JP5258790B2 - Rhoキナーゼインヒビター - Google Patents
Rhoキナーゼインヒビター Download PDFInfo
- Publication number
- JP5258790B2 JP5258790B2 JP2009544958A JP2009544958A JP5258790B2 JP 5258790 B2 JP5258790 B2 JP 5258790B2 JP 2009544958 A JP2009544958 A JP 2009544958A JP 2009544958 A JP2009544958 A JP 2009544958A JP 5258790 B2 JP5258790 B2 JP 5258790B2
- Authority
- JP
- Japan
- Prior art keywords
- benzamide
- benzyl
- tetrahydro
- dimethoxy
- ylcarbamoyl
- 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.)
- Expired - Fee Related
Links
- 239000003590 rho kinase inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 151
- 125000000217 alkyl group Chemical group 0.000 claims description 88
- -1 4-methyl-1-piperazinyl Chemical group 0.000 claims description 67
- 229910052799 carbon Inorganic materials 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 18
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 108010041788 rho-Associated Kinases Proteins 0.000 claims description 15
- 102000000568 rho-Associated Kinases Human genes 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 15
- 201000010099 disease Diseases 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 11
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 11
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
- MCIPSMFHIWYOIN-UHFFFAOYSA-N 3-[[(4-cyanophenyl)carbamoylamino]methyl]-n-(1,2,3,4-tetrahydroisoquinolin-7-yl)benzamide Chemical compound C=1C=CC(C(=O)NC=2C=C3CNCCC3=CC=2)=CC=1CNC(=O)NC1=CC=C(C#N)C=C1 MCIPSMFHIWYOIN-UHFFFAOYSA-N 0.000 claims description 7
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical group C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000004434 sulfur atom Chemical group 0.000 claims description 7
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 7
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- AOTJVGQNGQYEAY-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-(1,2,3,4-tetrahydroisoquinolin-7-ylcarbamoyl)phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CNCCC3=CC=2)=C1 AOTJVGQNGQYEAY-UHFFFAOYSA-N 0.000 claims description 6
- FDNORQUIWSIWKF-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[(5-methyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridin-2-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3CN(C)CCC=3N=2)=C1 FDNORQUIWSIWKF-UHFFFAOYSA-N 0.000 claims description 6
- QDAQEKNRPXBKCO-NRFANRHFSA-N 3,4-dimethoxy-n-[[3-[[(6s)-6-morpholin-4-yl-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3C[C@H](CCC=3N=2)N2CCOCC2)=C1 QDAQEKNRPXBKCO-NRFANRHFSA-N 0.000 claims description 6
- SCIFUGGHOXNSJC-UHFFFAOYSA-N 3-[[(4-carbamoylphenyl)carbamoylamino]methyl]-n-(1,2,3,4-tetrahydroisoquinolin-7-yl)benzamide Chemical compound C1=CC(C(=O)N)=CC=C1NC(=O)NCC1=CC=CC(C(=O)NC=2C=C3CNCCC3=CC=2)=C1 SCIFUGGHOXNSJC-UHFFFAOYSA-N 0.000 claims description 6
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 6
- WVKXLPYVWVUFQT-UHFFFAOYSA-N 2-bromo-4,5-dimethoxy-n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC(Br)=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(C)CCC3=CC=2)=C1 WVKXLPYVWVUFQT-UHFFFAOYSA-N 0.000 claims description 5
- XAAZBMINIBYRPX-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-(2-piperidin-3-ylethylcarbamoyl)phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NCCC2CNCCC2)=C1 XAAZBMINIBYRPX-UHFFFAOYSA-N 0.000 claims description 5
- HSKITMMIPIGXTH-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-(4,5,6,7-tetrahydro-[1,3]thiazolo[5,4-c]pyridin-2-ylcarbamoyl)phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3CNCCC=3N=2)=C1 HSKITMMIPIGXTH-UHFFFAOYSA-N 0.000 claims description 5
- AQYDBKYCZFZNAF-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[2-(1-methylpiperidin-3-yl)ethylcarbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NCCC2CN(C)CCC2)=C1 AQYDBKYCZFZNAF-UHFFFAOYSA-N 0.000 claims description 5
- QDAQEKNRPXBKCO-OAQYLSRUSA-N 3,4-dimethoxy-n-[[3-[[(6r)-6-morpholin-4-yl-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3C[C@@H](CCC=3N=2)N2CCOCC2)=C1 QDAQEKNRPXBKCO-OAQYLSRUSA-N 0.000 claims description 5
- ZMYOSCXCQCZDAA-FQEVSTJZSA-N 3,4-dimethoxy-n-[[3-[[(6s)-6-(propylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C([C@@H](CC=1S2)NCCC)CC=1N=C2NC(=O)C(C=1)=CC=CC=1CNC(=O)C1=CC=C(OC)C(OC)=C1 ZMYOSCXCQCZDAA-FQEVSTJZSA-N 0.000 claims description 5
- DDXSWRNQMBOYNX-UHFFFAOYSA-N 3-[[(4-cyanophenyl)carbamoylamino]methyl]-n-(2-piperidin-3-ylethyl)benzamide Chemical compound C=1C=C(C#N)C=CC=1NC(=O)NCC(C=1)=CC=CC=1C(=O)NCCC1CCCNC1 DDXSWRNQMBOYNX-UHFFFAOYSA-N 0.000 claims description 5
- LCJBYZGNYPVZSS-UHFFFAOYSA-N 3-[[(4-cyanophenyl)carbamoylamino]methyl]-n-[4-(dimethylamino)butyl]benzamide Chemical compound CN(C)CCCCNC(=O)C1=CC=CC(CNC(=O)NC=2C=CC(=CC=2)C#N)=C1 LCJBYZGNYPVZSS-UHFFFAOYSA-N 0.000 claims description 5
- SLQFIGXWLZRJJN-UHFFFAOYSA-N 3-[[benzyl-[(4-cyanophenyl)carbamoyl]amino]methyl]-n-(5-methyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridin-2-yl)benzamide Chemical compound S1C=2CN(C)CCC=2N=C1NC(=O)C(C=1)=CC=CC=1CN(C(=O)NC=1C=CC(=CC=1)C#N)CC1=CC=CC=C1 SLQFIGXWLZRJJN-UHFFFAOYSA-N 0.000 claims description 5
- OQXFACQMBUZLKB-UHFFFAOYSA-N n-[3-[[(3,4-dimethoxybenzoyl)amino]methyl]phenyl]-4,5,6,7-tetrahydro-[1,3]thiazolo[5,4-c]pyridine-2-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(NC(=O)C=2SC=3CNCCC=3N=2)=C1 OQXFACQMBUZLKB-UHFFFAOYSA-N 0.000 claims description 5
- YGNSENLWUQWPRG-UHFFFAOYSA-N n-[3-[[(4-cyanophenyl)carbamoylamino]methyl]phenyl]-2-methyl-3,4-dihydro-1h-isoquinoline-7-carboxamide Chemical compound C1=C2CN(C)CCC2=CC=C1C(=O)NC(C=1)=CC=CC=1CNC(=O)NC1=CC=C(C#N)C=C1 YGNSENLWUQWPRG-UHFFFAOYSA-N 0.000 claims description 5
- WDMKCBKSWLBWPX-QGZVFWFLSA-N n-[[3-[[(6r)-6-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3C[C@H](N)CCC=3N=2)=C1 WDMKCBKSWLBWPX-QGZVFWFLSA-N 0.000 claims description 5
- MDBFMZNSFPEUHN-FQEVSTJZSA-N n-[[3-[[(6s)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-4-methoxy-3-methylbenzamide Chemical compound C1=C(C)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3C[C@H](CCC=3N=2)N(C)C)=C1 MDBFMZNSFPEUHN-FQEVSTJZSA-N 0.000 claims description 5
- MMCAPCFOJJDVNO-UHFFFAOYSA-N n-benzyl-3,4-dimethoxy-n-[[3-[(5-methyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridin-2-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)N(CC=1C=C(C=CC=1)C(=O)NC=1SC=2CN(C)CCC=2N=1)CC1=CC=CC=C1 MMCAPCFOJJDVNO-UHFFFAOYSA-N 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- VGQMQYBEZDGNSS-UHFFFAOYSA-N 2-methyl-3,4-dihydro-1h-isoquinoline-7-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2CN(C)CCC2=C1 VGQMQYBEZDGNSS-UHFFFAOYSA-N 0.000 claims description 4
- FOKGJTSJFODPDR-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-(piperidin-4-ylmethylcarbamoyl)phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NCC2CCNCC2)=C1 FOKGJTSJFODPDR-UHFFFAOYSA-N 0.000 claims description 4
- BPSAUZOYNCGXMG-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[(2-morpholin-4-yl-2,3-dihydro-1h-inden-5-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CC(CC3=CC=2)N2CCOCC2)=C1 BPSAUZOYNCGXMG-UHFFFAOYSA-N 0.000 claims description 4
- ZIFGVEYZJHMWOM-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[(4-piperidin-2-ylphenyl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=CC(=CC=2)C2NCCCC2)=C1 ZIFGVEYZJHMWOM-UHFFFAOYSA-N 0.000 claims description 4
- QHCRSVGJAASCNH-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[[5-(2-morpholin-4-ylethyl)-1,3-thiazol-2-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC(CCN3CCOCC3)=CN=2)=C1 QHCRSVGJAASCNH-UHFFFAOYSA-N 0.000 claims description 4
- NYJFHHNFZGMFKT-UHFFFAOYSA-N 3-[[(3,4-dimethoxyphenyl)carbamoylamino]methyl]-n-[4-[(dimethylamino)methyl]phenyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)NCC1=CC=CC(C(=O)NC=2C=CC(CN(C)C)=CC=2)=C1 NYJFHHNFZGMFKT-UHFFFAOYSA-N 0.000 claims description 4
- XXLBWBWONGRALC-UHFFFAOYSA-N 3-[[(3-chloro-4-cyanophenyl)carbamoylamino]methyl]-n-[4-[(dimethylamino)methyl]phenyl]benzamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)NC=2C=C(Cl)C(C#N)=CC=2)=C1 XXLBWBWONGRALC-UHFFFAOYSA-N 0.000 claims description 4
- DUHXWABMQUOFII-UHFFFAOYSA-N 3-[[[4-(difluoromethoxy)benzoyl]amino]methyl]-n-(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)benzamide Chemical compound C1=C2CN(C)CCC2=CC=C1NC(=O)C(C=1)=CC=CC=1CNC(=O)C1=CC=C(OC(F)F)C=C1 DUHXWABMQUOFII-UHFFFAOYSA-N 0.000 claims description 4
- TUUPJFPIQZBWBD-UHFFFAOYSA-N 3-chloro-4-methoxy-n-[[3-[(5-methyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridin-2-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(Cl)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3CN(C)CCC=3N=2)=C1 TUUPJFPIQZBWBD-UHFFFAOYSA-N 0.000 claims description 4
- VRXYOJOPGLAOQW-IBGZPJMESA-N 3-chloro-4-methoxy-n-[[3-[[(6s)-6-(propylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C([C@@H](CC=1S2)NCCC)CC=1N=C2NC(=O)C(C=1)=CC=CC=1CNC(=O)C1=CC=C(OC)C(Cl)=C1 VRXYOJOPGLAOQW-IBGZPJMESA-N 0.000 claims description 4
- WWKGSLZIGCEEEZ-FQEVSTJZSA-N 3-chloro-4-methoxy-n-[[3-[[(6s)-6-morpholin-4-yl-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(Cl)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3C[C@H](CCC=3N=2)N2CCOCC2)=C1 WWKGSLZIGCEEEZ-FQEVSTJZSA-N 0.000 claims description 4
- ARCOISRMIVSDHR-GOSISDBHSA-N 3-chloro-n-[[3-[[(6r)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-4-methoxybenzamide Chemical compound C1=C(Cl)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3C[C@@H](CCC=3N=2)N(C)C)=C1 ARCOISRMIVSDHR-GOSISDBHSA-N 0.000 claims description 4
- ARCOISRMIVSDHR-SFHVURJKSA-N 3-chloro-n-[[3-[[(6s)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-4-methoxybenzamide Chemical compound C1=C(Cl)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3C[C@H](CCC=3N=2)N(C)C)=C1 ARCOISRMIVSDHR-SFHVURJKSA-N 0.000 claims description 4
- CBVODQKZOOSINP-NRFANRHFSA-N 4-methoxy-3-methyl-n-[[3-[[(6s)-6-(propylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C([C@@H](CC=1S2)NCCC)CC=1N=C2NC(=O)C(C=1)=CC=CC=1CNC(=O)C1=CC=C(OC)C(C)=C1 CBVODQKZOOSINP-NRFANRHFSA-N 0.000 claims description 4
- SSYXZESTUAIROQ-QFIPXVFZSA-N 4-methoxy-3-methyl-n-[[3-[[(6s)-6-morpholin-4-yl-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(C)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3C[C@H](CCC=3N=2)N2CCOCC2)=C1 SSYXZESTUAIROQ-QFIPXVFZSA-N 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
- CQCKKISDOFZHAN-UHFFFAOYSA-N methyl 2-[7-[[3-[[(3,4-dimethoxybenzoyl)amino]methyl]benzoyl]amino]-3,4-dihydro-1h-isoquinolin-2-yl]acetate Chemical compound C1=C2CN(CC(=O)OC)CCC2=CC=C1NC(=O)C(C=1)=CC=CC=1CNC(=O)C1=CC=C(OC)C(OC)=C1 CQCKKISDOFZHAN-UHFFFAOYSA-N 0.000 claims description 4
- IWHUGDMSMDVZOY-UHFFFAOYSA-N n-[3-[2-(3,4-dimethoxyanilino)-2-oxoethyl]phenyl]-3-piperidin-3-ylpropanamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)CC1=CC=CC(NC(=O)CCC2CNCCC2)=C1 IWHUGDMSMDVZOY-UHFFFAOYSA-N 0.000 claims description 4
- RGUHTIWGUPVADN-UHFFFAOYSA-N n-[3-[[(3,4-dimethoxybenzoyl)amino]methyl]phenyl]-2-methyl-3,4-dihydro-1h-isoquinoline-6-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(NC(=O)C=2C=C3CCN(C)CC3=CC=2)=C1 RGUHTIWGUPVADN-UHFFFAOYSA-N 0.000 claims description 4
- FARBCDMPQBPCIY-UHFFFAOYSA-N n-[[3-[(2-benzyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CC=4C=CC=CC=4)CCC3=CC=2)=C1 FARBCDMPQBPCIY-UHFFFAOYSA-N 0.000 claims description 4
- QWDXYCMZQIBKIH-UHFFFAOYSA-N n-[[3-[3-(dimethylamino)propylcarbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NCCCN(C)C)=C1 QWDXYCMZQIBKIH-UHFFFAOYSA-N 0.000 claims description 4
- GKBAYDIXMMANQN-LJQANCHMSA-N n-[[3-[[(6r)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3C[C@@H](CCC=3N=2)N(C)C)=C1 GKBAYDIXMMANQN-LJQANCHMSA-N 0.000 claims description 4
- MDBFMZNSFPEUHN-HXUWFJFHSA-N n-[[3-[[(6r)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-4-methoxy-3-methylbenzamide Chemical compound C1=C(C)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3C[C@@H](CCC=3N=2)N(C)C)=C1 MDBFMZNSFPEUHN-HXUWFJFHSA-N 0.000 claims description 4
- VUAKQQXGRWHENF-MRXNPFEDSA-N n-[[3-[[(6r)-6-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-3-chloro-4-methoxybenzamide Chemical compound C1=C(Cl)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3C[C@H](N)CCC=3N=2)=C1 VUAKQQXGRWHENF-MRXNPFEDSA-N 0.000 claims description 4
- COKNHADRCGAEMW-VWLOTQADSA-N n-[[3-[[(6s)-6-(1,3-dihydroisoindol-2-yl)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3C[C@H](CCC=3N=2)N2CC3=CC=CC=C3C2)=C1 COKNHADRCGAEMW-VWLOTQADSA-N 0.000 claims description 4
- GKBAYDIXMMANQN-IBGZPJMESA-N n-[[3-[[(6s)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3C[C@H](CCC=3N=2)N(C)C)=C1 GKBAYDIXMMANQN-IBGZPJMESA-N 0.000 claims description 4
- XSCPPIVJZTUFDL-SANMLTNESA-N n-[[3-[[(6s)-6-[benzyl(propyl)amino]-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-3-chloro-4-methoxybenzamide Chemical compound CCCN([C@@H]1CC=2SC(NC(=O)C=3C=C(CNC(=O)C=4C=C(Cl)C(OC)=CC=4)C=CC=3)=NC=2CC1)CC1=CC=CC=C1 XSCPPIVJZTUFDL-SANMLTNESA-N 0.000 claims description 4
- WDMKCBKSWLBWPX-KRWDZBQOSA-N n-[[3-[[(6s)-6-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3C[C@@H](N)CCC=3N=2)=C1 WDMKCBKSWLBWPX-KRWDZBQOSA-N 0.000 claims description 4
- VUAKQQXGRWHENF-INIZCTEOSA-N n-[[3-[[(6s)-6-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-3-chloro-4-methoxybenzamide Chemical compound C1=C(Cl)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3C[C@@H](N)CCC=3N=2)=C1 VUAKQQXGRWHENF-INIZCTEOSA-N 0.000 claims description 4
- KBELWXQYQJTLLV-SFHVURJKSA-N n-[[3-[[(6s)-6-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-4-methoxy-3-methylbenzamide Chemical compound C1=C(C)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3C[C@@H](N)CCC=3N=2)=C1 KBELWXQYQJTLLV-SFHVURJKSA-N 0.000 claims description 4
- LYORVENLHWRTDU-UHFFFAOYSA-N n-[[3-[[2-(2,2-difluoroethyl)-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CC(F)F)CCC3=CC=2)=C1 LYORVENLHWRTDU-UHFFFAOYSA-N 0.000 claims description 4
- QVWADFSTTCAAMY-UHFFFAOYSA-N n-[[3-[[2-[(3-fluorophenyl)methyl]-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CC=4C=C(F)C=CC=4)CCC3=CC=2)=C1 QVWADFSTTCAAMY-UHFFFAOYSA-N 0.000 claims description 4
- AGMSSUJJEHYBJT-UHFFFAOYSA-N n-[[3-[[4-(2-aminoethyl)-1,3-thiazol-2-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=C(CCN)N=2)=C1 AGMSSUJJEHYBJT-UHFFFAOYSA-N 0.000 claims description 4
- DJOZLTJBFXEBSM-UHFFFAOYSA-N n-[[3-[[4-[(dimethylamino)methyl]-1,3-thiazol-2-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=C(CN(C)C)N=2)=C1 DJOZLTJBFXEBSM-UHFFFAOYSA-N 0.000 claims description 4
- CJLDEBMSVPBFQY-UHFFFAOYSA-N n-[[3-[[5-[(dimethylamino)methyl]-1,3-thiazol-2-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC(CN(C)C)=CN=2)=C1 CJLDEBMSVPBFQY-UHFFFAOYSA-N 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- JXDIHMPDMUCOTI-UHFFFAOYSA-N 1-methyl-n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]-6-oxopyridine-3-carboxamide Chemical compound C1=C2CN(C)CCC2=CC=C1NC(=O)C(C=1)=CC=CC=1CNC(=O)C=1C=CC(=O)N(C)C=1 JXDIHMPDMUCOTI-UHFFFAOYSA-N 0.000 claims description 3
- VUBLTFWGVBUVGZ-UHFFFAOYSA-N 2,4,5-trimethoxy-n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC(OC)=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(C)CCC3=CC=2)=C1 VUBLTFWGVBUVGZ-UHFFFAOYSA-N 0.000 claims description 3
- RHNAQSUNHOXWMV-UHFFFAOYSA-N 2-cyano-4-methyl-n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C2CN(C)CCC2=CC=C1NC(=O)C(C=1)=CC=CC=1CNC(=O)C1=CC=C(C)C=C1C#N RHNAQSUNHOXWMV-UHFFFAOYSA-N 0.000 claims description 3
- UYBJKTJNTQGNFZ-UHFFFAOYSA-N 3,4-diethoxy-n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OCC)C(OCC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(C)CCC3=CC=2)=C1 UYBJKTJNTQGNFZ-UHFFFAOYSA-N 0.000 claims description 3
- ULXYUIOTBNWJFH-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-(2-piperidin-4-ylethylcarbamoyl)phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NCCC2CCNCC2)=C1 ULXYUIOTBNWJFH-UHFFFAOYSA-N 0.000 claims description 3
- SJBMXOXUSWRUJG-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-(3-piperidin-3-ylpropanoylamino)phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(NC(=O)CCC2CNCCC2)=C1 SJBMXOXUSWRUJG-UHFFFAOYSA-N 0.000 claims description 3
- HGBIXOMKAOZIAQ-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-(5,6,7,8-tetrahydro-1,6-naphthyridin-3-ylcarbamoyl)phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CNCCC3=NC=2)=C1 HGBIXOMKAOZIAQ-UHFFFAOYSA-N 0.000 claims description 3
- RUVNTEGYLMYXCF-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(C)CCC3=CC=2)=C1 RUVNTEGYLMYXCF-UHFFFAOYSA-N 0.000 claims description 3
- LPCZGZGBAPYZBC-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[(3-piperidin-3-ylphenyl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C(C=CC=2)C2CNCCC2)=C1 LPCZGZGBAPYZBC-UHFFFAOYSA-N 0.000 claims description 3
- YQXVEGAUEUXPQA-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[[2-(2,2,2-trifluoroethyl)-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CC(F)(F)F)CCC3=CC=2)=C1 YQXVEGAUEUXPQA-UHFFFAOYSA-N 0.000 claims description 3
- OHRNQFLSSSOXEU-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[[2-(2-methoxyethyl)-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C2CN(CCOC)CCC2=CC=C1NC(=O)C(C=1)=CC=CC=1CNC(=O)C1=CC=C(OC)C(OC)=C1 OHRNQFLSSSOXEU-UHFFFAOYSA-N 0.000 claims description 3
- UNIWGKNINBEPGO-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[[2-(3,3,3-trifluoropropyl)-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CCC(F)(F)F)CCC3=CC=2)=C1 UNIWGKNINBEPGO-UHFFFAOYSA-N 0.000 claims description 3
- YPLXWMXANHYRCY-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[[2-(pyridin-2-ylmethyl)-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CC=4N=CC=CC=4)CCC3=CC=2)=C1 YPLXWMXANHYRCY-UHFFFAOYSA-N 0.000 claims description 3
- SVJIUWDLHOVEDH-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[[2-(pyridin-3-ylmethyl)-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CC=4C=NC=CC=4)CCC3=CC=2)=C1 SVJIUWDLHOVEDH-UHFFFAOYSA-N 0.000 claims description 3
- YUUKRNQATZSALP-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[[2-(pyridin-4-ylmethyl)-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CC=4C=CN=CC=4)CCC3=CC=2)=C1 YUUKRNQATZSALP-UHFFFAOYSA-N 0.000 claims description 3
- SESXAZQVFXYCGY-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[[2-[(2-nitrophenyl)methyl]-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CC=4C(=CC=CC=4)[N+]([O-])=O)CCC3=CC=2)=C1 SESXAZQVFXYCGY-UHFFFAOYSA-N 0.000 claims description 3
- SAUBORSLPUDHEM-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[[2-[[2-(trifluoromethyl)phenyl]methyl]-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CC=4C(=CC=CC=4)C(F)(F)F)CCC3=CC=2)=C1 SAUBORSLPUDHEM-UHFFFAOYSA-N 0.000 claims description 3
- VVDGVOZUEVOBLC-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[[5-(2-methoxyethyl)-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridin-2-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound S1C=2CN(CCOC)CCC=2N=C1NC(=O)C(C=1)=CC=CC=1CNC(=O)C1=CC=C(OC)C(OC)=C1 VVDGVOZUEVOBLC-UHFFFAOYSA-N 0.000 claims description 3
- KSENRIABIKXSDJ-UHFFFAOYSA-N 3,4-dimethoxy-n-methyl-n-[[3-(1,2,3,4-tetrahydroisoquinolin-6-ylcarbamoyl)phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)N(C)CC1=CC=CC(C(=O)NC=2C=C3CCNCC3=CC=2)=C1 KSENRIABIKXSDJ-UHFFFAOYSA-N 0.000 claims description 3
- GXMYSRARUAZJAH-UHFFFAOYSA-N 3-[[(3,4-dimethoxyphenyl)carbamoylamino]methyl]-n-(2-piperidin-3-ylethyl)benzamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)NCC1=CC=CC(C(=O)NCCC2CNCCC2)=C1 GXMYSRARUAZJAH-UHFFFAOYSA-N 0.000 claims description 3
- VLZJBMGIVBANJC-UHFFFAOYSA-N 3-[[(3,4-dimethoxyphenyl)carbamoylamino]methyl]-n-(piperidin-3-ylmethyl)benzamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)NCC1=CC=CC(C(=O)NCC2CNCCC2)=C1 VLZJBMGIVBANJC-UHFFFAOYSA-N 0.000 claims description 3
- HZOWMRNBTWFJID-UHFFFAOYSA-N 3-[[(4-cyanophenyl)carbamoylamino]methyl]-n-(2-piperidin-4-ylethyl)benzamide Chemical compound C=1C=C(C#N)C=CC=1NC(=O)NCC(C=1)=CC=CC=1C(=O)NCCC1CCNCC1 HZOWMRNBTWFJID-UHFFFAOYSA-N 0.000 claims description 3
- YYEAXSONRWVIFC-UHFFFAOYSA-N 3-[[(4-cyanophenyl)carbamoylamino]methyl]-n-(5-methyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridin-2-yl)benzamide Chemical compound S1C=2CN(C)CCC=2N=C1NC(=O)C(C=1)=CC=CC=1CNC(=O)NC1=CC=C(C#N)C=C1 YYEAXSONRWVIFC-UHFFFAOYSA-N 0.000 claims description 3
- YUMCEAHGUJLRQA-UHFFFAOYSA-N 3-[[(4-cyanophenyl)carbamoylamino]methyl]-n-[3-(dimethylamino)propyl]benzamide Chemical compound CN(C)CCCNC(=O)C1=CC=CC(CNC(=O)NC=2C=CC(=CC=2)C#N)=C1 YUMCEAHGUJLRQA-UHFFFAOYSA-N 0.000 claims description 3
- RQLGHFOGWQQAPP-UHFFFAOYSA-N 3-[[(4-cyanophenyl)carbamoylamino]methyl]-n-[4-[2-(dimethylamino)ethyl]phenyl]benzamide Chemical compound C1=CC(CCN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)NC=2C=CC(=CC=2)C#N)=C1 RQLGHFOGWQQAPP-UHFFFAOYSA-N 0.000 claims description 3
- ITLPTFYFYJBZFM-UHFFFAOYSA-N 3-[[(4-cyanophenyl)carbamoylamino]methyl]-n-[5-(dimethylamino)pentyl]benzamide Chemical compound CN(C)CCCCCNC(=O)C1=CC=CC(CNC(=O)NC=2C=CC(=CC=2)C#N)=C1 ITLPTFYFYJBZFM-UHFFFAOYSA-N 0.000 claims description 3
- JYTWLVKIDTVMOY-UHFFFAOYSA-N 3-[[benzyl-[(3-cyanophenyl)carbamoyl]amino]methyl]-n-(5-methyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridin-2-yl)benzamide Chemical compound S1C=2CN(C)CCC=2N=C1NC(=O)C(C=1)=CC=CC=1CN(C(=O)NC=1C=C(C=CC=1)C#N)CC1=CC=CC=C1 JYTWLVKIDTVMOY-UHFFFAOYSA-N 0.000 claims description 3
- WNDISDQPUWIERI-UHFFFAOYSA-N 3-chloro-4-ethoxy-n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(Cl)C(OCC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(C)CCC3=CC=2)=C1 WNDISDQPUWIERI-UHFFFAOYSA-N 0.000 claims description 3
- HCTXXLLLMFRIEF-UHFFFAOYSA-N 3-chloro-4-ethyl-n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(Cl)C(CC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(C)CCC3=CC=2)=C1 HCTXXLLLMFRIEF-UHFFFAOYSA-N 0.000 claims description 3
- IPPDZBMRNHYGAN-UHFFFAOYSA-N 3-chloro-4-methoxy-n-[[3-(4,5,6,7-tetrahydro-[1,3]thiazolo[5,4-c]pyridin-2-ylcarbamoyl)phenyl]methyl]benzamide Chemical compound C1=C(Cl)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3CNCCC=3N=2)=C1 IPPDZBMRNHYGAN-UHFFFAOYSA-N 0.000 claims description 3
- PUSJOWHRCLFAPS-QFIPXVFZSA-N 3-chloro-4-methoxy-n-[[3-[2-methoxyethyl-[(6s)-6-(propylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C([C@@H](CC=1S2)NCCC)CC=1N=C2N(CCOC)C(=O)C(C=1)=CC=CC=1CNC(=O)C1=CC=C(OC)C(Cl)=C1 PUSJOWHRCLFAPS-QFIPXVFZSA-N 0.000 claims description 3
- JDXFTLZOVIJSMF-UHFFFAOYSA-N 3-chloro-n-[[3-(2,3-dihydro-1h-isoindol-5-ylcarbamoyl)phenyl]methyl]-4-methoxybenzamide Chemical compound C1=C(Cl)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CNCC3=CC=2)=C1 JDXFTLZOVIJSMF-UHFFFAOYSA-N 0.000 claims description 3
- PSINFMZLBPXVHX-UHFFFAOYSA-N 3-chloro-n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]-4-(trifluoromethoxy)benzamide Chemical compound C1=C2CN(C)CCC2=CC=C1NC(=O)C(C=1)=CC=CC=1CNC(=O)C1=CC=C(OC(F)(F)F)C(Cl)=C1 PSINFMZLBPXVHX-UHFFFAOYSA-N 0.000 claims description 3
- VYLVEERKOLDJOU-UHFFFAOYSA-N 3-chloro-n-[[3-[[4-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methyl]-4-methoxybenzamide Chemical compound C1=C(Cl)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=CC(CN(C)C)=CC=2)=C1 VYLVEERKOLDJOU-UHFFFAOYSA-N 0.000 claims description 3
- PKRNCWZIDOMDEO-UHFFFAOYSA-N 3-ethoxy-4-methoxy-n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OCC)=CC(C(=O)NCC=2C=C(C=CC=2)C(=O)NC=2C=C3CN(C)CCC3=CC=2)=C1 PKRNCWZIDOMDEO-UHFFFAOYSA-N 0.000 claims description 3
- CTGRBSPXVSCQLH-UHFFFAOYSA-N 3-fluoro-4-methoxy-n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(F)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(C)CCC3=CC=2)=C1 CTGRBSPXVSCQLH-UHFFFAOYSA-N 0.000 claims description 3
- NTDGNFMCBAKFAM-UHFFFAOYSA-N 3-hydroxy-4-methoxy-n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(O)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(C)CCC3=CC=2)=C1 NTDGNFMCBAKFAM-UHFFFAOYSA-N 0.000 claims description 3
- GVPUJOPQBQWLKH-UHFFFAOYSA-N 3-n-[[3-[[4-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methyl]benzene-1,3-dicarboxamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)C=2C=C(C=CC=2)C(N)=O)=C1 GVPUJOPQBQWLKH-UHFFFAOYSA-N 0.000 claims description 3
- UKRUTLIOWOYGLJ-UHFFFAOYSA-N 4-(difluoromethoxy)-3-ethoxy-n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC(F)F)C(OCC)=CC(C(=O)NCC=2C=C(C=CC=2)C(=O)NC=2C=C3CN(C)CCC3=CC=2)=C1 UKRUTLIOWOYGLJ-UHFFFAOYSA-N 0.000 claims description 3
- WFTCCEOYSFQDCN-UHFFFAOYSA-N 4-(difluoromethoxy)-3-methoxy-n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC(F)F)C(OC)=CC(C(=O)NCC=2C=C(C=CC=2)C(=O)NC=2C=C3CN(C)CCC3=CC=2)=C1 WFTCCEOYSFQDCN-UHFFFAOYSA-N 0.000 claims description 3
- NWLORKXDAKZPRC-UHFFFAOYSA-N 4-methoxy-3-methyl-n-[[3-(4,5,6,7-tetrahydro-[1,3]thiazolo[5,4-c]pyridin-2-ylcarbamoyl)phenyl]methyl]benzamide Chemical compound C1=C(C)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3CNCCC=3N=2)=C1 NWLORKXDAKZPRC-UHFFFAOYSA-N 0.000 claims description 3
- LNLWVTVALKFOBJ-UHFFFAOYSA-N 4-methoxy-3-methyl-n-[[3-[(5-methyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridin-2-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(C)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3CN(C)CCC=3N=2)=C1 LNLWVTVALKFOBJ-UHFFFAOYSA-N 0.000 claims description 3
- XBSZYGAILHLZML-UHFFFAOYSA-N 5-chloro-6-methoxy-n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]pyridine-3-carboxamide Chemical compound C1=C(Cl)C(OC)=NC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(C)CCC3=CC=2)=C1 XBSZYGAILHLZML-UHFFFAOYSA-N 0.000 claims description 3
- GJTCOWNBURMFJL-UHFFFAOYSA-N 6-methoxy-n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]pyridine-3-carboxamide Chemical compound C1=NC(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(C)CCC3=CC=2)=C1 GJTCOWNBURMFJL-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- FDSHCSSHSDBJQF-UHFFFAOYSA-N n-(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)-3-[[[4-(trifluoromethoxy)benzoyl]amino]methyl]benzamide Chemical compound C1=C2CN(C)CCC2=CC=C1NC(=O)C(C=1)=CC=CC=1CNC(=O)C1=CC=C(OC(F)(F)F)C=C1 FDSHCSSHSDBJQF-UHFFFAOYSA-N 0.000 claims description 3
- GTUXSPVFKGIBAM-UHFFFAOYSA-N n-[3-[2-(3,4-dimethoxyanilino)-2-oxoethyl]phenyl]-1,2,3,4-tetrahydroisoquinoline-7-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)CC1=CC=CC(NC(=O)C=2C=C3CNCCC3=CC=2)=C1 GTUXSPVFKGIBAM-UHFFFAOYSA-N 0.000 claims description 3
- VSCQEQICHJMHMM-UHFFFAOYSA-N n-[3-[2-(3,4-dimethoxyanilino)-2-oxoethyl]phenyl]-2-methyl-3,4-dihydro-1h-isoquinoline-7-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)CC1=CC=CC(NC(=O)C=2C=C3CN(C)CCC3=CC=2)=C1 VSCQEQICHJMHMM-UHFFFAOYSA-N 0.000 claims description 3
- YYZWQOSWWMFRMA-UHFFFAOYSA-N n-[3-[2-(3,4-dimethoxyanilino)-2-oxoethyl]phenyl]-4-[(dimethylamino)methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)CC1=CC=CC(NC(=O)C=2C=CC(CN(C)C)=CC=2)=C1 YYZWQOSWWMFRMA-UHFFFAOYSA-N 0.000 claims description 3
- VQCLUMVWFTVMSV-UHFFFAOYSA-N n-[3-[3-(3,4-dimethoxyanilino)-3-oxopropyl]phenyl]-3-piperidin-3-ylpropanamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)CCC1=CC=CC(NC(=O)CCC2CNCCC2)=C1 VQCLUMVWFTVMSV-UHFFFAOYSA-N 0.000 claims description 3
- NTOUYMSDUMWPSG-UHFFFAOYSA-N n-[3-[3-(4-cyanoanilino)-3-oxopropyl]phenyl]-1,2,3,4-tetrahydroisoquinoline-7-carboxamide Chemical compound C=1C=CC(NC(=O)C=2C=C3CNCCC3=CC=2)=CC=1CCC(=O)NC1=CC=C(C#N)C=C1 NTOUYMSDUMWPSG-UHFFFAOYSA-N 0.000 claims description 3
- IEHQDPSPRZPKQS-UHFFFAOYSA-N n-[3-[3-(4-cyanoanilino)-3-oxopropyl]phenyl]-3-piperidin-3-ylpropanamide Chemical compound C=1C=CC(CCC(=O)NC=2C=CC(=CC=2)C#N)=CC=1NC(=O)CCC1CCCNC1 IEHQDPSPRZPKQS-UHFFFAOYSA-N 0.000 claims description 3
- MGMQCNHCEFKXJR-UHFFFAOYSA-N n-[3-[[(3,4-dimethoxybenzoyl)amino]methyl]phenyl]-2-methyl-3,4-dihydro-1h-isoquinoline-7-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(NC(=O)C=2C=C3CN(C)CCC3=CC=2)=C1 MGMQCNHCEFKXJR-UHFFFAOYSA-N 0.000 claims description 3
- GNOCXMSCHWQYGZ-UHFFFAOYSA-N n-[3-[[(3,4-dimethoxybenzoyl)amino]methyl]phenyl]-5-methyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-2-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(NC(=O)C=2SC=3CN(C)CCC=3N=2)=C1 GNOCXMSCHWQYGZ-UHFFFAOYSA-N 0.000 claims description 3
- ZAPZMLYNSKIPSW-UHFFFAOYSA-N n-[3-[[(4-cyanophenyl)carbamoylamino]methyl]phenyl]-3-piperidin-3-ylpropanamide Chemical compound C=1C=CC(CNC(=O)NC=2C=CC(=CC=2)C#N)=CC=1NC(=O)CCC1CCCNC1 ZAPZMLYNSKIPSW-UHFFFAOYSA-N 0.000 claims description 3
- XIAWNXZYZQNYEO-UHFFFAOYSA-N n-[4-[(dimethylamino)methyl]phenyl]-3-[[[4-(trifluoromethoxy)benzoyl]amino]methyl]benzamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)C=2C=CC(OC(F)(F)F)=CC=2)=C1 XIAWNXZYZQNYEO-UHFFFAOYSA-N 0.000 claims description 3
- KGEIDCPSOPICSD-UHFFFAOYSA-N n-[[3-(2,3-dihydro-1h-isoindol-5-ylcarbamoyl)phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CNCC3=CC=2)=C1 KGEIDCPSOPICSD-UHFFFAOYSA-N 0.000 claims description 3
- MIIJFRXWNMSXIR-UHFFFAOYSA-N n-[[3-(2,3-dihydro-1h-isoindol-5-ylcarbamoyl)phenyl]methyl]-4-methoxy-3-methylbenzamide Chemical compound C1=C(C)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CNCC3=CC=2)=C1 MIIJFRXWNMSXIR-UHFFFAOYSA-N 0.000 claims description 3
- MYFIZIOBEROQOO-UHFFFAOYSA-N n-[[3-[(2-amino-2,3-dihydro-1h-inden-5-yl)carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CC(N)CC3=CC=2)=C1 MYFIZIOBEROQOO-UHFFFAOYSA-N 0.000 claims description 3
- QIQIRFJNTGGNOS-UHFFFAOYSA-N n-[[3-[(2-ethyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C2CN(CC)CCC2=CC=C1NC(=O)C(C=1)=CC=CC=1CNC(=O)C1=CC=C(OC)C(OC)=C1 QIQIRFJNTGGNOS-UHFFFAOYSA-N 0.000 claims description 3
- XRZQTOXHXVWMRQ-UHFFFAOYSA-N n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]-6-oxo-1h-pyridine-3-carboxamide Chemical compound C1=C2CN(C)CCC2=CC=C1NC(=O)C(C=1)=CC=CC=1CNC(=O)C1=CC=C(O)N=C1 XRZQTOXHXVWMRQ-UHFFFAOYSA-N 0.000 claims description 3
- GQOWNDGLRIZSPF-UHFFFAOYSA-N n-[[3-[(5-benzyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridin-2-yl)carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3CN(CC=4C=CC=CC=4)CCC=3N=2)=C1 GQOWNDGLRIZSPF-UHFFFAOYSA-N 0.000 claims description 3
- PQEBVKCYFFQIHS-UHFFFAOYSA-N n-[[3-[4-(dimethylamino)butylcarbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NCCCCN(C)C)=C1 PQEBVKCYFFQIHS-UHFFFAOYSA-N 0.000 claims description 3
- CFBBLHWLVWOAOI-UHFFFAOYSA-N n-[[3-[5-(dimethylamino)pentylcarbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NCCCCCN(C)C)=C1 CFBBLHWLVWOAOI-UHFFFAOYSA-N 0.000 claims description 3
- OVJCKUUPMRRUCG-UHFFFAOYSA-N n-[[3-[6-(dimethylamino)hexylcarbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NCCCCCCN(C)C)=C1 OVJCKUUPMRRUCG-UHFFFAOYSA-N 0.000 claims description 3
- OXEQSWQMHCRZLU-NRFANRHFSA-N n-[[3-[[(6s)-6-(1,1-dioxo-1,4-thiazinan-4-yl)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3C[C@H](CCC=3N=2)N2CCS(=O)(=O)CC2)=C1 OXEQSWQMHCRZLU-NRFANRHFSA-N 0.000 claims description 3
- SREURCVVXMSGAN-UHFFFAOYSA-N n-[[3-[[2-(2,2-dimethylpropyl)-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CC(C)(C)C)CCC3=CC=2)=C1 SREURCVVXMSGAN-UHFFFAOYSA-N 0.000 claims description 3
- PRGFJFUKJVTHIT-UHFFFAOYSA-N n-[[3-[[2-(2-amino-2-oxoethyl)-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CC(N)=O)CCC3=CC=2)=C1 PRGFJFUKJVTHIT-UHFFFAOYSA-N 0.000 claims description 3
- WPLZNVHCFPVSDT-UHFFFAOYSA-N n-[[3-[[2-(2-cyanoethyl)-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CCC#N)CCC3=CC=2)=C1 WPLZNVHCFPVSDT-UHFFFAOYSA-N 0.000 claims description 3
- LDXQUDUSFIPJNY-UHFFFAOYSA-N n-[[3-[[2-(2-fluoroethyl)-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CCF)CCC3=CC=2)=C1 LDXQUDUSFIPJNY-UHFFFAOYSA-N 0.000 claims description 3
- KPZPLZWAEPTTOX-UHFFFAOYSA-N n-[[3-[[2-[(2,3-difluorophenyl)methyl]-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CC=4C(=C(F)C=CC=4)F)CCC3=CC=2)=C1 KPZPLZWAEPTTOX-UHFFFAOYSA-N 0.000 claims description 3
- WYLMKIUJTMUPPD-UHFFFAOYSA-N n-[[3-[[2-[(2,4-difluorophenyl)methyl]-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CC=4C(=CC(F)=CC=4)F)CCC3=CC=2)=C1 WYLMKIUJTMUPPD-UHFFFAOYSA-N 0.000 claims description 3
- RQTYJZADHPMGPQ-UHFFFAOYSA-N n-[[3-[[2-[(2,6-difluorophenyl)methyl]-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CC=4C(=CC=CC=4F)F)CCC3=CC=2)=C1 RQTYJZADHPMGPQ-UHFFFAOYSA-N 0.000 claims description 3
- PBYWJANFHRBCQB-UHFFFAOYSA-N n-[[3-[[2-[(2-cyanophenyl)methyl]-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CC=4C(=CC=CC=4)C#N)CCC3=CC=2)=C1 PBYWJANFHRBCQB-UHFFFAOYSA-N 0.000 claims description 3
- FAOYDADVELCWMY-UHFFFAOYSA-N n-[[3-[[2-[(3,5-difluorophenyl)methyl]-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CC=4C=C(F)C=C(F)C=4)CCC3=CC=2)=C1 FAOYDADVELCWMY-UHFFFAOYSA-N 0.000 claims description 3
- KGECKSUFLDSCJA-UHFFFAOYSA-N n-[[3-[[3-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C(CN(C)C)C=CC=2)=C1 KGECKSUFLDSCJA-UHFFFAOYSA-N 0.000 claims description 3
- JHAMKJGGGMLIGX-UHFFFAOYSA-N n-[[3-[[4-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methyl]-4-methoxy-3-(trifluoromethyl)benzamide Chemical compound C1=C(C(F)(F)F)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=CC(CN(C)C)=CC=2)=C1 JHAMKJGGGMLIGX-UHFFFAOYSA-N 0.000 claims description 3
- PWFHHGIUVHLZME-UHFFFAOYSA-N n-[[3-[[4-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methyl]quinoline-6-carboxamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)C=2C=C3C=CC=NC3=CC=2)=C1 PWFHHGIUVHLZME-UHFFFAOYSA-N 0.000 claims description 3
- AXHQDLMVUMZMCN-UHFFFAOYSA-N n-[[3-[[4-[2-(dimethylamino)ethyl]phenyl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=CC(CCN(C)C)=CC=2)=C1 AXHQDLMVUMZMCN-UHFFFAOYSA-N 0.000 claims description 3
- DCKNHVGKPZOFQS-UHFFFAOYSA-N n-[[3-[[5-(2,2-difluoroethyl)-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridin-2-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3CN(CC(F)F)CCC=3N=2)=C1 DCKNHVGKPZOFQS-UHFFFAOYSA-N 0.000 claims description 3
- DXAVMMHZLHOUCW-UHFFFAOYSA-N 2-chloro-4-[[3-[[4-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methylcarbamoylamino]benzamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)NC=2C=C(Cl)C(C(N)=O)=CC=2)=C1 DXAVMMHZLHOUCW-UHFFFAOYSA-N 0.000 claims description 2
- IKWVQFQVIJTYCU-UHFFFAOYSA-N 3,4-dichloro-n-[[3-[[4-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)C=2C=C(Cl)C(Cl)=CC=2)=C1 IKWVQFQVIJTYCU-UHFFFAOYSA-N 0.000 claims description 2
- SUMNRYIGGVFLDC-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-(1,2,3,4-tetrahydroisoquinolin-5-ylcarbamoyl)phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=3CCNCC=3C=CC=2)=C1 SUMNRYIGGVFLDC-UHFFFAOYSA-N 0.000 claims description 2
- NCJPTEBNRKVZEU-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-(1,2,3,4-tetrahydroisoquinolin-6-ylcarbamoyl)phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CCNCC3=CC=2)=C1 NCJPTEBNRKVZEU-UHFFFAOYSA-N 0.000 claims description 2
- OJSMZBDNWAIEDU-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-(2,3,4,5-tetrahydro-1h-2-benzazepin-8-ylcarbamoyl)phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CNCCCC3=CC=2)=C1 OJSMZBDNWAIEDU-UHFFFAOYSA-N 0.000 claims description 2
- SQASYMBFHFMBSF-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-(2,3,4,5-tetrahydro-1h-3-benzazepin-7-ylcarbamoyl)phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CCNCCC3=CC=2)=C1 SQASYMBFHFMBSF-UHFFFAOYSA-N 0.000 claims description 2
- LXJRDCVVYKHKOW-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[(1-methylpiperidin-4-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC2CCN(C)CC2)=C1 LXJRDCVVYKHKOW-UHFFFAOYSA-N 0.000 claims description 2
- GBZBMQSMOPCRKV-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[(6-methyl-7,8-dihydro-5h-1,6-naphthyridin-3-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(C)CCC3=NC=2)=C1 GBZBMQSMOPCRKV-UHFFFAOYSA-N 0.000 claims description 2
- UTPFOZVJQRUYTC-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[[3-(pyrazol-1-ylmethyl)phenyl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C(CN3N=CC=C3)C=CC=2)=C1 UTPFOZVJQRUYTC-UHFFFAOYSA-N 0.000 claims description 2
- CPABIQAZZVLIBR-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[[4-(2-morpholin-4-ylethoxy)benzoyl]amino]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(NC(=O)C=2C=CC(OCCN3CCOCC3)=CC=2)=C1 CPABIQAZZVLIBR-UHFFFAOYSA-N 0.000 claims description 2
- DAPHVFQYJQDRRL-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[[4-(2-morpholin-4-ylethoxy)phenyl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=CC(OCCN3CCOCC3)=CC=2)=C1 DAPHVFQYJQDRRL-UHFFFAOYSA-N 0.000 claims description 2
- PEXJILNYZQWGGZ-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[[4-[(5-methyl-1h-1,2,4-triazol-3-yl)methyl]phenyl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=CC(CC=3NC(C)=NN=3)=CC=2)=C1 PEXJILNYZQWGGZ-UHFFFAOYSA-N 0.000 claims description 2
- VIIPYIIVNUWTMO-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[[5-(2-morpholin-4-ylethyl)-1,3,4-thiadiazol-2-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC(CCN3CCOCC3)=NN=2)=C1 VIIPYIIVNUWTMO-UHFFFAOYSA-N 0.000 claims description 2
- GAVNDFOFQJVZCG-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[[5-[2-(4-methylpiperazin-1-yl)ethyl]-1,3-thiazol-2-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC(CCN3CCN(C)CC3)=CN=2)=C1 GAVNDFOFQJVZCG-UHFFFAOYSA-N 0.000 claims description 2
- IVVANNSYKVZGPX-UHFFFAOYSA-N 3-[[(3,4-dimethoxyphenyl)carbamoylamino]methyl]-n-(1,2,3,4-tetrahydroisoquinolin-6-yl)benzamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)NCC1=CC=CC(C(=O)NC=2C=C3CCNCC3=CC=2)=C1 IVVANNSYKVZGPX-UHFFFAOYSA-N 0.000 claims description 2
- VBWXDGZYWJFRCV-UHFFFAOYSA-N 3-[[(3-carbamoylphenyl)carbamoylamino]methyl]-n-[4-[(dimethylamino)methyl]phenyl]benzamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)NC=2C=C(C=CC=2)C(N)=O)=C1 VBWXDGZYWJFRCV-UHFFFAOYSA-N 0.000 claims description 2
- CIUYISXIYCGRIU-UHFFFAOYSA-N 3-[[(3-cyanophenyl)carbamoylamino]methyl]-n-(2-piperidin-3-ylethyl)benzamide Chemical compound C=1C=CC(C#N)=CC=1NC(=O)NCC(C=1)=CC=CC=1C(=O)NCCC1CCCNC1 CIUYISXIYCGRIU-UHFFFAOYSA-N 0.000 claims description 2
- ANYOJLMYGDPTHX-UHFFFAOYSA-N 3-[[(3-cyanophenyl)carbamoylamino]methyl]-n-[4-[(dimethylamino)methyl]phenyl]benzamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)NC=2C=C(C=CC=2)C#N)=C1 ANYOJLMYGDPTHX-UHFFFAOYSA-N 0.000 claims description 2
- CXIAHIQUZUIHBM-UHFFFAOYSA-N 3-[[(3-ethynylphenyl)carbamoylamino]methyl]-n-(5-methyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridin-2-yl)benzamide Chemical compound S1C=2CN(C)CCC=2N=C1NC(=O)C(C=1)=CC=CC=1CNC(=O)NC1=CC=CC(C#C)=C1 CXIAHIQUZUIHBM-UHFFFAOYSA-N 0.000 claims description 2
- MSMWPPBCSAITML-UHFFFAOYSA-N 3-[[(4-acetylphenyl)carbamoylamino]methyl]-n-[4-[(dimethylamino)methyl]phenyl]benzamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)NC=2C=CC(=CC=2)C(C)=O)=C1 MSMWPPBCSAITML-UHFFFAOYSA-N 0.000 claims description 2
- RZNZSTXLRMIFPT-UHFFFAOYSA-N 3-[[(4-carbamoylphenyl)carbamoylamino]methyl]-n-[4-[(dimethylamino)methyl]phenyl]benzamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)NC=2C=CC(=CC=2)C(N)=O)=C1 RZNZSTXLRMIFPT-UHFFFAOYSA-N 0.000 claims description 2
- AOMLHURUTKIYJI-UHFFFAOYSA-N 3-[[(4-chlorophenyl)carbamoylamino]methyl]-n-[4-[(dimethylamino)methyl]phenyl]benzamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)NC=2C=CC(Cl)=CC=2)=C1 AOMLHURUTKIYJI-UHFFFAOYSA-N 0.000 claims description 2
- RXEBZMMATZDNTI-UHFFFAOYSA-N 3-[[(4-cyanobenzoyl)amino]methyl]-n-[4-[(dimethylamino)methyl]phenyl]benzamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)C=2C=CC(=CC=2)C#N)=C1 RXEBZMMATZDNTI-UHFFFAOYSA-N 0.000 claims description 2
- AZWXKWPFYCFFOQ-UHFFFAOYSA-N 3-[[(4-cyanophenyl)carbamoylamino]methyl]-n-(1,2,3,4-tetrahydroisoquinolin-6-yl)benzamide Chemical compound C=1C=CC(C(=O)NC=2C=C3CCNCC3=CC=2)=CC=1CNC(=O)NC1=CC=C(C#N)C=C1 AZWXKWPFYCFFOQ-UHFFFAOYSA-N 0.000 claims description 2
- MBWBQWVICWBWLB-UHFFFAOYSA-N 3-[[(4-cyanophenyl)carbamoylamino]methyl]-n-[3-[(dimethylamino)methyl]phenyl]benzamide Chemical compound CN(C)CC1=CC=CC(NC(=O)C=2C=C(CNC(=O)NC=3C=CC(=CC=3)C#N)C=CC=2)=C1 MBWBQWVICWBWLB-UHFFFAOYSA-N 0.000 claims description 2
- BXCQIDVVQQYTNJ-UHFFFAOYSA-N 3-[[(4-cyanophenyl)carbamoylamino]methyl]-n-[4-[(dimethylamino)methyl]phenyl]benzamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)NC=2C=CC(=CC=2)C#N)=C1 BXCQIDVVQQYTNJ-UHFFFAOYSA-N 0.000 claims description 2
- CJALBDABJVVHEX-UHFFFAOYSA-N 3-chloro-4-methoxy-n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(Cl)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(C)CCC3=CC=2)=C1 CJALBDABJVVHEX-UHFFFAOYSA-N 0.000 claims description 2
- CLHFYZQTYYWLHB-UHFFFAOYSA-N 3-chloro-4-methoxy-n-[[3-[[4-(2-pyrrolidin-1-ylethyl)phenyl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(Cl)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=CC(CCN3CCCC3)=CC=2)=C1 CLHFYZQTYYWLHB-UHFFFAOYSA-N 0.000 claims description 2
- ZTYIVWUODCAPMA-UHFFFAOYSA-N 3-chloro-n-[[3-[(5-methyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridin-2-yl)carbamoyl]phenyl]methyl]-4-(trifluoromethoxy)benzamide Chemical compound S1C=2CN(C)CCC=2N=C1NC(=O)C(C=1)=CC=CC=1CNC(=O)C1=CC=C(OC(F)(F)F)C(Cl)=C1 ZTYIVWUODCAPMA-UHFFFAOYSA-N 0.000 claims description 2
- IBYCIYXZTCCNFB-UHFFFAOYSA-N 3-chloro-n-[[3-[[4-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methyl]-4-(trifluoromethoxy)benzamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)C=2C=C(Cl)C(OC(F)(F)F)=CC=2)=C1 IBYCIYXZTCCNFB-UHFFFAOYSA-N 0.000 claims description 2
- JICNXTXAHJVCEL-UHFFFAOYSA-N 4-chloro-n-[[3-[[4-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methyl]-3-methoxybenzamide Chemical compound C1=C(Cl)C(OC)=CC(C(=O)NCC=2C=C(C=CC=2)C(=O)NC=2C=CC(CN(C)C)=CC=2)=C1 JICNXTXAHJVCEL-UHFFFAOYSA-N 0.000 claims description 2
- YITLKTTYZDOJKD-UHFFFAOYSA-N 4-cyano-n-[[3-[[4-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methyl]-3-fluorobenzamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)C=2C=C(F)C(C#N)=CC=2)=C1 YITLKTTYZDOJKD-UHFFFAOYSA-N 0.000 claims description 2
- JSLIEZKRKUGNEF-UHFFFAOYSA-N 4-methoxy-3-methyl-n-[[3-[[4-(2-pyrrolidin-1-ylethyl)phenyl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(C)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=CC(CCN3CCCC3)=CC=2)=C1 JSLIEZKRKUGNEF-UHFFFAOYSA-N 0.000 claims description 2
- VYVXFNZKVUMLOE-UHFFFAOYSA-N 4-n-[[3-[[4-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methyl]benzene-1,4-dicarboxamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)C=2C=CC(=CC=2)C(N)=O)=C1 VYVXFNZKVUMLOE-UHFFFAOYSA-N 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- CZIGHEXPEQCNAN-UHFFFAOYSA-N n-[3-(aminomethyl)phenyl]-3-[[(4-cyanophenyl)carbamoylamino]methyl]benzamide Chemical compound NCC1=CC=CC(NC(=O)C=2C=C(CNC(=O)NC=3C=CC(=CC=3)C#N)C=CC=2)=C1 CZIGHEXPEQCNAN-UHFFFAOYSA-N 0.000 claims description 2
- DZRVPIWFAXTRMP-UHFFFAOYSA-N n-[3-[2-(3,4-dimethoxyanilino)-2-oxoethyl]phenyl]-1,2,3,4-tetrahydroisoquinoline-6-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)CC1=CC=CC(NC(=O)C=2C=C3CCNCC3=CC=2)=C1 DZRVPIWFAXTRMP-UHFFFAOYSA-N 0.000 claims description 2
- TZUNCUIZOSKMJW-UHFFFAOYSA-N n-[3-[2-(3,4-dimethoxyanilino)-2-oxoethyl]phenyl]-4-(2-morpholin-4-ylethoxy)benzamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)CC1=CC=CC(NC(=O)C=2C=CC(OCCN3CCOCC3)=CC=2)=C1 TZUNCUIZOSKMJW-UHFFFAOYSA-N 0.000 claims description 2
- QRRLWZXAXAWIKA-UHFFFAOYSA-N n-[3-[2-(3,4-dimethoxyanilino)-2-oxoethyl]phenyl]-5-[(dimethylamino)methyl]furan-2-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)CC1=CC=CC(NC(=O)C=2OC(CN(C)C)=CC=2)=C1 QRRLWZXAXAWIKA-UHFFFAOYSA-N 0.000 claims description 2
- OSOQZDIFOCNJEQ-UHFFFAOYSA-N n-[3-[3-(4-cyanoanilino)-3-oxopropyl]phenyl]-1,2,3,4-tetrahydroisoquinoline-6-carboxamide Chemical compound C=1C=CC(NC(=O)C=2C=C3CCNCC3=CC=2)=CC=1CCC(=O)NC1=CC=C(C#N)C=C1 OSOQZDIFOCNJEQ-UHFFFAOYSA-N 0.000 claims description 2
- SIUBWJDIJCBDRM-UHFFFAOYSA-N n-[3-[[(3,4-dimethoxybenzoyl)amino]methyl]phenyl]-5-[(dimethylamino)methyl]furan-2-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(NC(=O)C=2OC(CN(C)C)=CC=2)=C1 SIUBWJDIJCBDRM-UHFFFAOYSA-N 0.000 claims description 2
- NIZLWKWVLBADQA-UHFFFAOYSA-N n-[4-(aminomethyl)cyclohexyl]-3-[[(4-cyanophenyl)carbamoylamino]methyl]benzamide Chemical compound C1CC(CN)CCC1NC(=O)C1=CC=CC(CNC(=O)NC=2C=CC(=CC=2)C#N)=C1 NIZLWKWVLBADQA-UHFFFAOYSA-N 0.000 claims description 2
- SFLBZARATFKMJY-UHFFFAOYSA-N n-[4-(aminomethyl)phenyl]-3-[[(4-cyanophenyl)carbamoylamino]methyl]benzamide Chemical compound C1=CC(CN)=CC=C1NC(=O)C1=CC=CC(CNC(=O)NC=2C=CC(=CC=2)C#N)=C1 SFLBZARATFKMJY-UHFFFAOYSA-N 0.000 claims description 2
- QYGZIWRUFABGJQ-UHFFFAOYSA-N n-[4-[(dimethylamino)methyl]phenyl]-3-[[(3-methoxybenzoyl)amino]methyl]benzamide Chemical compound COC1=CC=CC(C(=O)NCC=2C=C(C=CC=2)C(=O)NC=2C=CC(CN(C)C)=CC=2)=C1 QYGZIWRUFABGJQ-UHFFFAOYSA-N 0.000 claims description 2
- UBDJJWZXAPQTDN-UHFFFAOYSA-N n-[4-[(dimethylamino)methyl]phenyl]-3-[[(3-methoxyphenyl)carbamoylamino]methyl]benzamide Chemical compound COC1=CC=CC(NC(=O)NCC=2C=C(C=CC=2)C(=O)NC=2C=CC(CN(C)C)=CC=2)=C1 UBDJJWZXAPQTDN-UHFFFAOYSA-N 0.000 claims description 2
- AEJQRRFSBQFOIE-UHFFFAOYSA-N n-[4-[(dimethylamino)methyl]phenyl]-3-[[(3-methylsulfanylbenzoyl)amino]methyl]benzamide Chemical compound CSC1=CC=CC(C(=O)NCC=2C=C(C=CC=2)C(=O)NC=2C=CC(CN(C)C)=CC=2)=C1 AEJQRRFSBQFOIE-UHFFFAOYSA-N 0.000 claims description 2
- SEIRCQAHBRWCEM-UHFFFAOYSA-N n-[4-[(dimethylamino)methyl]phenyl]-3-[[(4-methoxy-2-methylphenyl)carbamoylamino]methyl]benzamide Chemical compound CC1=CC(OC)=CC=C1NC(=O)NCC1=CC=CC(C(=O)NC=2C=CC(CN(C)C)=CC=2)=C1 SEIRCQAHBRWCEM-UHFFFAOYSA-N 0.000 claims description 2
- BFIRBXUGLIZKLJ-UHFFFAOYSA-N n-[4-[(dimethylamino)methyl]phenyl]-3-[[(4-methoxybenzoyl)amino]methyl]benzamide Chemical compound C1=CC(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=CC(CN(C)C)=CC=2)=C1 BFIRBXUGLIZKLJ-UHFFFAOYSA-N 0.000 claims description 2
- OCDZHXBZSVPCLL-UHFFFAOYSA-N n-[4-[(dimethylamino)methyl]phenyl]-3-[[(4-methoxyphenyl)carbamoylamino]methyl]benzamide Chemical compound C1=CC(OC)=CC=C1NC(=O)NCC1=CC=CC(C(=O)NC=2C=CC(CN(C)C)=CC=2)=C1 OCDZHXBZSVPCLL-UHFFFAOYSA-N 0.000 claims description 2
- HKDVENGCVKSWHN-UHFFFAOYSA-N n-[4-[(dimethylamino)methyl]phenyl]-3-[[(4-methylsulfanylbenzoyl)amino]methyl]benzamide Chemical compound C1=CC(SC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=CC(CN(C)C)=CC=2)=C1 HKDVENGCVKSWHN-UHFFFAOYSA-N 0.000 claims description 2
- YWCUAPIFVOPZEI-UHFFFAOYSA-N n-[4-[(dimethylamino)methyl]phenyl]-3-[[[3-(trifluoromethyl)benzoyl]amino]methyl]benzamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=C1 YWCUAPIFVOPZEI-UHFFFAOYSA-N 0.000 claims description 2
- PNOLMXKLLUNTIR-UHFFFAOYSA-N n-[[3-[(2,2-dimethyl-3,4-dihydro-1h-isoquinolin-2-ium-7-yl)carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide;formate Chemical compound [O-]C=O.C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3C[N+](C)(C)CCC3=CC=2)=C1 PNOLMXKLLUNTIR-UHFFFAOYSA-N 0.000 claims description 2
- OPAFLRFBWAHCCR-UHFFFAOYSA-N n-[[3-[(4-aminocyclohexyl)methylcarbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NCC2CCC(N)CC2)=C1 OPAFLRFBWAHCCR-UHFFFAOYSA-N 0.000 claims description 2
- PVAPSVGVWCVTJZ-UHFFFAOYSA-N n-[[3-[(6-ethyl-4,5,7,8-tetrahydro-[1,3]oxazolo[4,5-d]azepin-2-yl)carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound O1C=2CCN(CC)CCC=2N=C1NC(=O)C(C=1)=CC=CC=1CNC(=O)C1=CC=C(OC)C(OC)=C1 PVAPSVGVWCVTJZ-UHFFFAOYSA-N 0.000 claims description 2
- WXXLFODGMMSQRK-GOSISDBHSA-N n-[[3-[[(6r)-2-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl]carbamoyl]phenyl]methyl]-4-methoxy-3-methylbenzamide Chemical compound C1=C(C)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)N[C@H]2CC=3SC(N)=NC=3CC2)=C1 WXXLFODGMMSQRK-GOSISDBHSA-N 0.000 claims description 2
- AHJYPRHNOXXVRT-KRWDZBQOSA-N n-[[3-[[(6s)-2-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)N[C@@H]2CC=3SC(N)=NC=3CC2)=C1 AHJYPRHNOXXVRT-KRWDZBQOSA-N 0.000 claims description 2
- YVMIXSTVVNYUGE-UHFFFAOYSA-N n-[[3-[[2-[(2-fluorophenyl)methyl]-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CC=4C(=CC=CC=4)F)CCC3=CC=2)=C1 YVMIXSTVVNYUGE-UHFFFAOYSA-N 0.000 claims description 2
- FYNOIZBZIYKAGA-UHFFFAOYSA-N n-[[3-[[2-[(4-fluorophenyl)methyl]-3,4-dihydro-1h-isoquinolin-7-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CC=4C=CC(F)=CC=4)CCC3=CC=2)=C1 FYNOIZBZIYKAGA-UHFFFAOYSA-N 0.000 claims description 2
- GPEMGGFDBKPUNW-UHFFFAOYSA-N n-[[3-[[3-(aminomethyl)phenyl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C(CN)C=CC=2)=C1 GPEMGGFDBKPUNW-UHFFFAOYSA-N 0.000 claims description 2
- QGRUSYVGVZGMCI-UHFFFAOYSA-N n-[[3-[[4-(aminomethyl)cyclohexyl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC2CCC(CN)CC2)=C1 QGRUSYVGVZGMCI-UHFFFAOYSA-N 0.000 claims description 2
- CBQDNNONUMGAAV-UHFFFAOYSA-N n-[[3-[[4-(aminomethyl)phenyl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=CC(CN)=CC=2)=C1 CBQDNNONUMGAAV-UHFFFAOYSA-N 0.000 claims description 2
- BQZWAEKWKGMNHA-UHFFFAOYSA-N n-[[3-[[4-(dimethylamino)cyclohexyl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC2CCC(CC2)N(C)C)=C1 BQZWAEKWKGMNHA-UHFFFAOYSA-N 0.000 claims description 2
- TUIMIEFLRCNSCI-UHFFFAOYSA-N n-[[3-[[4-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methyl]-2,4-dimethoxybenzamide Chemical compound COC1=CC(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=CC(CN(C)C)=CC=2)=C1 TUIMIEFLRCNSCI-UHFFFAOYSA-N 0.000 claims description 2
- ONERQDONRMNOLJ-UHFFFAOYSA-N n-[[3-[[4-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methyl]-3,4,5-trimethoxybenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)NCC=2C=C(C=CC=2)C(=O)NC=2C=CC(CN(C)C)=CC=2)=C1 ONERQDONRMNOLJ-UHFFFAOYSA-N 0.000 claims description 2
- MMRPIWYTUYGTFQ-UHFFFAOYSA-N n-[[3-[[4-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=CC(CN(C)C)=CC=2)=C1 MMRPIWYTUYGTFQ-UHFFFAOYSA-N 0.000 claims description 2
- ZNMZMLILKIXZHP-UHFFFAOYSA-N n-[[3-[[4-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methyl]-3,5-dimethoxybenzamide Chemical compound COC1=CC(OC)=CC(C(=O)NCC=2C=C(C=CC=2)C(=O)NC=2C=CC(CN(C)C)=CC=2)=C1 ZNMZMLILKIXZHP-UHFFFAOYSA-N 0.000 claims description 2
- NDUNRHQNNNHQFV-UHFFFAOYSA-N n-[[3-[[4-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methyl]-3-fluoro-4-methoxybenzamide Chemical compound C1=C(F)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=CC(CN(C)C)=CC=2)=C1 NDUNRHQNNNHQFV-UHFFFAOYSA-N 0.000 claims description 2
- ZAAATGOITDPPKG-UHFFFAOYSA-N n-[[3-[[4-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methyl]-4-methoxy-3,5-dimethylbenzamide Chemical compound C1=C(C)C(OC)=C(C)C=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=CC(CN(C)C)=CC=2)=C1 ZAAATGOITDPPKG-UHFFFAOYSA-N 0.000 claims description 2
- SFICHRQXHBPAGM-UHFFFAOYSA-N n-[[3-[[4-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methyl]-4-methoxy-3-(methoxymethyl)benzamide Chemical compound C1=C(OC)C(COC)=CC(C(=O)NCC=2C=C(C=CC=2)C(=O)NC=2C=CC(CN(C)C)=CC=2)=C1 SFICHRQXHBPAGM-UHFFFAOYSA-N 0.000 claims description 2
- ZHYPMHNQQRIWRP-UHFFFAOYSA-N n-[[3-[[4-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methyl]-4-methoxy-3-methylbenzamide Chemical compound C1=C(C)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=CC(CN(C)C)=CC=2)=C1 ZHYPMHNQQRIWRP-UHFFFAOYSA-N 0.000 claims description 2
- PAYRKVARELJZIS-UHFFFAOYSA-N n-[[3-[[4-[2-(dimethylamino)ethyl]-1,3-thiazol-2-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=C(CCN(C)C)N=2)=C1 PAYRKVARELJZIS-UHFFFAOYSA-N 0.000 claims description 2
- KRXZSFFGVMQHQP-UHFFFAOYSA-N n-[[3-[[5-(2-fluoroethyl)-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridin-2-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3CN(CCF)CCC=3N=2)=C1 KRXZSFFGVMQHQP-UHFFFAOYSA-N 0.000 claims description 2
- 208000024891 symptom Diseases 0.000 claims description 2
- AUURLQGRNJUOMW-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[[5-(morpholin-4-ylmethyl)-1,3-thiazol-2-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC(CN3CCOCC3)=CN=2)=C1 AUURLQGRNJUOMW-UHFFFAOYSA-N 0.000 claims 1
- GECRSSMIDGGRNK-MRXNPFEDSA-N CC(C(CC1=CC(C(NC2=NC(CC[C@H](C3)N)=C3S2)=O)=CC=C1)=C(C=C1)C(N)=O)=C1OC Chemical compound CC(C(CC1=CC(C(NC2=NC(CC[C@H](C3)N)=C3S2)=O)=CC=C1)=C(C=C1)C(N)=O)=C1OC GECRSSMIDGGRNK-MRXNPFEDSA-N 0.000 claims 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 claims 1
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 1
- ZVWFGLKVXHSPEU-UHFFFAOYSA-N n-[3-[[(3,4-dimethoxybenzoyl)amino]methyl]phenyl]-1,2,3,4-tetrahydroisoquinoline-6-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(NC(=O)C=2C=C3CCNCC3=CC=2)=C1 ZVWFGLKVXHSPEU-UHFFFAOYSA-N 0.000 claims 1
- VZFURBLTNQNJJW-UHFFFAOYSA-N n-[3-[[(4-cyanophenyl)carbamoylamino]methyl]phenyl]-1,2,3,4-tetrahydroisoquinoline-6-carboxamide Chemical compound C=1C=CC(NC(=O)C=2C=C3CCNCC3=CC=2)=CC=1CNC(=O)NC1=CC=C(C#N)C=C1 VZFURBLTNQNJJW-UHFFFAOYSA-N 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 238000003419 tautomerization reaction Methods 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 156
- 239000000203 mixture Substances 0.000 description 129
- 238000000034 method Methods 0.000 description 106
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 93
- 239000007921 spray Substances 0.000 description 72
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 57
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 52
- 239000000047 product Substances 0.000 description 49
- 239000000543 intermediate Substances 0.000 description 46
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 46
- 239000000243 solution Substances 0.000 description 45
- 239000000460 chlorine Substances 0.000 description 41
- 239000011541 reaction mixture Substances 0.000 description 40
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- 239000002904 solvent Substances 0.000 description 28
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 25
- 238000002953 preparative HPLC Methods 0.000 description 25
- 239000011435 rock Substances 0.000 description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 24
- 230000015572 biosynthetic process Effects 0.000 description 24
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 23
- 238000004458 analytical method Methods 0.000 description 23
- 235000019253 formic acid Nutrition 0.000 description 23
- 239000007787 solid Substances 0.000 description 23
- 238000003786 synthesis reaction Methods 0.000 description 23
- 235000019439 ethyl acetate Nutrition 0.000 description 22
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 20
- 239000012267 brine Substances 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- 229920006395 saturated elastomer Polymers 0.000 description 19
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 206010020772 Hypertension Diseases 0.000 description 17
- 239000002253 acid Substances 0.000 description 17
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 16
- 239000007864 aqueous solution Substances 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 0 CN(*)C1CC1 Chemical compound CN(*)C1CC1 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 238000005859 coupling reaction Methods 0.000 description 11
- 230000004048 modification Effects 0.000 description 11
- 238000012986 modification Methods 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 10
- 230000008878 coupling Effects 0.000 description 10
- 238000010168 coupling process Methods 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000002552 dosage form Substances 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 8
- 229910004298 SiO 2 Inorganic materials 0.000 description 8
- 125000003118 aryl group Chemical group 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 150000004675 formic acid derivatives Chemical class 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 101100356682 Caenorhabditis elegans rho-1 gene Proteins 0.000 description 7
- 101150111584 RHOA gene Proteins 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 208000006011 Stroke Diseases 0.000 description 7
- 239000004202 carbamide Substances 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- LQDOTXNMBCRQLN-UHFFFAOYSA-N 1-[(3-aminophenyl)methyl]-3-(4-cyanophenyl)urea Chemical compound NC1=CC=CC(CNC(=O)NC=2C=CC(=CC=2)C#N)=C1 LQDOTXNMBCRQLN-UHFFFAOYSA-N 0.000 description 6
- ASOANNUCZGAKQA-UHFFFAOYSA-N 3-[[(3,4-dimethoxybenzoyl)amino]methyl]benzoic acid Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(O)=O)=C1 ASOANNUCZGAKQA-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 206010007559 Cardiac failure congestive Diseases 0.000 description 6
- 208000010228 Erectile Dysfunction Diseases 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 230000036772 blood pressure Effects 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 201000001881 impotence Diseases 0.000 description 6
- 208000017169 kidney disease Diseases 0.000 description 6
- 208000010412 Glaucoma Diseases 0.000 description 5
- 206010019280 Heart failures Diseases 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 208000006673 asthma Diseases 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 125000001072 heteroaryl group Chemical group 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 208000001286 intracranial vasospasm Diseases 0.000 description 5
- 239000012948 isocyanate Substances 0.000 description 5
- CYRNDFLGKMDDMZ-UHFFFAOYSA-N n-[(3-aminophenyl)methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(N)=C1 CYRNDFLGKMDDMZ-UHFFFAOYSA-N 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 210000002460 smooth muscle Anatomy 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- QVFKAXVIOVRQEX-UHFFFAOYSA-N 4-methoxy-3-methyl-n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(C)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(C)CCC3=CC=2)=C1 QVFKAXVIOVRQEX-UHFFFAOYSA-N 0.000 description 4
- 206010002383 Angina Pectoris Diseases 0.000 description 4
- 206010003225 Arteriospasm coronary Diseases 0.000 description 4
- 201000001320 Atherosclerosis Diseases 0.000 description 4
- 239000005711 Benzoic acid Substances 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 208000003890 Coronary Vasospasm Diseases 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 239000012131 assay buffer Substances 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 201000011634 coronary artery vasospasm Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- NGOGFTYYXHNFQH-UHFFFAOYSA-N fasudil Chemical compound C=1C=CC2=CN=CC=C2C=1S(=O)(=O)N1CCCNCC1 NGOGFTYYXHNFQH-UHFFFAOYSA-N 0.000 description 4
- 229960002435 fasudil Drugs 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- 208000028867 ischemia Diseases 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 208000002815 pulmonary hypertension Diseases 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- UOWRPTFJISFGPI-UHFFFAOYSA-N (3-methoxycarbonylphenyl)methylazanium;chloride Chemical compound Cl.COC(=O)C1=CC=CC(CN)=C1 UOWRPTFJISFGPI-UHFFFAOYSA-N 0.000 description 3
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 3
- QSQDCPYGWHTMHI-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[[4-(morpholin-4-ylmethyl)-1,3-thiazol-2-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=C(CN3CCOCC3)N=2)=C1 QSQDCPYGWHTMHI-UHFFFAOYSA-N 0.000 description 3
- IJHIPGCCTZVVBB-UHFFFAOYSA-N 3-(aminomethyl)-n-[4-[(dimethylamino)methyl]phenyl]benzamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CN)=C1 IJHIPGCCTZVVBB-UHFFFAOYSA-N 0.000 description 3
- IDDDVXIUIXWAGJ-DDSAHXNVSA-N 4-[(1r)-1-aminoethyl]-n-pyridin-4-ylcyclohexane-1-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H](N)C)CCC1C(=O)NC1=CC=NC=C1 IDDDVXIUIXWAGJ-DDSAHXNVSA-N 0.000 description 3
- TVSXDZNUTPLDKY-UHFFFAOYSA-N 4-isocyanatobenzonitrile Chemical compound O=C=NC1=CC=C(C#N)C=C1 TVSXDZNUTPLDKY-UHFFFAOYSA-N 0.000 description 3
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 208000012902 Nervous system disease Diseases 0.000 description 3
- 208000025966 Neurological disease Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 208000005764 Peripheral Arterial Disease Diseases 0.000 description 3
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 3
- 108091000080 Phosphotransferase Proteins 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 206010063837 Reperfusion injury Diseases 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 3
- 229920001429 chelating resin Polymers 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000003456 ion exchange resin Substances 0.000 description 3
- 229920003303 ion-exchange polymer Polymers 0.000 description 3
- 150000002513 isocyanates Chemical class 0.000 description 3
- HBPUVIARTMVZHB-UHFFFAOYSA-N methyl 3-[(benzylamino)methyl]benzoate Chemical compound COC(=O)C1=CC=CC(CNCC=2C=CC=CC=2)=C1 HBPUVIARTMVZHB-UHFFFAOYSA-N 0.000 description 3
- 201000006417 multiple sclerosis Diseases 0.000 description 3
- KBELWXQYQJTLLV-GOSISDBHSA-N n-[[3-[[(6r)-6-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-4-methoxy-3-methylbenzamide Chemical compound C1=C(C)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3C[C@H](N)CCC=3N=2)=C1 KBELWXQYQJTLLV-GOSISDBHSA-N 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 208000004296 neuralgia Diseases 0.000 description 3
- 102000020233 phosphotransferase Human genes 0.000 description 3
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 208000037803 restenosis Diseases 0.000 description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 description 3
- 208000020431 spinal cord injury Diseases 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000011593 sulfur Chemical group 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- DRRYZHHKWSHHFT-BYPYZUCNSA-N (6s)-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine Chemical compound C1[C@@H](N)CCC2=C1SC(N)=N2 DRRYZHHKWSHHFT-BYPYZUCNSA-N 0.000 description 2
- QEMYLDYQDFRTRT-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinolin-2-ium-6-carboxylate Chemical compound C1NCCC2=CC(C(=O)O)=CC=C21 QEMYLDYQDFRTRT-UHFFFAOYSA-N 0.000 description 2
- SUNMBRGCANLOEG-UHFFFAOYSA-N 1,3-dichloroacetone Chemical compound ClCC(=O)CCl SUNMBRGCANLOEG-UHFFFAOYSA-N 0.000 description 2
- ZWXDAANEJMSCEX-UHFFFAOYSA-N 1-(3-anilinophenyl)ethanone Chemical compound CC(=O)C1=CC=CC(NC=2C=CC=CC=2)=C1 ZWXDAANEJMSCEX-UHFFFAOYSA-N 0.000 description 2
- FJJYHTVHBVXEEQ-UHFFFAOYSA-N 2,2-dimethylpropanal Chemical compound CC(C)(C)C=O FJJYHTVHBVXEEQ-UHFFFAOYSA-N 0.000 description 2
- QXZROQLPDVYROK-UHFFFAOYSA-N 2-(2-amino-1,3-thiazol-5-yl)ethanol Chemical compound NC1=NC=C(CCO)S1 QXZROQLPDVYROK-UHFFFAOYSA-N 0.000 description 2
- UHOIFEOHBGCPHE-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonyl]-3,4-dihydro-1h-isoquinoline-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2CN(C(=O)OC(C)(C)C)CCC2=C1 UHOIFEOHBGCPHE-UHFFFAOYSA-N 0.000 description 2
- HWFCHCRFQWEFMU-UHFFFAOYSA-N 2-bromo-4,5-dimethoxybenzoic acid Chemical compound COC1=CC(Br)=C(C(O)=O)C=C1OC HWFCHCRFQWEFMU-UHFFFAOYSA-N 0.000 description 2
- MKNYDQXDYYRFSG-UHFFFAOYSA-N 2-hydroxy-3,4-dimethoxy-n-[[3-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)carbamoyl]phenyl]methyl]benzamide Chemical compound OC1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(C)CCC3=CC=2)=C1 MKNYDQXDYYRFSG-UHFFFAOYSA-N 0.000 description 2
- RBBFIFDZNMBKHS-UHFFFAOYSA-N 2-morpholin-4-yl-2,3-dihydro-1h-inden-5-amine Chemical compound C1C2=CC(N)=CC=C2CC1N1CCOCC1 RBBFIFDZNMBKHS-UHFFFAOYSA-N 0.000 description 2
- LGDHZCLREKIGKJ-UHFFFAOYSA-N 3,4-dimethoxyaniline Chemical compound COC1=CC=C(N)C=C1OC LGDHZCLREKIGKJ-UHFFFAOYSA-N 0.000 description 2
- DAUAQNGYDSHRET-UHFFFAOYSA-N 3,4-dimethoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1OC DAUAQNGYDSHRET-UHFFFAOYSA-N 0.000 description 2
- KCKKJVXUNQPAPS-UHFFFAOYSA-N 3-(aminomethyl)-n-(5-methyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridin-2-yl)benzamide Chemical compound S1C=2CN(C)CCC=2N=C1NC(=O)C1=CC=CC(CN)=C1 KCKKJVXUNQPAPS-UHFFFAOYSA-N 0.000 description 2
- ZVYVZEUADCRFHK-UHFFFAOYSA-N 3-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-3-yl]propanoic acid Chemical compound CC(C)(C)OC(=O)N1CCCC(CCC(O)=O)C1 ZVYVZEUADCRFHK-UHFFFAOYSA-N 0.000 description 2
- DNXGHJGVBQLMAG-UHFFFAOYSA-N 3-[[(4-cyanophenyl)carbamoylamino]methyl]benzoic acid Chemical compound OC(=O)C1=CC=CC(CNC(=O)NC=2C=CC(=CC=2)C#N)=C1 DNXGHJGVBQLMAG-UHFFFAOYSA-N 0.000 description 2
- CGCTVPOHSSOTEU-UHFFFAOYSA-N 3-[[(4-methoxybenzoyl)amino]methyl]-n-(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)benzamide Chemical compound C1=CC(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(C)CCC3=CC=2)=C1 CGCTVPOHSSOTEU-UHFFFAOYSA-N 0.000 description 2
- IBCQUQXCTOPJOD-UHFFFAOYSA-N 3-chloro-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1Cl IBCQUQXCTOPJOD-UHFFFAOYSA-N 0.000 description 2
- VXQUMBMJRAFIEJ-UHFFFAOYSA-N 4-(5-nitro-2,3-dihydro-1h-inden-2-yl)morpholine Chemical compound C1C2=CC([N+](=O)[O-])=CC=C2CC1N1CCOCC1 VXQUMBMJRAFIEJ-UHFFFAOYSA-N 0.000 description 2
- SAFPFEWXCCYGOX-UHFFFAOYSA-N 5-methyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridin-2-amine Chemical compound C1N(C)CCC2=C1SC(N)=N2 SAFPFEWXCCYGOX-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 201000000057 Coronary Stenosis Diseases 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 239000007821 HATU Substances 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 206010053159 Organ failure Diseases 0.000 description 2
- 238000003248 PKLight Methods 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- 208000001647 Renal Insufficiency Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- GPVDHNVGGIAOQT-UHFFFAOYSA-N Veratric acid Natural products COC1=CC=C(C(O)=O)C(OC)=C1 GPVDHNVGGIAOQT-UHFFFAOYSA-N 0.000 description 2
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 description 2
- OBJOSEYCLZTEIS-HNNXBMFYSA-N benzyl n-[(6s)-6-morpholin-4-yl-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamate Chemical compound N1([C@H]2CCC=3N=C(SC=3C2)NC(=O)OCC=2C=CC=CC=2)CCOCC1 OBJOSEYCLZTEIS-HNNXBMFYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000012292 cell migration Effects 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 208000037765 diseases and disorders Diseases 0.000 description 2
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 239000008241 heterogeneous mixture Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000004047 hyperresponsiveness Effects 0.000 description 2
- 230000001631 hypertensive effect Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 201000006370 kidney failure Diseases 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- WLNUPPJTOYTPPV-UHFFFAOYSA-N methyl 3-[[(3,4-dimethoxybenzoyl)amino]methyl]benzoate Chemical compound COC(=O)C1=CC=CC(CNC(=O)C=2C=C(OC)C(OC)=CC=2)=C1 WLNUPPJTOYTPPV-UHFFFAOYSA-N 0.000 description 2
- HSEOVRZDUXVMBC-UHFFFAOYSA-N methyl 3-[[benzyl-[(4-cyanophenyl)carbamoyl]amino]methyl]benzoate Chemical compound COC(=O)C1=CC=CC(CN(CC=2C=CC=CC=2)C(=O)NC=2C=CC(=CC=2)C#N)=C1 HSEOVRZDUXVMBC-UHFFFAOYSA-N 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- NBUKMHXINQOFDI-UHFFFAOYSA-N n-[4-(chloromethyl)-1,3-thiazol-2-yl]acetamide Chemical compound CC(=O)NC1=NC(CCl)=CS1 NBUKMHXINQOFDI-UHFFFAOYSA-N 0.000 description 2
- XBWPUPBLCWESMS-UHFFFAOYSA-N n-[4-[(dimethylamino)methyl]-1,3-thiazol-2-yl]acetamide Chemical compound CN(C)CC1=CSC(NC(C)=O)=N1 XBWPUPBLCWESMS-UHFFFAOYSA-N 0.000 description 2
- RKMMCTSKTFCJKW-UHFFFAOYSA-N n-[5-[(dimethylamino)methyl]-1,3-thiazol-2-yl]acetamide;hydrochloride Chemical compound Cl.CN(C)CC1=CN=C(NC(C)=O)S1 RKMMCTSKTFCJKW-UHFFFAOYSA-N 0.000 description 2
- FXBVTHOJFYZPOQ-UNTBIKODSA-N n-[[3-[[(6r)-6-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-3,4-dimethoxybenzamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3C[C@H](N)CCC=3N=2)=C1 FXBVTHOJFYZPOQ-UNTBIKODSA-N 0.000 description 2
- 125000006574 non-aromatic ring group Chemical group 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 238000005897 peptide coupling reaction Methods 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- BMLHPGOMLGKYIJ-UHFFFAOYSA-N tert-butyl 2-amino-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC2=C1SC(N)=N2 BMLHPGOMLGKYIJ-UHFFFAOYSA-N 0.000 description 2
- TYYCRHDLXCEVQS-UHFFFAOYSA-N tert-butyl 3-[[3-[[(3,4-dimethoxybenzoyl)amino]methyl]benzoyl]amino]-7,8-dihydro-5h-1,6-naphthyridine-6-carboxylate Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CN(CCC3=NC=2)C(=O)OC(C)(C)C)=C1 TYYCRHDLXCEVQS-UHFFFAOYSA-N 0.000 description 2
- CBTULJANIYAMDM-ZETCQYMHSA-N tert-butyl n-[(6s)-2-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl]carbamate Chemical compound C1[C@@H](NC(=O)OC(C)(C)C)CCC2=C1SC(N)=N2 CBTULJANIYAMDM-ZETCQYMHSA-N 0.000 description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- CEUHLMXMONTRMD-UHFFFAOYSA-N (2-amino-1,3-thiazol-4-yl)methanol;hydrochloride Chemical compound Cl.NC1=NC(CO)=CS1 CEUHLMXMONTRMD-UHFFFAOYSA-N 0.000 description 1
- NZLGPLMYXLCJRB-UHFFFAOYSA-N (3,4-dimethoxyphenyl)methyl carbonochloridate Chemical compound COC1=CC=C(COC(Cl)=O)C=C1OC NZLGPLMYXLCJRB-UHFFFAOYSA-N 0.000 description 1
- CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 1
- QSMKHHDCUCRZMR-JZGIKJSDSA-N (6s)-6-morpholin-4-yl-4,5,6,7-tetrahydro-1,3-benzothiazol-2-amine;dihydrobromide Chemical compound Br.Br.N1([C@H]2CCC=3N=C(SC=3C2)N)CCOCC1 QSMKHHDCUCRZMR-JZGIKJSDSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- KRXCVARURSAWNK-UHFFFAOYSA-N 1,3-bis(3-chloro-4-cyanophenyl)urea Chemical compound C1=C(C#N)C(Cl)=CC(NC(=O)NC=2C=C(Cl)C(C#N)=CC=2)=C1 KRXCVARURSAWNK-UHFFFAOYSA-N 0.000 description 1
- 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- FOZVXADQAHVUSV-UHFFFAOYSA-N 1-bromo-2-(2-bromoethoxy)ethane Chemical compound BrCCOCCBr FOZVXADQAHVUSV-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 1
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 description 1
- FVSMPBZNTTUSOZ-NDNWHDOQSA-N 2,3-dihydroxybutanedioic acid;(6s)-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine;trihydrate Chemical compound O.O.O.OC(=O)C(O)C(O)C(O)=O.C1[C@@H](N)CCC2=C1SC(N)=N2 FVSMPBZNTTUSOZ-NDNWHDOQSA-N 0.000 description 1
- RWGPAMBILZOZBK-UHFFFAOYSA-N 2-(2-oxoethoxy)acetaldehyde Chemical compound O=CCOCC=O RWGPAMBILZOZBK-UHFFFAOYSA-N 0.000 description 1
- ZMOALEHZNXGBIV-UHFFFAOYSA-N 2-(3-aminophenyl)-n-(3,4-dimethoxyphenyl)acetamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)CC1=CC=CC(N)=C1 ZMOALEHZNXGBIV-UHFFFAOYSA-N 0.000 description 1
- MSCZZRXBIBUPKG-UHFFFAOYSA-N 2-(3-nitrophenyl)propanoic acid Chemical compound OC(=O)C(C)C1=CC=CC([N+]([O-])=O)=C1 MSCZZRXBIBUPKG-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- HTCSFFGLRQDZDE-UHFFFAOYSA-N 2-azaniumyl-2-phenylpropanoate Chemical compound OC(=O)C(N)(C)C1=CC=CC=C1 HTCSFFGLRQDZDE-UHFFFAOYSA-N 0.000 description 1
- JVYROUWXXSWCMI-UHFFFAOYSA-N 2-bromo-1,1-difluoroethane Chemical compound FC(F)CBr JVYROUWXXSWCMI-UHFFFAOYSA-N 0.000 description 1
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 1
- 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- RLJOYSOPEJBIAA-UHFFFAOYSA-N 2-nitro-2,3-dihydroinden-1-one Chemical compound C1=CC=C2C(=O)C([N+](=O)[O-])CC2=C1 RLJOYSOPEJBIAA-UHFFFAOYSA-N 0.000 description 1
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
- LGQLLHFSZQUISF-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-(1,2,3,4-tetrahydroisoquinolin-7-ylcarbamoyl)phenyl]methyl]benzamide;hydrochloride Chemical compound Cl.C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2C=C3CNCCC3=CC=2)=C1 LGQLLHFSZQUISF-UHFFFAOYSA-N 0.000 description 1
- GXDBHAGXKRQWMG-UHFFFAOYSA-N 3,4-dimethoxy-n-[[3-[[5-(3,3,3-trifluoropropyl)-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridin-2-yl]carbamoyl]phenyl]methyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NC=2SC=3CN(CCC(F)(F)F)CCC=3N=2)=C1 GXDBHAGXKRQWMG-UHFFFAOYSA-N 0.000 description 1
- XNDZRGTVUVVHQT-UHFFFAOYSA-N 3,4-dimethoxybenzamide Chemical compound COC1=CC=C(C(N)=O)C=C1OC XNDZRGTVUVVHQT-UHFFFAOYSA-N 0.000 description 1
- WTDMSRZVILGEOP-UHFFFAOYSA-N 3-(3-aminophenyl)-n-(3,4-dimethoxyphenyl)propanamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)CCC1=CC=CC(N)=C1 WTDMSRZVILGEOP-UHFFFAOYSA-N 0.000 description 1
- OYDSIKZVQUABLT-UHFFFAOYSA-N 3-(3-aminophenyl)-n-(4-cyanophenyl)propanamide Chemical compound NC1=CC=CC(CCC(=O)NC=2C=CC(=CC=2)C#N)=C1 OYDSIKZVQUABLT-UHFFFAOYSA-N 0.000 description 1
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 1
- WCSYNOQMLVSKPI-UHFFFAOYSA-N 3-(aminomethyl)-n-(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)benzamide Chemical compound C1=C2CN(C)CCC2=CC=C1NC(=O)C1=CC=CC(CN)=C1 WCSYNOQMLVSKPI-UHFFFAOYSA-N 0.000 description 1
- YKCQLTGYYVJEIV-UHFFFAOYSA-N 3-(aminomethyl)-n-(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)benzamide;dihydrochloride Chemical compound Cl.Cl.C1=C2CN(C)CCC2=CC=C1NC(=O)C1=CC=CC(CN)=C1 YKCQLTGYYVJEIV-UHFFFAOYSA-N 0.000 description 1
- AURMSWVWITWZNR-UHFFFAOYSA-N 3-(aminomethyl)-n-[[3-[(dimethylamino)methyl]phenyl]methyl]benzamide Chemical compound CN(C)CC1=CC=CC(CNC(=O)C=2C=C(CN)C=CC=2)=C1 AURMSWVWITWZNR-UHFFFAOYSA-N 0.000 description 1
- ZNMNSGCDOCUHAM-UHFFFAOYSA-N 3-(carbamoylamino)benzoic acid;urea Chemical compound NC(N)=O.NC(=O)NC1=CC=CC(C(O)=O)=C1 ZNMNSGCDOCUHAM-UHFFFAOYSA-N 0.000 description 1
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
- WOJBIBHVUSZAGS-UHFFFAOYSA-N 3-[(dimethylamino)methyl]aniline Chemical compound CN(C)CC1=CC=CC(N)=C1 WOJBIBHVUSZAGS-UHFFFAOYSA-N 0.000 description 1
- JZVULXRCJQKJOJ-UHFFFAOYSA-N 3-[3-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]propanoic acid Chemical compound CC(C)(C)OC(=O)NC1=CC=CC(CCC(O)=O)=C1 JZVULXRCJQKJOJ-UHFFFAOYSA-N 0.000 description 1
- MQNHKLMHRZYTBZ-UHFFFAOYSA-N 3-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]benzoic acid Chemical compound CC(C)(C)OC(=O)NCC1=CC=CC(C(O)=O)=C1 MQNHKLMHRZYTBZ-UHFFFAOYSA-N 0.000 description 1
- DMWCFYGMHBNWGZ-UHFFFAOYSA-N 3-[[(3,4-dimethoxybenzoyl)-methylamino]methyl]benzoic acid Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)N(C)CC1=CC=CC(C(O)=O)=C1 DMWCFYGMHBNWGZ-UHFFFAOYSA-N 0.000 description 1
- ZGCIPGSTCVXCCO-UHFFFAOYSA-N 3-[[(3-cyanobenzoyl)amino]methyl]-n-[4-[(dimethylamino)methyl]phenyl]benzamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)C=2C=C(C=CC=2)C#N)=C1 ZGCIPGSTCVXCCO-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- CNQYFXKQVFSIDF-UHFFFAOYSA-N 3-chloro-4-methoxybenzoic acid;dihydrochloride Chemical compound Cl.Cl.COC1=CC=C(C(O)=O)C=C1Cl CNQYFXKQVFSIDF-UHFFFAOYSA-N 0.000 description 1
- GYLKKXHEIIFTJH-UHFFFAOYSA-N 3-cyanobenzoic acid Chemical compound OC(=O)C1=CC=CC(C#N)=C1 GYLKKXHEIIFTJH-UHFFFAOYSA-N 0.000 description 1
- NNKQLUVBPJEUOR-UHFFFAOYSA-N 3-ethynylaniline Chemical compound NC1=CC=CC(C#C)=C1 NNKQLUVBPJEUOR-UHFFFAOYSA-N 0.000 description 1
- AWGAMNRCCCIYLX-UHFFFAOYSA-N 4-(2-aminoethyl)-1,3-thiazol-2-amine Chemical compound NCCC1=CSC(N)=N1 AWGAMNRCCCIYLX-UHFFFAOYSA-N 0.000 description 1
- GSAMTLRIAXVZHZ-UHFFFAOYSA-N 4-(morpholin-4-ylmethyl)-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(CN2CCOCC2)=C1 GSAMTLRIAXVZHZ-UHFFFAOYSA-N 0.000 description 1
- CPCKXHABKBZGCV-UHFFFAOYSA-N 4-[(dimethylamino)methyl]-1,3-thiazol-2-amine;dihydrochloride Chemical compound Cl.Cl.CN(C)CC1=CSC(N)=N1 CPCKXHABKBZGCV-UHFFFAOYSA-N 0.000 description 1
- NNCCQALFJIMRKB-UHFFFAOYSA-N 4-[(dimethylamino)methyl]aniline Chemical compound CN(C)CC1=CC=C(N)C=C1 NNCCQALFJIMRKB-UHFFFAOYSA-N 0.000 description 1
- ZFBKYGFPUCUYIF-UHFFFAOYSA-N 4-amino-2-chlorobenzonitrile Chemical compound NC1=CC=C(C#N)C(Cl)=C1 ZFBKYGFPUCUYIF-UHFFFAOYSA-N 0.000 description 1
- YBAZINRZQSAIAY-UHFFFAOYSA-N 4-aminobenzonitrile Chemical compound NC1=CC=C(C#N)C=C1 YBAZINRZQSAIAY-UHFFFAOYSA-N 0.000 description 1
- ARWXHCROZUJRTQ-UHFFFAOYSA-N 5-(2-chloroethyl)-1,3-thiazol-2-amine hydrochloride Chemical compound Cl.NC1=NC=C(CCCl)S1 ARWXHCROZUJRTQ-UHFFFAOYSA-N 0.000 description 1
- ZNYIPAKHYPNSEB-UHFFFAOYSA-N 5-(2-morpholin-4-ylethyl)-1,3-thiazol-2-amine Chemical compound S1C(N)=NC=C1CCN1CCOCC1 ZNYIPAKHYPNSEB-UHFFFAOYSA-N 0.000 description 1
- SXSSFMHYVSDYHP-UHFFFAOYSA-N 5-[(dimethylamino)methyl]-1,3-thiazol-2-amine;dihydrochloride Chemical compound Cl.Cl.CN(C)CC1=CN=C(N)S1 SXSSFMHYVSDYHP-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 102100023818 ADP-ribosylation factor 3 Human genes 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 102000005862 Angiotensin II Human genes 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- 108010064733 Angiotensins Proteins 0.000 description 1
- 102000015427 Angiotensins Human genes 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- FBKFSCLWKHPPPU-UHFFFAOYSA-N CCOc(ccc(C(NCc1cc(C(Nc2ccc(C3NCCCC3)cc2)=O)ccc1)=O)c1)c1OC Chemical compound CCOc(ccc(C(NCc1cc(C(Nc2ccc(C3NCCCC3)cc2)=O)ccc1)=O)c1)c1OC FBKFSCLWKHPPPU-UHFFFAOYSA-N 0.000 description 1
- HYQAPLLDHDEUSD-UHFFFAOYSA-N CN(C)Cc1c[s]c(N)n1 Chemical compound CN(C)Cc1c[s]c(N)n1 HYQAPLLDHDEUSD-UHFFFAOYSA-N 0.000 description 1
- OUZPQGQOMNSWDS-UHFFFAOYSA-N CN1Cc2cc(NC(c3cccc(CNC(c(cc4[Cl]=C)cnc4OC)=O)c3)=O)ccc2CC1 Chemical compound CN1Cc2cc(NC(c3cccc(CNC(c(cc4[Cl]=C)cnc4OC)=O)c3)=O)ccc2CC1 OUZPQGQOMNSWDS-UHFFFAOYSA-N 0.000 description 1
- DJQMUJDYWBPCBD-UHFFFAOYSA-N COC=1C=C(C=CC1OC)NC(=O)CCC=1C=C(C=CC1)NC(O)=O Chemical compound COC=1C=C(C=CC1OC)NC(=O)CCC=1C=C(C=CC1)NC(O)=O DJQMUJDYWBPCBD-UHFFFAOYSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 229940126639 Compound 33 Drugs 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 description 1
- 102400000686 Endothelin-1 Human genes 0.000 description 1
- 101800004490 Endothelin-1 Proteins 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 101000684275 Homo sapiens ADP-ribosylation factor 3 Proteins 0.000 description 1
- 101001000061 Homo sapiens Protein phosphatase 1 regulatory subunit 12A Proteins 0.000 description 1
- 101001130437 Homo sapiens Ras-related protein Rap-2b Proteins 0.000 description 1
- 101000669917 Homo sapiens Rho-associated protein kinase 1 Proteins 0.000 description 1
- 101000669921 Homo sapiens Rho-associated protein kinase 2 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108010037801 Myosin-Light-Chain Phosphatase Proteins 0.000 description 1
- 102000011131 Myosin-Light-Chain Phosphatase Human genes 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
- 102100036547 Protein phosphatase 1 regulatory subunit 12A Human genes 0.000 description 1
- 208000002200 Respiratory Hypersensitivity Diseases 0.000 description 1
- 102100039313 Rho-associated protein kinase 1 Human genes 0.000 description 1
- 102100039314 Rho-associated protein kinase 2 Human genes 0.000 description 1
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 239000012317 TBTU Substances 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 102000050488 Urotensin II Human genes 0.000 description 1
- 108010018369 Urotensin II Proteins 0.000 description 1
- 206010047295 Ventricular hypertrophy Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- IYOZTVGMEWJPKR-IJLUTSLNSA-N Y-27632 Chemical compound C1C[C@@H]([C@H](N)C)CC[C@@H]1C(=O)NC1=CC=NC=C1 IYOZTVGMEWJPKR-IJLUTSLNSA-N 0.000 description 1
- QHROUSQARCATTN-UHFFFAOYSA-N [3-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]methylazanium;chloride Chemical compound [Cl-].CC(C)(C)OC(=O)NC1=CC=CC(C[NH3+])=C1 QHROUSQARCATTN-UHFFFAOYSA-N 0.000 description 1
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 208000037883 airway inflammation Diseases 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 238000010976 amide bond formation reaction Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- GHIGTWWCICTREG-AWEZNQCLSA-N benzyl n-[(6s)-6-[(2-methylpropan-2-yl)oxycarbonylamino]-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamate Chemical compound C([C@@H](CC=1S2)NC(=O)OC(C)(C)C)CC=1N=C2NC(=O)OCC1=CC=CC=C1 GHIGTWWCICTREG-AWEZNQCLSA-N 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000021953 cytokinesis Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 125000005046 dihydronaphthyl group Chemical group 0.000 description 1
- 125000005805 dimethoxy phenyl group Chemical group 0.000 description 1
- 125000004276 dioxalanyl group Chemical group 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 229940013688 formic acid Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000035874 hyperreactivity Effects 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- APNSGVMLAYLYCT-UHFFFAOYSA-N isobutyl nitrite Chemical compound CC(C)CON=O APNSGVMLAYLYCT-UHFFFAOYSA-N 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000002514 liquid chromatography mass spectrum Methods 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- ULLQUTOWSHLEGM-UHFFFAOYSA-M lithium;5-[(2-methylpropan-2-yl)oxycarbonyl]-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-2-carboxylate Chemical compound [Li+].C1N(C(=O)OC(C)(C)C)CCC2=C1SC(C([O-])=O)=N2 ULLQUTOWSHLEGM-UHFFFAOYSA-M 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- BTRHEGJEBOGNAU-UHFFFAOYSA-N methyl 1,2,3,4-tetrahydroisoquinoline-7-carboxylate Chemical compound C1CNCC2=CC(C(=O)OC)=CC=C21 BTRHEGJEBOGNAU-UHFFFAOYSA-N 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- CDNLQQWJIPRYEA-UHFFFAOYSA-N methyl 2-methyl-3,4-dihydro-1h-isoquinoline-7-carboxylate Chemical compound C1CN(C)CC2=CC(C(=O)OC)=CC=C21 CDNLQQWJIPRYEA-UHFFFAOYSA-N 0.000 description 1
- CANIDQGAPAHUJM-UHFFFAOYSA-N methyl 3-(carbamoylamino)benzoate Chemical compound COC(=O)C1=CC=CC(NC(N)=O)=C1 CANIDQGAPAHUJM-UHFFFAOYSA-N 0.000 description 1
- UBYFGKITPFZODE-UHFFFAOYSA-N methyl 3-[[(3,4-dimethoxybenzoyl)-methylamino]methyl]benzoate Chemical compound COC(=O)C1=CC=CC(CN(C)C(=O)C=2C=C(OC)C(OC)=CC=2)=C1 UBYFGKITPFZODE-UHFFFAOYSA-N 0.000 description 1
- KFQOXBKVWLWWNY-UHFFFAOYSA-N methyl 3-[[(4-cyanophenyl)carbamoylamino]methyl]benzoate Chemical compound COC(=O)C1=CC=CC(CNC(=O)NC=2C=CC(=CC=2)C#N)=C1 KFQOXBKVWLWWNY-UHFFFAOYSA-N 0.000 description 1
- LVLHGMHKAJESPH-UHFFFAOYSA-N methyl 3-[[benzyl-(3,4-dimethoxybenzoyl)amino]methyl]benzoate Chemical compound COC(=O)C1=CC=CC(CN(CC=2C=CC=CC=2)C(=O)C=2C=C(OC)C(OC)=CC=2)=C1 LVLHGMHKAJESPH-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- GCOWZPRIMFGIDQ-UHFFFAOYSA-N n',n'-dimethylbutane-1,4-diamine Chemical compound CN(C)CCCCN GCOWZPRIMFGIDQ-UHFFFAOYSA-N 0.000 description 1
- NUJAPVSRDGSINW-UHFFFAOYSA-N n'-phenylmethanediamine Chemical compound NCNC1=CC=CC=C1 NUJAPVSRDGSINW-UHFFFAOYSA-N 0.000 description 1
- WXPLRSVMGRAIGW-UHFFFAOYSA-N n-(1,3-thiazol-2-yl)acetamide Chemical compound CC(=O)NC1=NC=CS1 WXPLRSVMGRAIGW-UHFFFAOYSA-N 0.000 description 1
- LWIOPAZKEBLCPB-UHFFFAOYSA-N n-(3,4-dimethoxyphenyl)-2-(3-nitrophenyl)acetamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)CC1=CC=CC([N+]([O-])=O)=C1 LWIOPAZKEBLCPB-UHFFFAOYSA-N 0.000 description 1
- FRBSRAOTMVSYPV-UHFFFAOYSA-N n-(4-cyanophenyl)-3-(3-nitrophenyl)propanamide Chemical compound [O-][N+](=O)C1=CC=CC(CCC(=O)NC=2C=CC(=CC=2)C#N)=C1 FRBSRAOTMVSYPV-UHFFFAOYSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- QUZCCVXIHCIHPV-UHFFFAOYSA-N n-[3-[3-(4-cyanoanilino)-3-oxopropyl]phenyl]-3-piperidin-3-ylpropanamide;n-[3-[3-(3,4-dimethoxyanilino)-3-oxopropyl]phenyl]-3-piperidin-3-ylpropanamide Chemical compound C=1C=CC(CCC(=O)NC=2C=CC(=CC=2)C#N)=CC=1NC(=O)CCC1CCCNC1.C1=C(OC)C(OC)=CC=C1NC(=O)CCC1=CC=CC(NC(=O)CCC2CNCCC2)=C1 QUZCCVXIHCIHPV-UHFFFAOYSA-N 0.000 description 1
- HHPBFFQPPXXZAP-UHFFFAOYSA-N n-[4-[(dimethylamino)methyl]phenyl]benzamide Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC=C1 HHPBFFQPPXXZAP-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- VMXAIJCDNKFKPO-UHFFFAOYSA-N n-ethynylaniline Chemical compound C#CNC1=CC=CC=C1 VMXAIJCDNKFKPO-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000008692 neointimal formation Effects 0.000 description 1
- 230000007971 neurological deficit Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000004963 pathophysiological condition Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 206010038464 renal hypertension Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 230000016160 smooth muscle contraction Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 230000002966 stenotic effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- XCBHHKQAWFCCNI-UHFFFAOYSA-N tert-butyl 1h-isoquinoline-2-carboxylate Chemical compound C1=CC=C2C=CN(C(=O)OC(C)(C)C)CC2=C1 XCBHHKQAWFCCNI-UHFFFAOYSA-N 0.000 description 1
- RXXKNZKFRAFFOH-UHFFFAOYSA-N tert-butyl 2-bromo-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC2=C1SC(Br)=N2 RXXKNZKFRAFFOH-UHFFFAOYSA-N 0.000 description 1
- GYLAYRXNMUUXJS-UHFFFAOYSA-N tert-butyl 3-(2-aminoethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(CCN)C1 GYLAYRXNMUUXJS-UHFFFAOYSA-N 0.000 description 1
- OPHHRHRRTOBJOD-UHFFFAOYSA-N tert-butyl 3-[2-[[3-[[(3,4-dimethoxybenzoyl)amino]methyl]benzoyl]amino]ethyl]piperidine-1-carboxylate Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(C(=O)NCCC2CN(CCC2)C(=O)OC(C)(C)C)=C1 OPHHRHRRTOBJOD-UHFFFAOYSA-N 0.000 description 1
- HFJZQSVDRGJLOF-UHFFFAOYSA-N tert-butyl 3-[3-[3-[3-(3,4-dimethoxyanilino)-3-oxopropyl]anilino]-3-oxopropyl]piperidine-1-carboxylate Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)CCC1=CC=CC(NC(=O)CCC2CN(CCC2)C(=O)OC(C)(C)C)=C1 HFJZQSVDRGJLOF-UHFFFAOYSA-N 0.000 description 1
- UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- NLTXJWBGVNLQBB-UHFFFAOYSA-N tert-butyl 6-[[3-[[(3,4-dimethoxybenzoyl)amino]methyl]phenyl]carbamoyl]-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(NC(=O)C=2C=C3CCN(CC3=CC=2)C(=O)OC(C)(C)C)=C1 NLTXJWBGVNLQBB-UHFFFAOYSA-N 0.000 description 1
- OXEDRFZZEGGMDA-UHFFFAOYSA-N tert-butyl 6-[[3-[[(4-cyanophenyl)carbamoylamino]methyl]phenyl]carbamoyl]-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C=1C=C2CN(C(=O)OC(C)(C)C)CCC2=CC=1C(=O)NC(C=1)=CC=CC=1CNC(=O)NC1=CC=C(C#N)C=C1 OXEDRFZZEGGMDA-UHFFFAOYSA-N 0.000 description 1
- DRYXRJFHCMCAJM-UHFFFAOYSA-N tert-butyl 7-[[3-[[(4-cyanophenyl)carbamoylamino]methyl]benzoyl]amino]-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C1=C2CN(C(=O)OC(C)(C)C)CCC2=CC=C1NC(=O)C(C=1)=CC=CC=1CNC(=O)NC1=CC=C(C#N)C=C1 DRYXRJFHCMCAJM-UHFFFAOYSA-N 0.000 description 1
- AGRBXKCSGCUXST-UHFFFAOYSA-N tert-butyl 7-amino-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C1=C(N)C=C2CN(C(=O)OC(C)(C)C)CCC2=C1 AGRBXKCSGCUXST-UHFFFAOYSA-N 0.000 description 1
- QQWYQAQQADNEIC-RVDMUPIBSA-N tert-butyl [(z)-[cyano(phenyl)methylidene]amino] carbonate Chemical compound CC(C)(C)OC(=O)O\N=C(/C#N)C1=CC=CC=C1 QQWYQAQQADNEIC-RVDMUPIBSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- IIILZIJRVHFCGL-UHFFFAOYSA-N tert-butyl n-[2-(2-amino-1,3-thiazol-4-yl)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCC1=CSC(N)=N1 IIILZIJRVHFCGL-UHFFFAOYSA-N 0.000 description 1
- NXQNEOIMZVWHQW-UHFFFAOYSA-N tert-butyl n-[3-(aminomethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC(CN)=C1 NXQNEOIMZVWHQW-UHFFFAOYSA-N 0.000 description 1
- OHQBRJKQUSHFNH-UHFFFAOYSA-N tert-butyl n-[3-[[(3,4-dimethoxybenzoyl)amino]methyl]phenyl]carbamate Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=CC(NC(=O)OC(C)(C)C)=C1 OHQBRJKQUSHFNH-UHFFFAOYSA-N 0.000 description 1
- ULSNPRHJFCXTCR-UHFFFAOYSA-N tert-butyl n-[[3-[[4-[(dimethylamino)methyl]phenyl]carbamoyl]phenyl]methyl]carbamate Chemical compound C1=CC(CN(C)C)=CC=C1NC(=O)C1=CC=CC(CNC(=O)OC(C)(C)C)=C1 ULSNPRHJFCXTCR-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- ISXOBTBCNRIIQO-UHFFFAOYSA-N tetrahydrothiophene 1-oxide Chemical compound O=S1CCCC1 ISXOBTBCNRIIQO-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- BUGOPWGPQGYYGR-UHFFFAOYSA-N thiane 1,1-dioxide Chemical compound O=S1(=O)CCCCC1 BUGOPWGPQGYYGR-UHFFFAOYSA-N 0.000 description 1
- NNLBRYQGMOYARS-UHFFFAOYSA-N thiane 1-oxide Chemical compound O=S1CCCCC1 NNLBRYQGMOYARS-UHFFFAOYSA-N 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- WCNFFKHKJLERFM-UHFFFAOYSA-N thiomorpholinyl sulfone group Chemical group N1(CCSCC1)S(=O)(=O)N1CCSCC1 WCNFFKHKJLERFM-UHFFFAOYSA-N 0.000 description 1
- ZCAGUOCUDGWENZ-UHFFFAOYSA-N thiomorpholinyl sulfoxide group Chemical group N1(CCSCC1)S(=O)N1CCSCC1 ZCAGUOCUDGWENZ-UHFFFAOYSA-N 0.000 description 1
- 125000000464 thioxo group Chemical group S=* 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- YFHICDDUDORKJB-UHFFFAOYSA-N trimethylene carbonate Chemical compound O=C1OCCCO1 YFHICDDUDORKJB-UHFFFAOYSA-N 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- HFNHAPQMXICKCF-USJMABIRSA-N urotensin-ii Chemical compound N([C@@H](CC(O)=O)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@@H](C(C)C)C(O)=O)C(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@H](N)CCC(O)=O)[C@@H](C)O HFNHAPQMXICKCF-USJMABIRSA-N 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/30—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by halogen atoms, or by nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/32—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms
- C07C275/34—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms having nitrogen atoms of urea groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/38—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by doubly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/42—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
- C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
- C07D285/135—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Gynecology & Obstetrics (AREA)
- Psychiatry (AREA)
- Reproductive Health (AREA)
- Vascular Medicine (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Furan Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87862507P | 2007-01-03 | 2007-01-03 | |
| US60/878,625 | 2007-01-03 | ||
| PCT/US2008/050014 WO2008086047A1 (en) | 2007-01-03 | 2008-01-02 | Rho kinase inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2010514842A JP2010514842A (ja) | 2010-05-06 |
| JP2010514842A5 JP2010514842A5 (enExample) | 2011-02-24 |
| JP5258790B2 true JP5258790B2 (ja) | 2013-08-07 |
Family
ID=39313484
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009544958A Expired - Fee Related JP5258790B2 (ja) | 2007-01-03 | 2008-01-02 | Rhoキナーゼインヒビター |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US8093266B2 (enExample) |
| EP (1) | EP2114869B1 (enExample) |
| JP (1) | JP5258790B2 (enExample) |
| AR (1) | AR064726A1 (enExample) |
| CA (1) | CA2674389A1 (enExample) |
| CL (1) | CL2007003874A1 (enExample) |
| TW (1) | TW200843770A (enExample) |
| WO (1) | WO2008086047A1 (enExample) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0721333D0 (en) * | 2007-10-31 | 2007-12-12 | Motac Neuroscience Ltd | Medicaments |
| JPWO2010024258A1 (ja) * | 2008-08-29 | 2012-01-26 | 塩野義製薬株式会社 | Pi3k阻害活性を有する縮環アゾール誘導体 |
| US20120225862A1 (en) * | 2009-07-21 | 2012-09-06 | Auckland Univservices Limited | Heteroaryl benzamides, compositions and methods of use |
| US9126978B2 (en) | 2009-11-17 | 2015-09-08 | The Regents Of The University Of Michigan | 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties |
| US8835444B2 (en) * | 2010-02-02 | 2014-09-16 | Novartis Ag | Cyclohexyl amide derivatives as CRF receptor antagonists |
| US9079880B2 (en) * | 2010-07-07 | 2015-07-14 | Boehringer Ingelheim International Gmbh | Rho kinase inhibitors |
| US8697911B2 (en) | 2010-07-07 | 2014-04-15 | Boehringer Ingelheim International Gmbh | Rho kinase inhibitors |
| WO2012054367A1 (en) | 2010-10-19 | 2012-04-26 | Boehringer Ingelheim International Gmbh | Rho kinase inhibitors |
| AR083855A1 (es) * | 2010-11-15 | 2013-03-27 | Abbott Lab | Inhibidores de nampt y rock |
| US9029370B2 (en) * | 2011-06-10 | 2015-05-12 | Hoffmann-La Roche Inc. | Substituted benzamide derivatives |
| WO2013057944A1 (ja) | 2011-10-19 | 2013-04-25 | 興和株式会社 | 新規なスピロインドリン化合物、及びそれを含有する医薬 |
| CN104011026B (zh) | 2011-12-20 | 2016-07-20 | 拜耳知识产权股份有限公司 | 杀虫用芳酰胺 |
| AU2013318206B2 (en) | 2012-09-20 | 2018-07-26 | Temple University - Of The Commonwealth System Of Higher Education | Substituted alkyl diaryl derivatives, methods of preparation and uses |
| JP6488239B2 (ja) | 2013-01-18 | 2019-03-20 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | Rock阻害剤としてのフタラジノンおよびイソキノリノン |
| WO2014177699A1 (en) * | 2013-05-03 | 2014-11-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Rhoa (rock) inhibitors for the treatment of enflammatory bowel disease |
| US9902702B2 (en) | 2014-07-15 | 2018-02-27 | Bristol-Myers Squibb Company | Spirocycloheptanes as inhibitors of rock |
| WO2016028971A1 (en) | 2014-08-21 | 2016-02-25 | Bristol-Myers Squibb Company | Tied-back benzamide derivatives as potent rock inhibitors |
| JP6883173B2 (ja) | 2015-05-12 | 2021-06-09 | ヘモストッド エスエー | 改善された血小板産生のための薬理学的特徴およびマイクロ流体特徴の組み合わせ |
| KR20180011843A (ko) | 2015-06-11 | 2018-02-02 | 바실리어 파마슈티카 인터내셔널 리미티드 | 유출-펌프 억제제 및 이의 치료적 용도 |
| CN105195114B (zh) * | 2015-10-29 | 2017-08-25 | 重庆郑博生物科技有限公司 | 脓毒症多种致病因子的吸附材料及其制备方法和用途 |
| TWI730032B (zh) | 2016-01-13 | 2021-06-11 | 美商必治妥美雅史谷比公司 | 作為rock抑制劑之螺庚烷水楊酸醯胺及相關化合物 |
| US10787450B2 (en) | 2016-07-07 | 2020-09-29 | Bristol-Myers Squibb Company | Spiro-fused cyclic ureas as inhibitors of rock |
| 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 |
| KR102644889B1 (ko) | 2017-07-12 | 2024-03-06 | 브리스톨-마이어스 스큅 컴퍼니 | Rock 억제제로서의 스피로헵타닐 히단토인 |
| 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 |
| 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 |
| WO2020047229A1 (en) | 2018-08-29 | 2020-03-05 | University Of Massachusetts | Inhibition of protein kinases to treat friedreich ataxia |
| WO2023091565A1 (en) * | 2021-11-17 | 2023-05-25 | The University Of North Carolina At Chapel Hill | Nsd2-targeted chemical degraders and compositions and methods of use thereof |
| WO2024076155A1 (ko) * | 2022-10-04 | 2024-04-11 | 노보렉스 주식회사 | Yeats 도메인 억제제로서 신규한 화합물 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20000065219A (ko) * | 1996-05-20 | 2000-11-06 | 마르크 젠너 | 티엔에프 저해제 및 피디이-4 저해제로서의 퀴놀린 카르복사미드 |
| JPH11139969A (ja) * | 1997-08-07 | 1999-05-25 | Tanabe Seiyaku Co Ltd | 医薬組成物 |
| JPH11130751A (ja) * | 1997-10-30 | 1999-05-18 | Yoshitomi Pharmaceut Ind Ltd | アミド化合物およびそれらの酸付加塩の標識化合物 |
| US7217722B2 (en) * | 2000-02-01 | 2007-05-15 | Kirin Beer Kabushiki Kaisha | Nitrogen-containing compounds having kinase inhibitory activity and drugs containing the same |
| WO2002100833A1 (en) * | 2001-06-12 | 2002-12-19 | Sumitomo Pharmaceuticals Company, Limited | Rho KINASE INHIBITORS |
| DE10357510A1 (de) * | 2003-12-09 | 2005-07-07 | Bayer Healthcare Ag | Heteroarylsubstituierte Benzole |
| JP2007519754A (ja) * | 2004-01-30 | 2007-07-19 | スミスクライン ビーチャム コーポレーション | 化合物 |
-
2007
- 2007-12-28 CL CL200703874A patent/CL2007003874A1/es unknown
-
2008
- 2008-01-02 US US12/521,817 patent/US8093266B2/en active Active
- 2008-01-02 AR ARP080100007A patent/AR064726A1/es unknown
- 2008-01-02 CA CA002674389A patent/CA2674389A1/en not_active Abandoned
- 2008-01-02 EP EP08727346.2A patent/EP2114869B1/en not_active Not-in-force
- 2008-01-02 TW TW097100054A patent/TW200843770A/zh unknown
- 2008-01-02 JP JP2009544958A patent/JP5258790B2/ja not_active Expired - Fee Related
- 2008-01-02 WO PCT/US2008/050014 patent/WO2008086047A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| CA2674389A1 (en) | 2008-07-17 |
| AR064726A1 (es) | 2009-04-22 |
| JP2010514842A (ja) | 2010-05-06 |
| EP2114869A1 (en) | 2009-11-11 |
| WO2008086047A1 (en) | 2008-07-17 |
| CL2007003874A1 (es) | 2008-05-16 |
| US20100041645A1 (en) | 2010-02-18 |
| EP2114869B1 (en) | 2014-07-23 |
| US8093266B2 (en) | 2012-01-10 |
| TW200843770A (en) | 2008-11-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5258790B2 (ja) | Rhoキナーゼインヒビター | |
| JP5739527B2 (ja) | RhoキナーゼインヒビターとしてのN−環式−3−(環状カルボニルアミノメチル)ベンズアミド誘導体 | |
| JP5799479B2 (ja) | Rhoキナーゼインヒビター | |
| AU2002220195B2 (en) | Anilinopyrimidine derivatives as IKK inhibitors and compositions and methods related thereto | |
| CN101636397B (zh) | 脲类化合物、其制备方法及其医药用途 | |
| EP2468717B1 (en) | Heterocyclic Amide Compounds Useful as Kinase Inhibitors | |
| RU2677697C1 (ru) | Производные триазолопиридина в качестве модуляторов активности tnf | |
| EP2128156A1 (en) | Novel oxadiazole derivatives and thiadiazole derivatives having neovascularization inhibiting activity | |
| EP2630144B1 (en) | Rho kinase inhibitors | |
| AU2013369241A1 (en) | Protein kinase inhibitors | |
| JP2011173915A (ja) | 新規な化合物 | |
| WO2004106293A2 (en) | Oxazolyl - and thiazolyl - purine based tricyclic compounds. | |
| US9475817B2 (en) | Pyrazole substituted imidazopyrazines as casein kinase 1 d/e inhibitors | |
| WO2012044090A2 (ko) | 단백질 키나제 억제 활성을 갖는 신규한 아미노퀴나졸린 화합물 | |
| EA024295B1 (ru) | N-[4-(1H-ПИРАЗОЛО[3,4-b]ПИРАЗИН-6-ИЛ)ФЕНИЛ]СУЛЬФОНАМИДЫ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ЛЕКАРСТВЕННЫХ СРЕДСТВ | |
| CN109843879B (zh) | 作为dyrk1抑制剂的苯并噻唑衍生物 | |
| JP5205276B2 (ja) | 酵素阻害剤 | |
| CA2779951A1 (en) | Imidazopyridine derivatives | |
| JP2009506127A (ja) | 糖尿病の処置に有用なアニリノピラゾール誘導体 | |
| JP5587914B2 (ja) | キマーゼ阻害剤として有用なアザキナゾリンジオン | |
| US7714010B2 (en) | Pyrrolobenzimidazolones and their use as anti-proliferative agents | |
| CN114206868B (zh) | 作为hdac6抑制剂的3-(2-(杂芳基)-吡啶-4-基)-5-(三氟甲基)-1,2,4-噁二唑衍生物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110104 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20110104 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20130312 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20130325 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130423 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20160502 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |