ES2534804T3 - Indazoles - Google Patents
Indazoles Download PDFInfo
- Publication number
- ES2534804T3 ES2534804T3 ES11778335.7T ES11778335T ES2534804T3 ES 2534804 T3 ES2534804 T3 ES 2534804T3 ES 11778335 T ES11778335 T ES 11778335T ES 2534804 T3 ES2534804 T3 ES 2534804T3
- Authority
- ES
- Spain
- Prior art keywords
- methyl
- alkyl
- oxo
- indazol
- pyridinyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
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- 150000002473 indoazoles Chemical class 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 280
- -1 substituted Chemical class 0.000 claims abstract description 227
- 229910003827 NRaRb Inorganic materials 0.000 claims abstract description 131
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 124
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 108
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims abstract description 89
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 89
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 87
- 125000003118 aryl group Chemical group 0.000 claims abstract description 79
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 79
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 69
- 125000005843 halogen group Chemical group 0.000 claims abstract description 60
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 56
- 239000001257 hydrogen Substances 0.000 claims abstract description 54
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 53
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 46
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 44
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 44
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 42
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 36
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 36
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims abstract description 35
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims abstract description 32
- 150000003839 salts Chemical class 0.000 claims abstract description 31
- 229910052701 rubidium Inorganic materials 0.000 claims abstract description 29
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 28
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 24
- 150000001602 bicycloalkyls Chemical group 0.000 claims abstract description 21
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 19
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 17
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 16
- 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 claims abstract description 14
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 14
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 13
- 229910052717 sulfur Chemical group 0.000 claims abstract description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 10
- 229910006074 SO2NH2 Inorganic materials 0.000 claims abstract description 9
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 9
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 9
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000001301 oxygen Substances 0.000 claims abstract description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 7
- 239000011593 sulfur Chemical group 0.000 claims abstract description 7
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 3
- 238000011282 treatment Methods 0.000 claims description 55
- 206010028980 Neoplasm Diseases 0.000 claims description 43
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 43
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 34
- 201000011510 cancer Diseases 0.000 claims description 27
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 26
- 125000001188 haloalkyl group Chemical group 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- IGRUIXGIDUANQR-UHFFFAOYSA-N 6-bromo-n-[(6-methyl-2-oxo-4-propyl-1h-pyridin-3-yl)methyl]-1-propan-2-ylindazole-4-carboxamide Chemical compound C1=C(C)NC(=O)C(CNC(=O)C=2C=3C=NN(C=3C=C(Br)C=2)C(C)C)=C1CCC IGRUIXGIDUANQR-UHFFFAOYSA-N 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 206010025323 Lymphomas Diseases 0.000 claims description 15
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- FWNJJCIQEURUTI-UHFFFAOYSA-N 6-bromo-1-cyclopentyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]indazole-4-carboxamide Chemical compound O=C1NC(C)=CC(C)=C1CNC(=O)C1=CC(Br)=CC2=C1C=NN2C1CCCC1 FWNJJCIQEURUTI-UHFFFAOYSA-N 0.000 claims description 10
- RNEUKQLFDMRMOV-UHFFFAOYSA-N 6-bromo-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylindazole-4-carboxamide Chemical compound C1=C(Br)C=C2N(C(C)C)N=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O RNEUKQLFDMRMOV-UHFFFAOYSA-N 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 125000000304 alkynyl group Chemical group 0.000 claims description 10
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 8
- OLASLWWQIDMLQW-UHFFFAOYSA-N 6-bromo-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-1-propan-2-ylindazole-4-carboxamide Chemical compound C1=C(Br)C=C2N(C(C)C)N=C(C)C2=C1C(=O)NCC1=C(C)C=C(C)NC1=O OLASLWWQIDMLQW-UHFFFAOYSA-N 0.000 claims description 8
- BXDZOYLPNAIDOC-UHFFFAOYSA-N N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethyl]piperidine-4-carboxamide Chemical compound CC(C)(C)c1cnc(CSc2cnc(NC(=O)C3CCN(CC(=O)NCCOCCOCCOCCNc4cccc5C(=O)N(C6CCC(=O)NC6=O)C(=O)c45)CC3)s2)o1 BXDZOYLPNAIDOC-UHFFFAOYSA-N 0.000 claims description 8
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 8
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 8
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 8
- 206010039491 Sarcoma Diseases 0.000 claims description 8
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 8
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 8
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 8
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 8
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 8
- 238000002560 therapeutic procedure Methods 0.000 claims description 8
- UEBBCHPIFFPKKL-UHFFFAOYSA-N 1h-indazole-4-carboxamide Chemical compound NC(=O)C1=CC=CC2=C1C=NN2 UEBBCHPIFFPKKL-UHFFFAOYSA-N 0.000 claims description 7
- ZGOJVLXLWFOHNA-UHFFFAOYSA-N 6-bromo-3-methyl-n-[(6-methyl-2-oxo-4-propyl-1h-pyridin-3-yl)methyl]-1-propan-2-ylindazole-4-carboxamide Chemical compound C1=C(C)NC(=O)C(CNC(=O)C=2C=3C(C)=NN(C=3C=C(Br)C=2)C(C)C)=C1CCC ZGOJVLXLWFOHNA-UHFFFAOYSA-N 0.000 claims description 7
- 125000004442 acylamino group Chemical group 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 210000000481 breast Anatomy 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 5
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 210000004072 lung Anatomy 0.000 claims description 5
- DFOGUQBUSZYUGI-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-1-propan-2-yl-6-pyridin-3-ylindazole-4-carboxamide Chemical compound C1=C2N(C(C)C)N=C(C)C2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=CN=C1 DFOGUQBUSZYUGI-UHFFFAOYSA-N 0.000 claims description 5
- 210000002307 prostate Anatomy 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims description 4
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 4
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 claims description 4
- BVOCDORKYUBPEM-UHFFFAOYSA-N 6-bromo-1-cyclopropyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]indazole-4-carboxamide Chemical compound O=C1NC(C)=CC(C)=C1CNC(=O)C1=CC(Br)=CC2=C1C=NN2C1CC1 BVOCDORKYUBPEM-UHFFFAOYSA-N 0.000 claims description 4
- BVXRLMQXDFUWKE-UHFFFAOYSA-N 6-bromo-n-[(4-ethyl-6-methyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylindazole-4-carboxamide Chemical compound C1=C(C)NC(=O)C(CNC(=O)C=2C=3C=NN(C=3C=C(Br)C=2)C(C)C)=C1CC BVXRLMQXDFUWKE-UHFFFAOYSA-N 0.000 claims description 4
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 4
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 claims description 4
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 4
- DPOPAJRDYZGTIR-UHFFFAOYSA-N Tetrazine Chemical compound C1=CN=NN=N1 DPOPAJRDYZGTIR-UHFFFAOYSA-N 0.000 claims description 4
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 4
- 208000008383 Wilms tumor Diseases 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 4
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 claims description 4
- 210000001072 colon Anatomy 0.000 claims description 4
- 230000002496 gastric effect Effects 0.000 claims description 4
- 208000005017 glioblastoma Diseases 0.000 claims description 4
- TXMUSRGMRSEYEF-UHFFFAOYSA-N n-[(6-methyl-2-oxo-4-propyl-1h-pyridin-3-yl)methyl]-1-propan-2-yl-6-(1h-pyrazol-4-yl)indazole-4-carboxamide Chemical compound C1=C(C)NC(=O)C(CNC(=O)C=2C=3C=NN(C=3C=C(C=2)C2=CNN=C2)C(C)C)=C1CCC TXMUSRGMRSEYEF-UHFFFAOYSA-N 0.000 claims description 4
- UNEADCSXFLNROG-UHFFFAOYSA-N n-[(6-methyl-2-oxo-4-propyl-1h-pyridin-3-yl)methyl]-1-propan-2-yl-6-thiophen-3-ylindazole-4-carboxamide Chemical compound C1=C(C)NC(=O)C(CNC(=O)C=2C=3C=NN(C=3C=C(C=2)C2=CSC=C2)C(C)C)=C1CCC UNEADCSXFLNROG-UHFFFAOYSA-N 0.000 claims description 4
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 4
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 4
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 4
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 4
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 4
- 229930192474 thiophene Natural products 0.000 claims description 4
- 150000003852 triazoles Chemical class 0.000 claims description 4
- GJSJWJVRDINZMM-UHFFFAOYSA-N 3-methyl-n-[(6-methyl-2-oxo-4-propyl-1h-pyridin-3-yl)methyl]-1-propan-2-yl-6-(1h-pyrrolo[2,3-b]pyridin-5-yl)indazole-4-carboxamide Chemical compound C1=C(C)NC(=O)C(CNC(=O)C=2C=3C(C)=NN(C=3C=C(C=2)C=2C=C3C=CNC3=NC=2)C(C)C)=C1CCC GJSJWJVRDINZMM-UHFFFAOYSA-N 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- RCYCPGOMWYHJQG-UHFFFAOYSA-N 6-[3-[(dimethylamino)methyl]phenyl]-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylindazole-4-carboxamide Chemical compound C1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=CC(CN(C)C)=C1 RCYCPGOMWYHJQG-UHFFFAOYSA-N 0.000 claims description 3
- NXXGIDJYUSXAGR-UHFFFAOYSA-N 6-[4-(dimethylamino)piperidin-1-yl]-n-[(6-methyl-2-oxo-4-propyl-1h-pyridin-3-yl)methyl]-1-propan-2-ylindazole-4-carboxamide Chemical compound C1=C(C)NC(=O)C(CNC(=O)C=2C=3C=NN(C=3C=C(C=2)N2CCC(CC2)N(C)C)C(C)C)=C1CCC NXXGIDJYUSXAGR-UHFFFAOYSA-N 0.000 claims description 3
- VCTVCAHXSCBTIV-UHFFFAOYSA-N 6-amino-1-cyclopentyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]indazole-4-carboxamide Chemical compound O=C1NC(C)=CC(C)=C1CNC(=O)C1=CC(N)=CC2=C1C=NN2C1CCCC1 VCTVCAHXSCBTIV-UHFFFAOYSA-N 0.000 claims description 3
- OVBSOJWDIWHWAC-UHFFFAOYSA-N 6-bromo-1-ethyl-n-[(6-methyl-2-oxo-4-propyl-1h-pyridin-3-yl)methyl]indazole-4-carboxamide Chemical compound C1=C(C)NC(=O)C(CNC(=O)C=2C=3C=NN(CC)C=3C=C(Br)C=2)=C1CCC OVBSOJWDIWHWAC-UHFFFAOYSA-N 0.000 claims description 3
- CYJJFWKYQORJPX-UHFFFAOYSA-N 6-bromo-n-[(4-cyclohexyl-6-methyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylindazole-4-carboxamide Chemical compound C1=C(Br)C=C2N(C(C)C)N=CC2=C1C(=O)NCC(C(NC(C)=C1)=O)=C1C1CCCCC1 CYJJFWKYQORJPX-UHFFFAOYSA-N 0.000 claims description 3
- IXXVIPIZRVJMQU-UHFFFAOYSA-N 6-bromo-n-[(6-methyl-2-oxo-4-propyl-1h-pyridin-3-yl)methyl]-1-propylindazole-4-carboxamide Chemical compound C1=C(C)NC(=O)C(CNC(=O)C=2C=3C=NN(CCC)C=3C=C(Br)C=2)=C1CCC IXXVIPIZRVJMQU-UHFFFAOYSA-N 0.000 claims description 3
- RBWPGWVOALJICT-UHFFFAOYSA-N 6-chloro-1-cyclopentyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]indazole-4-carboxamide Chemical compound O=C1NC(C)=CC(C)=C1CNC(=O)C1=CC(Cl)=CC2=C1C=NN2C1CCCC1 RBWPGWVOALJICT-UHFFFAOYSA-N 0.000 claims description 3
- YKCJCGRGAMZXDQ-UHFFFAOYSA-N 6-cyano-1-cyclopentyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]indazole-4-carboxamide Chemical compound O=C1NC(C)=CC(C)=C1CNC(=O)C1=CC(C#N)=CC2=C1C=NN2C1CCCC1 YKCJCGRGAMZXDQ-UHFFFAOYSA-N 0.000 claims description 3
- 206010018338 Glioma Diseases 0.000 claims description 3
- 210000004556 brain Anatomy 0.000 claims description 3
- 210000003128 head Anatomy 0.000 claims description 3
- 208000032839 leukemia Diseases 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- NGRCZIIXFAVIKW-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-1-propan-2-yl-6-(1h-pyrazol-4-yl)indazole-4-carboxamide Chemical compound C1=C2N(C(C)C)N=C(C)C2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C=1C=NNC=1 NGRCZIIXFAVIKW-UHFFFAOYSA-N 0.000 claims description 3
- SUZBIHASJDTMLT-UHFFFAOYSA-N n-[(4-cyclohexyl-6-methyl-2-oxo-1h-pyridin-3-yl)methyl]-6-cyclopropyl-1-propan-2-ylindazole-4-carboxamide Chemical compound C1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C2CCCCC2)=O)C=C1C1CC1 SUZBIHASJDTMLT-UHFFFAOYSA-N 0.000 claims description 3
- 210000003739 neck Anatomy 0.000 claims description 3
- 201000008968 osteosarcoma Diseases 0.000 claims description 3
- 230000002611 ovarian Effects 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 210000003932 urinary bladder Anatomy 0.000 claims description 3
- JWEHQNHCUMVORM-UHFFFAOYSA-N 1-cyclopentyl-6-[4-[(dimethylamino)methyl]phenyl]-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]indazole-4-carboxamide Chemical compound C1=CC(CN(C)C)=CC=C1C1=CC(C(=O)NCC=2C(NC(C)=CC=2C)=O)=C(C=NN2C3CCCC3)C2=C1 JWEHQNHCUMVORM-UHFFFAOYSA-N 0.000 claims description 2
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- UPQLMUFNEBEHQI-UHFFFAOYSA-N 1-cyclopentyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(1-methylpyrazol-4-yl)indazole-4-carboxamide Chemical compound O=C1NC(C)=CC(C)=C1CNC(=O)C1=CC(C2=CN(C)N=C2)=CC2=C1C=NN2C1CCCC1 UPQLMUFNEBEHQI-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
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- Pulmonology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33231210P | 2010-05-07 | 2010-05-07 | |
| US332312P | 2010-05-07 | ||
| PCT/US2011/035340 WO2011140325A1 (en) | 2010-05-07 | 2011-05-05 | Indazoles |
Publications (1)
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| ES2534804T3 true ES2534804T3 (es) | 2015-04-28 |
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| ES11778335.7T Active ES2534804T3 (es) | 2010-05-07 | 2011-05-05 | Indazoles |
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| US (2) | US8846935B2 (https=) |
| EP (1) | EP2566328B1 (https=) |
| JP (1) | JP5864546B2 (https=) |
| ES (1) | ES2534804T3 (https=) |
| WO (1) | WO2011140325A1 (https=) |
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| EA023788B1 (ru) * | 2010-05-07 | 2016-07-29 | ГЛЭКСОСМИТКЛАЙН ЭлЭлСи | Производные индола и фармацевтические композиции на их основе |
| WO2011160206A1 (en) | 2010-06-23 | 2011-12-29 | Morin Ryan D | Biomarkers for non-hodgkin lymphomas and uses thereof |
| BR112013005806B1 (pt) | 2010-09-10 | 2022-05-10 | Epizyme, Inc | Métodos para detectar se um indivíduo é um candidato para o tratamento com ou responsivo a um inibidor de ezh2 e usos terapêuticos do dito inibidor de ezh2 |
| US9175331B2 (en) | 2010-09-10 | 2015-11-03 | Epizyme, Inc. | Inhibitors of human EZH2, and methods of use thereof |
| EP2646020B1 (en) * | 2010-12-01 | 2016-09-21 | Glaxosmithkline LLC | Indoles |
| WO2012118812A2 (en) * | 2011-02-28 | 2012-09-07 | Epizyme, Inc. | Substituted 6,5-fused bicyclic heteroaryl compounds |
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