.09(s, 1H), 9.77(brs, 1H), 10.63(s, 1H), 12.86(brs, 1H). HRMS(ESI);C20H24N5O3S[M+H] + Calculated value: 414.1595, measured value: 414.1594.

[0891] 1-Methyl-N-(5-phenyl-1H-indazol-3-yl)piperidine-4-carboxamide hydrochloride (Compound 93) [(I), R1 = phenyl, R7 = R2 = 1-methylpiperidine, R3 = H]

[0892] [ka]

[0893] 0.033 g (93% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.86-1.99(m, 2H), 2.08-2.18(m, 2H), 2.69-2.7 6(m, 1H), 2.77-2.80(m, 3H), 2.95-3.05(m, 2H), 3.45-3.54(m, 2H), 7.31-7. 41(m, 1H), 7.44-7.50(m, 2H), 7.51-7.56(m, 1H), 7.59-7.68(m, 3H), 7.95-8 .05(m, 1H), 9.66-10.03(m, 1H), 10.53-10.62(m, 1H), 12.65-13.06(m, 1H). HRMS(ESI);C20H23N4O[M+H] + Calculated value: 335.1867, measured value: 335.1865.

[0894] N-{5-[2-chloro-5-(trifluoromethyl)phenyl]-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide hydrochloride (Compound 94) [(I), R1 = 2-chloro-5-(trifluoromethyl)phenyl, R2 = 1-methylpiperidine, R3 = H]

[0895] [ka]

[0896] 0.031 g (90% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.82-1.93(m, 2H), 2.04-2.11(m, 2H), 2.71(t, J= 11.90Hz, 1H), 2.76(d, J=4.42Hz, 3H), 2.93-3.03(m, 2H), 3.45-3.52(m, 2H), 7.41-7.46(m, 1H), 7.55(d, J=8.69Hz, 1H), 7.72-7.76(m, 1H), 7.77-7.80(m, 1H), 7.83-7.93(m, 2H), 9.61(brs, 1H), 10.58-10.65(m, 1H), 12.90(brs, 1H). HRMS(ESI);C21H21ClF3N4O[M+H] + Calculated value: 437.1351, measured value: 437.1359.

[0897] N-[5-(2-fluoropyridin-3-yl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide dihydrochloride (Compound 95) [(I), R1 = 2-fluoropyridin-3-yl, R2 = 1-methylpiperidine, R3 = H]

[0898] [ka]

[0899] 0.035 g (92% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.84-1.98 (m, 2H), 2.09 (d, J=13.57Hz, 2H), 2.68 -2.74(m, 1H), 2.77(d, J=4.42Hz, 3H), 2.94-3.06(m, 2H), 3.47-3.52(m, 2H), 7.46-7.51(m, 1H), 7.57(s, 2H), 8.00(s, 1H), 8.09(ddd, J=9.95, 7.66, 1.75H z, 1H), 8.23(d, J=5.19Hz, 1H), 9.73(brs, 1H), 10.64(s, 1H), 12.90(brs, 1H). HRMS(ESI); CHFNO[M+H] + Calculated value: 354.1725, measured value: 354.1729.

[0900] N-[5-(2-Methoxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 96) [(I), R1 = 2-methoxyphenyl, R2 = 1-methylpiperidine, R3 = H]

[0901] [ka]

[0902] 0.034 g (94% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.80-1.96(m, 2H), 2.08(d, J=14.03Hz, 2H), 2.71(tt, J=12.16, 3.85 Hz, 1H), 2.77(d, J=4.73Hz, 3H), 2.87-3.05(m, 2H), 3.48(d, J=10.68Hz, 2H), 3.75(s, 3H), 7.03( td, J=7.44, 0.69Hz, 1H), 7.11(d, J=8.08Hz, 1H), 7.26(dd, J=7.47, 1.37Hz, 1H), 7.34(ddd, J=8. 20, 7.50, 1.68Hz, 1H), 7.45(s, 2H), 7.74(s, 1H), 9.63(brs, 1H), 10.52(s, 1H), 12.72(brs, 1H). HRMS(ESI);C21H25N4O2[M+H] + Calculated value: 365.972, measured value: 365.1968.

[0903] N-[5-(2,3-dichlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 97) [(I), R1 = 2,3-dichlorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0904] [ka]

[0905] 0.028 g (91% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.77-1.94(m, 2H), 2.07(d, J=14.00Hz, 2H), 2.71(tt, J=1 2.32, 3.55Hz, 1H), 2.76(d, J=4.58Hz, 3H), 2.88-3.04(m, 2H), 3.44-3.52(m, 2H), 7.36 -7.42(m, 2H), 7.45(t, J=7.80Hz, 1H), 7.53(d, J=8.69Hz, 1H), 7.67(dd, J=7.93, 1.68 Hz, 1H), 7.80 (dd, J=1.37, 0.61Hz, 1H), 9.62 (brs, 1H), 10.62 (s, 1H), 12.87 (brs, 1H). HRMS(ESI);C20H21Cl2N4O[M+H] + Calculated value: 403.1087, measured value: 403.1088.

[0906] N-[5-(2-chloro-6-methoxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 98) [(I), R1 = 2-chloro-6-methoxyphenyl, R2 = 1-methylpiperidine, R3 = H]

[0907] [ka]

[0908] 0.029 g (95% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.76-1.93(m, 2H), 2.06(d, J=14.64Hz, 2H), 2.69(tt, J=12. 09, 3.47Hz, 1H), 2.76(d, J=4.73Hz, 3H), 2.91-3.04(m, 2H), 3.44-3.52(m, 2H), 3.67(s, 3 H), 7.10(d, J=8.39Hz, 1H), 7.12-7.18(m, 2H), 7.34-7.41(m, 1H), 7.47(d, J=8.54Hz, 1H) ), 7.59(dd, J=1.37, 0.76Hz, 1H), 9.61(brs, 1H), 10.53(s, 1H), 12.76(d, J=6.41Hz, 1H). HRMS(ESI);C21H24ClN4O2[M+H]+ Calculated value: 399.1583, measured value: 399.1582.

[0909] N-[5-(2,3-difluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 99) [(I), R1 = 2,3-difluorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0910] [ka]

[0911] 0.039 g (93% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.82-1.96(m, 2H), 2.06-2.18(m, 2H), 2.68-2.75(m, 1H), 2.77(d, J=4.58Hz, 3H), 2.90-3.04(m, 2H), 3.48(d, J=12) .35Hz, 2H), 7.27-7.38(m, 2H), 7.39-7.47(m, 1H), 7.51-7.59(m, 2H), 7 .95-8.02(m, 1H), 9.64(brs, 1H), 10.59-10.67(m, 1H), 12.89(brs, 1H). HRMS(ESI);C20H21F2N4O[M+H] + Calculated value: 371.1678, measured value: 371.1687.

[0912] 1-Methyl-N-{5-[3-(methylsulfonyl)phenyl]-1H-indazol-3-yl}piperidine-4-carboxamide hydrochloride (Compound 100) [(I), R1 = 3-(methylsulfonyl)phenyl, R2 = 1-methylpiperidine, R3 = H]

[0913] [ka]

[0914] 0.025 g (88% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.81-1.99 (m, 2H), 2.12 (m, J=13.57Hz, 2H), 2.65-2.8 2(m, 4H), 2.95-3.08(m, 2H), 3.30(s, 3H), 3.50(d, J=10.07Hz, 2H), 7.59(d, J=8.6 9Hz, 1H), 7.69-7.80(m, 2H), 7.90(dd, J=7.24, 1.14Hz, 1H), 7.99(d, J=7.93Hz, 1H ), 8.10(s, 1H), 8.12(s, 1H), 9.67(brs, 1H), 10.22-11.04(m, 1H), 12.88(brs, 1H). HRMS(ESI);C21H25N4O3S[M+H] + Calculated value: 413.1642, measured value: 413.1653.

[0915] N-[5-(3-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 101) [(I), R1 = 3-fluorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0916] [ka]

[0917] 0.031 g (89% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.86-1.98(m, 2H), 2.12(m, J=14.18Hz, 2H), 2.73(m, J=3.97Hz, 1H), 2.77-2.81(m, 3H), 2.94-3.05(m, 2H), 3.50(m, J =12.51Hz, 2H), 7.14-7.22(m, 1H), 7.41-7.57(m, 4H), 7.64-7.72(m, 1H) , 8.01-8.12(m, 1H), 9.68(brs, 1H) 10.48-10.79(m, 1H), 12.82(brs, 1H). HRMS (ESI); C20H20Cl2N3O [M+H] + Calculated value: 388.0978, measured value: 388.0981.

[0918] N-[5-(2-hydroxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 102) [(I), R1 = 2-hydroxyphenyl, R2 = 1-methylpiperidine, R3 = H]

[0919] [ka]

[0920] 0.030 g (95% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.83-1.95(m, 2H), 2.05-2.13(m, 2H), 2.68-2.73(m, 1H), 2.77(d, J=4.73Hz , 3H), 2.92-3.04(m, 2H), 3.46-3.51(m, 2H), 6.88(td, J=7.44, 0.99Hz, 1H), 6.94(d, J=8.08Hz, 1H), 7.15 (td, J=7.70, 1.68Hz, 1H), 7.18-7.27(m, 1H), 7.28-7.33(m, 1H), 7.44(d, J=8.85Hz, 1H), 7.53(dd, J=8.6 9, 1.22Hz, 1H), 7.78-7.86(m, 1H), 9.45(brs, 1H), 9.66(brs, 1H), 10.45-10.54(m, 1H), 12.69(brs, 1H). HRMS(ESI);C20H23N4O2[M+H] + Calculated value: 351.1816, measured value: 351.1811.

[0921] N-[5-(biphenyl-2-yl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 103) [(I), R1 = biphenyl-2-yl, R2 = 1-methylpiperidine, R3 = H]

[0922] [ka]

[0923] 0.038 g (95% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.79-1.93(m, 2H), 1.97-2.13(m, 2H), 2.64-2.72(m, 1H), 2.74-2.82(m, 3H), 2.92-3.05(m, 2H), 3.47-3.53(m, 2H), 6.84-6.98(m, 1H), 7.06-7.13(m, 2H), 7.15-7.27(m, 4H), 7.38-7.51(m , 4H), 7.60-7.67(m, 1H), 9.71(brs, 1H), 10.47(s, 1H), 12.65(brs, 1H). HRMS(ESI);C26H27N4O[M+H] + Calculated value: 411.2180, measured value: 411.2183.

[0924] 1-Methyl-N-{5-[2-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-4-carboxamide hydrochloride (Compound 104) [(I), R1 = 2-(trifluoromethyl)phenyl, R2 = 1-methylpiperidine, R3 = H]

[0925] [ka]

[0926] 0.039 g (99% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.81-1.92(m, 2H), 2.00-2.15(m, 2H), 2.65-2.7 3(m, 1H), 2.75(d, J=4.58Hz, 3H), 2.85-3.03(m, 2H), 7.28(d, J=8.69Hz, 1H), 7.43(d, J=7.47Hz, 1H), 7.47-7.51(m, 1H), 7.59-7.65(m, 1H), 7.68-7.76(m , 2H), 7.84 (d, J=7.78Hz, 1H), 9.68 (brs, 1H), 10.58 (s, 1H), 12.85 (brs, 1H). HRMS(ESI);C21H22F3N4O[M+H] + Calculated value: 403.1740, measured value: 403.1736.

[0927] N-[5-(2,6-difluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 105) [(I), R1 = 2,6-difluorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0928] [ka]

[0929] 0.022 g (98% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.82-1.94(m, 2H), 2.04-2.13(m, 2H), 2.71(t, J= 12.12Hz, 1H), 2.75-2.79(m, 2H), 2.93-3.05(m, 2H), 3.47(d, J=10.98Hz, 3H) , 7.16-7.27(m, 2H), 7.38(d, J=8.85Hz, 1H), 7.42-7.52(m, 1H), 7.56(d, J=8. 69Hz, 1H), 7.86(s, 1H), 9.64(brs, 1H), 10.59-10.64(m, 1H), 12.89(brs, 1H). HRMS(ESI);C20H21F2N4O[M+H] + Calculated value: 371.1678, measured value: 371.1679.

[0930] N-[5-(2,4-dichlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 106) [(I), R1 = 2,4-dichlorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0931] [ka]

[0932] After completion of the reaction, the crude material was purified by flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:01) to give 0.028 g (75% yield). 1H NMR (500MHz, DMSO-d6) δppm1.61-1.72(m, 2H), 1.79(d, J=11.59Hz, 2H), 1.88(t, J=10.75Hz, 2H), 2.16(s, 3H), 2.41(brs, 1H), 2.81(d, J=11.29Hz, 2 H), 7.37(dd, J=8.62, 1.60Hz, 1H), 7.43-7.46(m, 1H), 7.48-7.55(m, 2H), 7.73(d, J=2.14Hz, 1H), 7.78-7.80(m, 1H), 10.36(s, 1H), 12.78(brs, 1H). HRMS (ESI); C20H21Cl2N4O [M+H] + Calculated value: 403.1087, measured value: 403.1087.

[0933] N-[5-(4-amino-2-chlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide dihydrochloride (Compound 107) [(I), R1 = 4-amino-2-chlorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0934] [ka]

[0935] 0.055 g (99% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.82-1.95(m, 2H), 2.03-2.11(m, 2H), 2.66-2.73(m, 1 H), 2.77(d, J=4.73Hz, 3H), 2.93-3.04(m, 2H), 3.14-3.25(m, 2H), 6.83(d, J=6.71 Hz, 1H), 6.96(brs, 1H), 7.18-7.20(m, 1H), 7.33-7.38(m, 1H), 7.46(d, J=8.69Hz, 1H), 7.68-7.76(m, 1H), 9.77(brs, 1H), 10.50-10.58(m, 1H), 12.58-13.12(m, 1H). HRMS(ESI);C20H23ClN5O[M+H] + Calculated value: 384.1586, measured value: 384.1582.

[0936] 1-Methyl-N-[5-(2,4,6-trichlorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 108) [(I), R1 = 2,4,6-trichlorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0937] [ka]

[0938] 0.021 g (79% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.78-2.01(m, 2H), 2.04-2.17(m, 2H), 2.70(t, J=11.97Hz, 1H), 2.76(d, J=4.88Hz, 3H), 2.88-3.02(m, 2H), 3.47(d, J=11) .44Hz, 2H), 7.19(dd, J=8.69, 1.53Hz, 1H), 7.55(d, J=8.69Hz, 1H), 7.76( s, 1H), 7.81(s, 2H), 9.63(brs, 1H), 10.52-10.66(m, 1H), 12.89(brs, 1H). HRMS (ESI); C20H20Cl3N4O [M+H] + Calculated value: 437.0697, measured value: 437.0691.

[0939] N-[5-(4-carbamoylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 109) [(I), R1 = 4-carbamoylphenyl, R2 = 1-methylpiperidine, R3 = H]

[0940] [ka]

[0941] 0.032 g (92% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.86-2.06 (m, 2H), 2.12 (d, J=13.57Hz, 2H), 2.69-2.7 6(m, 1H), 2.76-2.81(m, 3H), 2.92-3.06(m, 2H), 3.50(d, J=11.90Hz, 2H), 7.39(br s, 1H), 7.55(d, J=8.69Hz, 1H), 7.69-7.75(m, 3H), 7.97(d, J=8.54Hz, 2H), 8.02(b rs, 1H), 8.06-8.13(m, 1H), 9.69(brs, 1H), 10.56-10.64(m, 1H), 12.95(brs, 1H). HRMS(ESI);C21H24N5O2[M+H] + Calculated value: 378.1925, measured value: 378.1923.

[0942] N-[5-(4-cyanophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 110) [(I), R1 = 4-cyanophenyl, R2 = 1-methylpiperidine, R3 = H]

[0943] [ka]

[0944] 0.027 g (88% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.87-2.00 (m, 2H), 2.11 (d, J=13.42Hz, 2H), 2. 69-2.76(m, 1H), 2.76-2.80(m, 3H), 2.90-3.06(m, 2H), 7.57(d, J=8.69Hz, 1 H), 7.73(dd, J=8.77, 1.45Hz, 1H), 7.84(d, J=6.86Hz, 2H), 7.94(d, J=6.86 Hz, 2H), 8.14(s, 1H), 9.79(brs, 1H), 10.59-10.75(m, 1H), 12.90(brs, 1H). HRMS(ESI);C21H22N5O[M+H] + Calculated value: 360.1819, Measured value: 360.1814

[0945] N-[5-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 111) [(I), R1 = 2-chloro-4-hydroxyphenyl, R2 = 1-methylpiperidine, R3 = H]

[0946] [ka]

[0947] 0.029 g (75% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.83-1.92(m, 2H), 2.04-2.09(m, 2H), 2.68-2.73(m, 1H), 2.76(d, J=4.58Hz, 3H), 2.94-2.99(m, 2H), 6.83(dd, J=8.24, 2.44Hz, 1H), 6 .94(d, J=2.44Hz, 1H), 7.45-7.49(m, 2H), 7.34-7.35(m, 1H), 7.70(dd, J=1.53, 0 .76Hz, 1H), 9.65(brs, 1H), 9.98(brs, 1H), 10.36-10.76(m, 1H), 12.77(brs, 1H). HRMS(ESI);C20H22ClN4O2[M+H] + Calculated value: 385.1426, measured value: 385.1427.

[0948] N-[5-(4-amino-3-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 112) [(I), R1 = 4-amino-3-fluorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0949] [ka]

[0950] 0.031 g (99% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.74-1.83(m, 2H), 1.89-1.99(m, 2H), 2.02-2.14(m, 2H), 2.70-2.78(m, 4H), 2.91-3.03(m, 2H), 6.95-6.03(m, 1H), 7. 25-7.38(m, 1H), 7.44-7.49(m, 1H), 7.54-7.86(m, 1H), 7.83(dd, J=9.00, 1.37Hz, 1H), 7.89(s, 1H), 9.87(brs, 2H), 10.54(s, 1H), 12.77(brs, 1H). HRMS(ESI); CHFNO[M+H] + Calculated value: 368.1881, measured value: 368.1882.

[0951] N-[5-(4-cyano-2-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 113) [(I), R1 = 4-cyano-2-methylphenyl, R2 = 1-methylpiperidine, R3 = H]

[0952] [ka]

[0953] 0.024 g (94% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.83-1.92(m, 2H), 2.01-2.17(m, 2H), 2.28(s, 3H), 2.7 0(m, 1H), 2.76(d, J=4.58Hz, 3H), 2.89-3.02(m, 2H), 3.45-3.50(m, 2H), 7.36(dd, J =8.62, 1.60Hz, 1H), 7.41(d, J=7.93Hz, 1H), 7.53(d, J=8.69Hz, 1H), 7.70-7.77(m, 2H), 7.81(d, J=1.22Hz, 1H), 9.70(brs, 1H), 10.51-10.69(m, 1H), 12.86(brs, 1H). HRMS(ESI);C22H24N5O[M+H] + Calculated value: 374.1976, measured value: 374.1976.

[0954] N-[5-(2,6-dimethylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide trifluoroacetate (Compound 114) [(I), R1 = 2,6-dimethylphenyl, R2 = 1-methylpiperidine, R3 = H]

[0955] [ka]

[0956] 0.066 g (90% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.75-1.88(m, 2H), 1.97(s, 6H), 2.03-2.17(m, 2H), 2.68(m, 1H), 2.77(d, J=4.58Hz, 3H), 2.9 1-3.03(m, 2H), 3.42-3.49(m, 2H), 7.05-7.20(m, 5H), 7.40-7.58(m, 2H), 9.19(brs, 1H), 10.52(s, 1H), 12.75(brs, 1H). HRMS(ESI);C22H27N4O[M+H] + Calculated value: 363.2180, measured value: 363.2176.

[0957] N-[5-(2-fluoro-5-nitrophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 115) [(I), R1 = 2-fluoro-5-nitrophenyl, R2 = 1-methylpiperidine, R3 = H]

[0958] [ka]

[0959] 0.047 g (98% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.83-1.97(m, 2H), 2.04-2.14(m, 2H), 2.68-2.75(m, 1H), 2.77(d, J=4.88Hz, 3H), 2.91-3.02(m, 2H), 3.45-3.5 2(m, 2H), 7.60-7.63(m, 2H), 7.65(t, J=9.38Hz, 1H), 8.06(s, 1H), 8.26-8.36(m, 2H), 9.70(brs, 1H), 10.63-10.70(m, 1H), 12.95(brs, 1H). HRMS(ESI);C20H21FN5O3[M+H] + Calculated value: 398.1623, measured value: 398.1620.

[0960] N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide trifluoroacetate (Compound 116) [(I), R1 = 2-chloro-5-cyanophenyl, R2 = 1-methylpiperidine, R3 = H]

[0961] [ka]

[0962] 0.035 g (91% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.77-1.90(m, 2H), 2.06-2.15(m, 2H), 2.71(m, 1H), 2.7 9(brs, 3H), 2.95-3.04(m, 2H), 3.48-351(m, 2H), 7.42(dd, J=8.85, 1.22Hz, 1H), 7. 55(d, J=8.54Hz, 1H), 7.81(d, J=8.24Hz, 1H), 7.85(s, 1H)7.89(dd, J=8.24, 1.98Hz , 1H), 7.93(d, J=1.98Hz, 1H), 9.20(brs, 1H), 10.58-10.66(m, 1H), 12.89(brs, 1H). HRMS(ESI);C21H21ClN5O[M+H] + Calculated value: 394.1429, measured value: 394.1435.

[0963] N-[5-(5-carbamoyl-2-chlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide trifluoroacetate (Compound 117) [(I), R1 = 5-carbamoyl-2-chlorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0964] [ka]

[0965] 0.058 g (77% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.77-1.91(m, 2H), 2.06-2.18(m, 2H), 2.70(m, 1H), 2.79( d, J=4.42Hz, 3H), 2.94-3.03(m, 2H), 3.49(d, J=11.74Hz, 2H), 7.43(dd, J=8.54, 1.22 Hz, 1H), 7.50 (s, 1H), 7.54 (d, J = 8.54 Hz, 1H), 7.82 (s, 1H), 7.88 (dd, J = 8.39, 2.14 Hz, 1H), 7.92 (d, J = 1.98 Hz, 1H), 8.12 (s, 1H), 9.20 (brs, 1H), 10.61 (s, 1H), 12.86 (s, 1H). HRMS (ESI); calculated for CHClNO [M+H]: + 412.1535, Actual value: 412.1537.

[0966] N-[5-(2-fluoro-4-formylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 118) [(I), R1 = 2-fluoro-4-formylphenyl, R2 = 1-methylpiperidine, R3 = H]

[0967] [ka]

[0968] 0.024 g (90% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.85-1.98(m, 2H), 2.04-2.15(m, 2H), 2.73(m, 1H) ), 2.77(d, J=4.58Hz, 3H), 2.94-3.04(m, 2H), 3.49(d, J=11.29Hz, 2H), 7.57-7 .60(m, 2H), 7.79(m, 1H), 7.83(d, J=10.68Hz, 1H), 7.88(dd, J=7.78, 1.37Hz, 1 H), 8.06(s, 1H), 9.63(brs, 1H), 10.05(s, 1H), 10.66(s, 1H), 12.92(brs, 1H). HRMS(ESI);C21H22FN4O2[M+H] + Calculated value: 381.1722, measured value: 378.1718.

[0969] N-[5-(2-fluoro-4-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 119) [(I), R1 = 2-fluoro-4-methylphenyl, R2 = 1-methylpiperidine, R3 = H]

[0970] [ka]

[0971] 0.022 g (68% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.82-1.95(m, 2H), 2.06-2.15(m, 2H), 2.36(s, 3H), 2.72(m, 1H), 2.77(d, J=4.88Hz, 2H), 2.94-3.06(m, 1H), 3.48(d. HRMS(ESI);C21H24FN4O[M+H] + Calculated value: 367.1929, measured value: 367.1922.

[0972] N-[5-(2,6-difluoro-4-methoxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 120) [(I), R1 = 2,6-difluoro-4-methoxyphenyl, R2 = 1-methylpiperidine, R3 = H]

[0973] [ka]

[0974] 0.013 g (75% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.83-1.97(m, 2H), 2.05-2.13(m, 2H), 2.71(m, 1H), 2.77(d, J=4.73Hz, 3H), 2.94-3.04(m, 2H), 3.48(d, J=10.68Hz, 2 H), 3.83(s, 3H), 6.82-6.89(m, 2H), 7.33(d, J=8.54Hz, 1H), 7.53(d, J=8.69Hz, 1H), 7.79(s, 1H), 9.60(brs, 1H), 10.59(s, 1H), 12.85(brs, 1H). HRMS(ESI);C21H23F2N4O2[M+H] + Calculated value: 401.1784, measured value: 401.1778.

[0975] 1-Methyl-N-[5-(1H-pyrazol-4-yl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 121) [(I), R1 = 1H-pyrazol-4-yl, R2 = 1-methylpiperidine, R3 = H]

[0976] [ka]

[0977] 0.036 g (88% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.83-2.00(m, 2H), 2.08-2.14(m, 2H), 2.75-2.81(m, 4H), 2.90-3.06(m, 2H), 7.44(d, J=8.5 4Hz, 1H), 7.60(dd, J=8.62, 1.14Hz, 1H), 7.83(s, 1H), 7.96-8.01(m, 2H), 9.72(brs, 1H), 10.44(s, 1H), 12.69(brs, 1H). HRMS(ESI);C17H21N6O[M+H] + Calculated value: 325.1772, measured value: 325.1772.

[0978] 1-Methyl-N-[5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 122) [(I), R1 = 1-methyl-1H-pyrazol-4-yl, R2 = 1-methylpiperidine, R3 = H]

[0979] [ka]

[0980] 0.045 g (87% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.85-2.02(m, 2H), 2.04-2.16(m, 2H), 2.67-2.75(m, 1H), 2.77(d, J=4.73Hz, 3H), 2.93-3.07(m, 2H), 3.87(s, 3) H), 7.43(d, J=8.69Hz, 1H), 7.55(dd, J=8.69, 1.37Hz, 1H), 7.74-7.84(m, 2H), 8.05(s, 1H), 9.85(brs, 1H), 10.46(s, 1H), 12.69(brs, 1H). HRMS(ESI);C18H23N6O[M+H] + Calculated value: 339.1928, measured value: 339.1926.

[0981] 1-Methyl-N-[5-(2,4,6-trifluorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 123) [(I), R1 = 2,4,6-trifluorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0982] [ka]

[0983] 0.005 g (71% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.80-1.96(m, 2H), 2.05-2.13(m, 2H), 2.71(m, 1H), 2.77(d, J=4.73Hz, 3H), 2.93-3.03(m, 2H), 3. 48(d, J=10.83Hz, 2H), 7.27-7.41(m, 3H), 7.56(d, J=8.54Hz, 1H), 7.84(s, 1H), 9.59(brs, 1H), 10.62(s, 1H), 12.90(brs, 1H). HRMS(ESI);C20H20F3N4O[M+H] + Calculated value: 389.1584, measured value: 389.1585.

[0984] N-[5-(2,4-difluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 124) [(I), R1 = 2,4-difluorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0985] [ka]

[0986] 0.037 g (84% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.83-1.96(m, 2H), 2.05-2.10(m, 2H), 2.72(m, 1H), 2.77(d, J=4.58Hz, 3H), 2.89-3.05(m, 2H), 3.48(d, J=12.96Hz, 2H), 7.21(td, J =8.50, 2.52Hz, 1H), 7.37(ddd, J=11.17, 9.19, 2.52Hz, 1H), 7.45-7.49(m, 1H), 7.54-7.60(m, 2H), 7.89(s, 1H), 9.66(brs, 1H), 10.61(s, 1H), 12.85(brs, 1H). HRMS(ESI);C20H21F2N4O[M+H] + Calculated value: 371.1678, measured value: 371.1677.

[0987] 1-Methyl-N-[5-(1H-pyrazol-3-yl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 125) [(I), R1 = 1H-pyrazol-3-yl, R2 = 1-methylpiperidine, R3 = H]

[0988] [ka]

[0989] 0.022 g (88% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.84-2.07(m, 2H), 2.12(d, J=13.57Hz, 2H), 2.73(m, 1H), 2.78(t, J=11.97Hz, 3H), 2.95-3.08(m, 2H), 6.60 -6.66(m, 1H), 7.47(d, J=8.85Hz, 1H), 7.72(s, 1H), 7.80(d, J=8.69Hz, 1H), 8.11(s, 1H), 9.72(brs, 1H), 10.50(s, 1H), 12.75(brs, 1H). HRMS(ESI);C17H21N6O[M+H] + Calculated value: 325.1772, measured value: 328.1769.

[0990] 1-Methyl-N-[5-(2,4,5-trifluorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 126) [(I), R1 = 2,4,5-trifluorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0991] [ka]

[0992] 0.030 g (93% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.81-2.04(m, 2H), 2.04-2.23(m, 2H), 2.72(m, 1H), 2.77(d, J=4.58Hz, 3H), 2.86-3.07(m, 2H), 3.49(d, J=12. 51Hz, 2H), 7.49(d, J=8.39Hz, 1H), 7.54(d, J=8.69Hz, 1H), 7.60-7.73(m, 2H), 7.93(s, 1H), 9.65(brs, 1H), 10.62(s, 1H), 12.88(brs, 1H). HRMS(ESI);C20H20F3N4O[M+H] + Calculated value: 389.1584, measured value: 389.1590.

[0993] 1-Methyl-N-{5-[2,4,6-trifluoro-3-(propan-2-yloxy)phenyl]-1H-indazol-3-yl}piperidine-4-carboxamide hydrochloride (Compound 127) [(I), R1 = 2,4,6-trifluoro-3-(propan-2-yloxy)phenyl, R2 = 1-methylpiperidine, R3 = H]

[0994] [ka]

[0995] 0.044 g (96% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.29(d, J=6.10Hz, 6H), 1.77-2.04(m, 2H), 2.04-2.21(m, 2H), 2.71(m, 1H), 2.77(d, J=4.88Hz, 3H), 2.88-3.05(m, 2H) ), 3.48(d, J=11.90Hz, 2H), 4.35(m, 1H), 7.32-7.45(m, 2H), 7.56(d, J=8.69Hz, 1H), 7.85(s, 1H), 9.62(brs, 1H), 10.62(s, 1H), 12.90(brs, 1H). HRMS(ESI);C23H26F3N4O2[M+H] + Calculated value: 447.2003, measured value: 447.20.

[0996] 1-Methyl-N-[5-(2,3,4-trifluorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 128) [(I), R1 = 2,3,4-trifluorophenyl, R2 = 1-methylpiperidine, R3 = H]

[0997] [ka]

[0998] 0.051 g (97% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.84-1.96(m, 2H), 2.06-2.19(m, 2H), 2.72(m, 1H), 2.77(d, J=4.58Hz, 3H), 2.94-3.07(m, 2H), 3.43-3.54(m, 2H), 7.34-7.47(m, 2H), 7.49(d, J=8.85Hz, 1H), 7.56(d, J=8.69Hz, 1H), 7.91-8.00(m, 1H), 9.67(brs, 1H), 10.64(s, 1H), 12.90(brs, 1H). HRMS(ESI);C20H20F3N4O[M+H] + Calculated value: 389.1584, measured value: 389.1585.

[0999] N-[5-(4-fluoro-2-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide trifluoroacetate (Compound 129) [(I), R1 = 4-fluoro-2-methylphenyl, R2 = 1-methylpiperidine, R3 = H]

[1000] [ka]

[1001] 0.034 g (88% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.77-1.92(m, 2H), 2.04-2.13(m, 2H), 2.22(s, 3H), 2.70(m, 1H)2. 79(d, J=4.58Hz, 3H), 2.93-3.04(m, 2H), 3.49(d, J=12.05Hz, 2H), 7.09(td, J=8.54, 2.75Hz, 1 H), 7.17(dd, J=10.14, 2.67Hz, 1H), 7.23(dd, J=8.39, 6.25Hz, 1H), 7.30(dd, J=8.54, 1.37Hz, 1H), 7.50(d, J=8.54Hz, 1H), 7.64-7.73(m, 1H), 9.19(brs, 1H), 10.56(s, 1H), 12.77(brs, 1H). HRMS(ESI);C21H24FN4O[M+H] + Calculated value: 367.1929, measured value: 367.1929.

[1002] N-[5-(4-amino-2-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide dihydrochloride (Compound 130) [(I), R1 = 4-amino-2-methylphenyl, R2 = 1-methylpiperidine, R3 = H]

[1003] [ka]

[1004] 0.028 g (91% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.85-1.95(m, 2H), 2.03-2.11(m, 2H), 2.25(s, 3H), 2.70(m, 1H), 2.75(d, J=4.27Hz, 3H), 2.92-3.03(m, 2 H), 7.15-7.25(m, 2H), 7.27-7.34(m, 2H), 7.50(d, J=8.69Hz, 1H), 7.65-7.76(m, 1H), 9.93(brs, 2H), 10.59(s, 1H), 12.81(brs, 1H). HRMS(ESI);C21H26N5O[M+H] + Calculated value: 364.2132, measured value: 364.2133.

[1005] 1-Methyl-N-[5-(2,4,6-trifluoro-3-methoxyphenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 131) [(I), R1 = 2,4,6-trifluoro-3-methoxyphenyl, R2 = 1-methylpiperidine, R3 = H]

[1006] [ka]

[1007] 0.037 g (94% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.78-1.97(m, 2H), 2.04-2.18(m, 2H), 2.72(m, 1H), 2.77(d, J=4.58Hz, 3H), 2.91-3.05(m, 2H), 3.48(d, J=1 2.05Hz, 2H), 3.93(s, 3H), 7.32-7.44(m, 2H), 7.56(d, J=8.69Hz, 1H), 7.83-7.91(m, 1H), 9.66(brs, 1H), 10.63(s, 1H), 12.91(brs, 1H). HRMS(ESI);C21H22F3N4O2[M+H] + Calculated value: 419.1690, measured value: 419.1698.

[1008] N-[5-(2,3-difluoro-4-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 132) [(I), R1 = 2,3-difluoro-4-methylphenyl, R2 = 1-methylpiperidine, R3 = H]

[1009] [ka]

[1010] 0.026 g (79% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.83-1.96(m, 2H), 2.05-2.15(m, 2H), 2.33(m, 3H), 2.72(m, 1H), 2.77(d, J=4.42Hz, 3H), 2.92-3.04(m, 2 H), 3.48(d, J=11.44Hz, 2H), 7.15-7.27(m, 2H), 7.49-7.56(m, 2H), 7.92-7.98(m, 1H), 9.67(brs, 1H), 10.61(s, 1H), 12.86(brs, 1H). HRMS(ESI);C21H23F2N4O[M+H] + Calculated value: 385.1835, measured value: 385.1835.

[1011] N-[5-(2-chloro-4-fluoro-3-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 133) [(I), R1 = 2-chloro-4-fluoro-3-methylphenyl, R2 = 1-methylpiperidine, R3 = H]

[1012] [ka]

[1013] 0.029 g (74% yield) was obtained. 1H NMR (500MHz, DMSO-d6) δppm1.79-1.93(m, 2H), 2.02-2.12(m, 2H), 2.34(m, 3H), 2.70(m, 1H), 2.76(d, J=4.58Hz, 3H), 2.92-3.05(m, 2H), 3.47(d, J=11. 29Hz, 2H), 7.28-7.29(m, 2H), 7.34(dd, J=8.62, 1.45Hz, 1H), 7.50(d, J=8.8 5Hz, 1H), 7.72-7.81(m, 1H), 9.65(brs, 1H), 10.59(s, 1H), 12.83(brs, 1H). HRMS(ESI);C21H23ClFN4O[M+H] + Calculated value: 401.1539, measured value: 401.1533.

[1014] N-[5-(3-cyano-2,6-difluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide (Compound 134) [(I), R1 = 3-cyano-2,6-difluorophenyl, R2 = 1-methylpiperidine, R3 = H]

[1015] [ka]

[1016] After completion of the reaction, the crude material was purified by flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.1) to give 0.051 g (82% yield). 1 H NMR (500MHz, DMSO-d6) δppm1.61-1.71(m, 2H), 1.79(d, J=12.66Hz, 2H), 1.82-1.91(m, 2H), 2.15(s, 3H), 2.40(m, 1H), 2.80(d, J=11.29Hz, 2H), 7.41( d, J=8.69Hz, 1H), 7.49(t, J=8.24Hz, 1H), 7.58(d, J=8.69Hz, 1H), 7.93(s, 1H), 8.06(ddd, J=8.66, 7.44, 6.02Hz, 1H), 10.40(s, 1H), 12.89(brs, 1H). HRMS(ESI);C21H20F2N5O[M+H] +Calculated value: 396.1631, measured value: 396.1650.

[1017] N-[5-(3-cyano-4-hydroxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 135) [(I), R1 = 3-cyano-4-hydroxyphenyl, R2 = 1-methylpiperidine, R3 = H]

[1018] [ka]

[1019] 0.032 g (98% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.88-2.03(m, 2H), 2.11-2.19(m, 2H), 2.76(m, 1H), 2.81(d, J =4.58Hz, 3H), 2.97-3.09(m, 2H), 3.53(d, J=11.59Hz, 2H), 7.17(d, J=8.69Hz, 1H), 7.54(d , J=8.69Hz, 1H), 7.65(d, J=8.69Hz, 1H), 7.79(dd, J=8.69, 2.29Hz, 1H), 7.86(d, J=2.13H) z, 1H), 7.94-8.00(m, 1H), 9.69(brs, 1H), 10.59(s, 1H), 11.24(brs, 1H), 12.81(brs, 1H). HRMS(ESI);C21H22N5O2[M+H] + Calculated value: 376.1768, measured value: 376.1776.

[1020] N-[5-(2-cyano-5-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 136) [(I), R1 = 2-cyano-5-fluorophenyl, R2 = 1-methylpiperidine, R3 = H]

[1021] [ka]

[1022] 0.052 g (87% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.83-2.04(m, 2H), 2.05-2.21(m, 2H), 2.73(m, 1H), 2.77(d, J=4.58Hz, 3H), 2.92-3.04(m, 2H), 3.49(d, J=11.59Hz, 2H), 7.46(td, J= 8.46, 2.59Hz, 1H), 7.53(dd, J=9.68, 2.52Hz, 1H), 7.55-7.63(m, 2H), 8.01(s, 1H) ), 8.06 (dd, J=8.69, 5.64Hz, 1H), 9.62 (brs, 1H), 10.68 (s, 1H), 12.97 (brs, 1H). HRMS(ESI);C21H21FN5O[M+H] + Calculated value: 378.1725, measured value: 378.1730.

[1023] N-[5-(2-chloro-5-nitrophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide trifluoroacetate (Compound 137) [(I), R1 = 2-chloro-5-nitrophenyl, R2 = 1-methylpiperidine, R3 = H]

[1024] [ka]

[1025] 0.023 g (72% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.76-1.92(m, 2H), 2.04-2.15(m, 2H), 2.71(m, 1H) , 2.79(d, J=4.58Hz, 3H), 2.93-3.06(m, 2H), 3.49(d, J=12.35Hz, 3H), 7.47(dd , J=8.69, 1.37Hz, 1H), 7.58(d, J=8.54Hz, 1H), 7.86-7.97(m, 2H), 8.18(m, 1H) , 8.25(dd, J=8.77, 2.82Hz, 1H), 9.19(brs, 1H), 10.65(s, 1H), 12.93(brs, 1H). HRMS (ESI); C20H21ClN5O3 [M+H] +Calculated value: 414.1328, measured value: 414.1323.

[1026] N-[5-(2,6-difluoro-4-hydroxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide trifluoroacetate (Compound 138) [(I), R1 = 2,6-difluoro-4-hydroxyphenyl, R2 = 1-methylpiperidine, R3 = H]

[1027] [ka]

[1028] To a solution of N-[5-(2,6-difluoro-4-methoxyphenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide (0.076 g, 0.118 mmol) in dry DCM (2 mL) cooled to −10° C., was added boron tribromide (1.0 M A DCM solution (0.47 mL, 0.47 mmol) was added dropwise. The resulting suspension was stirred at room temperature overnight and carefully basified with 33% aqueous ammonia (10 mL). The mixture was extracted with DCM (5 x 10 mL), and the combined organic phases were dried over anhydrous NaSO, filtered, and evaporated to dryness. The crude material was purified by preparative HPLC to give N-[5-(2,6-difluoro-4-hydroxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide (0.045 g, 76% yield) as the trifluoroacetate salt. 1 H NMR (500MHz, DMSO-d6) δppm1.79-1.94(m, 2H), 2.08-2.18(m, 2H), 2.74(m, 1H), 2.82(d, J=4.42Hz, 3H), 3.02(m, 2H), 3.53(d, J=12.20Hz, 2H), 6.60 (d, J=9.61Hz, 2H), 7.34(d, J=8.54Hz, 1H), 7.53(d, J=8.69Hz, 1H), 7.79( s, 1H), 8.97-9.49(m, 1H), 10.50(brs, 1H), 10.61(s, 1H), 12.85(brs, 1H). HRMS(ESI);C20H21F2N4O2[M+H]+ Calculated value: 387.1627, measured value: 387.1631.

[1029] Following this same method but using the appropriate intermediates, the following compounds were prepared:

[1030] 1-Methyl-N-[5-(2,4,6-trifluoro-3-hydroxyphenyl)-1H-indazol-3-yl]piperidine-4-carboxamide (Compound 139) [(I), R1 = 2,4,6-trifluoro-3-hydroxyphenyl, R2 = 1-methylpiperidine, R3 = H]

[1031] [ka]

[1032] 1-Methyl-N-[5-(2,4,6-trifluoro-3-methoxyphenyl)-1-trityl-1H-indazol-3-yl]piperidine-4-carboxamide. Purified by flash column chromatography (DCM / MeOH / 33% aqueous ammonia 90:10:0.1). 0.035 g (64% yield) was obtained. 1 H NMR (500MHz, DMSO-d6) δppm1.57-1.71(m, 2H), 1.78(d, J=11.13Hz, 2H), 1.86(t, J=10.90Hz, 2H), 2.15(s, 3H), 2.39(m, 1H), 2.80(d , J=11.13Hz, 2H), 7.24(t, J=9.76Hz, 1H), 7.33(d, J=8.85Hz, 1H), 7.52(d, J=8.54Hz, 1H), 7.82(s, 1H), 10.36(s, 1H), 12.80(s, 1H). HRMS(ESI);C20H20F3N4O2[M+H] + Calculated value: 405.1533, measured value: 405.1532.

[1033] Step 1d (Scheme 1)

[1034] [ka]

[1035] The compound was prepared following the same procedure as reported for step 1b (Scheme 1).

[1036] 5-(2,6-dichloro-phenyl)-1-trityl-1H-indazol-3-ylamine [(XII), R1 = 2,6-dichloro-phenyl, R9 = 1,1′,1″-methanetriyltribenzene]

[1037] [ka]

[1038] 5-Bromo-1-trityl-1H-indazol-3-ylamine and 2-(2,6-dichlorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane. Starting from flash column chromatography (hexane / EtOAc 70:30). Obtained 3.13 g (91% yield). 1 H NMR (500MHz, DMSO-d6) δppm5.71(s, 2H), 6.36(d, J=8.69Hz, 1H), 6.86(dd, J=8.77, 1.7 5Hz, 1H), 7.19-7.25(m, 3H), 7.27-7.34(m, 6H), 7.36-7.40(m, 7H), 7.52-7.58(m, 3H). HRMS(ESI);C32H24Cl2N3Na[M+H+Na] + Calculated value: 542.1161, measured value: 542.1164.

[1039] 3-(3-amino-1-trityl-1H-indazol-5-yl)-4-chloro-benzonitrile [(XII), R1 = 2-chloro-5-cyanophenyl, R9 = 1,1′,1″-methanetriyltribenzene]

[1040] [ka]

[1041] Starting from 5-bromo-1-trityl-1H-indazol-3-ylamine and (2-chloro-5-cyanophenyl)boronic acid, flash column chromatography (hexane / EtOAc 70:30) gave 0.750 g (85% yield). 1 H NMR (500MHz, DMSO-d6) δppm5.75(s, 2H), 6.36(d, J=9.00Hz, 1H), 7.12(dd, J=8.77, 1.75Hz, 1H), 7.20-7.25(m, 3H), 7.28-7.33(m, 7H), 7.35-7.39(m, 6H), 7.75-7.78(m, 1H), 7.82(d, J=1.98Hz, 2H), 7.88(d, J=1.98Hz, 1H). HRMS(ESI);C33H24ClN4Na[M+H+Na] + Calculated value: 533.1503, measured value: 533.1528.

[1042] 5-(2-chloro-6-fluorophenyl)-1-trityl-1H-indazol-3-amine [(XII), R1 = 2-chloro-6-fluorophenyl, R9 = 1,1′,1″-methanetriyltribenzene]

[1043] [ka]

[1044] Starting from 5-bromo-1-trityl-1H-indazol-3-ylamine and (2-chloro-6-fluorophenyl)boronic acid. Flash column chromatography (hexane / EtOAc 80:20). Obtained 0.27 g (48% yield). LCMS (ESI) m / z 504 (M+H). + .

[1045] Step 1e (Scheme 1)

[1046] [ka]

[1047] The compound was prepared following the same procedure as reported for step 1a (Scheme 1).

[1048] N-[5-(2,6-dichlorophenyl)-1-trityl-1H-indazol-3-yl]-3-oxocyclobutanecarboxamide [(XIII), R1 = 2,6-dichlorophenyl, R2 = 3-oxocyclobutane, R9 = 1,1′,1″-methanetriyltribenzene]

[1049] [ka]

[1050] Starting from 5-(2,6-dichlorophenyl)-1-trityl-1H-indazol-3-amine and 3-oxo-cyclobutanecarboxylic acid, flash column chromatography (hexane / EtOAc 70:30) gave 0.054 g (76% yield). 1 H NMR (500MHz, DMSO-d6) δppm3.26(m, 4H), 3.45(m, 1H), 6.48(d, J=8.85Hz, 1H), 6.94(d, J=8.69Hz, 1H), 7.23-7.38(m, 15H), 7.40(dd, J=8.46, 7.70Hz, 1H), 7.56(d, J=8.08Hz, 2H), 7.77(s, 1H), 10.87(s, 1H). HRMS(ESI);C37H28Cl2N3O2Na[M+H+Na] + Calculated value: 638.1372, measured value: 638.1383.

[1051] N-[5-(2-chloro-5-cyanophenyl)-1-trityl-1H-indazol-3-yl]-3-oxocyclobutanecarboxamide [(XIII), R1 = 2-chloro-5-cyanophenyl, R2 = 3-oxocyclobutane, R9 = 1,1′,1″-methanetriyltribenzene]

[1052] [ka]

[1053] Starting from 3-(3-amino-1-trityl-1H-indazol-5-yl)-4-chlorobenzonitrile and 3-oxo-cyclobutanecarboxylic acid. Flash column chromatography (hexane / EtOAc 70:30). Obtained 0.580 g (89% yield). 1 H NMR (500MHz, DMSO-d6) δppm3.24-3.32(m, 2H), 3.45(m, 1H), 6.48(d, J=8.85Hz, 1H), 7.16(d, J=8.85Hz, 1H), 7.24(d, J=7.47Hz, 6H), 7 .28-7.31(m, 3H), 7.34-7.37(m, 6H), 7.77(d, J=8.39Hz, 1H), 7.84(dd, J=8.24, 1.98Hz, 1H), 7.88(s, 1H), 7.93(s, 1H), 10.89(s, 1H). HRMS(ESI);C38H28ClN4O2Na[M+H+Na] + Calculated value: 629.1715, measured value: 629.1725.

[1054] N-[5-(2,6-dichlorophenyl)-1-trityl-1H-indazol-3-yl]-4-oxocyclohexanecarboxamide [(XIII), R1 = 2,6-dichlorophenyl, R2 = 4-oxocyclohexane, R9 = 1,1′,1″-methanetriyltribenzene]

[1055] [ka]

[1056] Starting from 5-(2,6-dichloro-phenyl)-1-trityl-1H-indazol-3-ylamine and 4-oxo-cyclohexanecarboxylic acid. Flash column chromatography (hexane / EtOAc 50:50). Obtained 0.121 g (49% yield). 1H NMR (500MHz, DMSO-d6) δppm1.73-1.92(m, 2H), 2.12(d, J=3.36Hz, 2H), 2.27( d, J=14.18Hz, 2H), 2.37-2.44(m, 2H), 2.93(m, 1H), 6.47(d, J=8.85Hz, 1H), 6. 94(d, J=8.54Hz, 1H), 7.28(dd, J=18.15, 7.47Hz, 9H), 7.32-7.38(m, 6H), 7.40 (dd, J=8.39, 7.78Hz, 1H), 7.55(d, J=8.08Hz, 2H), 7.68(s, 1H), 10.63(s, 1H). HRMS(ESI);C39H32Cl2N3O2Na[M+H+Na] + Calculated value: 666.1685, measured value: 666.1703.

[1057] N-[5-(2,6-dichlorophenyl)-1-trityl-1H-indazol-3-yl]tetrahydro-2H-pyran-4-carboxamide [(XIII), R1 = 2,6-dichlorophenyl, R2 = tetrahydro-2H-pyran, R9 = 1,1′,1″-methanetriyltribenzene]

[1058] [ka]

[1059] Starting from 5-(2,6-dichlorophenyl)-1-trityl-1H-indazol-3-ylamine and tetrahydro-2H-pyran-4-carboxylic acid, flash column chromatography (hexane / EtOAc 50:50) gave 0.058 g (68% yield). 1H NMR (500MHz, DMSO-d6) δppm1.56-1.67(m, 2H), 1.67-1.78(m, 2H), 2.71(tt, J=10. 98, 4.10Hz, 1H), 3.30(t, J=12.10Hz, 2H), 3.87(d, J=9.91Hz, 2H), 6.47(d, J=8.85H) z, 1H), 6.94(d, J=8.54Hz, 1H), 7.21-7.28(m, 6H), 7.28-7.32(m, 3H), 7.32-7.38( m, 6H), 7.41(t, J=8.54Hz, 1H), 7.56(d, J=8.08Hz, 2H), 7.67(s, 1H), 10.51(s, 1H). HRMS(ESI);C38H32Cl2N3O2[M+H] + Calculated value: 632.1866, measured value: 632.1854.

[1060] tert-Butyl 3-{[5-(2,6-dichlorophenyl)-1-trityl-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate [(XIII), R1 = 2,6-dichlorophenyl, R2 = tert-butylpiperidine-1-carboxylate, R9 = 1,1′,1″-methanetriyltribenzene]

[1061] [ka]

[1062] Starting from 5-(2,6-dichlorophenyl)-1-trityl-1H-indazol-3-ylamine and 1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid. Flash column chromatography (hexane / EtOAc 75:25). Obtained 0.110 g (95% yield). LCMS (ESI) m / z 731 (M+H). + .

[1063] 1-Cyclopropyl-N-[5-(2,6-dichlorophenyl)-1-trityl-1H-indazol-3-yl]piperidine-4-carboxamide [(XIII), R1 = 2,6-dichlorophenyl, R2 = 1-cyclopropylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[1064] [ka]

[1065] Starting from 5-(2,6-dichlorophenyl)-1-trityl-1H-indazol-3-ylamine and 1-cyclopropylpiperidine-4-carboxylic acid. Flash column chromatography (DCM / MeOH 95:5). Obtained 0.066 g (79% yield). LCMS (ESI) m / z 671 (M+H). + .

[1066] N-[5-(2,6-dichlorophenyl)-1-trityl-1H-indazol-3-yl]-1-phenylpiperidine-4-carboxamide [(XIII), R1 = 2,6-dichlorophenyl, R2 = 1-phenylpiperidine, R9 = 1,1′,1″-methanetriyltribenzene]

[1067] [ka]

[1068] Starting from 5-(2,6-dichlorophenyl)-1-trityl-1H-indazol-3-ylamine and 1-phenylpiperidine-4-carboxylic acid, flash column chromatography (DCM / MeOH 97:3) gave 0.041 g (90% yield). LCMS (ESI) m / z 707 (M+H) + .

[1069] N-[5-(2,6-dichlorophenyl)-1-trityl-1H-indazol-3-yl]-1-azabicyclo[2.2.2]octane-4-carboxamide [(XIII), R1 = 2,6-dichlorophenyl, R2 = 1-azabicyclo[2.2.2]octane, R9 = 1,1′,1″-methanetriyltribenzene]

[1070] [ka]

[1071] Starting from 5-(2,6-dichlorophenyl)-1-trityl-1H-indazol-3-ylamine and 1-azabicyclo[2.2.2]octane-4-carboxylic acid, flash column chromatography (DCM / MeOH / 33% aqueous ammonia 95:5:0.2) yielded 0.120 g (82% yield). LCMS (ESI) m / z 657 (M+H) + .

[1072] N-[5-(2-chloro-6-fluorophenyl)-1-trityl-1H-indazol-3-yl]-1-methylpiperidine-3-carboxamide [(XIII), R...

Claims

1. A compound of formula (I) or a pharma- ceutically acceptable salt thereof: 【Chemistry 1】 [In the formula, R1 is Optionally substituted linear or branched (C1-C6) alkyl; optionally substituted (C3-C7)cycloalkyl; an optionally substituted 5- to 7-membered heterocycle; Optionally substituted aryl; 5- or 6-membered heteroaryl selected from the group consisting of pyridyl, pyrimidinyl, pyrrolyl, and pyrazolyl; or A group of formula (II): 【Chemistry 2】 and Here, R4 is Optionally substituted linear or branched (C2-C6) alkyl; optionally substituted (C3-C7)cycloalkyl; or Optionally substituted 5- to 7-membered heterocycle and R2 is, Linear or branched (C2-C6) alkyl; optionally substituted (C3-C7)cycloalkyl; an optionally substituted heterocycle; a 5-6 membered heterocyclic methyl group [-CH2-Het], wherein the heterocyclic ring is selected from the group consisting of pyrrolidinyl, methylpiperazinyl and piperidinyl; or A group of formula (III): 【Chemistry 3】 and Here, R5 is hydrogen; Optionally substituted linear or branched (C1-C6) alkyl; optionally substituted (C3-C7)cycloalkyl; Optionally substituted aryl; an optionally substituted heterocycle; or Optionally substituted heteroaryl and R6 is, Optionally substituted linear or branched (C1-C6) alkyl; optionally substituted (C3-C7)cycloalkyl; Optionally substituted aryl; an optionally substituted heterocycle; or Optionally substituted heteroaryl and R3 is hydrogen or a group of formula (IV): 【Chemistry 4】 and Here, R7 is Optionally substituted linear or branched (C1-C6) alkyl; optionally substituted (C3-C7)cycloalkyl; Optionally substituted aryl; an optionally substituted heterocycle; or Optionally substituted heteroaryl and however, R1 is 【Chemistry 5】 isn't it.]

2. R1 is, mono-, di- or tri-substituted phenyl; an optionally substituted 5- or 6-membered heteroaryl selected from the group consisting of pyridyl, pyrrolyl, and pyrazolyl, wherein the substituents are each independently selected from the group consisting of halogen, linear or branched (C1-C6) alkyl, alkoxy, hydroxyalkyl, polyfluorinated alkyl, polyfluorinated alkoxy, cyano, amino, alkylsulfonyl, aminosulfonyl, phenyl, hydroxy, aminocarbonyl, alkylaminocarbonyl, hydroxyalkylaminocarbonyl, formyl, formylamino, nitro, alkylcarbonyl, alkyloxycarbonyl, and oxadiazolyl; or A group of formula (II): 【Chemistry 6】 and Here, R4 is linear or branched (C2-C6) alkyl, C3-C7) cycloalkyl, optionally substituted by halogen or alkoxy; R2 is, (C3-C7)cycloalkyl optionally substituted with hydroxy, aminoalkyl, alkylamino, dialkylamino, alkylaminoalkyl, heterocycle, C3-C7 cycloalkylamino, or haloalkylamino; a 5- to 7-membered heterocycle optionally substituted with 1 to 2 heteroatoms selected from N and O; 1-Azabicyclo[2.2.2]octanyl; 2-Azabicyclo[2.2.2]octanyl; or A group of formula (III): 【Chemistry 7】 and Here, R5 is hydrogen; Optionally substituted linear or branched (C1-C6) alkyl; or Optionally substituted (C3-C7)cycloalkyl and R6, Optionally substituted linear or branched (C1-C6) alkyl; optionally substituted (C3-C7)cycloalkyl; optionally substituted phenyl; an optionally substituted heterocycle; or 5- or 6-membered heteroaryl optionally substituted with 1 to 2 nitrogen atoms and R3 is Hydrogen, or Group of formula (IV) and Here, R7 is linear or branched (C1-C6)alkyl optionally substituted with (C3-C7)cycloalkyl, alkylthio, alkoxy, or alkoxy(C1-C6)alkoxy; or (C3-C7) cycloalkyl and However, R1 is 【Chemistry 8】 2. The compound of formula (I) according to claim 1, which is not:

3. R1 is, disubstituted phenyl; an optionally substituted 5- or 6-membered heteroaryl selected from the group consisting of pyridyl and pyrazolyl, wherein the substituents are each independently selected from the group consisting of halogen, linear or branched (C1-C6) alkylalkoxy, hydroxyalkyl, polyfluorinated alkyl, polyfluorinated alkoxy, cyano, amino, alkylsulfonyl, aminosulfonyl, phenyl, hydroxy, aminocarbonyl, alkylaminocarbonyl, hydroxyalkylaminocarbonyl, formyl, formylamino, nitro, alkylcarbonyl, alkyloxycarbonyl, and oxadiazolyl; or The group of formula (II) and R2 is, (C3-C7)cycloalkyl selected from the group consisting of cyclopropyl, cyclobutyl, and cyclohexyl, wherein said cycloalkyl is optionally substituted with hydroxy, aminoalkyl, alkylamino, dialkylamino, haloalkylamino, alkylaminoalkyl, morpholinyl, (C3-C7)cycloalkylamino; a heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, morpholinyl, tetrahydropyranyl, and azepanyl, wherein said heterocycle is optionally substituted with linear or branched (C1-C6) alkyl, (C3-C6) cycloalkyl, spiro (C4-C6) cycloalkyl, aminoalkyl, alkoxyalkyl, hydroxyalkyl, phenyl, polyfluorinated alkyl, C3-C7 cycloalkylamino, and hydroxy; or Group of formula (III) 3. The compound of formula (I) according to claim 2, which is: or a pharma- ceutically acceptable salt thereof.

4. N-[5-(4-amino-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide dihydrochloride (Compound 1); N-[5-(2,4-dichlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-3-carboxamide hydrochloride (Compound 2); N-[5-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 3); N-[5-(2,5-dichlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 4); (3R)-N-[5-(4-amino-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide dihydrochloride (Compound 5); (3R)-N-[5-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 6); (3S)-N-[5-(4-amino-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide dihydrochloride (Compound 7); (3R)-N-[5-(2-chloro-4-methylphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 8); N-[5-(5-carbamoyl-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 9); (3S)-N-[5-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 10); N-[5-(3-amino-2-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 11); (3S)-N-[5-(2-chloro-4-methylphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 12); (3R)-N-[5-(2,5-dichlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 13); (3R)-N-[5-(2,4-dichlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 14); N-{5-[5-chloro-2-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide trifluoroacetate (Compound 15); N-[5-(5-acetyl-2-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 16); N-[5-(2-chloro-5-methoxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 17); (3R)-N-[5-(2-chloro-5-methoxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 18); (3R)-N-[5-(5-acetyl-2-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 19); (3R)-N-[5-(2-fluoro-5-methoxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 20); (3R)-N-[5-(5-chloro-2-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 21); (3R)-N-[5-(5-ethoxy-2-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 22); (3R)-N-{5-[2-fluoro-5-(trifluoromethoxy)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (Compound 23); (3R)-N-[5-(5-cyano-2-methylphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 24); (3R)-N-[5-(5-cyano-2-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 25); (3R)-N-[5-(2-chloro-5-nitrophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 26); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-6-oxopiperidine-3-carboxamide (compound 27); N-[5-(5-acetyl-2-fluorophenyl)-1H-indazol-3-yl]-6-oxopiperidine-3-carboxamide (compound 28); Methyl 4-chloro-3-(3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (Compound 29); (3R)-N-[5-(2,4-difluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 30); (3R)-N-{5-[4-methoxy-2-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (compound 31); (3R)-N-[5-(2-fluoro-5-methylphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 32); (3R)-N-[5-(5-acetyl-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 33); (3R)-N-[5-(5-amino-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide dihydrochloride (compound 34); (3R)-N-[5-(2,5-difluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 35); (3R)-N-{5-[4-methyl-2-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (compound 36); Methyl 4-chloro-3-(3-{[(3R)-pyrrolidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (Compound 37); (3R)-N-[5-(5-acetyl-2-chlorophenyl)-1H-indazol-3-yl]pyrrolidine-3-carboxamide hydrochloride (compound 38); (3R)-N-{5-[2-chloro-5-(methylcarbamoyl)phenyl]-1H-indazol-3-yl}pyrrolidine-3-carboxamide hydrochloride (compound 39); Methyl 4-cyano-3-(3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (compound 40); (3R)-N-[5-(2-chloro-5-hydroxyphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 41); Methyl 2,4-dichloro-5-(3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (compound 42); (3R)-N-[5-(2-chloro-5-propanoylphenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 43); (3R)-N-{5-[2-chloro-4-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (compound 44); (3R)-N-{5-[4-chloro-2-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (compound 45); (3R)-N-{5-[5-fluoro-2-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (compound 46); (3R)-N-[5-(2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 47); (3R)-N-{5-[2-chloro-5-(propan-2-yl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (compound 48); (3R)-N-(5-phenyl-1H-indazol-3-yl)piperidine-3-carboxamide hydrochloride (compound 49); Methyl 2,4-difluoro-5-(3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (Compound 50); (3R)-N-[5-(5-tert-butyl-2-chlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 51); (3R)-N-[5-(2-chloro-5-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 52); (3R)-N-[5-(2,5-dicyanophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 53); Methyl 2-amino-4-chloro-5-(3-{[(3R)-pyrrolidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate dihydrochloride (Compound 54); (3R)-N-{5-[2-cyano-5-(methylcarbamoyl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide hydrochloride (compound 55); Propan-2-yl 4-chloro-3-(3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (compound 56); Methyl 2,4-dichloro-3-(3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazol-5-yl)benzoate hydrochloride (Compound 57); (3R)-N-{5-[2-chloro-5-(1,2,4-oxadiazol-3-yl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide dihydrochloride (compound 58); (3R)-N-{5-[2-chloro-5-(1,3,4-oxadiazol-2-yl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide trifluoroacetate (compound 59); (3R)-N-{5-[2-chloro-5-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-1H-indazol-3-yl}piperidine-3-carboxamide dihydrochloride (compound 60); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 61); N-[5-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]-3-(dimethylamino)cyclobutanecarboxamide hydrochloride (Compound 62); N-[5-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]-3-(methylamino)cyclobutanecarboxamide hydrochloride (Compound 63); N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 64); 1-Butyl-N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 65); 1-(3-aminopropyl)-N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide dihydrochloride (compound 66); N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]-1-(1-methoxypropan-2-yl)piperidine-4-carboxamide hydrochloride (compound 67); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide (compound 68); 1-Butyl-N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide (compound 69); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-1-(2-methylpropyl)piperidine-4-carboxamide (compound 70); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-1-(3-hydroxy-2,2-dimethylpropyl)piperidine-4-carboxamide (compound 71); N-[5-(6-chloro-2-fluoro-3-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (compound 72); N-[5-(2-chloro-6-fluoro-3-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (compound 73); N-[5-(5-chloro-2-fluoro-3-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (compound 74); N-{5-[2-methoxy-5-(propan-2-yl)phenyl]-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide hydrochloride (Compound 75); 1-Methyl-N-{5-[3-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-4-carboxamide hydrochloride (Compound 76); N-{5-[2-chloro-5-(hydroxymethyl)phenyl]-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide p-toluenesulfonate (Compound 77); N-[5-(2-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (compound 78); N-[5-(2-cyanophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide p-toluenesulfonate (Compound 79); N-[5-(2,5-dichlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 80); N-[5-(3-carbamoylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 81); N-{5-[4-(hydroxymethyl)phenyl]-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide p-toluenesulfonate (Compound 82); N-{5-[3-(hydroxymethyl)phenyl]-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide p-toluenesulfonate (Compound 83); 1-Methyl-N-[5-(pyridin-3-yl)-1H-indazol-3-yl]piperidine-4-carboxamide dihydrochloride (Compound 84); N-[5-(2-chlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 85); N-[5-(2-chloro-5-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (compound 86); N-[5-(4-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 87); N-[5-(2-ethylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (compound 88); N-[5-(3-cyanophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (compound 89); N-[5-(4-aminophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide dihydrochloride (compound 90); N-[5-(2-aminophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide dihydrochloride (Compound 91); 1-Methyl-N-[5-(4-sulfamoylphenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 92); 1-Methyl-N-(5-phenyl-1H-indazol-3-yl)piperidine-4-carboxamide hydrochloride (Compound 93); N-{5-[2-chloro-5-(trifluoromethyl)phenyl]-1H-indazol-3-yl}-1-methylpiperidine-4-carboxamide hydrochloride (Compound 94); N-[5-(2-fluoropyridin-3-yl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide dihydrochloride (Compound 95); N-[5-(2-methoxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (compound 96); N-[5-(2,3-dichlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 97); N-[5-(2-chloro-6-methoxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (compound 98); N-[5-(2,3-difluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 99); 1-Methyl-N-{5-[3-(methylsulfonyl)phenyl]-1H-indazol-3-yl}piperidine-4-carboxamide hydrochloride (Compound 100); N-[5-(3-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 101); N-[5-(2-hydroxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 102); N-[5-(biphenyl-2-yl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 103); 1-Methyl-N-{5-[2-(trifluoromethyl)phenyl]-1H-indazol-3-yl}piperidine-4-carboxamide hydrochloride (Compound 104); N-[5-(2,6-difluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 105); N-[5-(2,4-dichlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 106); N-[5-(4-amino-2-chlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide dihydrochloride (Compound 107); 1-Methyl-N-[5-(2,4,6-trichlorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 108); N-[5-(4-carbamoylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 109); N-[5-(4-cyanophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 110); N-[5-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 111); N-[5-(4-amino-3-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 112); N-[5-(4-cyano-2-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 113); N-[5-(2,6-dimethylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide trifluoroacetate (Compound 114); N-[5-(2-fluoro-5-nitrophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 115); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide trifluoroacetate (Compound 116); N-[5-(5-carbamoyl-2-chlorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide trifluoroacetate (Compound 117); N-[5-(2-fluoro-4-formylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 118); N-[5-(2-fluoro-4-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 119); N-[5-(2,6-difluoro-4-methoxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 120); 1-Methyl-N-[5-(1H-pyrazol-4-yl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 121); 1-Methyl-N-[5-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 122); 1-Methyl-N-[5-(2,4,6-trifluorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 123); N-[5-(2,4-difluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 124); 1-Methyl-N-[5-(1H-pyrazol-3-yl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 125); 1-Methyl-N-[5-(2,4,5-trifluorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 126); 1-Methyl-N-{5-[2,4,6-trifluoro-3-(propan-2-yloxy)phenyl]-1H-indazol-3-yl}piperidine-4-carboxamide hydrochloride (Compound 127); 1-Methyl-N-[5-(2,3,4-trifluorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 128); N-[5-(4-fluoro-2-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide trifluoroacetate (Compound 129); N-[5-(4-amino-2-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide dihydrochloride (Compound 130); 1-Methyl-N-[5-(2,4,6-trifluoro-3-methoxyphenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 131); N-[5-(2,3-difluoro-4-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (compound 132); N-[5-(2-chloro-4-fluoro-3-methylphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (compound 133); N-[5-(3-cyano-2,6-difluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide (compound 134); N-[5-(3-cyano-4-hydroxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 135); N-[5-(2-cyano-5-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide hydrochloride (Compound 136); N-[5-(2-chloro-5-nitrophenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide trifluoroacetate (Compound 137); N-[5-(2,6-difluoro-4-hydroxyphenyl)-1H-indazol-3-yl]-1-methylpiperidine-4-carboxamide trifluoroacetate (Compound 138); 1-Methyl-N-[5-(2,4,6-trifluoro-3-hydroxyphenyl)-1H-indazol-3-yl]piperidine-4-carboxamide (compound 139); 1-Butyl-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 140); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-1-propylpiperidine-4-carboxamide hydrochloride (Compound 141); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-1-pentylpiperidine-4-carboxamide hydrochloride (Compound 142); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-1-(propan-2-yl)piperidine-4-carboxamide hydrochloride (compound 143); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-4-(methylamino)cyclohexanecarboxamide hydrochloride (Compound 144); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-3-(methylamino)cyclobutanecarboxamide hydrochloride (Compound 145); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-(methylamino)cyclobutanecarboxamide hydrochloride (Compound 146); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-(dimethylamino)cyclobutanecarboxamide hydrochloride (Compound 147); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-(propan-2-ylamino)cyclobutanecarboxamide hydrochloride (Compound 148); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-(morpholin-4-yl)cyclobutanecarboxamide hydrochloride (Compound 149); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-[(2,2,2-trifluoroethyl)amino]cyclobutanecarboxamide hydrochloride (Compound 150); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-[(2-fluoroethyl)amino]cyclobutanecarboxamide hydrochloride (Compound 151); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-(ethylamino)cyclobutanecarboxamide hydrochloride (Compound 152); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-(cyclobutylamino)cyclobutanecarboxamide hydrochloride (Compound 153); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-(cyclopentylamino)cyclobutanecarboxamide hydrochloride (Compound 154); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-3-(cyclopropylamino)cyclobutanecarboxamide hydrochloride (Compound 155); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]tetrahydro-2H-pyran-4-carboxamide (compound 156); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 157); 1-Cyclopropyl-N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]piperidine-4-carboxamide hydrochloride (Compound 158); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-1-phenylpiperidine-4-carboxamide hydrochloride (Compound 159); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-1-azabicyclo[2.2.2]octane-4-carboxamide (compound 160); N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]-1-methylpiperidine-3-carboxamide hydrochloride (Compound 161); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-2-[(2S)-pyrrolidin-2-yl]acetamide hydrochloride (compound 162); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-2-(piperidin-4-yl)acetamide hydrochloride (Compound 163); trans-4-(aminomethyl)-N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]cyclohexanecarboxamide hydrochloride (Compound 164); N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 165); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-4-(dimethylamino)cyclohexanecarboxamide hydrochloride (Compound 166); (3R)-N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]pyrrolidine-3-carboxamide hydrochloride (compound 167); (3S)-N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]pyrrolidine-3-carboxamide hydrochloride (compound 168); (3R)-N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 169); (3S)-N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 170); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 171); (3R)-N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 172); (3S)-N-[5-(2-chloro-6-fluorophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 173); (3R)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 174); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-b-alaninamide hydrochloride (Compound 175); (3R)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]pyrrolidine-3-carboxamide hydrochloride (compound 176); (3R,6S)-N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-6-methylpiperidine-3-carboxamide trifluoroacetate (Compound 177); (3R,6R)-N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-6-methylpiperidine-3-carboxamide trifluoroacetate (Compound 178); (3R,6R)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-6-methylpiperidine-3-carboxamide trifluoroacetate (Compound 179); (3R,6S)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-6-(trifluoromethyl)piperidine-3-carboxamide (compound 180); (3S)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 181); (2R)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]morpholine-2-carboxamide hydrochloride (compound 182); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]azepane-3-carboxamide hydrochloride (compound 183); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-6,6-dimethylpiperidine-3-carboxamide hydrochloride (Compound 184); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-6-azaspiro[4.5]decane-8-carboxamide hydrochloride (Compound 185); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-1-azaspiro[5.5]undecane-3-carboxamide hydrochloride (Compound 186); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-2-azabicyclo[2.2.2]octane-4-carboxamide hydrochloride (compound 187); N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-1-azabicyclo[2.2.2]octane-3-carboxamide hydrochloride (compound 188); 1-[(2,2-dimethylpentanoyl)oxy]ethyl (3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate (compound 189); 1-[(2-methylpropanoyl)oxy]ethyl (3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate (compound 190); (Acetyloxy)methyl (3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate (Compound 191); [(2-methylpropanoyl)oxy]methyl (3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate (compound 192); [(2,2-dimethylpropanoyl)oxy]methyl (3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate (compound 193); 1-(acetyloxy)ethyl (3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate (compound 194); 1-[(2,2-dimethylpropanoyl)oxy]ethyl (3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate (compound 195); 2-Methyl-1-[(2-methylpropanoyl)oxy]propyl(3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate (compound 196); 1-[(2,2-dimethylpropanoyl)oxy]-2-methylpropyl(3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate (compound 197); 1-{[(1-methylcyclohexyl)carbonyl]oxy}ethyl (3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate (compound 198); 1-[(tetrahydro-2H-pyran-4-ylcarbonyl)oxy]ethyl (3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}piperidine-1-carboxylate (compound 199); 1-[(2,2-dimethylpropanoyl)oxy]propyl(3R)-3-{[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]carbamoyl}-piperidine-1-carboxylate (compound 200); N-[5-(2,6-dichlorophenyl)-1H-indazol-3-yl]-4-hydroxycyclohexanecarboxamide (compound 201); (+)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-6,6-dimethylpiperidine-3-carboxamide (Compound 202); (−)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-6,6-dimethylpiperidine-3-carboxamide (compound 203); (8+)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-6-azaspiro[4.5]decane-8-carboxamide hydrochloride (Compound 204); (8-)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-6-azaspiro[4.5]decane-8-carboxamide hydrochloride (Compound 205); (3+)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-1-azaspiro[5.5]undecane-3-carboxamide (compound 206); (3-)-N-[5-(2-chloro-5-cyanophenyl)-1H-indazol-3-yl]-1-azaspiro[5.5]undecane-3-carboxamide (compound 207); Butyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (Compound 208); Ethyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (Compound 209); Propan-2-yl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (Compound 210); Hexyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (Compound 211); 2,2-Dimethylpropyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (Compound 212); 2-Methylpropyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (Compound 213); Pentyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (Compound 214); 2-Methoxyethyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (Compound 215); Cyclobutyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (Compound 216); Pentan-3-yl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (Compound 217); Cyclohexylmethyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate hydrochloride (Compound 218); Cyclopropylmethyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate formate (compound 219); 2-(Ethylsulfanyl)ethyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate formate (compound 220); 3-(3-Methoxypropoxy)propyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate formate (compound 221); 4-Methylpentyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate formate (compound 222); Cyclopentyl 5-(2-chloro-5-cyanophenyl)-3-{[(3R)-piperidin-3-ylcarbonyl]amino}-1H-indazole-1-carboxylate formate (compound 223); 2,2-Dimethylpropyl 5-(2-chloro-5-cyanophenyl)-3-({[(3+)-6,6-dimethylpiperidin-3-yl]carbonyl}amino)-1H-indazole-1-carboxylate hydrochloride (Compound 224); Hexyl 5-(2-chloro-5-cyanophenyl)-3-({[(3R)-6,6-dimethylpiperidin-3-yl]carbonyl}amino)-1H-indazole-1-carboxylate hydrochloride (Compound 225); Propan-2-yl 5-(2-chloro-5-cyanophenyl)-3-({[(3R)-6,6-dimethylpiperidin-3-yl]carbonyl}amino)-1H-indazole-1-carboxylate hydrochloride (compound 226); (3R)-N-[5-(2-fluoroethoxy)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 227); (3R)-N-[5-(2-methoxyethoxy)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (Compound 228); (3R)-N-(5-ethoxy-1H-indazol-3-yl)piperidine-3-carboxamide hydrochloride (Compound 229); (3R)-N-[5-(propan-2-yloxy)-1H-indazol-3-yl]piperidine-3-carboxamide hydrochloride (compound 230); and (3R)-N-(5-butoxy-1H-indazol-3-yl)piperidine-3-carboxamide hydrochloride (Compound 231) 4. A compound of formula (I) according to claim 1, 2 or 3 selected from the group consisting of: or a pharma- ceutically acceptable salt thereof.

5. A process for preparing a compound of formula (I) as defined in claim 1 or a pharma- ceutically acceptable salt thereof, comprising the steps of: Step 1) Mixing a compound of formula (III): Step 1a) Compound of formula (V): 【Chemistry 9】 [R8 is bromine or 4,4,5,5-tetramethyl-[1,3,2]dioxaborolane, and R9 is a protecting group such as 1,1',1"-methanetriyltribenzene or tert-butyloxycarbonyl.] with a compound of formula (VI): 【Chemistry 10】 [R2 is as defined in claim 1.] reacting with Step 1b') Obtaining intermediate of formula (VII): 【Chemistry 11】 [R2 and R9 are as defined above in step 1a, and R8 is bromine.] with a compound of formula (VIII) or (IX): 【Chemistry 12】 [R1 is optionally substituted linear or branched (C1-C6) alkyl, (C3-C7) cycloalkyl, heterocycle, aryl, and 5- or 6-membered heteroaryl.] mixing with or Step 1b″) The intermediate of formula (VII), wherein R8 is 4,4,5,5-tetramethyl-[1,3,2]dioxaborolane, and R2 and R9 are as defined above in Step 1a, is converted into a compound of formula (X): 【Chemistry 13】 [R1 is as defined above in step 1b' and X is a halogen.] reacting with Step 1c) Obtaining intermediate (XI): 【Chemistry 14】 [R1, R2 and R9 are as defined above in steps 1b' and 1b''.] with a suitable deprotecting agent to give a compound of formula (I): 【Chemistry 15】 [R3 is hydrogen, R1 is as defined in claim 1, and R2 is as defined above.] obtaining or Step 1d) Compound of formula (V): 【Chemistry 16】 [R8 is bromine and R9 is as defined above in step 1a.] with a compound of formula (VIII) or (IX): 【Chemistry 17】 [R1 is as defined above in step 1b'.] reacting with Step 1e) Obtaining intermediate (XII): 【Chemistry 18】 [R1 and R9 are as defined above in step 1c.] with a compound of formula (VI): 【Chemistry 19】 [R2 is as defined above in step 1a.] mixing with; Step 1f) Obtaining intermediate (XIII): 【Chemistry 20】 [R1, R2 and R9 are as defined above.] with a suitable deprotecting agent to give a compound of formula (I): 【Chemistry 21】 [R3 is hydrogen and R1 and R2 are as defined above in step 1c.] obtaining Alternatively, a first compound of formula (VII) or (XII) can be converted to a second compound of formula (VII) or (XII), respectively, by operating according to the transformations described below: Transformation A) Compound of formula (VIIa): 【Chemical 22】 wherein R2 is an optionally substituted heterocycle and R9 is as defined above in step 1a. is first converted to a compound of formula (VIIb) by removing the protecting group, and then the resulting derivative is reacted under reductive amination conditions in the presence of a suitable reducing agent with a compound of formula R10R11CO (XIV), wherein R10 and R11 are optionally substituted groups selected from hydrogen, linear or branched (C1-C6) alkyl, (C3-C7) cycloalkyl, or R10 and R11 together can form an optionally substituted (C3-C7) cycloalkyl and heterocycle group; Transformation B) Compound of formula (VIId): 【Chemistry 23】 [R2 is (C4-C6)cycloalkyloxo] with a compound of formula R10R11NH (XV) [R10 and R11 are as defined above in transformation A] under reductive amination conditions in the presence of a suitable reducing agent to convert it into a compound of formula (VIIe); Conversion C) Compound of formula (XIIIa): 【Chemistry 24】 [R2 is an optionally substituted heterocycle and R9 is as defined above in step 1a.] is first converted to a compound of formula (XIIIb) by removing the protecting group, and then the resulting derivative is reacted with a compound of formula R10R11CO (XIV) [R10 and R11 are as defined above in transformation A.] under reductive amination conditions in the presence of a suitable reducing agent; Transformation D) Compound of formula (XIIId): 【Chemistry 25】 [R2 is (C4-C6)cycloalkyloxo] with a compound of formula R10R11NH (XV) [R10 and R11 are as defined above in transformation A] under reductive amination conditions in the presence of a suitable reducing agent to convert it to a compound of formula (XIIIe); Transformation E) Compound of formula (XIIIf): 【Chemistry 26】 first with a compound of formula R5CHClOCOCl (XVI) [R5 is as defined in claim 1] to convert to a compound of formula (XIIIg) and then under basic conditions with a compound of formula R6COOH (XVII) to convert to a compound of formula (XIIIh) [R6 is as defined in claim 1]; or A first compound of formula (I) can be conveniently converted to a second compound of formula (I) by operating according to the transformations described below; Conversion 1) Compound of formula (I): 【Chemical 27】 [R1 is as defined above in step 1b' and R2 is an optionally substituted linear or branched (C2-C6) alkyl, (C3-C7) cycloalkyl, heterocycle and 5-6 membered heterocycle methyl, said heterocycle being selected from the group consisting of pyrrolidinyl and piperidinyl], reacted under basic conditions with a compound of formula R7OCOCl (XIX) [R7 is as defined in claim 1] to convert to a compound of formula (I); or The compound of formula (I), wherein R1 is a group of formula (II) and R4 is an optionally substituted linear or branched (C2-C6) alkyl, (C3-C7) cycloalkyl or heterocycle, can be prepared according to a process comprising the steps of: Step 2a) Compound of formula (XX): 【Chemistry 28】 [R9 is as defined above in step 1a.] with a compound of formula (XXI): 【Chemical 29】 [R4 is as defined in claim 1.] reacting with Step 2b) Obtaining intermediate (XXII): 【Chemistry 30】 with a suitable deprotecting agent; Step 2c) Obtaining intermediate (XXIII): 【Chemistry 31】 with a compound of formula (VI): 【Chemistry 32】 [R2 is as defined above in step 1a.] mixing with; Step 2d) Obtaining intermediate (XXIV): 【Chemical 33】 with a suitable deprotecting agent to give a compound of formula (I): 【Chemical 34】 [R3 is hydrogen, and R2 and R4 are as defined in claim 1.] The process of obtaining The method includes:

6. A compound of formula (I) as defined in claim 1 or a pharma- ceutically acceptable salt thereof for use in a method for the treatment of a disease caused by and / or associated with dysregulated CDK11 kinase activity, said method comprising administering to a mammal, preferably a human, in need of treatment an effective amount of a compound of formula (I) as defined in claim 1 or a pharma- ceutically acceptable salt thereof.

7. 7. The compound for use according to claim 6, wherein the disease is selected from the group consisting of cancer, cell proliferative disorders and immune-related disorders.

8. 8. The compound for use according to claim 7, wherein the disease is cancer.

9. The cancer is selected from the group consisting of carcinomas such as bladder cancer, breast cancer, kidney cancer, liver cancer, colon cancer, lung cancer including small cell lung cancer, esophageal cancer, gallbladder cancer, ovarian cancer, pancreatic cancer, gastric cancer, cervical cancer, prostate cancer, and skin cancer including squamous cell carcinoma; lymphoid hematopoietic tumors including leukemia, acute lymphocytic leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, B cell lymphoma, angioimmunoblastic T cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, hairy cell lymphoma, and Burkitt's lymphoma B; acute and chronic myeloid leukemia, myelodysplastic syndromes, and promyeloma.

9. The compound for use according to claim 8, which is selected from the group consisting of hematopoietic tumors of myeloid lineage, including myeloid leukemia; tumors of mesenchymal origin, including fibrosarcoma and rhabdomyosarcoma; tumors of the central and peripheral nervous system, including glioma, glioblastoma, glioblastoma multiforme, astrocytoma, oligodendroglioma, paraglioma, neuroblastoma and schwannoma; and carcinomas such as melanoma, seminoma, teratocarcinoma, osteosarcoma, xeroderma pigmentosum, keratoxanthoma, thyroid carcinoma, such as papillary and medullary thyroid carcinoma, Kaposi's sarcoma, chondrosarcoma and other tumors including cholangiocarcinoma.

10. 10. A compound of formula (I) as defined in claim 1 or a pharma- ceutically acceptable salt thereof for use as a medicine.

11. A method for the treatment of a disease caused by and / or associated with dysregulated CDK11 kinase activity, comprising administering to a mammal, preferably a human, in need of treatment an effective amount of a compound of formula (I) as defined in claim 1.

12. 12. The method of claim 11, wherein the disease is selected from the group consisting of cancer, a cell proliferative disorder, and an immune-related disorder.

13. The method of claim 12, wherein the disease is cancer.

14. The cancer may be carcinomas such as bladder cancer, breast cancer, kidney cancer, liver cancer, colon cancer, lung cancer including small cell lung cancer, esophageal cancer, gallbladder cancer, ovarian cancer, pancreatic cancer, gastric cancer, cervical cancer, prostate cancer, and squamous cell skin cancer; lymphoid hematopoietic tumors including leukemia, acute lymphocytic leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, B cell lymphoma, angioimmunoblastic T cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, hairy cell lymphoma, and Burkitt's lymphoma B; acute and chronic myeloid leukemia, myelodysplastic syndromes, and promyelocytic leukemia.

12. The method of claim 11, wherein the tumor is selected from the group consisting of hematopoietic tumors of myeloid lineage, including myeloid leukemia; tumors of mesenchymal origin, including fibrosarcoma and rhabdomyosarcoma; tumors of the central and peripheral nervous system, including glioma, glioblastoma, glioblastoma multiforme, astrocytoma, oligodendroglioma, paraglioma, neuroblastoma and schwannoma; and carcinomas such as melanoma, seminoma, teratocarcinoma, osteosarcoma, xeroderma pigmentosum, keratoxanthoma, thyroid cancer, such as papillary and medullary thyroid carcinoma, Kaposi's sarcoma, chondrosarcoma and other tumors including cholangiocarcinoma.

15. 10. A pharmaceutical composition comprising a compound of formula (I) as defined in claim 1 or a pharma- ceutically acceptable salt thereof, together with a pharma- ceutically acceptable excipient, carrier or diluent.

16. 16. The pharmaceutical composition of claim 15, further comprising one or more chemotherapeutic agents.

17. 13. A product or kit comprising a compound of formula (I) as defined in claim 1 or a pharma- ceutically acceptable salt thereof and one or more chemotherapeutic agents as a combined preparation for simultaneous, separate or sequential use in anti-cancer therapy.

18. 13. The use of a compound of formula (I) as defined in claim 1 or a pharma- ceutically acceptable salt thereof in the manufacture of a medicament having anticancer activity.

19. 11. The method of claim 10 in combination with radiation therapy or chemotherapy.

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