ES2616464T3 - Derivados de 3-Oxo-2,3-dihidro-1H-indazol-4-carboxamida como inhibidores de PARP-1 - Google Patents
Derivados de 3-Oxo-2,3-dihidro-1H-indazol-4-carboxamida como inhibidores de PARP-1 Download PDFInfo
- Publication number
- ES2616464T3 ES2616464T3 ES12737279.5T ES12737279T ES2616464T3 ES 2616464 T3 ES2616464 T3 ES 2616464T3 ES 12737279 T ES12737279 T ES 12737279T ES 2616464 T3 ES2616464 T3 ES 2616464T3
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- ES
- Spain
- Prior art keywords
- oxo
- dihydro
- indazol
- carboxamide
- alkyl
- Prior art date
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- 108010064218 Poly (ADP-Ribose) Polymerase-1 Proteins 0.000 title description 30
- 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 title description 14
- 239000003112 inhibitor Substances 0.000 title description 9
- VRGAOHSVOHSIER-UHFFFAOYSA-N 3-oxo-1,2-dihydroindazole-4-carboxamide Chemical class NC(=O)C1=CC=CC2=C1C(=O)NN2 VRGAOHSVOHSIER-UHFFFAOYSA-N 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 201
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 110
- 125000003118 aryl group Chemical group 0.000 claims abstract description 60
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 45
- 239000001257 hydrogen Substances 0.000 claims abstract description 45
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 43
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 40
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 30
- 150000002367 halogens Chemical group 0.000 claims abstract description 29
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 21
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 21
- 101100295741 Gallus gallus COR4 gene Chemical group 0.000 claims abstract description 21
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 15
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 9
- 101100134922 Gallus gallus COR5 gene Chemical group 0.000 claims abstract description 3
- -1 4,4-difluorocyclohexyl Chemical group 0.000 claims description 69
- 238000006243 chemical reaction Methods 0.000 claims description 40
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 39
- 238000000034 method Methods 0.000 claims description 38
- 206010028980 Neoplasm Diseases 0.000 claims description 25
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 230000008569 process Effects 0.000 claims description 13
- 108090000623 proteins and genes Proteins 0.000 claims description 13
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 102000004169 proteins and genes Human genes 0.000 claims description 11
- 229940127089 cytotoxic agent Drugs 0.000 claims description 10
- 230000005764 inhibitory process Effects 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- 239000002246 antineoplastic agent Substances 0.000 claims description 9
- 201000011510 cancer Diseases 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- 229940100198 alkylating agent Drugs 0.000 claims description 8
- 239000002168 alkylating agent Substances 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 230000007062 hydrolysis Effects 0.000 claims description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims description 7
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 6
- 238000005658 halogenation reaction Methods 0.000 claims description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- WEUSDVLSZAFNCO-UHFFFAOYSA-N 2-[1-(4,4-difluorocyclohexyl)piperidin-4-yl]-3-oxo-1h-indazole-4-carboxamide Chemical compound O=C1C=2C(C(=O)N)=CC=CC=2NN1C(CC1)CCN1C1CCC(F)(F)CC1 WEUSDVLSZAFNCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- QTAAMFZROWGTBV-UHFFFAOYSA-N 1-methyl-3-oxo-2-(1-propan-2-ylpiperidin-4-yl)indazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1N1C(=O)C2=C(C(N)=O)C=CC=C2N1C QTAAMFZROWGTBV-UHFFFAOYSA-N 0.000 claims description 3
- TVMQVMPQEYUIGQ-UHFFFAOYSA-N 1-methyl-3-oxo-2-[1-(thiophen-2-ylmethyl)piperidin-4-yl]indazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(C)N1C(CC1)CCN1CC1=CC=CS1 TVMQVMPQEYUIGQ-UHFFFAOYSA-N 0.000 claims description 3
- XCMZWTDSYWVLET-UHFFFAOYSA-N 1-methyl-3-oxo-2-piperidin-4-ylindazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(C)N1C1CCNCC1 XCMZWTDSYWVLET-UHFFFAOYSA-N 0.000 claims description 3
- QNLAVJXTBVYHBB-UHFFFAOYSA-N 2-(1-cyclobutylpiperidin-4-yl)-1-methyl-3-oxoindazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(C)N1C(CC1)CCN1C1CCC1 QNLAVJXTBVYHBB-UHFFFAOYSA-N 0.000 claims description 3
- VPFGQWNBEHLGLL-UHFFFAOYSA-N 2-(1-cyclobutylpiperidin-4-yl)-3-oxo-1h-indazole-4-carboxamide Chemical compound O=C1C=2C(C(=O)N)=CC=CC=2NN1C(CC1)CCN1C1CCC1 VPFGQWNBEHLGLL-UHFFFAOYSA-N 0.000 claims description 3
- XPKUFZAKPWQMOR-UHFFFAOYSA-N 2-(1-cyclohexylpiperidin-4-yl)-1-methyl-3-oxoindazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(C)N1C(CC1)CCN1C1CCCCC1 XPKUFZAKPWQMOR-UHFFFAOYSA-N 0.000 claims description 3
- PQXUCBRUEQVEIZ-UHFFFAOYSA-N 2-(1-cyclohexylpiperidin-4-yl)-6-fluoro-1-methyl-3-oxoindazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=C(F)C=C2N(C)N1C(CC1)CCN1C1CCCCC1 PQXUCBRUEQVEIZ-UHFFFAOYSA-N 0.000 claims description 3
- OKBDXGNRRUXLQE-UHFFFAOYSA-N 2-(1-cyclohexylpiperidin-4-yl)-6-fluoro-3-oxo-1h-indazole-4-carboxamide Chemical compound O=C1C=2C(C(=O)N)=CC(F)=CC=2NN1C(CC1)CCN1C1CCCCC1 OKBDXGNRRUXLQE-UHFFFAOYSA-N 0.000 claims description 3
- NPMKKPKCZJHHCM-UHFFFAOYSA-N 2-(1-cyclopentylpiperidin-4-yl)-1-methyl-3-oxoindazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(C)N1C(CC1)CCN1C1CCCC1 NPMKKPKCZJHHCM-UHFFFAOYSA-N 0.000 claims description 3
- OVJIYLSTZRNOLG-UHFFFAOYSA-N 2-(1-cyclopentylpiperidin-4-yl)-3-oxo-1h-indazole-4-carboxamide Chemical compound O=C1C=2C(C(=O)N)=CC=CC=2NN1C(CC1)CCN1C1CCCC1 OVJIYLSTZRNOLG-UHFFFAOYSA-N 0.000 claims description 3
- SBXCLTZHGFAEGE-UHFFFAOYSA-N 2-(1-methylpiperidin-4-yl)-3-oxo-1h-indazole-4-carboxamide Chemical compound C1CN(C)CCC1N1C(=O)C2=C(C(N)=O)C=CC=C2N1 SBXCLTZHGFAEGE-UHFFFAOYSA-N 0.000 claims description 3
- SBDYFIHZQFQZCK-UHFFFAOYSA-N 2-[1-(cyclohex-3-en-1-ylmethyl)piperidin-4-yl]-1-methyl-3-oxoindazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(C)N1C(CC1)CCN1CC1CCC=CC1 SBDYFIHZQFQZCK-UHFFFAOYSA-N 0.000 claims description 3
- MHOBIUHIHRMJRE-UHFFFAOYSA-N 2-[1-(cyclohex-3-en-1-ylmethyl)piperidin-4-yl]-3-oxo-1h-indazole-4-carboxamide Chemical compound O=C1C=2C(C(=O)N)=CC=CC=2NN1C(CC1)CCN1CC1CCC=CC1 MHOBIUHIHRMJRE-UHFFFAOYSA-N 0.000 claims description 3
- HHODORPGMSMXQA-UHFFFAOYSA-N 2-[1-(cyclohexylmethyl)piperidin-4-yl]-1-methyl-3-oxoindazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(C)N1C(CC1)CCN1CC1CCCCC1 HHODORPGMSMXQA-UHFFFAOYSA-N 0.000 claims description 3
- SGRIRZRNZXPWOL-UHFFFAOYSA-N 2-[1-(furan-2-ylmethyl)piperidin-4-yl]-1-methyl-3-oxoindazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(C)N1C(CC1)CCN1CC1=CC=CO1 SGRIRZRNZXPWOL-UHFFFAOYSA-N 0.000 claims description 3
- FRGMDGKFVLOUCT-UHFFFAOYSA-N 2-[1-(furan-2-ylmethyl)piperidin-4-yl]-3-oxo-1h-indazole-4-carboxamide Chemical compound O=C1C=2C(C(=O)N)=CC=CC=2NN1C(CC1)CCN1CC1=CC=CO1 FRGMDGKFVLOUCT-UHFFFAOYSA-N 0.000 claims description 3
- OLJDWQJXPVXMDC-UHFFFAOYSA-N 3-oxo-2-[1-(thiophen-2-ylmethyl)piperidin-4-yl]-1h-indazole-4-carboxamide Chemical compound O=C1C=2C(C(=O)N)=CC=CC=2NN1C(CC1)CCN1CC1=CC=CS1 OLJDWQJXPVXMDC-UHFFFAOYSA-N 0.000 claims description 3
- OQWUKVQDDJFORM-UHFFFAOYSA-N 3-oxo-2-piperidin-4-yl-1h-indazole-4-carboxamide Chemical compound O=C1C=2C(C(=O)N)=CC=CC=2NN1C1CCNCC1 OQWUKVQDDJFORM-UHFFFAOYSA-N 0.000 claims description 3
- LIGDLZRFUNWVFK-UHFFFAOYSA-N 6-fluoro-1-methyl-3-oxo-2-piperidin-4-ylindazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=C(F)C=C2N(C)N1C1CCNCC1 LIGDLZRFUNWVFK-UHFFFAOYSA-N 0.000 claims description 3
- QSOQCQWTGJEJJX-UHFFFAOYSA-N 6-fluoro-3-oxo-2-piperidin-4-yl-1h-indazole-4-carboxamide Chemical compound O=C1C=2C(C(=O)N)=CC(F)=CC=2NN1C1CCNCC1 QSOQCQWTGJEJJX-UHFFFAOYSA-N 0.000 claims description 3
- 230000008878 coupling Effects 0.000 claims description 3
- 238000010168 coupling process Methods 0.000 claims description 3
- 238000005859 coupling reaction Methods 0.000 claims description 3
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- YGWYOZIKVSOHMN-UHFFFAOYSA-N 1-ethyl-3-oxo-2-piperidin-4-ylindazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(CC)N1C1CCNCC1 YGWYOZIKVSOHMN-UHFFFAOYSA-N 0.000 claims description 2
- QBPZRWOAIYPXFL-UHFFFAOYSA-N 1-ethyl-6-fluoro-3-oxo-2-piperidin-4-ylindazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=C(F)C=C2N(CC)N1C1CCNCC1 QBPZRWOAIYPXFL-UHFFFAOYSA-N 0.000 claims description 2
- VJFVDUPSYQILQW-UHFFFAOYSA-N 1-methyl-2-(1-methylpiperidin-4-yl)-3-oxoindazole-4-carboxamide Chemical compound C1CN(C)CCC1N1C(=O)C2=C(C(N)=O)C=CC=C2N1C VJFVDUPSYQILQW-UHFFFAOYSA-N 0.000 claims description 2
- MGGYINOUFRKASP-UHFFFAOYSA-N 1-methyl-3-oxo-2-(1-phenylpiperidin-4-yl)indazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(C)N1C(CC1)CCN1C1=CC=CC=C1 MGGYINOUFRKASP-UHFFFAOYSA-N 0.000 claims description 2
- DQUPPBNAKKNJCG-UHFFFAOYSA-N 1-methyl-3-oxo-2-(1-pyridin-3-ylpiperidin-4-yl)indazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(C)N1C(CC1)CCN1C1=CC=CN=C1 DQUPPBNAKKNJCG-UHFFFAOYSA-N 0.000 claims description 2
- ISZXVGQBWFOMRH-UHFFFAOYSA-N 1-methyl-3-oxo-2-(1-pyridin-4-ylpiperidin-4-yl)indazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(C)N1C(CC1)CCN1C1=CC=NC=C1 ISZXVGQBWFOMRH-UHFFFAOYSA-N 0.000 claims description 2
- OKQHBZNTIODWFQ-UHFFFAOYSA-N 1-methyl-3-oxo-2-(4-piperidin-4-ylphenyl)indazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(C)N1C(C=C1)=CC=C1C1CCNCC1 OKQHBZNTIODWFQ-UHFFFAOYSA-N 0.000 claims description 2
- CRRYCTZISQQIEO-UHFFFAOYSA-N 1-methyl-3-oxo-2-(4-pyridin-4-ylphenyl)indazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(C)N1C(C=C1)=CC=C1C1=CC=NC=C1 CRRYCTZISQQIEO-UHFFFAOYSA-N 0.000 claims description 2
- AFJWZGCQRIBDPC-UHFFFAOYSA-N 1-methyl-3-oxo-2-[1-(1h-pyrrol-2-ylmethyl)piperidin-4-yl]indazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(C)N1C(CC1)CCN1CC1=CC=CN1 AFJWZGCQRIBDPC-UHFFFAOYSA-N 0.000 claims description 2
- YPXYVWLWTAQXOJ-UHFFFAOYSA-N 1-methyl-3-oxo-2-[1-(1h-pyrrol-3-ylmethyl)piperidin-4-yl]indazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(C)N1C(CC1)CCN1CC=1C=CNC=1 YPXYVWLWTAQXOJ-UHFFFAOYSA-N 0.000 claims description 2
- UUQRRSAKFTVLLN-UHFFFAOYSA-N 2-(1-benzylpiperidin-4-yl)-1-methyl-3-oxoindazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(C)N1C(CC1)CCN1CC1=CC=CC=C1 UUQRRSAKFTVLLN-UHFFFAOYSA-N 0.000 claims description 2
- KLJGXEJQJQJADT-UHFFFAOYSA-N 2-(1-benzylpiperidin-4-yl)-3-oxo-1h-indazole-4-carboxamide Chemical compound O=C1C=2C(C(=O)N)=CC=CC=2NN1C(CC1)CCN1CC1=CC=CC=C1 KLJGXEJQJQJADT-UHFFFAOYSA-N 0.000 claims description 2
- WTZNVEJNRDYVFN-UHFFFAOYSA-N 2-(1-cyclobutylpiperidin-4-yl)-6-fluoro-1-methyl-3-oxoindazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=C(F)C=C2N(C)N1C(CC1)CCN1C1CCC1 WTZNVEJNRDYVFN-UHFFFAOYSA-N 0.000 claims description 2
- DHHMUTDEQQNNOC-UHFFFAOYSA-N 2-(1-cyclobutylpiperidin-4-yl)-6-fluoro-3-oxo-1h-indazole-4-carboxamide Chemical compound O=C1C=2C(C(=O)N)=CC(F)=CC=2NN1C(CC1)CCN1C1CCC1 DHHMUTDEQQNNOC-UHFFFAOYSA-N 0.000 claims description 2
- LQCUWVHLGPGETP-UHFFFAOYSA-N 2-(1-cyclohexylazetidin-3-yl)-1-methyl-3-oxoindazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(C)N1C(C1)CN1C1CCCCC1 LQCUWVHLGPGETP-UHFFFAOYSA-N 0.000 claims description 2
- UXDSIJGLPLQLFE-UHFFFAOYSA-N 2-(1-cyclohexylazetidin-3-yl)-3-oxo-1h-indazole-4-carboxamide Chemical compound O=C1C=2C(C(=O)N)=CC=CC=2NN1C(C1)CN1C1CCCCC1 UXDSIJGLPLQLFE-UHFFFAOYSA-N 0.000 claims description 2
- FGIOTWXUGHYOKV-UHFFFAOYSA-N 2-(1-cyclohexylazetidin-3-yl)-6-fluoro-1-methyl-3-oxoindazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=C(F)C=C2N(C)N1C(C1)CN1C1CCCCC1 FGIOTWXUGHYOKV-UHFFFAOYSA-N 0.000 claims description 2
- FEKOIQNXQNTNKL-UHFFFAOYSA-N 2-(1-cyclohexylpiperidin-4-yl)-1-ethyl-3-oxoindazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(CC)N1C(CC1)CCN1C1CCCCC1 FEKOIQNXQNTNKL-UHFFFAOYSA-N 0.000 claims description 2
- XEWGITPSXRGTBO-UHFFFAOYSA-N 2-(1-cyclohexylpiperidin-4-yl)-3-oxo-1h-indazole-4-carboxamide Chemical compound O=C1C=2C(C(=O)N)=CC=CC=2NN1C(CC1)CCN1C1CCCCC1 XEWGITPSXRGTBO-UHFFFAOYSA-N 0.000 claims description 2
- SAMGXLVBURJEJM-UHFFFAOYSA-N 2-(1-ethylpiperidin-4-yl)-1-methyl-3-oxoindazole-4-carboxamide Chemical compound C1CN(CC)CCC1N1C(=O)C2=C(C(N)=O)C=CC=C2N1C SAMGXLVBURJEJM-UHFFFAOYSA-N 0.000 claims description 2
- ZQZRXPFBEJPPKJ-UHFFFAOYSA-N 2-(1-ethylpiperidin-4-yl)-3-oxo-1h-indazole-4-carboxamide Chemical compound C1CN(CC)CCC1N1C(=O)C2=C(C(N)=O)C=CC=C2N1 ZQZRXPFBEJPPKJ-UHFFFAOYSA-N 0.000 claims description 2
- NWULWFVQKLIALI-UHFFFAOYSA-N 2-[1-(4,4-dichlorocyclohexyl)piperidin-4-yl]-1-methyl-3-oxoindazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(C)N1C(CC1)CCN1C1CCC(Cl)(Cl)CC1 NWULWFVQKLIALI-UHFFFAOYSA-N 0.000 claims description 2
- DNUXFVBNRHFGHK-UHFFFAOYSA-N 2-[1-(4,4-difluorocyclohexyl)piperidin-4-yl]-6-fluoro-1-methyl-3-oxoindazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=C(F)C=C2N(C)N1C(CC1)CCN1C1CCC(F)(F)CC1 DNUXFVBNRHFGHK-UHFFFAOYSA-N 0.000 claims description 2
- VFQDKRSLDGWGBS-UHFFFAOYSA-N 2-[1-(furan-3-ylmethyl)piperidin-4-yl]-1-methyl-3-oxoindazole-4-carboxamide Chemical compound O=C1C2=C(C(N)=O)C=CC=C2N(C)N1C(CC1)CCN1CC=1C=COC=1 VFQDKRSLDGWGBS-UHFFFAOYSA-N 0.000 claims description 2
- QKJLENNBYDTENH-UHFFFAOYSA-N 2-[1-(furan-3-ylmethyl)piperidin-4-yl]-3-oxo-1h-indazole-4-carboxamide Chemical compound O=C1C=2C(C(=O)N)=CC=CC=2NN1C(CC1)CCN1CC=1C=COC=1 QKJLENNBYDTENH-UHFFFAOYSA-N 0.000 claims description 2
- JHOLYZMPGXNVHM-UHFFFAOYSA-N 3-oxo-2-(1-phenylpiperidin-4-yl)-1h-indazole-4-carboxamide Chemical compound O=C1C=2C(C(=O)N)=CC=CC=2NN1C(CC1)CCN1C1=CC=CC=C1 JHOLYZMPGXNVHM-UHFFFAOYSA-N 0.000 claims description 2
- XTQOVBDMXJLDKF-UHFFFAOYSA-N 3-oxo-2-(1-propan-2-ylpiperidin-4-yl)-1h-indazole-4-carboxamide Chemical compound C1CN(C(C)C)CCC1N1C(=O)C2=C(C(N)=O)C=CC=C2N1 XTQOVBDMXJLDKF-UHFFFAOYSA-N 0.000 claims description 2
- OSXUFLZXPJVGDL-UHFFFAOYSA-N 3-oxo-2-(1-propylpiperidin-4-yl)-1h-indazole-4-carboxamide Chemical compound C1CN(CCC)CCC1N1C(=O)C2=C(C(N)=O)C=CC=C2N1 OSXUFLZXPJVGDL-UHFFFAOYSA-N 0.000 claims description 2
- WIZBDMUANSAVNW-UHFFFAOYSA-N 3-oxo-2-(1-pyridin-3-ylpiperidin-4-yl)-1h-indazole-4-carboxamide Chemical compound O=C1C=2C(C(=O)N)=CC=CC=2NN1C(CC1)CCN1C1=CC=CN=C1 WIZBDMUANSAVNW-UHFFFAOYSA-N 0.000 claims description 2
- ZPNWGLVAEKFEGJ-UHFFFAOYSA-N 3-oxo-2-(1-pyridin-4-ylpiperidin-4-yl)-1h-indazole-4-carboxamide Chemical compound O=C1C=2C(C(=O)N)=CC=CC=2NN1C(CC1)CCN1C1=CC=NC=C1 ZPNWGLVAEKFEGJ-UHFFFAOYSA-N 0.000 claims description 2
- RXSSHKKBZKSMAA-UHFFFAOYSA-N 3-oxo-2-(4-piperidin-4-ylphenyl)-1h-indazole-4-carboxamide Chemical compound O=C1C=2C(C(=O)N)=CC=CC=2NN1C(C=C1)=CC=C1C1CCNCC1 RXSSHKKBZKSMAA-UHFFFAOYSA-N 0.000 claims description 2
- IXTUKDJLYHRMHS-UHFFFAOYSA-N 3-oxo-2-(4-pyridin-3-ylphenyl)-1h-indazole-4-carboxamide Chemical compound O=C1C=2C(C(=O)N)=CC=CC=2NN1C(C=C1)=CC=C1C1=CC=CN=C1 IXTUKDJLYHRMHS-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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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
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
-
- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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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
- 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
- C07D401/10—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 carbon chain containing aromatic rings
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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
- C07D401/14—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 three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11175355 | 2011-07-26 | ||
| EP11175355 | 2011-07-26 | ||
| EP12167336 | 2012-05-09 | ||
| EP12167336 | 2012-05-09 | ||
| PCT/EP2012/064054 WO2013014038A1 (en) | 2011-07-26 | 2012-07-18 | 3-oxo-2,3-dihydro-1h-indazole-4-carboxamide derivatives as parp-1 inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2616464T3 true ES2616464T3 (es) | 2017-06-13 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES12737279.5T Active ES2616464T3 (es) | 2011-07-26 | 2012-07-18 | Derivados de 3-Oxo-2,3-dihidro-1H-indazol-4-carboxamida como inhibidores de PARP-1 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US9073893B2 (enExample) |
| EP (1) | EP2736896B1 (enExample) |
| JP (1) | JP5902299B2 (enExample) |
| ES (1) | ES2616464T3 (enExample) |
| WO (1) | WO2013014038A1 (enExample) |
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|---|---|---|---|---|
| CN104230896A (zh) * | 2013-06-17 | 2014-12-24 | 上海汇伦生命科技有限公司 | 苯并咪唑-2-哌嗪杂环类化合物、其药物组合物及其制备方法和用途 |
| UY36628A (es) | 2015-04-17 | 2016-11-30 | Abbvie Inc | Indazolonas como moduladores de la señalización de tnf |
| EP3288939A1 (en) | 2015-04-17 | 2018-03-07 | AbbVie Inc. | Tricyclic modulators of tnf signaling |
| UY36629A (es) | 2015-04-17 | 2016-11-30 | Abbvie Inc | Indazolonas como moduladores de la señalización de tnf |
| IL317573A (en) | 2022-06-15 | 2025-02-01 | Astrazeneca Ab | Combination therapy for cancer treatment |
| WO2024231548A1 (en) | 2023-05-11 | 2024-11-14 | Astrazeneca Ab | Combination of a parp1 inhibitor and a selective estrogen degrader for treating cancer |
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| US5036083A (en) | 1988-07-15 | 1991-07-30 | Ici Pharma | Heterocyclic agents |
| IL143303A0 (en) * | 1998-11-27 | 2002-04-21 | Basf Ag | Substituted benzimidazoles and their use as parp inhibitors |
| DE19918211A1 (de) * | 1999-04-22 | 2000-10-26 | Basf Ag | Cycloalkylsubstituierte Benzimidazole, deren Herstellung und Anwendung |
| AU7314200A (en) * | 1999-09-17 | 2001-04-24 | Yamanouchi Pharmaceutical Co., Ltd. | Benzimidazole derivatives |
| JPWO2002100833A1 (ja) | 2001-06-12 | 2004-09-24 | 住友製薬株式会社 | Rhoキナーゼ阻害剤 |
| DE602004023062D1 (en) * | 2003-03-31 | 2009-10-22 | Lilly Co Eli | 3-oxo-1,3-dihydro-indazol-2-carbonsäureamid derivate als phospholipase inhibitoren |
| CN101316834A (zh) * | 2005-09-29 | 2008-12-03 | 艾博特公司 | 在2位取代有苯基的1h-苯并咪唑-4-甲酰胺是强效parp抑制剂 |
| US7462724B2 (en) * | 2005-11-15 | 2008-12-09 | Abbott Laboratories | Substituted 1H-benzimidazole-4-carboxamides are potent PARP inhibitors |
| AU2007232297B2 (en) * | 2006-04-03 | 2012-09-20 | Msd Italia S.R.L. | Amide substituted indazole and benzotriazole derivatives as poly(ADP-ribose)polymerase (PARP) inhibitors |
| EP3536690A1 (en) * | 2007-01-10 | 2019-09-11 | MSD Italia S.r.l. | Amide substituted indazoles as poly(adp-ribose)polymerase (parp) inhibitors |
| WO2008141385A1 (en) * | 2007-05-21 | 2008-11-27 | Biota Scientific Management Pty Ltd | Viral polymerase inhibitors |
| US8067613B2 (en) * | 2007-07-16 | 2011-11-29 | Abbott Laboratories | Benzimidazole poly(ADP ribose)polymerase inhibitors |
| TWI499418B (zh) | 2009-05-21 | 2015-09-11 | Nerviano Medical Sciences Srl | 異喹啉-1(2h)-酮衍生物 |
| US8765972B2 (en) * | 2009-07-14 | 2014-07-01 | Nerviano Medical Sciences S.R.L. | 3-oxo-2,3-dihydro-1H-isoindole-4-carboxamides with selective PARP-1 inhibition |
| ES2759751T3 (es) * | 2009-07-14 | 2020-05-12 | Nerviano Medical Sciences Srl | 3-oxo-2,3-dihidro-1H-isoindol-4-carboxamidas |
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- 2012-07-18 EP EP12737279.5A patent/EP2736896B1/en active Active
- 2012-07-18 US US14/233,963 patent/US9073893B2/en active Active
- 2012-07-18 JP JP2014522035A patent/JP5902299B2/ja active Active
Also Published As
| Publication number | Publication date |
|---|---|
| EP2736896B1 (en) | 2016-12-14 |
| JP5902299B2 (ja) | 2016-04-13 |
| WO2013014038A1 (en) | 2013-01-31 |
| JP2014521620A (ja) | 2014-08-28 |
| US9073893B2 (en) | 2015-07-07 |
| US20140235675A1 (en) | 2014-08-21 |
| EP2736896A1 (en) | 2014-06-04 |
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