JP2017524026A5 - - Google Patents
Download PDFInfo
- 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
Links
- 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
- SRLAXAJAMODPPJ-UHFFFAOYSA-N N-(2,3-dihydro-1H-inden-1-yl)-3-methoxy-4-pyrazolidin-4-ylbenzamide Chemical compound COc1cc(ccc1C1CNNC1)C(=O)NC1CCc2ccccc12 SRLAXAJAMODPPJ-UHFFFAOYSA-N 0.000 claims 2
- 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
- LFDSTBVLFOCHBB-JNOFKKGSSA-N N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-3-[(2R)-4-hydroxy-1-(3-methoxy-4-pyrazolidin-4-ylbenzoyl)pyrrolidin-2-yl]benzamide Chemical compound CCN1CCC[C@H]1CNC(=O)c1cccc(c1)[C@H]1CC(O)CN1C(=O)c1ccc(C2CNNC2)c(OC)c1 LFDSTBVLFOCHBB-JNOFKKGSSA-N 0.000 claims 2
- FDPAMZALCWZLOA-ANWICMFUSA-N N-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-3-[(2R)-4-hydroxy-1-[3-methoxy-4-(1H-pyrazol-4-yl)benzoyl]pyrrolidin-2-yl]benzamide Chemical compound FC1=C(C=CC(=C1)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 FDPAMZALCWZLOA-ANWICMFUSA-N 0.000 claims 2
- FVVYEPMWGRPANR-JFGZAKSSSA-N N-cyclobutyl-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)NC1CCC1 FVVYEPMWGRPANR-JFGZAKSSSA-N 0.000 claims 2
- ASAQCVQGDNPOAJ-JOCHJYFZSA-N N-cyclopropyl-3-[(2R)-1-(3-methoxy-4-pyrazolidin-4-ylbenzoyl)pyrrolidin-2-yl]benzamide Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCC[C@@H]1c1cccc(c1)C(=O)NC1CC1 ASAQCVQGDNPOAJ-JOCHJYFZSA-N 0.000 claims 2
- KNOZSCBOYSGGOH-LWMIZPGFSA-N N-cyclopropyl-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)NC1CC1 KNOZSCBOYSGGOH-LWMIZPGFSA-N 0.000 claims 2
- QCQUZYVLPSPASD-UUSAFJCLSA-N N1N=CC2=CC=C(C=C12)[C@H]1CC(CN1C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)O Chemical compound N1N=CC2=CC=C(C=C12)[C@H]1CC(CN1C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)O QCQUZYVLPSPASD-UUSAFJCLSA-N 0.000 claims 2
- PYDDKWQVJJSEMC-WHCXFUJUSA-N OC1C[C@@H](N(C1)C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)C=1C=C(C(=O)O)C=CC=1 Chemical compound OC1C[C@@H](N(C1)C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)C=1C=C(C(=O)O)C=CC=1 PYDDKWQVJJSEMC-WHCXFUJUSA-N 0.000 claims 2
- XBNRYBRQZKTKLK-VGAJERRHSA-N [(2R)-2-[3-(3,3-difluoroazetidine-1-carbonyl)phenyl]-4-hydroxypyrrolidin-1-yl]-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CC(O)C[C@@H]1c1cccc(c1)C(=O)N1CC(F)(F)C1 XBNRYBRQZKTKLK-VGAJERRHSA-N 0.000 claims 2
- GTXZULFIOXALEU-ZDUSSCGKSA-N [(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCC[C@H]1CO GTXZULFIOXALEU-ZDUSSCGKSA-N 0.000 claims 2
- CNOZWCDPHDSSDX-UHFFFAOYSA-N [2-(1,3-benzodioxol-5-yl)pyrrolidin-1-yl]-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC1c1ccc2OCOc2c1 CNOZWCDPHDSSDX-UHFFFAOYSA-N 0.000 claims 2
- QUCFRSBSFMABIH-UHFFFAOYSA-N [2-(2-chlorophenyl)pyrrolidin-1-yl]-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC1c1ccccc1Cl QUCFRSBSFMABIH-UHFFFAOYSA-N 0.000 claims 2
- ZEBFFVFSYXJJDA-UHFFFAOYSA-N [2-(2-fluorophenyl)pyrrolidin-1-yl]-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC1c1ccccc1F ZEBFFVFSYXJJDA-UHFFFAOYSA-N 0.000 claims 2
- MGQFASDSSNXEOJ-UHFFFAOYSA-N [2-(2-methoxyphenyl)pyrrolidin-1-yl]-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1ccccc1C1CCCN1C(=O)c1ccc(C2CNNC2)c(OC)c1 MGQFASDSSNXEOJ-UHFFFAOYSA-N 0.000 claims 2
- XJQANDPVLJRJNH-UHFFFAOYSA-N [2-(3-bromophenyl)pyrrolidin-1-yl]-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC1c1cccc(Br)c1 XJQANDPVLJRJNH-UHFFFAOYSA-N 0.000 claims 2
- LFAMLDIJMFLDPH-UHFFFAOYSA-N [2-(3-hydroxyphenyl)pyrrolidin-1-yl]-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC1c1cccc(O)c1 LFAMLDIJMFLDPH-UHFFFAOYSA-N 0.000 claims 2
- IRJGFWCAOSRJNJ-UHFFFAOYSA-N [2-(4-chlorophenyl)pyrrolidin-1-yl]-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC1c1ccc(Cl)cc1 IRJGFWCAOSRJNJ-UHFFFAOYSA-N 0.000 claims 2
- IVMHHJMOHGKPLP-UHFFFAOYSA-N [2-(4-fluorophenyl)pyrrolidin-1-yl]-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC1c1ccc(F)cc1 IVMHHJMOHGKPLP-UHFFFAOYSA-N 0.000 claims 2
- QUBGCNURUDNLKI-UHFFFAOYSA-N [2-(4-methoxyphenyl)pyrrolidin-1-yl]-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1ccc(cc1)C1CCCN1C(=O)c1ccc(C2CNNC2)c(OC)c1 QUBGCNURUDNLKI-UHFFFAOYSA-N 0.000 claims 2
- ZRGRYRXHTHAJMC-UHFFFAOYSA-N [2-[3-(3,5-dimethyl-1,2-oxazol-4-yl)phenyl]pyrrolidin-1-yl]-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC1c1cccc(c1)-c1c(C)noc1C ZRGRYRXHTHAJMC-UHFFFAOYSA-N 0.000 claims 2
- CMUUXZYJVAVSAY-UHFFFAOYSA-N [2-[3-(furan-3-yl)phenyl]pyrrolidin-1-yl]-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC1c1cccc(c1)-c1ccoc1 CMUUXZYJVAVSAY-UHFFFAOYSA-N 0.000 claims 2
- KLPABZGHJWCRDF-UHFFFAOYSA-N [2-[3-[1-(2-hydroxy-2-methylpropyl)pyrazol-4-yl]phenyl]pyrrolidin-1-yl]-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCCC1c1cccc(c1)-c1cnn(CC(C)(C)O)c1 KLPABZGHJWCRDF-UHFFFAOYSA-N 0.000 claims 2
- ZXZBYBDPCGFDAW-RDTXWAMCSA-N [3-(difluoromethoxy)-4-pyrazolidin-4-ylphenyl]-[(2R,4R)-2-(2-fluorophenyl)-4-hydroxypyrrolidin-1-yl]methanone Chemical compound O[C@@H]1C[C@@H](N(C1)C(=O)c1ccc(C2CNNC2)c(OC(F)F)c1)c1ccccc1F ZXZBYBDPCGFDAW-RDTXWAMCSA-N 0.000 claims 2
- ZXZBYBDPCGFDAW-KBXCAEBGSA-N [3-(difluoromethoxy)-4-pyrazolidin-4-ylphenyl]-[(2R,4S)-2-(2-fluorophenyl)-4-hydroxypyrrolidin-1-yl]methanone Chemical compound O[C@H]1C[C@@H](N(C1)C(=O)c1ccc(C2CNNC2)c(OC(F)F)c1)c1ccccc1F ZXZBYBDPCGFDAW-KBXCAEBGSA-N 0.000 claims 2
- QKQFEFDBTIVCSC-UHFFFAOYSA-N [4-(2-fluoropyridin-4-yl)-3-methoxyphenyl]-[2-(3-methoxyphenyl)pyrrolidin-1-yl]methanone Chemical compound FC1=NC=CC(=C1)C1=C(C=C(C=C1)C(=O)N1C(CCC1)C1=CC(=CC=C1)OC)OC QKQFEFDBTIVCSC-UHFFFAOYSA-N 0.000 claims 2
- ORZVPXAJJMRXLQ-UHFFFAOYSA-N [4-(3-fluoropyridin-4-yl)-3-methoxyphenyl]-[2-(3-methoxyphenyl)pyrrolidin-1-yl]methanone Chemical compound FC=1C=NC=CC=1C1=C(C=C(C=C1)C(=O)N1C(CCC1)C1=CC(=CC=C1)OC)OC ORZVPXAJJMRXLQ-UHFFFAOYSA-N 0.000 claims 2
- RUZZPLKXUFCBBU-UHFFFAOYSA-N [4-hydroxy-2-(3-methylsulfonylphenyl)pyrrolidin-1-yl]-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl]methanone Chemical compound CS(=O)(=O)C1=CC=CC(=C1)C1CC(O)CN1C(=O)C1=CC=C(C=C1)C1=CC=NC2=C1C=CN2 RUZZPLKXUFCBBU-UHFFFAOYSA-N 0.000 claims 2
- 125000002837 carbocyclic group Chemical group 0.000 claims 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 2
- 125000005842 heteroatom Chemical group 0.000 claims 2
- JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 claims 2
- 210000002460 smooth muscle Anatomy 0.000 claims 2
- GEHZSAHDBHLADN-MRXNPFEDSA-N tert-butyl (2R)-1-(3-methoxy-4-pyrazolidin-4-ylbenzoyl)pyrrolidine-2-carboxylate Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CCC[C@@H]1C(=O)OC(C)(C)C GEHZSAHDBHLADN-MRXNPFEDSA-N 0.000 claims 2
- SQCWZXJNMRKBPO-LWMIZPGFSA-N 3-[(2R)-4-hydroxy-1-(3-methoxy-4-pyrazolidin-4-ylbenzoyl)pyrrolidin-2-yl]-N-(1-methylcyclopropyl)benzamide Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CC(O)C[C@@H]1c1cccc(c1)C(=O)NC1(C)CC1 SQCWZXJNMRKBPO-LWMIZPGFSA-N 0.000 claims 1
- AOZFFYXNYXBVCN-SYIFMXBLSA-N 3-[(2R)-4-hydroxy-1-(3-methoxy-4-pyrazolidin-4-ylbenzoyl)pyrrolidin-2-yl]-N-(oxan-4-yl)benzamide Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CC(O)C[C@@H]1c1cccc(c1)C(=O)NC1CCOCC1 AOZFFYXNYXBVCN-SYIFMXBLSA-N 0.000 claims 1
- JTEZDTPVNWFIBQ-LWMIZPGFSA-N 3-[(2R)-4-hydroxy-1-(3-methoxy-4-pyrazolidin-4-ylbenzoyl)pyrrolidin-2-yl]-N-propan-2-ylbenzamide Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CC(O)C[C@@H]1c1cccc(c1)C(=O)NC(C)C JTEZDTPVNWFIBQ-LWMIZPGFSA-N 0.000 claims 1
- ZRBUHAPKOGLTMG-JFGZAKSSSA-N 3-[(2R)-4-hydroxy-1-[3-methoxy-4-(1H-pyrazol-4-yl)benzoyl]pyrrolidin-2-yl]-N-(1-methylcyclobutyl)benzamide Chemical compound OC1C[C@@H](N(C1)C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)C=1C=C(C(=O)NC2(CCC2)C)C=CC=1 ZRBUHAPKOGLTMG-JFGZAKSSSA-N 0.000 claims 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 1
- 206010002383 Angina Pectoris Diseases 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- KJNZNLPATZAFAD-GWQXNCQPSA-N COC=1C=C(C(=O)N2CC(C[C@@H]2C2=CC(=CC=C2)C(=O)N2CC(C2)OC)O)C=CC=1C=1C=NNC=1 Chemical compound COC=1C=C(C(=O)N2CC(C[C@@H]2C2=CC(=CC=C2)C(=O)N2CC(C2)OC)O)C=CC=1C=1C=NNC=1 KJNZNLPATZAFAD-GWQXNCQPSA-N 0.000 claims 1
- 208000010228 Erectile Dysfunction Diseases 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- LRPYEYDXUDLHIL-ROPPNANJSA-N FC(CNC(C1=CC(=CC=C1)[C@@H]1N(CC(C1)O)C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)=O)F Chemical compound FC(CNC(C1=CC(=CC=C1)[C@@H]1N(CC(C1)O)C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)=O)F LRPYEYDXUDLHIL-ROPPNANJSA-N 0.000 claims 1
- 206010016654 Fibrosis Diseases 0.000 claims 1
- 208000010412 Glaucoma Diseases 0.000 claims 1
- 206010019280 Heart failures Diseases 0.000 claims 1
- 206010020772 Hypertension Diseases 0.000 claims 1
- 208000012902 Nervous system disease Diseases 0.000 claims 1
- 208000025966 Neurological disease Diseases 0.000 claims 1
- UKLSXQSZGSTNGJ-JFGZAKSSSA-N OC1C[C@@H](N(C1)C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)C=1C=C(C(=O)N2CC(C2)C#N)C=CC=1 Chemical compound OC1C[C@@H](N(C1)C(C1=CC(=C(C=C1)C=1C=NNC=1)OC)=O)C=1C=C(C(=O)N2CC(C2)C#N)C=CC=1 UKLSXQSZGSTNGJ-JFGZAKSSSA-N 0.000 claims 1
- 208000031481 Pathologic Constriction Diseases 0.000 claims 1
- 208000018262 Peripheral vascular disease Diseases 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 claims 1
- 201000009594 Systemic Scleroderma Diseases 0.000 claims 1
- 206010042953 Systemic sclerosis Diseases 0.000 claims 1
- 206010047163 Vasospasm Diseases 0.000 claims 1
- IVZXVTNSPXDWBW-LWMIZPGFSA-N [(2R)-2-[3-(3-fluoroazetidine-1-carbonyl)phenyl]-4-hydroxypyrrolidin-1-yl]-(3-methoxy-4-pyrazolidin-4-ylphenyl)methanone Chemical compound COc1cc(ccc1C1CNNC1)C(=O)N1CC(O)C[C@@H]1c1cccc(c1)C(=O)N1CC(F)C1 IVZXVTNSPXDWBW-LWMIZPGFSA-N 0.000 claims 1
- 230000002159 abnormal effect Effects 0.000 claims 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 208000006673 asthma Diseases 0.000 claims 1
- 208000026106 cerebrovascular disease Diseases 0.000 claims 1
- 208000029078 coronary artery disease Diseases 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 230000004761 fibrosis Effects 0.000 claims 1
- 201000001881 impotence Diseases 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 claims 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims 1
- 208000002551 irritable bowel syndrome Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- 230000001613 neoplastic effect Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 230000000069 prophylactic effect Effects 0.000 claims 1
- 208000002815 pulmonary hypertension Diseases 0.000 claims 1
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 1
- 208000037804 stenosis Diseases 0.000 claims 1
- 230000036262 stenosis Effects 0.000 claims 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 0 CC(C1OC1N(*)*SC)=C Chemical compound CC(C1OC1N(*)*SC)=C 0.000 description 6
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462040044P | 2014-08-21 | 2014-08-21 | |
| US62/040,044 | 2014-08-21 | ||
| PCT/US2015/046032 WO2016028971A1 (en) | 2014-08-21 | 2015-08-20 | Tied-back benzamide derivatives as potent rock inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017524026A JP2017524026A (ja) | 2017-08-24 |
| JP2017524026A5 true JP2017524026A5 (cg-RX-API-DMAC7.html) | 2018-09-27 |
| JP6633618B2 JP6633618B2 (ja) | 2020-01-22 |
Family
ID=54011128
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017510314A Active JP6633618B2 (ja) | 2014-08-21 | 2015-08-20 | 強力なｒｏｃｋ阻害剤としてのタイドバックのベンズアミド誘導体 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US10112939B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP3183248B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP6633618B2 (cg-RX-API-DMAC7.html) |
| CN (1) | CN107108581B (cg-RX-API-DMAC7.html) |
| ES (1) | ES2838573T3 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2016028971A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6779214B2 (ja) | 2015-01-09 | 2020-11-04 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | Ｒｏｃｋ阻害剤としての環状ウレア |
| TW201706265A (zh) | 2015-03-09 | 2017-02-16 | 必治妥美雅史谷比公司 | 做為Ｒｈｏ激酶（ＲＯＣＫ）抑制劑之內醯胺 |
| 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 |
| AR107354A1 (es) | 2016-01-13 | 2018-04-18 | Bristol Myers Squibb Co | Salicilamidas espiroheptanos y compuestos relacionados como inhibidores de rock |
| US10562887B2 (en) | 2016-05-27 | 2020-02-18 | Bristol-Myers Squibb Company | Triazolones and tetrazolones as inhibitors of ROCK |
| CN109661396B (zh) | 2016-07-07 | 2022-07-01 | 百时美施贵宝公司 | 作为rock抑制剂的螺稠合环状脲 |
| US10730858B2 (en) | 2016-07-07 | 2020-08-04 | Bristol-Myers Squibb Company | Lactam, cyclic urea and carbamate, and triazolone derivatives as potent and selective rock inhibitors |
| EP3481817B1 (en) | 2016-07-07 | 2020-08-19 | Bristol-Myers Squibb Company | Spirolactams as inhibitors of rock |
| ES2829400T3 (es) | 2016-11-30 | 2021-05-31 | Bristol Myers Squibb Co | Inhibidores tricíclicos de Rho cinasa |
| WO2018108156A1 (zh) * | 2016-12-16 | 2018-06-21 | 成都先导药物开发有限公司 | 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 |
| US11306081B2 (en) | 2017-07-12 | 2022-04-19 | Bristol-Myers Squibb Company | Phenylacetamides as inhibitors of rock |
| US12060341B2 (en) | 2017-07-12 | 2024-08-13 | Bristol-Myers Squibb Company | Spiroheptanyl hydantoins as ROCK inhibitors |
| US11299488B2 (en) | 2017-07-12 | 2022-04-12 | Bristol-Myers Squibb Company | Five membered-aminoheterocycle and 5,6-or 6,6-membered bicyclic aminoheterocyclic inhibitors of rock for the treatment of heart failure |
| CN110914257B (zh) | 2017-07-12 | 2023-05-26 | 百时美施贵宝公司 | 作为rock抑制剂的螺庚基乙内酰脲 |
| US11192891B2 (en) | 2017-11-03 | 2021-12-07 | Bristol-Myers Squibb Company | Diazaspiro ROCK inhibitors |
| EP3782987B1 (en) | 2018-04-18 | 2025-04-02 | 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 |
| CN114262322A (zh) * | 2020-09-16 | 2022-04-01 | 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 |
| WO2022100614A1 (zh) * | 2020-11-11 | 2022-05-19 | 南京明德新药研发有限公司 | 苯并脲环衍生物及其制备方法和应用 |
| JPWO2023085369A1 (cg-RX-API-DMAC7.html) | 2021-11-11 | 2023-05-19 |
Family Cites Families (66)
| 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 |
| WO1995011243A1 (en) | 1993-10-19 | 1995-04-27 | Smithkline Beecham Plc | Benzanilide derivatives as 5ht-1d receptor antagonists |
| 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 |
| CA2340100A1 (en) | 1998-08-11 | 2000-02-24 | Daiichi Pharmaceutical Co., Ltd. | Novel sulfonyl derivatives |
| RU2299206C9 (ru) | 1999-05-04 | 2007-11-20 | Шеринг Корпорейшн | Производные пиперазина, фармацевтические композиции, их содержащие, и применение в качестве антагонистов ccr5 |
| JP2003528072A (ja) * | 2000-03-17 | 2003-09-24 | ブリストル−マイヤーズ スクイブ ファーマ カンパニー | マトリックスメタロプロテアーゼおよびＴＮＦ−αの阻害剤としての環状β−アミノ酸誘導体 |
| 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 |
| RS26604A (sr) | 2001-10-01 | 2006-12-15 | Bristol Myers Squibb Company | Spiro-hidantoinska jedinjenja korisna kao anti-inflamatorna sredstva |
| AU2003245773A1 (en) * | 2002-02-15 | 2003-09-04 | Glaxo Group Limited | Vanilloid receptor modulators |
| TWI319387B (en) * | 2002-04-05 | 2010-01-11 | Astrazeneca Ab | Benzamide derivatives |
| WO2004011440A1 (ja) | 2002-07-30 | 2004-02-05 | Banyu Pharmaceutical Co., Ltd. | ベンズイミダゾール誘導体を有効成分とするメラニン凝集ホルモン受容体拮抗剤 |
| AU2003300902A1 (en) | 2002-12-13 | 2004-07-09 | Smithkline Beecham Corporation | Piperidine derivatives as CCR5 antagonists |
| CA2510471A1 (en) | 2002-12-19 | 2004-07-08 | 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 |
| CN103265477B (zh) | 2003-02-26 | 2017-01-11 | 苏根公司 | 作为蛋白激酶抑制剂的氨基杂芳基化合物 |
| EP2295433A3 (en) | 2003-03-06 | 2011-07-06 | Eisai R&D Management Co., Ltd. | JNK inhibitors |
| US20080275062A1 (en) * | 2004-01-30 | 2008-11-06 | David Harold Drewry | Chemical Compounds |
| EP1735278B1 (en) | 2004-04-01 | 2010-01-06 | Eli Lilly And Company | Histamine h3 receptor agents, preparation and therapeutic uses |
| ES2527058T3 (es) | 2005-05-19 | 2015-01-20 | Astellas Pharma Inc. | Derivado de pirrolidina o sus sales |
| WO2006127587A1 (en) * | 2005-05-20 | 2006-11-30 | Vertex Pharmaceuticals Incorporated | Pyrrolopyridines useful as inhibitors of protein kinase |
| EP1910308B1 (en) | 2005-06-27 | 2014-09-03 | Exelixis Patent Company LLC | Imidazole based lxr modulators |
| GB0514812D0 (en) | 2005-07-19 | 2005-08-24 | Glaxo Group Ltd | Compounds |
| JP2009523812A (ja) * | 2006-01-19 | 2009-06-25 | オーエスアイ・ファーマスーティカルズ・インコーポレーテッド | 融合へテロ二環式キナーゼ阻害剤 |
| 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 |
| ES2376668T3 (es) | 2006-09-05 | 2012-03-15 | Kyowa Hakko Kirin Co., Ltd. | Derivado de imidazol. |
| EP2068878B1 (en) | 2006-09-20 | 2019-04-10 | Aerie Pharmaceuticals, Inc. | 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 |
| WO2008133955A1 (en) | 2007-04-25 | 2008-11-06 | Exelixis, Inc. | 6-phenylpyrimidinones as pim modulators |
| WO2009019163A1 (en) | 2007-08-07 | 2009-02-12 | F. Hoffmann-La Roche Ag | Pyrrolidine aryl-ether as nk3 receptor antagonists |
| WO2009027392A1 (en) * | 2007-08-27 | 2009-03-05 | Abbott Gmbh & Co. Kg | 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 |
| PE20091093A1 (es) | 2007-12-03 | 2009-08-25 | Takeda Pharmaceutical | Compuesto heterociclico que contiene nitrogeno y su uso |
| CN102066321A (zh) | 2008-06-16 | 2011-05-18 | 弗·哈夫曼-拉罗切有限公司 | 作为nk2受体拮抗剂的吡咯烷衍生物 |
| EP2321274A1 (en) | 2008-07-08 | 2011-05-18 | 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 |
| MX2011003312A (es) | 2008-10-09 | 2011-04-26 | Hoffmann La Roche | Derivados de pirrolidina n-bencilo. |
| WO2010077624A1 (en) * | 2008-12-09 | 2010-07-08 | Merck Sharp & Dohme Corp. | Biaryl carboxamides |
| CA2746943A1 (en) * | 2008-12-18 | 2010-07-15 | Boehringer Ingelheim International Gmbh | Serotonin 5-ht2b receptor inhibitors |
| AU2010209825A1 (en) | 2009-01-30 | 2011-08-11 | F. Hoffmann-La Roche Ag | Piperidine derivatives as NK3 receptor antagonists |
| 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. |
| US9206173B2 (en) | 2009-05-28 | 2015-12-08 | 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 |
| CA2777734A1 (en) | 2009-10-16 | 2011-04-21 | Rib-X Pharmaceuticals, Inc. | Antimicrobial compounds and methods of making and using the same |
| JP6144913B2 (ja) * | 2009-12-18 | 2017-06-07 | オゲダ エス．エー． | 代謝異常の治療に使用されるｇタンパク質共役受容体４３（ｇｐｒ４３）作動薬としてのピロリジンカルボン酸誘導体、医薬組成物および方法 |
| US8633183B2 (en) | 2010-01-26 | 2014-01-21 | Boehringer Ingelheim International Gmbh | 5-alkynyl-pyrimidines |
| US9079880B2 (en) | 2010-07-07 | 2015-07-14 | Boehringer Ingelheim International Gmbh | Rho kinase inhibitors |
| US8507535B2 (en) | 2010-07-07 | 2013-08-13 | Hoffmann-La Roche Inc. | Methyl-pyrrolidine ether derivatives |
| JP6117104B2 (ja) | 2010-11-15 | 2017-04-19 | アッヴィ・インコーポレイテッド | Ｎａｍｐｔおよびｒｏｃｋ阻害薬 |
| MX2014001568A (es) * | 2011-08-09 | 2014-03-31 | Takeda Pharmaceutical | Compuesto de ciclopropanoamina. |
| MX2014012294A (es) | 2012-04-12 | 2015-06-05 | Ruga Corp | Benzamidas sustituidas y sus usos. |
| WO2013153539A1 (en) | 2012-04-13 | 2013-10-17 | Glenmark Pharmaceuticals S.A. | Tricyclic compounds as tec kinase inhibitors |
| US9580438B2 (en) | 2012-06-27 | 2017-02-28 | 4Sc Discovery Gmbh | Bifluorodioxalane-amino-benzimidazole kinase inhibitors for the treatment of cancer, autoimmuneinflammation and CNS disorders |
| PL2870150T3 (pl) * | 2012-07-03 | 2019-12-31 | 3-V Biosciences, Inc. | Heterocykliczne modulatory syntezy lipidów |
| 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 |
| PT2903618T (pt) | 2012-10-05 | 2022-08-19 | Kadmon Corp Llc | Inibidores de rho cinase |
| EP3418281B1 (en) * | 2012-12-07 | 2020-09-30 | Vertex Pharmaceuticals Inc. | Pyrazolo[1,5-a]pyrimidines useful as inhibitors of atr kinase for the treatment of cancer diseases |
| EP2945943B1 (en) | 2013-01-18 | 2018-05-30 | Bristol-Myers Squibb Company | Phthalazinones and isoquinolinones as rock 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 |
| JP6423372B2 (ja) | 2013-02-28 | 2018-11-14 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 強力なｒｏｃｋ１およびｒｏｃｋ２阻害剤としてのフェニルピラゾール誘導体 |
-
2015
- 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 US US15/503,419 patent/US10112939B2/en active Active
- 2015-08-20 JP JP2017510314A patent/JP6633618B2/ja active Active
- 2015-08-20 ES ES15756322T patent/ES2838573T3/es active Active
- 2015-08-20 EP EP15756322.2A patent/EP3183248B1/en active Active