JP6530758B2 - 抗酸化性炎症調節剤としてのアリールおよびアリールアルキル置換されたピラゾリルおよびピリミジニル三環式エノン類 - Google Patents

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Publication number

JP6530758B2

JP6530758B2 JP2016548158A JP2016548158A JP6530758B2 JP 6530758 B2 JP6530758 B2 JP 6530758B2 JP 2016548158 A JP2016548158 A JP 2016548158A JP 2016548158 A JP2016548158 A JP 2016548158A JP 6530758 B2 JP6530758 B2 JP 6530758B2

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JP

Japan

Prior art keywords

oxo

phenyl

carbonitrile

methyl

quinazoline

Prior art date

2014-01-24

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.)

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• 125000003118 aryl group Chemical group 0.000 title claims description 29
• 125000003710 aryl alkyl group Chemical group 0.000 title claims description 9
• 230000004054 inflammatory process Effects 0.000 title description 33
• 206010061218 Inflammation Diseases 0.000 title description 26
• 230000003078 antioxidant effect Effects 0.000 title description 7
• 125000003226 pyrazolyl group Chemical group 0.000 title description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims description 519
• -1 pyrrolidinocarbonyl Chemical group 0.000 claims description 357
• 229910052736 halogen Inorganic materials 0.000 claims description 222
• 150000002367 halogens Chemical group 0.000 claims description 218
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 202
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 198
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 195
• 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 185
• 229910052739 hydrogen Inorganic materials 0.000 claims description 151
• 239000001257 hydrogen Substances 0.000 claims description 151
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 117
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 96
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 75
• 125000004043 oxo group Chemical group O=* 0.000 claims description 74
• 238000000034 method Methods 0.000 claims description 49
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 45
• 150000003839 salts Chemical class 0.000 claims description 41
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 37
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 34
• 239000003814 drug Substances 0.000 claims description 31
• 125000005843 halogen group Chemical group 0.000 claims description 27
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
• 230000002757 inflammatory effect Effects 0.000 claims description 24
• 201000010099 disease Diseases 0.000 claims description 23
• 125000001072 heteroaryl group Chemical group 0.000 claims description 23
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 21
• 125000001424 substituent group Chemical group 0.000 claims description 21
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 17
• 238000004519 manufacturing process Methods 0.000 claims description 17
• 229910052757 nitrogen Inorganic materials 0.000 claims description 17
• 125000000217 alkyl group Chemical group 0.000 claims description 16
• 239000002253 acid Substances 0.000 claims description 15
• 125000004429 atom Chemical group 0.000 claims description 12
• 125000000623 heterocyclic group Chemical group 0.000 claims description 12
• 125000003545 alkoxy group Chemical group 0.000 claims description 10
• 239000008194 pharmaceutical composition Substances 0.000 claims description 10
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
• 229910052717 sulfur Inorganic materials 0.000 claims description 9
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
• 239000003937 drug carrier Substances 0.000 claims description 7
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 6
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 5
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
• AZVFCRSFDDZELR-QKMWGZLOSA-N (6aS,7S,10aR)-7-methyl-8-oxo-10a-phenyl-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound C[C@@H]1C(C(=C[C@]2([C@H]1CCC=1C=NC=NC21)C2=CC=CC=C2)C#N)=O AZVFCRSFDDZELR-QKMWGZLOSA-N 0.000 claims description 4
• RAWIZVKDCOKRFG-UHFFFAOYSA-N 2,6-dimethyl-7-oxo-3,9a-diphenyl-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound CN1N=C2C3(C(CCC2=C1C1=CC=CC=C1)C(C(C(=C3)C#N)=O)C)C3=CC=CC=C3 RAWIZVKDCOKRFG-UHFFFAOYSA-N 0.000 claims description 4
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
• LUQVCHRDAGWYMG-UHFFFAOYSA-N 4-phenylbenzamide Chemical compound C1=CC(C(=O)N)=CC=C1C1=CC=CC=C1 LUQVCHRDAGWYMG-UHFFFAOYSA-N 0.000 claims description 4
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
• 125000004245 indazol-3-yl group Chemical group [H]N1N=C(*)C2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 4
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 4
• HUHJYNHOCNVMFH-UHFFFAOYSA-N 1,6-dimethyl-7-oxo-3,9a-diphenyl-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound CN1N=C(C=2CCC3C(C12)(C=C(C(C3C)=O)C#N)C3=CC=CC=C3)C3=CC=CC=C3 HUHJYNHOCNVMFH-UHFFFAOYSA-N 0.000 claims description 3
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 3
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
• 125000005154 alkyl sulfonyl amino alkyl group Chemical group 0.000 claims description 3
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
• 125000004434 sulfur atom Chemical group 0.000 claims description 3
• NMMWZJOLCAXBSA-YSBYIQCSSA-N (5aS,6S,9aR)-1-[(4-bromophenyl)methyl]-6-methyl-7-oxo-9a-phenyl-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound BrC1=CC=C(CN2N=CC=3CC[C@@H]4[C@@](C23)(C=C(C([C@H]4C)=O)C#N)C4=CC=CC=C4)C=C1 NMMWZJOLCAXBSA-YSBYIQCSSA-N 0.000 claims description 2
• ATHDFANAWRPRAZ-QFMFQJCFSA-N (5aS,6S,9aR)-1-benzyl-6-methyl-7-oxo-9a-phenyl-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound C(C1=CC=CC=C1)N1N=CC=2CC[C@@H]3[C@@](C12)(C=C(C([C@H]3C)=O)C#N)C3=CC=CC=C3 ATHDFANAWRPRAZ-QFMFQJCFSA-N 0.000 claims description 2
• GTGHKFOYGLDTMC-YCYJEZDCSA-N (5aS,6S,9aR)-2,6-dimethyl-7-oxo-9a-phenyl-3-(3-pyridazin-4-ylphenyl)-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound CN1N=C2[C@@]3([C@@H](CCC2=C1C1=CC(=CC=C1)C1=CN=NC=C1)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3 GTGHKFOYGLDTMC-YCYJEZDCSA-N 0.000 claims description 2
• KMDYOZMRARBONF-XYQUQUKTSA-N (5aS,6S,9aR)-2,6-dimethyl-7-oxo-9a-phenyl-3-(4-pyridin-4-ylphenyl)-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound CN1N=C2[C@@]3([C@@H](CCC2=C1C1=CC=C(C=C1)C1=CC=NC=C1)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3 KMDYOZMRARBONF-XYQUQUKTSA-N 0.000 claims description 2
• OIATUVJFTWKQLG-YCYJEZDCSA-N (5aS,6S,9aR)-2,6-dimethyl-7-oxo-9a-phenyl-3-(4-pyrimidin-5-ylphenyl)-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound CN1N=C2[C@@]3([C@@H](CCC2=C1C1=CC=C(C=C1)C=1C=NC=NC1)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3 OIATUVJFTWKQLG-YCYJEZDCSA-N 0.000 claims description 2
• DJYICBIKGCEVCJ-DGSCHONISA-N (5aS,6S,9aR)-2,6-dimethyl-7-oxo-9a-phenyl-3-[3-(1H-pyrazol-4-yl)phenyl]-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound CN1N=C2[C@@]3([C@@H](CCC2=C1C1=CC(=CC=C1)C=1C=NNC1)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3 DJYICBIKGCEVCJ-DGSCHONISA-N 0.000 claims description 2
• BIIDHYPEVDDEAQ-ODLKPZKQSA-N (5aS,6S,9aR)-2-(2-aminoacetyl)-9a-(4-fluorophenyl)-6-methyl-7-oxo-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound FC1=CC=C(C=C1)[C@]12[C@@H](CCC3=CN(N=C13)C(CN)=O)[C@@H](C(C(=C2)C#N)=O)C BIIDHYPEVDDEAQ-ODLKPZKQSA-N 0.000 claims description 2
• YTFINPWBGPHHBL-QFMFQJCFSA-N (5aS,6S,9aR)-2-benzyl-6-methyl-7-oxo-9a-phenyl-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound C(C1=CC=CC=C1)N1N=C2[C@@]3([C@@H](CCC2=C1)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3 YTFINPWBGPHHBL-QFMFQJCFSA-N 0.000 claims description 2
• JUPXMAVHBZAZRZ-AWCXEYNZSA-N (5aS,6S,9aR)-3-(3-bromophenyl)-2,6-dimethyl-7-oxo-9a-phenyl-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound BrC=1C=C(C=CC1)C=1N(N=C2[C@@]3([C@@H](CCC12)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3)C JUPXMAVHBZAZRZ-AWCXEYNZSA-N 0.000 claims description 2
• OEIIAUFTELVOGV-VVIOKTKKSA-N (5aS,6S,9aR)-3-[3-(2-methoxypyrimidin-5-yl)phenyl]-2,6-dimethyl-7-oxo-9a-phenyl-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound COC1=NC=C(C=N1)C=1C=C(C=CC1)C=1N(N=C2[C@@]3([C@@H](CCC12)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3)C OEIIAUFTELVOGV-VVIOKTKKSA-N 0.000 claims description 2
• IVKVPTDHGYGGIE-OAAQJRNLSA-N (5aS,6S,9aR)-3-[3-(4-aminophenyl)phenyl]-2,6-dimethyl-7-oxo-9a-phenyl-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound NC1=CC=C(C=C1)C1=CC(=CC=C1)C=1N(N=C2[C@@]3([C@@H](CCC12)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3)C IVKVPTDHGYGGIE-OAAQJRNLSA-N 0.000 claims description 2
• UEMMLTWREZDAOT-FKHUDQKESA-N (5aS,6S,9aR)-6-methyl-7-oxo-9a-phenyl-3-pyridazin-4-yl-4,5,5a,6-tetrahydro-1H-benzo[g]indazole-8-carbonitrile Chemical compound C[C@@H]1C(C(=C[C@]2([C@H]1CCC1=C(NN=C21)C2=CN=NC=C2)C2=CC=CC=C2)C#N)=O UEMMLTWREZDAOT-FKHUDQKESA-N 0.000 claims description 2
• BINSJSYDSMEWJB-WQFAYQGZSA-N (5aS,6S,9aR)-9a-(3-fluorophenyl)-6-methyl-7-oxo-4,5,5a,6-tetrahydro-1H-benzo[g]indazole-8-carbonitrile Chemical compound FC=1C=C(C=CC1)[C@]12[C@@H](CCC3=CNN=C13)[C@@H](C(C(=C2)C#N)=O)C BINSJSYDSMEWJB-WQFAYQGZSA-N 0.000 claims description 2
• WWUZWZOMKLCHCW-WQFAYQGZSA-N (5aS,6S,9aR)-9a-(4-fluorophenyl)-6-methyl-7-oxo-4,5,5a,6-tetrahydro-1H-benzo[g]indazole-8-carbonitrile Chemical compound FC1=CC=C(C=C1)[C@]12[C@@H](CCC3=CNN=C13)[C@@H](C(C(=C2)C#N)=O)C WWUZWZOMKLCHCW-WQFAYQGZSA-N 0.000 claims description 2
• SKVGEYUPPXIOGD-CYFODOTGSA-N (5aS,6S,9aR)-9a-(4-methoxyphenyl)-6-methyl-7-oxo-4,5,5a,6-tetrahydro-1H-benzo[g]indazole-8-carbonitrile Chemical compound COC1=CC=C(C=C1)[C@]12[C@@H](CCC3=CNN=C13)[C@@H](C(C(=C2)C#N)=O)C SKVGEYUPPXIOGD-CYFODOTGSA-N 0.000 claims description 2
• GMYLFVJDSODESE-DOPOYZHKSA-N (6S,9aR)-2,6-dimethyl-7-oxo-9a-phenyl-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound CN1N=C2[C@@]3(C(CCC2=C1)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3 GMYLFVJDSODESE-DOPOYZHKSA-N 0.000 claims description 2
• BCZLHEKPDBAGID-BTOQJYRJSA-N (6S,9aR)-2-(2-hydroxyacetyl)-6-methyl-7-oxo-9a-phenyl-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound C(CO)(=O)N1N=C2[C@@]3(C(CCC2=C1)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3 BCZLHEKPDBAGID-BTOQJYRJSA-N 0.000 claims description 2
• MSKBQMXQARALCB-LJVBMILOSA-N (6S,9aR)-2-(benzenesulfonyl)-6-methyl-7-oxo-9a-phenyl-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound C[C@@H]1C(C(=C[C@]2(C1CCC1=CN(N=C21)S(=O)(=O)C2=CC=CC=C2)C2=CC=CC=C2)C#N)=O MSKBQMXQARALCB-LJVBMILOSA-N 0.000 claims description 2
• IANKUZOPOZLZFB-MVDNPXKASA-N (6S,9aR)-2-acetyl-6-methyl-7-oxo-9a-phenyl-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound C(C)(=O)N1N=C2[C@@]3(C(CCC2=C1)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3 IANKUZOPOZLZFB-MVDNPXKASA-N 0.000 claims description 2
• UALACOPEMJMVGN-BISKEDJESA-N (6S,9aR)-2-benzoyl-6-methyl-7-oxo-9a-phenyl-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound C(C1=CC=CC=C1)(=O)N1N=C2[C@@]3(C(CCC2=C1)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3 UALACOPEMJMVGN-BISKEDJESA-N 0.000 claims description 2
• CWZKSFMJWTXWJQ-UWRZYQEDSA-N (6S,9aR)-3-(3-hydroxyphenyl)-6-methyl-7-oxo-9a-phenyl-4,5,5a,6-tetrahydro-1H-benzo[g]indazole-8-carbonitrile Chemical compound OC=1C=C(C=CC1)C=1NN=C2[C@@]3(C(CCC12)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3 CWZKSFMJWTXWJQ-UWRZYQEDSA-N 0.000 claims description 2
• GFEROVFRRCQZTR-LXFBUAEQSA-N (6S,9aR)-3-(6-aminopyridin-3-yl)-6-methyl-7-oxo-9a-phenyl-4,5,5a,6-tetrahydro-1H-benzo[g]indazole-8-carbonitrile Chemical compound NC1=CC=C(C=N1)C=1NN=C2[C@@]3(C(CCC12)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3 GFEROVFRRCQZTR-LXFBUAEQSA-N 0.000 claims description 2
• FYEMHADBQMHVMU-FJTYFYTASA-N (6S,9aR)-3-[1-(2-hydroxyethyl)pyrazol-4-yl]-6-methyl-7-oxo-9a-phenyl-4,5,5a,6-tetrahydro-1H-benzo[g]indazole-8-carbonitrile Chemical compound OCCN1N=CC(=C1)C=1NN=C2[C@@]3(C(CCC12)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3 FYEMHADBQMHVMU-FJTYFYTASA-N 0.000 claims description 2
• UULJTNDJXZKKKE-UWRZYQEDSA-N (6S,9aR)-3-[5-(hydroxymethyl)pyridin-3-yl]-6-methyl-7-oxo-9a-phenyl-4,5,5a,6-tetrahydro-1H-benzo[g]indazole-8-carbonitrile Chemical compound OCC=1C=C(C=NC1)C=1NN=C2[C@@]3(C(CCC12)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3 UULJTNDJXZKKKE-UWRZYQEDSA-N 0.000 claims description 2
• DIXMVNYQPGHELS-DOPOYZHKSA-N (6S,9aR)-6-methyl-2-methylsulfonyl-7-oxo-9a-phenyl-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound C[C@@H]1C(C(=C[C@]2(C1CCC1=CN(N=C21)S(=O)(=O)C)C2=CC=CC=C2)C#N)=O DIXMVNYQPGHELS-DOPOYZHKSA-N 0.000 claims description 2
• IBCTVWRGHTZOCO-QKWRCOSUSA-N (6S,9aR)-6-methyl-3-(1-methylpyrazol-4-yl)-7-oxo-9a-phenyl-4,5,5a,6-tetrahydro-1H-benzo[g]indazole-8-carbonitrile Chemical compound C[C@@H]1C(C(=C[C@]2(C1CCC1=C(NN=C21)C=2C=NN(C2)C)C2=CC=CC=C2)C#N)=O IBCTVWRGHTZOCO-QKWRCOSUSA-N 0.000 claims description 2
• NGVKWRPAMFNWRM-BRASLUBNSA-N (6S,9aR)-6-methyl-7-oxo-9a-phenyl-2-(1,3-thiazole-4-carbonyl)-4,5,5a,6-tetrahydrobenzo[g]indazole-8-carbonitrile Chemical compound C[C@@H]1C(C(=C[C@]2(C1CCC1=CN(N=C21)C(=O)C=2N=CSC2)C2=CC=CC=C2)C#N)=O NGVKWRPAMFNWRM-BRASLUBNSA-N 0.000 claims description 2
• IPWFTHOLAOQTTB-FJTYFYTASA-N (6S,9aR)-6-methyl-7-oxo-9a-phenyl-3-pyridin-3-yl-4,5,5a,6-tetrahydro-1H-benzo[g]indazole-8-carbonitrile Chemical compound C[C@@H]1C(C(=C[C@]2(C1CCC1=C(NN=C21)C=2C=NC=CC2)C2=CC=CC=C2)C#N)=O IPWFTHOLAOQTTB-FJTYFYTASA-N 0.000 claims description 2
• RAXMUQCAGTVAGT-QKWRCOSUSA-N (6S,9aR)-6-methyl-7-oxo-9a-phenyl-3-pyrimidin-5-yl-4,5,5a,6-tetrahydro-1H-benzo[g]indazole-8-carbonitrile Chemical compound C[C@@H]1C(C(=C[C@]2(C1CCC1=C(NN=C21)C=2C=NC=NC2)C2=CC=CC=C2)C#N)=O RAXMUQCAGTVAGT-QKWRCOSUSA-N 0.000 claims description 2
• WWRYSJLVOMDRAJ-JFNNDOMUSA-N (6S,9aR)-6-methyl-7-oxo-9a-phenyl-4,5,5a,6-tetrahydro-1H-benzo[g]indazole-8-carbonitrile Chemical compound C[C@@H]1C(C(=C[C@]2(C1CCC1=CNN=C21)C2=CC=CC=C2)C#N)=O WWRYSJLVOMDRAJ-JFNNDOMUSA-N 0.000 claims description 2
• OOBOJZMKXLJTPT-MKVZMPEWSA-N (6S,9aR)-9a-(3-fluorophenyl)-3-[3-(3-hydroxypropyl)phenyl]-6-methyl-7-oxo-4,5,5a,6-tetrahydro-1H-benzo[g]indazole-8-carbonitrile Chemical compound FC=1C=C(C=CC1)[C@]12C(CCC3=C(NN=C13)C1=CC(=CC=C1)CCCO)[C@@H](C(C(=C2)C#N)=O)C OOBOJZMKXLJTPT-MKVZMPEWSA-N 0.000 claims description 2
• DUFNFTYAGCSURQ-ODUJOWDVSA-N (6S,9aR)-9a-(4-hydroxyphenyl)-6-methyl-7-oxo-4,5,5a,6-tetrahydro-1H-benzo[g]indazole-8-carbonitrile Chemical compound OC1=CC=C(C=C1)[C@]12C(CCC3=CNN=C13)[C@@H](C(C(=C2)C#N)=O)C DUFNFTYAGCSURQ-ODUJOWDVSA-N 0.000 claims description 2
• OMROOUUPQRXSJJ-OGLLEDLLSA-N (6aS,7S,10aR)-10a-(3-fluorophenyl)-2,7-dimethyl-8-oxo-4-pyrimidin-5-yl-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound FC=1C=C(C=CC1)[C@]12[C@@H](CCC=3C(=NC(=NC13)C)C=1C=NC=NC1)[C@@H](C(C(=C2)C#N)=O)C OMROOUUPQRXSJJ-OGLLEDLLSA-N 0.000 claims description 2
• OFLCZLMKGWREHS-CYFODOTGSA-N (6aS,7S,10aR)-10a-(3-hydroxyphenyl)-7-methyl-8-oxo-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound OC=1C=C(C=CC1)[C@]12[C@@H](CCC=3C=NC=NC13)[C@@H](C(C(=C2)C#N)=O)C OFLCZLMKGWREHS-CYFODOTGSA-N 0.000 claims description 2
• IFPXBZQPRFUNKA-LWLGHBPASA-N (6aS,7S,10aR)-10a-(4-fluorophenyl)-2,7-dimethyl-8-oxo-4-[4-(1H-pyrazol-5-yl)phenyl]-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound FC1=CC=C(C=C1)[C@]12[C@@H](CCC=3C(=NC(=NC13)C)C1=CC=C(C=C1)C1=CC=NN1)[C@@H](C(C(=C2)C#N)=O)C IFPXBZQPRFUNKA-LWLGHBPASA-N 0.000 claims description 2
• KDAZXMOWVRIKSJ-OGLLEDLLSA-N (6aS,7S,10aR)-10a-(4-fluorophenyl)-2,7-dimethyl-8-oxo-4-pyrimidin-5-yl-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound FC1=CC=C(C=C1)[C@]12[C@@H](CCC=3C(=NC(=NC13)C)C=1C=NC=NC1)[C@@H](C(C(=C2)C#N)=O)C KDAZXMOWVRIKSJ-OGLLEDLLSA-N 0.000 claims description 2
• KHMRQIYLSHTHMS-JOVVQLDHSA-N (6aS,7S,10aR)-10a-(4-fluorophenyl)-4-(1H-indazol-7-yl)-2,7-dimethyl-8-oxo-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound FC1=CC=C(C=C1)[C@]12[C@@H](CCC=3C(=NC(=NC13)C)C=1C=CC=C3C=NNC13)[C@@H](C(C(=C2)C#N)=O)C KHMRQIYLSHTHMS-JOVVQLDHSA-N 0.000 claims description 2
• MQSBFKFVRQTWLX-CYFODOTGSA-N (6aS,7S,10aR)-10a-(4-fluorophenyl)-7-methyl-8-oxo-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound FC1=CC=C(C=C1)[C@]12[C@@H](CCC=3C=NC=NC13)[C@@H](C(C(=C2)C#N)=O)C MQSBFKFVRQTWLX-CYFODOTGSA-N 0.000 claims description 2
• YUSZLMCTDZGGMR-CYFODOTGSA-N (6aS,7S,10aR)-10a-(4-hydroxyphenyl)-7-methyl-8-oxo-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound OC1=CC=C(C=C1)[C@]12[C@@H](CCC=3C=NC=NC13)[C@@H](C(C(=C2)C#N)=O)C YUSZLMCTDZGGMR-CYFODOTGSA-N 0.000 claims description 2
• CYFXOJBMPVPEGG-KCMSVQPVSA-N (6aS,7S,10aR)-10a-(4-methoxyphenyl)-2,7-dimethyl-4-(3-methylimidazol-4-yl)-8-oxo-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound COC1=CC=C(C=C1)[C@]12[C@@H](CCC=3C(=NC(=NC13)C)C1=CN=CN1C)[C@@H](C(C(=C2)C#N)=O)C CYFXOJBMPVPEGG-KCMSVQPVSA-N 0.000 claims description 2
• WUFVVUNDFNJTKP-LVAJYGNLSA-N (6aS,7S,10aR)-10a-(4-methoxyphenyl)-2,7-dimethyl-8-oxo-4-[4-(1H-pyrazol-5-yl)phenyl]-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound COC1=CC=C(C=C1)[C@]12[C@@H](CCC=3C(=NC(=NC13)C)C1=CC=C(C=C1)C1=CC=NN1)[C@@H](C(C(=C2)C#N)=O)C WUFVVUNDFNJTKP-LVAJYGNLSA-N 0.000 claims description 2
• BEXDMHJKPAPSBJ-CGLDCDAWSA-N (6aS,7S,10aR)-10a-(4-methoxyphenyl)-2,7-dimethyl-8-oxo-4-pyrimidin-5-yl-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound COC1=CC=C(C=C1)[C@]12[C@@H](CCC=3C(=NC(=NC13)C)C=1C=NC=NC1)[C@@H](C(C(=C2)C#N)=O)C BEXDMHJKPAPSBJ-CGLDCDAWSA-N 0.000 claims description 2
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• MVJLHSDKBOXXIJ-ZZTIUOAXSA-N (6aS,7S,10aR)-2,7-dimethyl-4-(2-methyl-1,3-thiazol-5-yl)-8-oxo-10a-phenyl-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound CC1=NC=2[C@@]3([C@@H](CCC2C(=N1)C1=CN=C(S1)C)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3 MVJLHSDKBOXXIJ-ZZTIUOAXSA-N 0.000 claims description 2
• VNDSSHCOQBRZLE-PCKXHRCSSA-N (6aS,7S,10aR)-2,7-dimethyl-4-(3-methylimidazol-4-yl)-8-oxo-10a-phenyl-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound CC1=NC=2[C@@]3([C@@H](CCC2C(=N1)C1=CN=CN1C)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3 VNDSSHCOQBRZLE-PCKXHRCSSA-N 0.000 claims description 2
• UYTJTEJQMMZOFE-VVIOKTKKSA-N (6aS,7S,10aR)-2,7-dimethyl-4-[4-(3-methylimidazol-4-yl)phenyl]-8-oxo-10a-phenyl-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound CC1=NC=2[C@@]3([C@@H](CCC2C(=N1)C1=CC=C(C=C1)C1=CN=CN1C)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3 UYTJTEJQMMZOFE-VVIOKTKKSA-N 0.000 claims description 2
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• QOBOEIPOZGNLHK-FGBDQBTKSA-N (6aS,7S,10aR)-2,7-dimethyl-8-oxo-10a-phenyl-4-(4-pyrimidin-5-ylphenyl)-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound CC1=NC=2[C@@]3([C@@H](CCC2C(=N1)C1=CC=C(C=C1)C=1C=NC=NC1)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3 QOBOEIPOZGNLHK-FGBDQBTKSA-N 0.000 claims description 2
• LRVAITHUZJQQCR-LVAJYGNLSA-N (6aS,7S,10aR)-2,7-dimethyl-8-oxo-10a-phenyl-4-(4-pyrimidin-5-ylphenyl)-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carboxamide Chemical compound CC1=NC=2[C@@]3([C@@H](CCC2C(=N1)C1=CC=C(C=C1)C=1C=NC=NC1)[C@@H](C(C(=C3)C(=O)N)=O)C)C3=CC=CC=C3 LRVAITHUZJQQCR-LVAJYGNLSA-N 0.000 claims description 2
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• QDVUBNTYGBPCTD-NIIFMQKASA-N (6aS,7S,10aR)-2-anilino-4-methoxy-7-methyl-8-oxo-10a-phenyl-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound N(C1=CC=CC=C1)C1=NC=2[C@@]3([C@@H](CCC2C(=N1)OC)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3 QDVUBNTYGBPCTD-NIIFMQKASA-N 0.000 claims description 2
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• FIMLNLXFIPIGOZ-CGLDCDAWSA-N (6aS,7S,10aR)-4-(1-acetylpyrazol-4-yl)-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound C(C)(=O)N1N=CC(=C1)C1=NC(=NC=2[C@@]3([C@@H](CCC12)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3)C FIMLNLXFIPIGOZ-CGLDCDAWSA-N 0.000 claims description 2
• LUBUCUGNQSSVMA-TXSNUYOVSA-N (6aS,7S,10aR)-4-(2,4-dioxo-1H-pyrimidin-5-yl)-10a-(4-fluorophenyl)-2,7-dimethyl-8-oxo-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound O=C1NC=C(C(N1)=O)C1=NC(=NC=2[C@@]3([C@@H](CCC12)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=C(C=C3)F)C LUBUCUGNQSSVMA-TXSNUYOVSA-N 0.000 claims description 2
• WRXZAEVSVSSTKZ-QFCZIGNWSA-N (6aS,7S,10aR)-4-(3-bromo-2H-indazol-7-yl)-10a-(4-fluorophenyl)-2,7-dimethyl-8-oxo-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound BrC1=NNC2=C(C=CC=C12)C1=NC(=NC=2[C@@]3([C@@H](CCC12)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=C(C=C3)F)C WRXZAEVSVSSTKZ-QFCZIGNWSA-N 0.000 claims description 2
• CVPYJVFMUMSARN-HNVUPHGUSA-N (6aS,7S,10aR)-4-(3-hydroxyphenyl)-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7-tetrahydrobenzo[h]quinazoline-9-carbonitrile Chemical compound OC=1C=C(C=CC1)C1=NC(=NC=2[C@@]3([C@@H](CCC12)[C@@H](C(C(=C3)C#N)=O)C)C3=CC=CC=C3)C CVPYJVFMUMSARN-HNVUPHGUSA-N 0.000 claims description 2
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