ES2814325T3 - Derivados de lactama, urea cíclica y carbamato y de triazolona como inhibidores potentes y selectivos de ROCK - Google Patents
Derivados de lactama, urea cíclica y carbamato y de triazolona como inhibidores potentes y selectivos de ROCK Download PDFInfo
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- ES2814325T3 ES2814325T3 ES17740240T ES17740240T ES2814325T3 ES 2814325 T3 ES2814325 T3 ES 2814325T3 ES 17740240 T ES17740240 T ES 17740240T ES 17740240 T ES17740240 T ES 17740240T ES 2814325 T3 ES2814325 T3 ES 2814325T3
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- substituted
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- phenyl
- crdrd
- alkyl
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- 239000011435 rock Substances 0.000 title description 38
- 150000003951 lactams Chemical class 0.000 title description 7
- FFSJPOPLSWBGQY-UHFFFAOYSA-N triazol-4-one Chemical compound O=C1C=NN=N1 FFSJPOPLSWBGQY-UHFFFAOYSA-N 0.000 title description 5
- 229940124639 Selective inhibitor Drugs 0.000 title description 3
- ZMGMDXCADSRNCX-UHFFFAOYSA-N 5,6-dihydroxy-1,3-diazepan-2-one Chemical compound OC1CNC(=O)NCC1O ZMGMDXCADSRNCX-UHFFFAOYSA-N 0.000 title description 2
- 150000004657 carbamic acid derivatives Chemical class 0.000 title description 2
- 230000003389 potentiating effect Effects 0.000 title description 2
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 216
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 143
- 150000001875 compounds Chemical class 0.000 claims abstract description 134
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 134
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 88
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 86
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 86
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 85
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 84
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 78
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 64
- 125000003118 aryl group Chemical group 0.000 claims abstract description 52
- 150000003839 salts Chemical class 0.000 claims abstract description 47
- 101150105130 RORB gene Proteins 0.000 claims abstract description 46
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 46
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 44
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 39
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 38
- 125000004452 carbocyclyl group Chemical group 0.000 claims abstract description 33
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 31
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 27
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims abstract description 19
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 19
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims abstract description 18
- 125000006706 (C3-C6) carbocyclyl group Chemical group 0.000 claims abstract description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 3
- 229910052702 rhenium Inorganic materials 0.000 claims description 148
- 229910052799 carbon Inorganic materials 0.000 claims description 128
- -1 2,3-dihydro-1H-indol-1-carbonyl Chemical group 0.000 claims description 89
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 34
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 25
- 238000011282 treatment Methods 0.000 claims description 23
- 201000010099 disease Diseases 0.000 claims description 18
- 230000000694 effects Effects 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 239000003937 drug carrier Substances 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 12
- 102100033380 Chordin Human genes 0.000 claims description 12
- 101000943798 Homo sapiens Chordin Proteins 0.000 claims description 12
- 206010020772 Hypertension Diseases 0.000 claims description 10
- 238000011321 prophylaxis Methods 0.000 claims description 10
- 108010041788 rho-Associated Kinases Proteins 0.000 claims description 9
- 102000000568 rho-Associated Kinases Human genes 0.000 claims description 9
- 208000006011 Stroke Diseases 0.000 claims description 8
- 208000035475 disorder Diseases 0.000 claims description 7
- 229910052701 rubidium Inorganic materials 0.000 claims description 6
- NOKBFRMKWIPMQW-UHFFFAOYSA-N 4-[4-[2-oxo-3-[3-(trifluoromethoxy)phenoxy]pyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound FC(F)(F)OC1=CC=CC(OC2CCN(C2=O)C2=CC=C(C=C2)C2=NNC(=O)C3=CC=CC=C23)=C1 NOKBFRMKWIPMQW-UHFFFAOYSA-N 0.000 claims description 5
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 5
- 206010019280 Heart failures Diseases 0.000 claims description 5
- 210000002460 smooth muscle Anatomy 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 206010002383 Angina Pectoris Diseases 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 230000001594 aberrant effect Effects 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 230000003176 fibrotic effect Effects 0.000 claims description 4
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 4
- PHNXYQCFZAMNIX-UHFFFAOYSA-N 3-[4-(4-oxo-3H-phthalazin-1-yl)phenyl]-4-phenyl-1,3-oxazolidin-2-one Chemical compound C1(=O)C2=CC=CC=C2C(C2=CC=C(N3C(C4=CC=CC=C4)COC3=O)C=C2)=NN1 PHNXYQCFZAMNIX-UHFFFAOYSA-N 0.000 claims description 3
- LDRICZIGBXSIDD-UHFFFAOYSA-N 4-[4-(2-oxo-3-phenylpyrrolidin-1-yl)phenyl]-2H-phthalazin-1-one Chemical compound O=C1C(CCN1C1=CC=C(C=C1)C1=NNC(=O)C2=CC=CC=C12)C1=CC=CC=C1 LDRICZIGBXSIDD-UHFFFAOYSA-N 0.000 claims description 3
- PLTLDAOTPTUTBE-UHFFFAOYSA-N 4-[4-(3-morpholin-4-yl-2-oxopyrrolidin-1-yl)phenyl]-2H-phthalazin-1-one Chemical compound C12=CC=CC=C1C(C1=CC=C(N3CCC(N4CCOCC4)C3=O)C=C1)=NNC2=O PLTLDAOTPTUTBE-UHFFFAOYSA-N 0.000 claims description 3
- XSYRIOMWWLBTDE-UHFFFAOYSA-N 4-[4-[3-[(2-methyl-1,3-benzothiazol-6-yl)amino]-2-oxopyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound CC1=NC2=CC=C(NC3CCN(C3=O)C3=CC=C(C=C3)C3=NNC(=O)C4=CC=CC=C34)C=C2S1 XSYRIOMWWLBTDE-UHFFFAOYSA-N 0.000 claims description 3
- BKXNSQNJWHGCEI-UHFFFAOYSA-N 4-[4-[3-[3-(difluoromethoxy)anilino]-2-oxopyrrolidin-1-yl]phenyl]-2H-isoquinolin-1-one Chemical compound FC(OC=1C=C(C=CC=1)NC1C(N(CC1)C1=CC=C(C=C1)C1=CNC(C2=CC=CC=C12)=O)=O)F BKXNSQNJWHGCEI-UHFFFAOYSA-N 0.000 claims description 3
- JAGCQTZNUQROMH-UHFFFAOYSA-N 4-[4-[3-[3-(difluoromethoxy)anilino]-2-oxopyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound FC(OC=1C=C(C=CC=1)NC1C(N(CC1)C1=CC=C(C=C1)C1=NNC(C2=CC=CC=C12)=O)=O)F JAGCQTZNUQROMH-UHFFFAOYSA-N 0.000 claims description 3
- CHMYEJFRFHWBDU-BPNWFJGMSA-N 4-[4-[3-[[(1R)-1-(3-methoxyphenyl)ethyl]amino]-2-oxopyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound C1=C2C(=CC=C1)C(C1=CC=C(N3C(=O)C(CC3)N[C@@H](C3=CC=CC(OC)=C3)C)C=C1)=NNC2=O CHMYEJFRFHWBDU-BPNWFJGMSA-N 0.000 claims description 3
- TWSMROBLVXOFLR-UHFFFAOYSA-N 4-[4-[4-[(3-methoxyphenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound C12=CC=CC=C1C(C1=CC=C(N3C(=O)N(CC4=CC(=CC=C4)OC)C=N3)C=C1)=NNC2=O TWSMROBLVXOFLR-UHFFFAOYSA-N 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 208000029078 coronary artery disease Diseases 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- DAEDUZRXEJEUFL-NYHFZMIOSA-N (4R,5S)-5-methyl-3-[4-(4-oxo-3H-phthalazin-1-yl)phenyl]-4-phenyl-1,3-oxazolidin-2-one Chemical compound C1=C2C(=CC=C1)C(C1=CC=C(N3[C@H](C4=CC=CC=C4)[C@@H](OC3=O)C)C=C1)=NNC2=O DAEDUZRXEJEUFL-NYHFZMIOSA-N 0.000 claims description 2
- RMPJFCRULORJLT-UHFFFAOYSA-N 1-[4-(4-benzyl-5-oxo-1,2,4-triazol-1-yl)phenyl]-3H-pyrrolo[1,2-d][1,2,4]triazin-4-one Chemical compound O=C1N(CC2=CC=CC=C2)C=NN1C1=CC=C(C=C1)C1=NNC(=O)N2C=CC=C12 RMPJFCRULORJLT-UHFFFAOYSA-N 0.000 claims description 2
- VTCFRBBODXWTCL-UHFFFAOYSA-N 2-oxo-1-[4-(4-oxo-3H-phthalazin-1-yl)phenyl]-N-phenylpyrrolidine-3-carboxamide Chemical compound C1=C2C(=CC=C1)C(C1=CC=C(N3C(=O)C(CC3)C(=O)NC3=CC=CC=C3)C=C1)=NNC2=O VTCFRBBODXWTCL-UHFFFAOYSA-N 0.000 claims description 2
- ZFUKIFBTPLIJTJ-UHFFFAOYSA-N 3-[4-(4-oxo-3H-phthalazin-1-yl)phenyl]-5-(2,2,2-trifluoro-1-hydroxy-1-phenylethyl)-1,3-oxazolidin-2-one Chemical compound C1=C2C(=CC=C1)C(C1=CC=C(N3C(=O)OC(C3)C(O)(C(F)(F)F)C3=CC=CC=C3)C=C1)=NNC2=O ZFUKIFBTPLIJTJ-UHFFFAOYSA-N 0.000 claims description 2
- XBFKWPJSFZZRIG-UHFFFAOYSA-N 3-[4-(4-oxo-3H-phthalazin-1-yl)phenyl]-5-phenyl-1,3-oxazolidin-2-one Chemical compound C1=C2C(=CC=C1)C(C1=CC=C(N3C(=O)OC(C4=CC=CC=C4)C3)C=C1)=NNC2=O XBFKWPJSFZZRIG-UHFFFAOYSA-N 0.000 claims description 2
- GQDITLDBPXDFKG-UHFFFAOYSA-N 3-[4-(4-oxo-3H-phthalazin-1-yl)phenyl]-5-propyl-1,3-oxazolidin-2-one Chemical compound CCCC1CN(C(=O)O1)C1=CC=C(C=C1)C1=NNC(=O)C2=CC=CC=C12 GQDITLDBPXDFKG-UHFFFAOYSA-N 0.000 claims description 2
- JOUKIPKNAFVMDW-UHFFFAOYSA-N 4-[4-(1-benzyl-2-oxopyrrolidin-3-yl)phenyl]-2H-phthalazin-1-one Chemical compound O=C1C2=CC=CC=C2C(C2=CC=C(C3CCN(C3=O)CC3=CC=CC=C3)C=C2)=NN1 JOUKIPKNAFVMDW-UHFFFAOYSA-N 0.000 claims description 2
- FDHNMSABZAMNHA-UHFFFAOYSA-N 4-[4-(2-oxo-1-phenylpyrrolidin-3-yl)phenyl]-2H-phthalazin-1-one Chemical compound O=C1C(CCN1C1=CC=CC=C1)C1=CC=C(C=C1)C1=NNC(=O)C2=CC=CC=C12 FDHNMSABZAMNHA-UHFFFAOYSA-N 0.000 claims description 2
- FERJKHMDMXODOJ-UHFFFAOYSA-N 4-[4-(2-oxo-3-phenylimidazolidin-1-yl)phenyl]-2H-phthalazin-1-one 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.O=C1N(CCN1c1ccc(cc1)-c1n[nH]c(=O)c2ccccc12)c1ccccc1 FERJKHMDMXODOJ-UHFFFAOYSA-N 0.000 claims description 2
- DRMNJKORTHCIDQ-UHFFFAOYSA-N 4-[4-(2-oxo-3-pyridin-3-ylimidazolidin-1-yl)phenyl]-2H-phthalazin-1-one Chemical compound C1=C2C(=CC=C1)C(C1=CC=C(C=C1)N1CCN(C1=O)C1=CC=CN=C1)=NNC2=O DRMNJKORTHCIDQ-UHFFFAOYSA-N 0.000 claims description 2
- BVKAOZUVJIRFNG-UHFFFAOYSA-N 4-[4-(2-oxo-4-phenylpyrrolidin-1-yl)phenyl]-2H-phthalazin-1-one Chemical compound O=C1CC(CN1C1=CC=C(C=C1)C1=NNC(=O)C2=CC=CC=C12)C1=CC=CC=C1 BVKAOZUVJIRFNG-UHFFFAOYSA-N 0.000 claims description 2
- GPQMTMACUICRFG-UHFFFAOYSA-N 4-[4-(3-benzyl-2-oxoimidazolidin-1-yl)phenyl]-2H-phthalazin-1-one Chemical compound C1=CC=C2C(C3=CC=C(N4CCN(C4=O)CC4=CC=CC=C4)C=C3)=NNC(=O)C2=C1 GPQMTMACUICRFG-UHFFFAOYSA-N 0.000 claims description 2
- CTJWPOIITVDJGA-UHFFFAOYSA-N 4-[4-[2-oxo-3-(1,2,3,4-tetrahydroisoquinolin-6-ylamino)pyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound C1=C2C(=CC=C1)C(C1=CC=C(C=C1)N1C(=O)C(NC3=CC=C4C(CCNC4)=C3)CC1)=NNC2=O CTJWPOIITVDJGA-UHFFFAOYSA-N 0.000 claims description 2
- OMBAQNQUSYKLCV-UHFFFAOYSA-N 4-[4-[2-oxo-3-(2-phenylethylamino)pyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound C1=C2C(=CC=C1)C(C1=CC=C(N3C(=O)C(CC3)NCCC3=CC=CC=C3)C=C1)=NNC2=O OMBAQNQUSYKLCV-UHFFFAOYSA-N 0.000 claims description 2
- MAEMMKFBENFITQ-UHFFFAOYSA-N 4-[4-[2-oxo-3-(3-propan-2-yloxyanilino)pyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound O=C1N(CCC1NC1=CC(=CC=C1)OC(C)C)C1=CC=C(C=C1)C1=NNC(C2=CC=CC=C12)=O MAEMMKFBENFITQ-UHFFFAOYSA-N 0.000 claims description 2
- ZOIFEAXDBZVKEL-UHFFFAOYSA-N 4-[4-[2-oxo-3-[(1-phenylpyrazol-4-yl)amino]pyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound C12=CC=CC=C1C(C1=CC=C(N3C(=O)C(NC=4C=NN(C=4)C4=CC=CC=C4)CC3)C=C1)=NNC2=O ZOIFEAXDBZVKEL-UHFFFAOYSA-N 0.000 claims description 2
- KPSWUVKYFARXAT-UHFFFAOYSA-N 4-[4-[2-oxo-3-[(1-propan-2-ylpyrazol-3-yl)amino]pyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound C1=C2C(=CC=C1)C(C1=CC=C(N3C(=O)C(NC=4C=CN(N=4)C(C)C)CC3)C=C1)=NNC2=O KPSWUVKYFARXAT-UHFFFAOYSA-N 0.000 claims description 2
- BFMOUERLZRRSFP-UHFFFAOYSA-N 4-[4-[2-oxo-3-[3-(trifluoromethoxy)anilino]pyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound C1=C2C(=CC=C1)C(C1=CC=C(N3C(=O)C(CC3)NC3=CC(OC(F)(F)F)=CC=C3)C=C1)=NNC2=O BFMOUERLZRRSFP-UHFFFAOYSA-N 0.000 claims description 2
- NQKJLSGGBZFHIN-UHFFFAOYSA-N 4-[4-[3-(1,3-benzodioxol-5-ylamino)-2-oxopyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound C12=CC=CC=C1C(C1=CC=C(N3CCC(NC4=CC=5OCOC=5C=C4)C3=O)C=C1)=NNC2=O NQKJLSGGBZFHIN-UHFFFAOYSA-N 0.000 claims description 2
- BHHDSIKFYYZAMR-UHFFFAOYSA-N 4-[4-[3-(2,3-dihydro-1H-inden-2-ylamino)-2-oxopyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound C1=2C(=O)NN=C(C=2C=CC=C1)C1=CC=C(N2C(=O)C(CC2)NC2CC3=C(C2)C=CC=C3)C=C1 BHHDSIKFYYZAMR-UHFFFAOYSA-N 0.000 claims description 2
- HAVCURSTIPWNRF-UHFFFAOYSA-N 4-[4-[3-(2,4-difluoro-3-methoxyanilino)-2-oxopyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound FC1=C(C=CC(=C1OC)F)NC1C(N(CC1)C1=CC=C(C=C1)C1=NNC(C2=CC=CC=C12)=O)=O HAVCURSTIPWNRF-UHFFFAOYSA-N 0.000 claims description 2
- YETQSEGMRWRSON-UHFFFAOYSA-N 4-[4-[3-(2-ethylanilino)-2-oxopyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound CCC1=C(NC2CCN(C2=O)C2=CC=C(C=C2)C2=NNC(=O)C3=CC=CC=C23)C=CC=C1 YETQSEGMRWRSON-UHFFFAOYSA-N 0.000 claims description 2
- ZEELWJOTJPXEFX-UHFFFAOYSA-N 4-[4-[3-(2-fluoro-5-methoxyanilino)-2-oxopyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound C1=C2C(=CC=C1)C(C1=CC=C(N3C(=O)C(CC3)NC3=CC(OC)=CC=C3F)C=C1)=NNC2=O ZEELWJOTJPXEFX-UHFFFAOYSA-N 0.000 claims description 2
- RVJULKBPJPNEDB-UHFFFAOYSA-N 4-[4-[3-(2-fluoro-5-methoxyphenoxy)-2-oxopyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound C12=CC=CC=C1C(C1=CC=C(N3C(=O)C(CC3)OC3=C(F)C=CC(OC)=C3)C=C1)=NNC2=O RVJULKBPJPNEDB-UHFFFAOYSA-N 0.000 claims description 2
- JHTARSDJPFDZBH-UHFFFAOYSA-N 4-[4-[3-(3-ethoxyanilino)-2-oxopyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound C1=CC2=C(C=C1)C(C1=CC=C(C=C1)N1C(=O)C(CC1)NC1=CC(OCC)=CC=C1)=NNC2=O JHTARSDJPFDZBH-UHFFFAOYSA-N 0.000 claims description 2
- IRGRFTUWICYNMA-UHFFFAOYSA-N 4-[4-[3-(3-fluoro-5-methoxyanilino)-2-oxopyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound C1=CC2=C(C=C1)C(C1=CC=C(N3CCC(NC4=CC(F)=CC(OC)=C4)C3=O)C=C1)=NNC2=O IRGRFTUWICYNMA-UHFFFAOYSA-N 0.000 claims description 2
- NNAWMAYRUJNSMU-UHFFFAOYSA-N 4-[4-[3-(3-methoxyanilino)-2-oxopyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound COC=1C=C(C=CC=1)NC1C(N(CC1)C1=CC=C(C=C1)C1=NNC(C2=CC=CC=C12)=O)=O NNAWMAYRUJNSMU-UHFFFAOYSA-N 0.000 claims description 2
- BCRFCBWMAUFGAI-UHFFFAOYSA-N 4-[4-[3-(3-methoxyphenoxy)-2-oxopyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.COc1cccc(OC2CCN(C2=O)c2ccc(cc2)-c2n[nH]c(=O)c3ccccc23)c1 BCRFCBWMAUFGAI-UHFFFAOYSA-N 0.000 claims description 2
- MTLAIGRFBRZPSL-UHFFFAOYSA-N 4-[4-[3-(3-methylsulfanylanilino)-2-oxopyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound CSC=1C=C(C=CC=1)NC1C(N(CC1)C1=CC=C(C=C1)C1=NNC(C2=CC=CC=C12)=O)=O MTLAIGRFBRZPSL-UHFFFAOYSA-N 0.000 claims description 2
- HJPXBUFNHGIQEC-UHFFFAOYSA-N 4-[4-[3-(4-fluoro-3-methoxyanilino)-2-oxopyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound C12=CC=CC=C1C(C1=CC=C(N3CCC(NC4=CC=C(F)C(OC)=C4)C3=O)C=C1)=NNC2=O HJPXBUFNHGIQEC-UHFFFAOYSA-N 0.000 claims description 2
- QAFFHOXHXHAQCZ-UHFFFAOYSA-N 4-[4-[3-(4-fluoro-3-methoxyphenoxy)-2-oxopyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound C1=C2C(=CC=C1)C(C1=CC=C(N3C(=O)C(CC3)OC3=CC(=C(C=C3)F)OC)C=C1)=NNC2=O QAFFHOXHXHAQCZ-UHFFFAOYSA-N 0.000 claims description 2
- LXGLTCMUDJFNQJ-UHFFFAOYSA-N 4-[4-[3-(benzylamino)-2-oxopyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound C12=CC=CC=C1C(C1=CC=C(N3C(=O)C(CC3)NCC3=CC=CC=C3)C=C1)=NNC2=O LXGLTCMUDJFNQJ-UHFFFAOYSA-N 0.000 claims description 2
- VXUMMCCGEOBQQR-UHFFFAOYSA-N 4-[4-[3-(cyclopentylamino)-2-oxopyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.O=C1C(CCN1c1ccc(cc1)-c1n[nH]c(=O)c2ccccc12)NC1CCCC1 VXUMMCCGEOBQQR-UHFFFAOYSA-N 0.000 claims description 2
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- TZYLUPKDDOQPFK-UHFFFAOYSA-N 4-[4-[3-[(6-fluoropyridin-2-yl)amino]-2-oxopyrrolidin-1-yl]phenyl]-2H-phthalazin-1-one Chemical compound C1=C2C(=CC=C1)C(C1=CC=C(N3C(=O)C(CC3)NC3=NC(F)=CC=C3)C=C1)=NNC2=O TZYLUPKDDOQPFK-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Immunology (AREA)
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- Rheumatology (AREA)
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- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662359341P | 2016-07-07 | 2016-07-07 | |
| PCT/US2017/040846 WO2018009622A1 (en) | 2016-07-07 | 2017-07-06 | Lactam, cyclic urea and carbamate, and triazolone derivatives as potent and selective rock inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2814325T3 true ES2814325T3 (es) | 2021-03-26 |
Family
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|---|---|---|---|
| ES17740240T Active ES2814325T3 (es) | 2016-07-07 | 2017-07-06 | Derivados de lactama, urea cíclica y carbamato y de triazolona como inhibidores potentes y selectivos de ROCK |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US10730858B2 (enExample) |
| EP (1) | EP3481816B1 (enExample) |
| JP (2) | JP6903731B2 (enExample) |
| KR (1) | KR102473481B1 (enExample) |
| CN (1) | CN110049977B (enExample) |
| ES (1) | ES2814325T3 (enExample) |
| WO (1) | WO2018009622A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| AR107354A1 (es) | 2016-01-13 | 2018-04-18 | Bristol Myers Squibb Co | Salicilamidas espiroheptanos y compuestos relacionados como inhibidores de rock |
| JP6987792B2 (ja) | 2016-05-27 | 2022-01-05 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | Ｒｏｃｋ阻害剤としてのトリアゾロンおよびテトラゾロン |
| ES2829550T3 (es) | 2016-07-07 | 2021-06-01 | Bristol Myers Squibb Co | Ureas cíclicas espiro-condensadas como inhibidores de ROCK |
| ES2821877T3 (es) | 2016-07-07 | 2021-04-28 | Bristol Myers Squibb Co | Espirolactamas como inhibidores de ROCK |
| KR102511441B1 (ko) | 2016-11-30 | 2023-03-16 | 브리스톨-마이어스 스큅 컴퍼니 | 트리시클릭 Rho 키나제 억제제 |
| JP7313331B2 (ja) | 2017-07-12 | 2023-07-24 | ブリストル－マイヤーズ スクイブ カンパニー | Ｒｏｃｋ阻害剤としてのスピロヘプタニルヒダントイン |
| JP7206253B2 (ja) | 2017-07-12 | 2023-01-17 | ブリストル－マイヤーズ スクイブ カンパニー | Ｒｏｃｋ阻害剤としてのフェニルアセトアミド |
| 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 |
| US12060341B2 (en) | 2017-07-12 | 2024-08-13 | Bristol-Myers Squibb Company | Spiroheptanyl hydantoins as ROCK inhibitors |
| KR102680160B1 (ko) | 2017-07-12 | 2024-06-28 | 브리스톨-마이어스 스큅 컴퍼니 | 심부전의 치료를 위한 rock의 5원-아미노헤테로사이클 및 5,6- 또는 6,6-원 비시클릭 아미노헤테로시클릭 억제제 |
| WO2019089868A1 (en) | 2017-11-03 | 2019-05-09 | Bristol-Myers Squibb Company | Diazaspiro rock inhibitors |
| US11248004B2 (en) | 2018-11-06 | 2022-02-15 | Cervello Therapeutics, Llc. | Substituted isoquinolines as rock kinase inhibitors |
| AU2019377087B2 (en) | 2018-11-06 | 2025-03-06 | Cervello Therapeutics, Llc | Rock kinase inhibitors |
| TW202122382A (zh) * | 2019-09-06 | 2021-06-16 | 日商小野藥品工業股份有限公司 | 乙內醯脲衍生物 |
| WO2021257863A1 (en) | 2020-06-19 | 2021-12-23 | Incyte Corporation | Pyrrolotriazine compounds as jak2 v617f inhibitors |
| US11691971B2 (en) | 2020-06-19 | 2023-07-04 | Incyte Corporation | Naphthyridinone compounds as JAK2 V617F inhibitors |
| IL299612A (en) | 2020-07-02 | 2023-03-01 | Incyte Corp | Tricyclic urea compounds as JAK2 V617F inhibitors |
| US11767323B2 (en) | 2020-07-02 | 2023-09-26 | Incyte Corporation | Tricyclic pyridone compounds as JAK2 V617F inhibitors |
| US11661422B2 (en) | 2020-08-27 | 2023-05-30 | Incyte Corporation | Tricyclic urea compounds as JAK2 V617F inhibitors |
| WO2022140231A1 (en) | 2020-12-21 | 2022-06-30 | Incyte Corporation | Deazaguaine compounds as jak2 v617f inhibitors |
| US11958861B2 (en) | 2021-02-25 | 2024-04-16 | Incyte Corporation | Spirocyclic lactams as JAK2 V617F inhibitors |
| AU2022380979A1 (en) | 2021-11-02 | 2024-06-06 | Flare Therapeutics Inc. | Pparg inverse agonists and uses thereof |
| WO2023085369A1 (ja) | 2021-11-11 | 2023-05-19 | 学校法人同志社 | 角膜内皮細胞の凍結保存製剤およびその製造法 |
| EP4493558A1 (en) | 2022-03-17 | 2025-01-22 | Incyte Corporation | Tricyclic urea compounds as jak2 v617f inhibitors |
| TW202508595A (zh) | 2023-05-04 | 2025-03-01 | 美商銳新醫藥公司 | 用於ｒａｓ相關疾病或病症之組合療法 |
| WO2025034702A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Rmc-6291 for use in the treatment of ras protein-related disease or disorder |
| WO2025080946A2 (en) | 2023-10-12 | 2025-04-17 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025240847A1 (en) | 2024-05-17 | 2025-11-20 | Revolution Medicines, Inc. | Ras inhibitors |
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| EP1713775A4 (en) | 2004-01-30 | 2009-08-12 | Smithkline Beecham Corp | CHEMICAL COMPOUNDS |
| EP1799651A2 (en) | 2004-09-28 | 2007-06-27 | Angion Biomedica Corp. | Small molecule modulators of cytokine activity |
| PH12012501544A1 (en) * | 2006-12-28 | 2024-06-03 | Abbvie Inc | Inhibitors of poly (adp-ribose) polymerase |
| CA2898440A1 (en) * | 2013-01-18 | 2014-07-24 | Bristol-Myers Squibb Company | Phthalazinones and isoquinolinones as rock inhibitors |
| 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 |
| EP2986611B1 (en) | 2013-04-18 | 2019-02-06 | Shanghai Fochon Pharmaceutical Co. Ltd | Certain protein kinase inhibitors |
| EP3016950B1 (en) | 2013-07-02 | 2017-06-07 | Bristol-Myers Squibb Company | Tricyclic pyrido-carboxamide derivatives as rock inhibitors |
| CN105492444B (zh) | 2013-07-02 | 2018-09-07 | 百时美施贵宝公司 | 作为rock抑制剂的三环吡啶-甲酰胺衍生物 |
| US9902702B2 (en) * | 2014-07-15 | 2018-02-27 | Bristol-Myers Squibb Company | Spirocycloheptanes as inhibitors of rock |
| JP6633618B2 (ja) | 2014-08-21 | 2020-01-22 | 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ｒｏｃｋ阻害剤としてのタイドバックのベンズアミド誘導体 |
| WO2016112236A1 (en) | 2015-01-09 | 2016-07-14 | Bristol-Myers Squibb Company | Cyclic ureas as inhibitors of rock |
| WO2016144936A1 (en) | 2015-03-09 | 2016-09-15 | Bristol-Myers Squibb Company | Lactams as inhibitors of rock |
| AR107354A1 (es) | 2016-01-13 | 2018-04-18 | Bristol Myers Squibb Co | Salicilamidas espiroheptanos y compuestos relacionados como inhibidores de rock |
| JP6987792B2 (ja) | 2016-05-27 | 2022-01-05 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | Ｒｏｃｋ阻害剤としてのトリアゾロンおよびテトラゾロン |
| ES2829550T3 (es) | 2016-07-07 | 2021-06-01 | Bristol Myers Squibb Co | Ureas cíclicas espiro-condensadas como inhibidores de ROCK |
| ES2821877T3 (es) | 2016-07-07 | 2021-04-28 | Bristol Myers Squibb Co | Espirolactamas como inhibidores de ROCK |
| KR102511441B1 (ko) | 2016-11-30 | 2023-03-16 | 브리스톨-마이어스 스큅 컴퍼니 | 트리시클릭 Rho 키나제 억제제 |
-
2017
- 2017-07-06 CN CN201780054580.4A patent/CN110049977B/zh active Active
- 2017-07-06 ES ES17740240T patent/ES2814325T3/es active Active
- 2017-07-06 US US16/315,674 patent/US10730858B2/en active Active
- 2017-07-06 JP JP2019500450A patent/JP6903731B2/ja active Active
- 2017-07-06 WO PCT/US2017/040846 patent/WO2018009622A1/en not_active Ceased
- 2017-07-06 EP EP17740240.1A patent/EP3481816B1/en active Active
- 2017-07-06 KR KR1020197003126A patent/KR102473481B1/ko active Active
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2021
- 2021-06-23 JP JP2021103777A patent/JP7225317B2/ja active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP2019520402A (ja) | 2019-07-18 |
| JP7225317B2 (ja) | 2023-02-20 |
| CN110049977B (zh) | 2022-01-18 |
| EP3481816A1 (en) | 2019-05-15 |
| US20190300510A1 (en) | 2019-10-03 |
| JP2021152061A (ja) | 2021-09-30 |
| CN110049977A (zh) | 2019-07-23 |
| KR102473481B1 (ko) | 2022-12-01 |
| US10730858B2 (en) | 2020-08-04 |
| EP3481816B1 (en) | 2020-06-24 |
| JP6903731B2 (ja) | 2021-07-14 |
| KR20190025960A (ko) | 2019-03-12 |
| WO2018009622A1 (en) | 2018-01-11 |
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