JP2017524026A5 - - Google Patents
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- Publication number
- JP2017524026A5 JP2017524026A5 JP2017510314A JP2017510314A JP2017524026A5 JP 2017524026 A5 JP2017524026 A5 JP 2017524026A5 JP 2017510314 A JP2017510314 A JP 2017510314A JP 2017510314 A JP2017510314 A JP 2017510314A JP 2017524026 A5 JP2017524026 A5 JP 2017524026A5
- Authority
- JP
- Japan
- Prior art keywords
- substituted
- alkyl
- methoxy
- pyrazol
- benzoyl
- 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.)
- Granted
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- 125000000217 alkyl group Chemical group 0.000 claims 115
- 229910052799 carbon Inorganic materials 0.000 claims 56
- 125000000623 heterocyclic group Chemical group 0.000 claims 49
- 229910052739 hydrogen Inorganic materials 0.000 claims 46
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 31
- -1 CN Inorganic materials 0.000 claims 29
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 25
- 229910052717 sulfur Inorganic materials 0.000 claims 21
- 229910052757 nitrogen Inorganic materials 0.000 claims 19
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 19
- 125000001072 heteroaryl group Chemical group 0.000 claims 18
- 125000003118 aryl group Chemical group 0.000 claims 15
- 229910052760 oxygen Inorganic materials 0.000 claims 15
- 150000001875 compounds Chemical class 0.000 claims 14
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 12
- 125000004452 carbocyclyl group Chemical group 0.000 claims 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 11
- 150000003839 salts Chemical class 0.000 claims 11
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims 10
- 125000006706 (C3-C6) carbocyclyl group Chemical group 0.000 claims 9
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 9
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 8
- VMVVGQBPWVSKFS-UHFFFAOYSA-N [2-(2-fluorophenyl)piperidin-1-yl]-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCCC1c1ccccc1F VMVVGQBPWVSKFS-UHFFFAOYSA-N 0.000 claims 7
- 125000000304 alkynyl group Chemical group 0.000 claims 7
- BSDRVXZZUUKHKX-UHFFFAOYSA-N 3-[1-(3-methoxy-4-pyrazolidin-4-ylbenzoyl)pyrrolidin-2-yl]-N-(1-methylpiperidin-4-yl)benzamide Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC1c1cccc(c1)C(=O)NC1CCN(C)CC1 BSDRVXZZUUKHKX-UHFFFAOYSA-N 0.000 claims 6
- VLOQOVXFFQKBIC-UHFFFAOYSA-N 3-[1-(3-methoxy-4-pyrazolidin-4-ylbenzoyl)pyrrolidin-2-yl]benzenesulfonamide Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC1c1cccc(c1)S(N)(=O)=O VLOQOVXFFQKBIC-UHFFFAOYSA-N 0.000 claims 6
- JUIGAHCFYDGFLH-UHFFFAOYSA-N [2-(3-methoxyphenyl)pyrrolidin-1-yl]-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1cccc(c1)C1CCCN1C(=O)c1ccc(C2CNNC2)c(OC)c1 JUIGAHCFYDGFLH-UHFFFAOYSA-N 0.000 claims 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims 6
- 125000004432 carbon atom Chemical group C* 0.000 claims 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 5
- 208000035475 disorder Diseases 0.000 claims 5
- CCSAUILZCRUPMI-UHFFFAOYSA-N (3-methoxy-4-pyrazolidin-4-ylphenyl)-(2-phenylpyrrolidin-1-yl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC1c1ccccc1 CCSAUILZCRUPMI-UHFFFAOYSA-N 0.000 claims 4
- YSOKIHZGSKPLLP-HXUWFJFHSA-N (3-methoxy-4-pyrazolidin-4-ylphenyl)-[(2R)-2-(3-methylsulfonylphenyl)pyrrolidin-1-yl]methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCC[C@@H]1c1cccc(c1)S(C)(=O)=O YSOKIHZGSKPLLP-HXUWFJFHSA-N 0.000 claims 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 4
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims 4
- 239000003112 inhibitor Substances 0.000 claims 4
- TZFRPVCQNMDLRW-UHFFFAOYSA-N [2-(3-methoxyphenyl)piperidin-1-yl]-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1cccc(c1)C1CCCCN1C(=O)c1ccc(C2CNNC2)c(OC)c1 TZFRPVCQNMDLRW-UHFFFAOYSA-N 0.000 claims 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 3
- 102000000568 rho-Associated Kinases Human genes 0.000 claims 3
- 108010041788 rho-Associated Kinases Proteins 0.000 claims 3
- OSCWGICCENEOQT-UHFFFAOYSA-N (2-benzylpyrrolidin-1-yl)-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC1Cc1ccccc1 OSCWGICCENEOQT-UHFFFAOYSA-N 0.000 claims 2
- KGUSODFCZAXSJP-UHFFFAOYSA-N (3-methoxy-4-pyrazolidin-4-ylphenyl)-(2-naphthalen-2-ylpyrrolidin-1-yl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC1c1ccc2ccccc2c1 KGUSODFCZAXSJP-UHFFFAOYSA-N 0.000 claims 2
- HKMJJQYAXILXDX-UHFFFAOYSA-N (3-methoxy-4-pyrazolidin-4-ylphenyl)-(3-phenylpiperidin-1-yl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC(C1)c1ccccc1 HKMJJQYAXILXDX-UHFFFAOYSA-N 0.000 claims 2
- PHQIZPCXPAIODW-UHFFFAOYSA-N (3-methoxy-4-pyrazolidin-4-ylphenyl)-(3-phenylpyrrolidin-1-yl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCC(C1)c1ccccc1 PHQIZPCXPAIODW-UHFFFAOYSA-N 0.000 claims 2
- GTDWOMSZSWVQQO-UHFFFAOYSA-N (3-methoxy-4-pyrazolidin-4-ylphenyl)-[2-(3-methylphenyl)pyrrolidin-1-yl]methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC1c1cccc(C)c1 GTDWOMSZSWVQQO-UHFFFAOYSA-N 0.000 claims 2
- ZPTJMQAPQZHLML-UHFFFAOYSA-N (3-methoxy-4-pyrazolidin-4-ylphenyl)-[2-(4-methylphenyl)pyrrolidin-1-yl]methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC1c1ccc(C)cc1 ZPTJMQAPQZHLML-UHFFFAOYSA-N 0.000 claims 2
- ODPGAHZNSIDODJ-UHFFFAOYSA-N (3-methoxy-4-pyrazolidin-4-ylphenyl)-[2-[3-(2-methylpyrazol-3-yl)phenyl]pyrrolidin-1-yl]methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC1c1cccc(c1)-c1ccnn1C ODPGAHZNSIDODJ-UHFFFAOYSA-N 0.000 claims 2
- GDUUDDPCTBVPQJ-UHFFFAOYSA-N (3-methoxy-4-pyrazolidin-4-ylphenyl)-[2-[4-(trifluoromethyl)phenyl]pyrrolidin-1-yl]methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC1c1ccc(cc1)C(F)(F)F GDUUDDPCTBVPQJ-UHFFFAOYSA-N 0.000 claims 2
- GSEBOZOUCDYCDV-UHFFFAOYSA-N 2,3-dihydroindol-1-yl-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCc2ccccc12 GSEBOZOUCDYCDV-UHFFFAOYSA-N 0.000 claims 2
- BNPIZBWLUCDRFK-OAQYLSRUSA-N 3-[(2R)-1-(3-methoxy-4-pyrazolidin-4-ylbenzoyl)pyrrolidin-2-yl]-N,N-dimethylbenzamide Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCC[C@@H]1c1cccc(c1)C(=O)N(C)C BNPIZBWLUCDRFK-OAQYLSRUSA-N 0.000 claims 2
- WURWQDYNMIVATK-LWMIZPGFSA-N 3-[(2R)-4-hydroxy-1-(3-methoxy-4-pyrazolidin-4-ylbenzoyl)pyrrolidin-2-yl]-N-(2-hydroxy-2-methylpropyl)benzamide Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CC(O)C[C@@H]1c1cccc(c1)C(=O)NCC(C)(C)O WURWQDYNMIVATK-LWMIZPGFSA-N 0.000 claims 2
- UJKVVIIGOOWGQB-LWMIZPGFSA-N 3-[(2R)-4-hydroxy-1-(3-methoxy-4-pyrazolidin-4-ylbenzoyl)pyrrolidin-2-yl]-N-(2-methoxyethyl)benzamide Chemical compound COCCNC(=O)c1cccc(c1)[C@H]1CC(O)CN1C(=O)c1ccc(C2CNNC2)c(OC)c1 UJKVVIIGOOWGQB-LWMIZPGFSA-N 0.000 claims 2
- RNSWTEXYQMGTBV-MQNHUJCZSA-N 3-[(2R)-4-hydroxy-1-(3-methoxy-4-pyrazolidin-4-ylbenzoyl)pyrrolidin-2-yl]-N-[(3-methyl-1,2-oxazol-5-yl)methyl]benzamide Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CC(O)C[C@@H]1c1cccc(c1)C(=O)NCc1cc(C)no1 RNSWTEXYQMGTBV-MQNHUJCZSA-N 0.000 claims 2
- NNBMALVKOJQOOJ-SYIFMXBLSA-N 3-[(2R)-4-hydroxy-1-(3-methoxy-4-pyrazolidin-4-ylbenzoyl)pyrrolidin-2-yl]-N-[(5-methyl-1,2-oxazol-3-yl)methyl]benzamide Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CC(O)C[C@@H]1c1cccc(c1)C(=O)NCc1cc(C)on1 NNBMALVKOJQOOJ-SYIFMXBLSA-N 0.000 claims 2
- MAIJXTAXWZOBIE-ROPPNANJSA-N 3-[(2R)-4-hydroxy-1-(3-methoxy-4-pyrazolidin-4-ylbenzoyl)pyrrolidin-2-yl]-N-methylbenzamide Chemical compound CNC(=O)c1cccc(c1)[C@H]1CC(O)CN1C(=O)c1ccc(C2CNNC2)c(OC)c1 MAIJXTAXWZOBIE-ROPPNANJSA-N 0.000 claims 2
- 208000023275 Autoimmune disease Diseases 0.000 claims 2
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims 2
- UGKKGFNXRUWUMD-FBLFFUNLSA-N C(C)C=1C=C(C(=O)N2CC(C[C@@H]2C2=C(C=CC=C2)F)O)C=CC=1C=1C=NNC=1 Chemical compound C(C)C=1C=C(C(=O)N2CC(C[C@@H]2C2=C(C=CC=C2)F)O)C=CC=1C=1C=NNC=1 UGKKGFNXRUWUMD-FBLFFUNLSA-N 0.000 claims 2
- GQSYZBKVWSBNAU-XSWBTSGESA-N C1(CC1)CN(C(C1=CC(=CC=C1)[C@@H]1N(CC(C1)OC)C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)=O)C Chemical compound C1(CC1)CN(C(C1=CC(=CC=C1)[C@@H]1N(CC(C1)OC)C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)=O)C GQSYZBKVWSBNAU-XSWBTSGESA-N 0.000 claims 2
- KZEQXPGKVYDAJL-UHFFFAOYSA-N COC1=C(C=CC(=C1)C(=O)N1C(CCC1)C1=CC(=CC=C1)C1=CC=NN1)C=1C=NNC=1 Chemical compound COC1=C(C=CC(=C1)C(=O)N1C(CCC1)C1=CC(=CC=C1)C1=CC=NN1)C=1C=NNC=1 KZEQXPGKVYDAJL-UHFFFAOYSA-N 0.000 claims 2
- CVIDSSWBXYGRRQ-UHFFFAOYSA-N COC1=C(C=CC(=C1)C(=O)N1C(CCC1)C1=CC(=CC=C1)C=1C=NNC=1)C=1C=NNC=1 Chemical compound COC1=C(C=CC(=C1)C(=O)N1C(CCC1)C1=CC(=CC=C1)C=1C=NNC=1)C=1C=NNC=1 CVIDSSWBXYGRRQ-UHFFFAOYSA-N 0.000 claims 2
- VRJQZYBEBLGVDH-UHFFFAOYSA-N COC1=C(C=CC(=C1)C(=O)N1C(CCC1)C1=CC(=CC=C1)OC)C1=C(C=NC=C1)C Chemical compound COC1=C(C=CC(=C1)C(=O)N1C(CCC1)C1=CC(=CC=C1)OC)C1=C(C=NC=C1)C VRJQZYBEBLGVDH-UHFFFAOYSA-N 0.000 claims 2
- DOZKTKXNIQDCCP-UHFFFAOYSA-N COC1=C(C=CC(=C1)C(=O)N1C(CCC1)C1=CC(=CC=C1)OC)C1=CC(=NC=C1)N Chemical compound COC1=C(C=CC(=C1)C(=O)N1C(CCC1)C1=CC(=CC=C1)OC)C1=CC(=NC=C1)N DOZKTKXNIQDCCP-UHFFFAOYSA-N 0.000 claims 2
- MXGBYRYEQKZISA-UHFFFAOYSA-N COC1=C(C=CC(=C1)C(=O)N1CCCC1C1=CC=CC(OC2CCN(C)CC2)=C1)C1=CNN=C1 Chemical compound COC1=C(C=CC(=C1)C(=O)N1CCCC1C1=CC=CC(OC2CCN(C)CC2)=C1)C1=CNN=C1 MXGBYRYEQKZISA-UHFFFAOYSA-N 0.000 claims 2
- RCGHIXWMAUWZLY-UHFFFAOYSA-N COC1=C(C=CC(=C1)C(=O)N1CCCC1C1=CC=CC(OCC2=NOC(C)=C2)=C1)C1=CNN=C1 Chemical compound COC1=C(C=CC(=C1)C(=O)N1CCCC1C1=CC=CC(OCC2=NOC(C)=C2)=C1)C1=CNN=C1 RCGHIXWMAUWZLY-UHFFFAOYSA-N 0.000 claims 2
- BUEVLTGWDZZMJU-OAQYLSRUSA-N COC1=C(C=CC(=C1)C(=O)N1CCC[C@@H]1C(=O)N1CCC2=CC=CC=C12)C1=CNN=C1 Chemical compound COC1=C(C=CC(=C1)C(=O)N1CCC[C@@H]1C(=O)N1CCC2=CC=CC=C12)C1=CNN=C1 BUEVLTGWDZZMJU-OAQYLSRUSA-N 0.000 claims 2
- WMXPKNPODQKIGC-UHFFFAOYSA-N COC1=C(C=CC(=C1)C(=O)N1CCNCC1C1=CC=CC=C1)C1=CNN=C1 Chemical compound COC1=C(C=CC(=C1)C(=O)N1CCNCC1C1=CC=CC=C1)C1=CNN=C1 WMXPKNPODQKIGC-UHFFFAOYSA-N 0.000 claims 2
- LGUIVJBIAVDGHZ-UHFFFAOYSA-N COC=1C=C(C(=O)N2C(CCC2)C2=CC(=CC=C2)OC)C=CC=1C1=C2C(=NC=C1)NC=C2 Chemical compound COC=1C=C(C(=O)N2C(CCC2)C2=CC(=CC=C2)OC)C=CC=1C1=C2C(=NC=C1)NC=C2 LGUIVJBIAVDGHZ-UHFFFAOYSA-N 0.000 claims 2
- WMKNHHXQPQWTOT-LJQANCHMSA-N COC=1C=C(C(=O)N2[C@H](CCC2)C(=O)NC2=CC=CC=C2)C=CC=1C=1C=NNC=1 Chemical compound COC=1C=C(C(=O)N2[C@H](CCC2)C(=O)NC2=CC=CC=C2)C=CC=1C=1C=NNC=1 WMKNHHXQPQWTOT-LJQANCHMSA-N 0.000 claims 2
- BSQMQLAMIUWBGE-LJQANCHMSA-N COC=1C=C(C(=O)N2[C@H](CCC2)C=2C=C(C(=O)O)C=CC=2)C=CC=1C=1C=NNC=1 Chemical compound COC=1C=C(C(=O)N2[C@H](CCC2)C=2C=C(C(=O)O)C=CC=2)C=CC=1C=1C=NNC=1 BSQMQLAMIUWBGE-LJQANCHMSA-N 0.000 claims 2
- UARIXOGHPPAEMY-UHFFFAOYSA-N COC=1C=C(C=CC=1C(=O)N1C(CCC1)C1=CC(=CC=C1)C=1C=NNC=1)C=1C=NNC=1 Chemical compound COC=1C=C(C=CC=1C(=O)N1C(CCC1)C1=CC(=CC=C1)C=1C=NNC=1)C=1C=NNC=1 UARIXOGHPPAEMY-UHFFFAOYSA-N 0.000 claims 2
- JXKOZTFRXXICFH-UHFFFAOYSA-N COC=1C=C(C=CC=1C=1C=NNC=1)C(=O)N1C(CCC1)C1=CC(=CC=C1)NC1CCN(CC1)C Chemical compound COC=1C=C(C=CC=1C=1C=NNC=1)C(=O)N1C(CCC1)C1=CC(=CC=C1)NC1CCN(CC1)C JXKOZTFRXXICFH-UHFFFAOYSA-N 0.000 claims 2
- AWGHZTHZMSMHIE-UUSAFJCLSA-N CS(=O)(=O)C=1C=C(C=CC=1)[C@H]1CC(CN1C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)O Chemical compound CS(=O)(=O)C=1C=C(C=CC=1)[C@H]1CC(CN1C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)O AWGHZTHZMSMHIE-UUSAFJCLSA-N 0.000 claims 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims 2
- SDBWBGQWWGQOPJ-UHFFFAOYSA-N FC(COC=1C=C(C=CC=1)C1N(CCC1)C(=O)C1=CC(=C(C=C1)C=1C=NNC=1)OC)F Chemical compound FC(COC=1C=C(C=CC=1)C1N(CCC1)C(=O)C1=CC(=C(C=C1)C=1C=NNC=1)OC)F SDBWBGQWWGQOPJ-UHFFFAOYSA-N 0.000 claims 2
- HULUTQNXAQIZHP-OTOKDRCRSA-N FC1=C(C=CC=C1)[C@@H]1N(CC(C1)O)C(=O)C=1C=CC(=C(C#N)C=1)C=1C=NNC=1 Chemical compound FC1=C(C=CC=C1)[C@@H]1N(CC(C1)O)C(=O)C=1C=CC(=C(C#N)C=1)C=1C=NNC=1 HULUTQNXAQIZHP-OTOKDRCRSA-N 0.000 claims 2
- HULUTQNXAQIZHP-OXQOHEQNSA-N FC1=C(C=CC=C1)[C@@H]1N(C[C@@H](C1)O)C(=O)C=1C=CC(=C(C#N)C=1)C=1C=NNC=1 Chemical compound FC1=C(C=CC=C1)[C@@H]1N(C[C@@H](C1)O)C(=O)C=1C=CC(=C(C#N)C=1)C=1C=NNC=1 HULUTQNXAQIZHP-OXQOHEQNSA-N 0.000 claims 2
- RNRNUGODTJKSIF-HNAYVOBHSA-N FC1=C(C=CC=C1)[C@H]1C[C@@H](CN1C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)N Chemical compound FC1=C(C=CC=C1)[C@H]1C[C@@H](CN1C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)N RNRNUGODTJKSIF-HNAYVOBHSA-N 0.000 claims 2
- XOONWRSAVXKANI-HNAYVOBHSA-N FC1=C(C=CC=C1)[C@H]1C[C@@H](CN1C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)O Chemical compound FC1=C(C=CC=C1)[C@H]1C[C@@H](CN1C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)O XOONWRSAVXKANI-HNAYVOBHSA-N 0.000 claims 2
- GFEQFEQFRYWQKE-DNVCBOLYSA-N FC1=C(C=CC=C1)[C@H]1C[C@H](CN1C(C1=C(C=C(C=C1)C=1C=NNC=1)OC)=O)O Chemical compound FC1=C(C=CC=C1)[C@H]1C[C@H](CN1C(C1=C(C=C(C=C1)C=1C=NNC=1)OC)=O)O GFEQFEQFRYWQKE-DNVCBOLYSA-N 0.000 claims 2
- RNRNUGODTJKSIF-DNVCBOLYSA-N FC1=C(C=CC=C1)[C@H]1C[C@H](CN1C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)N Chemical compound FC1=C(C=CC=C1)[C@H]1C[C@H](CN1C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)N RNRNUGODTJKSIF-DNVCBOLYSA-N 0.000 claims 2
- XOONWRSAVXKANI-DNVCBOLYSA-N FC1=C(C=CC=C1)[C@H]1C[C@H](CN1C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)O Chemical compound FC1=C(C=CC=C1)[C@H]1C[C@H](CN1C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)O XOONWRSAVXKANI-DNVCBOLYSA-N 0.000 claims 2
- YLHZOYUQSSIRCA-JUERFOTFSA-N FC=1C=C(C=C(C=1)C(F)(F)F)CNC(C1=CC(=CC=C1)[C@@H]1N(CC(C1)O)C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)=O Chemical compound FC=1C=C(C=C(C=1)C(F)(F)F)CNC(C1=CC(=CC=C1)[C@@H]1N(CC(C1)O)C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)=O YLHZOYUQSSIRCA-JUERFOTFSA-N 0.000 claims 2
- MMMICTOLPAOATQ-XCWJXAQQSA-N IC1=NNC2=CC(=CC=C12)[C@H]1CC(CN1C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)O Chemical compound IC1=NNC2=CC(=CC=C12)[C@H]1CC(CN1C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)O MMMICTOLPAOATQ-XCWJXAQQSA-N 0.000 claims 2
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- FMVUNDSNFXEOKU-JFGZAKSSSA-N N-(cyclopropylmethyl)-3-[(2R)-4-hydroxy-1-(3-methoxy-4-pyrazolidin-4-ylbenzoyl)pyrrolidin-2-yl]benzamide Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CC(O)C[C@@H]1c1cccc(c1)C(=O)NCC1CC1 FMVUNDSNFXEOKU-JFGZAKSSSA-N 0.000 claims 2
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| EP3268360B1 (en) | 2015-03-09 | 2019-04-24 | Bristol-Myers Squibb Company | Lactams as inhibitors of rock |
| CN106924254A (zh) * | 2015-12-31 | 2017-07-07 | 中国医学科学院药物研究所 | 黄连碱在制备预防和/或治疗系统性红斑狼疮及其并发症药物中的应用 |
| UY37073A (es) | 2016-01-13 | 2017-07-31 | Bristol-Myers Squibb Company Una Corporación Del Estado De Delaware | Salicilamidas espiroheptanos y compuestos relacionados como inhibidores de rock, y las composiciones que los contienen |
| ES2781309T3 (es) | 2016-05-27 | 2020-09-01 | Bristol Myers Squibb Co | Triazolonas y tetrazolonas como inhibidores de ROCK |
| WO2018009622A1 (en) | 2016-07-07 | 2018-01-11 | Bristol-Myers Squibb Company | Lactam, cyclic urea and carbamate, and triazolone derivatives as potent and selective rock inhibitors |
| EP3481828B1 (en) | 2016-07-07 | 2020-09-16 | Bristol-Myers Squibb Company | Spiro-fused cyclic ureas as inhibitors of rock |
| KR102491994B1 (ko) | 2016-07-07 | 2023-01-25 | 브리스톨-마이어스 스큅 컴퍼니 | Rock의 억제제로서의 스피로락탐 |
| ES2829400T3 (es) | 2016-11-30 | 2021-05-31 | Bristol Myers Squibb Co | Inhibidores tricíclicos de Rho cinasa |
| CN108203433B (zh) * | 2016-12-16 | 2020-07-03 | 成都先导药物开发股份有限公司 | 一种rock抑制剂及其应用 |
| AU2018294054B2 (en) * | 2017-06-30 | 2022-05-26 | Beijing Tide Pharmaceutical Co., Ltd. | Rho-associated protein kinase inhibitor, pharmaceutical composition comprising same, and preparation method and use thereof |
| TW201908293A (zh) | 2017-07-12 | 2019-03-01 | 美商必治妥美雅史谷比公司 | 作為rock抑制劑之5員及雙環雜環醯胺 |
| EP3652164B1 (en) | 2017-07-12 | 2023-06-21 | Bristol-Myers Squibb Company | Phenylacetamides as inhibitors of rock |
| KR102644889B1 (ko) | 2017-07-12 | 2024-03-06 | 브리스톨-마이어스 스큅 컴퍼니 | Rock 억제제로서의 스피로헵타닐 히단토인 |
| US12060341B2 (en) | 2017-07-12 | 2024-08-13 | Bristol-Myers Squibb Company | Spiroheptanyl hydantoins as ROCK inhibitors |
| EP3652165B1 (en) | 2017-07-12 | 2021-08-25 | Bristol-Myers Squibb Company | Five membered-aminoheterocyclic and 5,6-or 6,6-membered bicyclic aminoheterocyclic inhibitors of rock for the treatment of heart failure |
| WO2019089868A1 (en) | 2017-11-03 | 2019-05-09 | Bristol-Myers Squibb Company | Diazaspiro rock inhibitors |
| US11345678B2 (en) | 2018-04-18 | 2022-05-31 | Medshine Discovery Inc. | Benzopyrazole compound used as RHO kinase inhibitor |
| US11702400B2 (en) | 2019-10-18 | 2023-07-18 | Medshine Discovery Inc. | Salt types, crystal forms, and preparation methods for benzopyrazole compounds as RHO kinase inhibitors |
| CN114262322B (zh) * | 2020-09-16 | 2026-01-06 | 中国科学院上海有机化学研究所 | 一类细胞程序性坏死抑制剂及其制备方法和用途 |
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| JP6109934B2 (ja) * | 2012-07-03 | 2017-04-05 | ３−ブイ・バイオサイエンシーズ・インコーポレイテッド３−Ｖ Ｂｉｏｓｃｉｅｎｃｅｓ，Ｉｎｃ． | 脂質合成の複素環モジュレーター |
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| CN103664878A (zh) | 2012-09-12 | 2014-03-26 | 山东亨利医药科技有限责任公司 | 杂芳环及其衍生物类酪氨酸激酶抑制剂 |
| EP2903618B1 (en) | 2012-10-05 | 2022-06-01 | Kadmon Corporation, LLC | Rho kinase inhibitors |
| SMT202000713T1 (it) * | 2012-12-07 | 2021-03-15 | Vertex Pharma | Pirazolo [1,5-a] pirimidine utili come inibitori dell'atr chinasi per il trattamento di malattie del cancro |
| WO2014113620A2 (en) | 2013-01-18 | 2014-07-24 | Bristol-Myers Squibb Company | Phthalazinones and isoquinolinones as rock inhibitors |
| AR094929A1 (es) | 2013-02-28 | 2015-09-09 | Bristol Myers Squibb Co | Derivados de fenilpirazol como inhibidores potentes de rock1 y rock2 |
| WO2014134391A1 (en) | 2013-02-28 | 2014-09-04 | Bristol-Myers Squibb Company | Phenylpyrazole derivatives as potent rock1 and rock2 inhibitors |
-
2015
- 2015-08-20 WO PCT/US2015/046032 patent/WO2016028971A1/en not_active Ceased
- 2015-08-20 US US15/503,419 patent/US10112939B2/en active Active
- 2015-08-20 CN CN201580044710.7A patent/CN107108581B/zh active Active
- 2015-08-20 EP EP15756322.2A patent/EP3183248B1/en active Active
- 2015-08-20 JP JP2017510314A patent/JP6633618B2/ja active Active
- 2015-08-20 ES ES15756322T patent/ES2838573T3/es active Active
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