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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| CN109153663B (zh) | 2016-05-27 | 2021-08-13 | 百时美施贵宝公司 | 作为rock抑制剂的三唑酮类化合物和四唑酮类化合物 |
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| 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 |
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| CN112020496B (zh) | 2018-04-18 | 2023-04-28 | 南京明德新药研发有限公司 | 作为rho激酶抑制剂的苯并吡唑类化合物 |
| EP4046686B1 (en) * | 2019-10-18 | 2023-11-01 | 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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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0259559A (ja) | 1988-08-23 | 1990-02-28 | Mitsubishi Kasei Corp | ピリドン誘導体又はその塩類 |
| GB9119932D0 (en) * | 1991-09-18 | 1991-10-30 | Glaxo Group Ltd | Chemical compounds |
| EP0716650B1 (en) | 1993-09-03 | 1999-03-24 | Smithkline Beecham Plc | Indole and indoline derivatives as 5ht1d receptor antagonists |
| JPH09503773A (ja) * | 1993-10-19 | 1997-04-15 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | ５ｈｔ−１ｄレセプター拮抗剤用のベンズアニリド誘導体 |
| JP2002521408A (ja) * | 1998-07-28 | 2002-07-16 | スミスクライン・ビーチャム・コーポレイション | 化合物および方法 |
| AU5196399A (en) | 1998-08-11 | 2000-03-06 | Daiichi Pharmaceutical Co., Ltd. | Novel sulfonyl derivatives |
| TR200103214T2 (tr) * | 1999-05-04 | 2002-03-21 | Schering Corporation | CCR5 antagonistleri olarak yararlì piperazin trevleri. |
| WO2001070673A2 (en) * | 2000-03-17 | 2001-09-27 | Bristol-Myers Squibb Pharma Company | CYCLIC β-AMINO ACID DERIVATIVES AS INHIBITORS OF MATRIX METALLOPROTEASES AND TNF-$g(a) |
| GB2361003A (en) | 2000-04-07 | 2001-10-10 | Astrazeneca Ab | Novel compounds |
| US20020045613A1 (en) | 2000-04-27 | 2002-04-18 | Heinz Pauls | 1-aroyl-piperidinyl benzamidines |
| TWI243164B (en) * | 2001-02-13 | 2005-11-11 | Aventis Pharma Gmbh | Acylated indanyl amines and their use as pharmaceuticals |
| PL369337A1 (en) | 2001-10-01 | 2005-04-18 | Bristol-Myers Squibb Company | Spiro-hydantoin compounds useful as anti-inflammatory agents |
| JP2005526723A (ja) * | 2002-02-15 | 2005-09-08 | グラクソ グループ リミテッド | バニロイド受容体モジュレーター |
| TWI319387B (en) * | 2002-04-05 | 2010-01-11 | Astrazeneca Ab | Benzamide derivatives |
| US7541477B2 (en) | 2002-07-30 | 2009-06-02 | Banyu Pharmaceutical Co., Ltd. | Antagonists to melanin-concentrating hormone receptor comprising benzimidazole derivative as active ingredient |
| CN1744899A (zh) | 2002-12-13 | 2006-03-08 | 史密丝克莱恩比彻姆公司 | 作为ccr5拮抗剂的哌啶衍生物 |
| AU2003299797A1 (en) | 2002-12-19 | 2004-07-14 | Neurogen Corporation | Substituted biphenyl-4-carboxylic acid arylamide analogues as capsaicin receptor modulators |
| DE10306250A1 (de) | 2003-02-14 | 2004-09-09 | Aventis Pharma Deutschland Gmbh | Substituierte N-Arylheterozyklen, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| DK2476667T3 (da) | 2003-02-26 | 2014-09-15 | Sugen Inc | Aminoheteroaryl-forbindelser som proteinkinase-inhibitorer |
| WO2004078756A2 (en) | 2003-03-06 | 2004-09-16 | Eisai Co., Ltd. | Jnk inhibitors |
| US20080275062A1 (en) * | 2004-01-30 | 2008-11-06 | David Harold Drewry | Chemical Compounds |
| ATE454372T1 (de) * | 2004-04-01 | 2010-01-15 | Lilly Co Eli | Am histamin-h3-rezeptor wirksame mittel, herstellung und therapeutische anwendungen |
| WO2006123725A1 (ja) | 2005-05-19 | 2006-11-23 | Astellas Pharma Inc. | ピロリジン誘導体またはその塩 |
| KR20080016659A (ko) * | 2005-05-20 | 2008-02-21 | 버텍스 파마슈티칼스 인코포레이티드 | 단백질 키나제의 억제제로서 유용한 피롤로피리딘 |
| JP5244589B2 (ja) | 2005-06-27 | 2013-07-24 | エグゼリクシス パテント カンパニー エルエルシー | イミダゾールに基づくｌｘｒモジュレーター |
| GB0514812D0 (en) | 2005-07-19 | 2005-08-24 | Glaxo Group Ltd | Compounds |
| US20070208053A1 (en) * | 2006-01-19 | 2007-09-06 | Arnold Lee D | Fused heterobicyclic kinase inhibitors |
| TW200808751A (en) | 2006-04-13 | 2008-02-16 | Astrazeneca Ab | New compounds |
| US7601716B2 (en) | 2006-05-01 | 2009-10-13 | Cephalon, Inc. | Pyridopyrazines and derivatives thereof as ALK and c-Met inhibitors |
| CA2662112A1 (en) | 2006-09-05 | 2008-03-13 | Kyowa Hakko Kirin Co., Ltd. | Imidazole derivatives and their use as cannabinoid type 2 (cb2) receptor modulators |
| CA2664335C (en) | 2006-09-20 | 2014-12-02 | Boehringer Ingelheim International Gmbh | Rho kinase inhibitors |
| CL2007003874A1 (es) | 2007-01-03 | 2008-05-16 | Boehringer Ingelheim Int | Compuestos derivados de benzamida; composicion farmaceutica que comprende a dichos compuestos; y su uso para tratar enfermedades cardiovasculares, hipertension, aterosclerosis, reestenosis, ictus, insuficiencia cardiaca, lesion isquemica, hipertensio |
| KR20100017362A (ko) | 2007-04-25 | 2010-02-16 | 엑셀리시스, 인코포레이티드 | Ｐｉｍ 조절제로서 ６페닐피리미디논 |
| ES2367464T3 (es) | 2007-08-07 | 2011-11-03 | F. Hoffmann-La Roche Ag | Pirrolidina-aril-éteres como antagonistas de receptor de nk3. |
| US8445686B2 (en) * | 2007-08-27 | 2013-05-21 | Abbvie Inc. | 4-(4-pyridinyl)-benzamides and their use as rock activity modulators |
| CN102007101A (zh) | 2007-11-30 | 2011-04-06 | 生物区科学管理控股有限公司 | 作为抗菌剂的四氢-异喹啉ppat抑制剂 |
| US8470816B2 (en) * | 2007-12-03 | 2013-06-25 | Takeda Pharmaceutical Company Limited | Nitrogen-containing heterocyclic compound and use thereof |
| JP2011524397A (ja) | 2008-06-16 | 2011-09-01 | エフ．ホフマン−ラ ロシュ アーゲー | Ｎｋ受容体アンタゴニストとしてのピロリジン誘導体 |
| CA2730116A1 (en) | 2008-07-08 | 2010-01-14 | Boehringer Ingelheim International Gmbh | Pyrrolidinyl and piperidinyl compounds useful as nhe-1 inhibitors |
| CA2735204C (en) | 2008-08-25 | 2017-06-20 | Boehringer Ingelheim International Gmbh | Aryl- and heteroarylcarbonyl derivatives of substituted nortropanes, medicaments containing such compounds and their use |
| EP2331500A1 (en) | 2008-10-09 | 2011-06-15 | F. Hoffmann-La Roche AG | Pyrrolidine n-benzyl derivatives |
| US8367679B2 (en) * | 2008-12-09 | 2013-02-05 | Merck Sharp & Dohme Corp. | Biaryl carboxamides |
| US8609696B2 (en) * | 2008-12-18 | 2013-12-17 | Boehringer Ingelheim International Gmbh | Serotonin 5-HT2B receptor inhibitors |
| KR101372743B1 (ko) | 2009-01-30 | 2014-03-14 | 에프. 호프만-라 로슈 아게 | Ｎｋ3 수용체 길항제로서 피페리딘 유도체 |
| US8324250B2 (en) | 2009-03-19 | 2012-12-04 | Hoffmann-La Roche Inc. | Piperidine derivatives as NK3 receptor antagonists |
| AR076332A1 (es) | 2009-04-21 | 2011-06-01 | Boehringer Ingelheim Int | Derivados heterociclicos de 5-alquinil-piridinas, composiciones farmaceuticas que los comprenden y uso de los mismos para el tratamiento y/o prevencion del cancer, procesos inflamatorios, autoinmunes, y/o infecciones. |
| EP2435046B1 (en) | 2009-05-28 | 2013-09-04 | Otsuka Pharmaceutical Co., Ltd. | Heterocyclic compounds for the treatment of stress-related conditions |
| AR077033A1 (es) * | 2009-06-11 | 2011-07-27 | Hoffmann La Roche | Compuestos inhibidores de las quinasas de janus y su uso en el tratamiento de enfermedades inmunologicas |
| CN102712647B (zh) | 2009-10-16 | 2018-04-24 | 梅琳塔治疗公司 | 抗微生物化合物和其制备和使用方法 |
| SMT201800004T1 (it) | 2009-12-18 | 2018-03-08 | Ogeda Sa | Derivati di acido pirrolidin carbossilico come agonisti del recettore accoppiato a proteina g 43 (gpr43), composizione farmaceutica e metodi per l'uso nel trattamento di disturbi metabolici |
| US8633183B2 (en) | 2010-01-26 | 2014-01-21 | Boehringer Ingelheim International Gmbh | 5-alkynyl-pyrimidines |
| US8507535B2 (en) | 2010-07-07 | 2013-08-13 | Hoffmann-La Roche Inc. | Methyl-pyrrolidine ether derivatives |
| US9079880B2 (en) | 2010-07-07 | 2015-07-14 | Boehringer Ingelheim International Gmbh | Rho kinase inhibitors |
| SG10201602857UA (en) | 2010-11-15 | 2016-05-30 | Abbvie Inc | NAMPT And Rock Inhibitors |
| EA025529B1 (ru) | 2011-08-09 | 2017-01-30 | Такеда Фармасьютикал Компани Лимитед | Циклопропанаминовое соединение |
| WO2013155338A2 (en) | 2012-04-12 | 2013-10-17 | The Board Of Trustees Of The Leland Stanford Junior University | Substituted benzamides and their uses |
| WO2013153539A1 (en) * | 2012-04-13 | 2013-10-17 | Glenmark Pharmaceuticals S.A. | Tricyclic compounds as tec kinase inhibitors |
| BR112014032581A8 (pt) | 2012-06-27 | 2018-08-14 | 4Sc Discovery Gmbh | inibidores de bifluorodioxalano-amino-benzimidazol quinase para o tratamento de câncer, distúrbios do snc e inflamação autoimune |
| EP2870150B1 (en) * | 2012-07-03 | 2019-06-19 | 3-V Biosciences, Inc. | Heterocyclic modulators of lipid synthesis |
| EP2687528A1 (en) * | 2012-07-17 | 2014-01-22 | Ares Trading S.A. | Fused triazole derivatives as gamma secretase modulators |
| 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 |
| SI2903618T1 (sl) | 2012-10-05 | 2022-09-30 | Kadmon Corporation, Llc | Zaviralci RHO kinaze |
| US9340546B2 (en) * | 2012-12-07 | 2016-05-17 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| TW201443023A (zh) | 2013-01-18 | 2014-11-16 | 必治妥美雅史谷比公司 | 作爲ｒｏｃｋ抑制劑之酞□酮及異喹啉酮 |
| US9828345B2 (en) | 2013-02-28 | 2017-11-28 | Bristol-Myers Squibb Company | Phenylpyrazole derivatives as potent ROCK1 and ROCK2 inhibitors |
| TW201444798A (zh) | 2013-02-28 | 2014-12-01 | 必治妥美雅史谷比公司 | 作爲強效ｒｏｃｋ１及ｒｏｃｋ２抑制劑之苯基吡唑衍生物 |
-
2015
- 2015-08-20 EP EP15756322.2A patent/EP3183248B1/en active Active
- 2015-08-20 US US15/503,419 patent/US10112939B2/en active Active
- 2015-08-20 ES ES15756322T patent/ES2838573T3/es active Active
- 2015-08-20 CN CN201580044710.7A patent/CN107108581B/zh active Active
- 2015-08-20 WO PCT/US2015/046032 patent/WO2016028971A1/en not_active Ceased
- 2015-08-20 JP JP2017510314A patent/JP6633618B2/ja active Active
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