OA12544A - Pyridine matrix metalloproteinase inhibitors. - Google Patents
Pyridine matrix metalloproteinase inhibitors. Download PDFInfo
- Publication number
- OA12544A OA12544A OA1200300180A OA1200300180A OA12544A OA 12544 A OA12544 A OA 12544A OA 1200300180 A OA1200300180 A OA 1200300180A OA 1200300180 A OA1200300180 A OA 1200300180A OA 12544 A OA12544 A OA 12544A
- Authority
- OA
- OAPI
- Prior art keywords
- pyridine
- dicarboxylic acid
- acid bis
- amide
- benzylamide
- Prior art date
Links
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 title claims description 13
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 title claims description 7
- 239000003771 matrix metalloproteinase inhibitor Substances 0.000 title description 4
- 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 title description 4
- 102100027995 Collagenase 3 Human genes 0.000 claims abstract description 36
- 108050005238 Collagenase 3 Proteins 0.000 claims abstract description 34
- 125000005843 halogen group Chemical group 0.000 claims abstract description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 12
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 12
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 10
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 8
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 8
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 5
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims abstract description 5
- MJIVRKPEXXHNJT-UHFFFAOYSA-N lutidinic acid Chemical compound OC(=O)C1=CC=NC(C(O)=O)=C1 MJIVRKPEXXHNJT-UHFFFAOYSA-N 0.000 claims description 169
- -1 1,3-benzodioxol-5-ylmethyl Chemical group 0.000 claims description 135
- 150000001875 compounds Chemical class 0.000 claims description 94
- 239000002253 acid Substances 0.000 claims description 50
- MPFLRYZEEAQMLQ-UHFFFAOYSA-N dinicotinic acid Chemical compound OC(=O)C1=CN=CC(C(O)=O)=C1 MPFLRYZEEAQMLQ-UHFFFAOYSA-N 0.000 claims description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
- 201000010099 disease Diseases 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 25
- 230000002401 inhibitory effect Effects 0.000 claims description 22
- 150000001408 amides Chemical class 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 16
- QCTBMLYLENLHLA-UHFFFAOYSA-N aminomethylbenzoic acid Chemical compound NCC1=CC=C(C(O)=O)C=C1 QCTBMLYLENLHLA-UHFFFAOYSA-N 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 15
- 102000004190 Enzymes Human genes 0.000 claims description 14
- 108090000790 Enzymes Proteins 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 241000124008 Mammalia Species 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- GRRIMVWABNHKBX-UHFFFAOYSA-N (3-methoxyphenyl)methanamine Chemical compound COC1=CC=CC(CN)=C1 GRRIMVWABNHKBX-UHFFFAOYSA-N 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 239000011159 matrix material Substances 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 7
- 206010019280 Heart failures Diseases 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 230000001404 mediated effect Effects 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 claims description 5
- JIZMLVVNDWKPON-UHFFFAOYSA-N 2-[3,5-bis(benzylcarbamoyl)pyridin-2-yl]oxyacetic acid Chemical compound OC(=O)COC1=NC=C(C(=O)NCC=2C=CC=CC=2)C=C1C(=O)NCC1=CC=CC=C1 JIZMLVVNDWKPON-UHFFFAOYSA-N 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims description 5
- YMVFJGSXZNNUDW-UHFFFAOYSA-N (4-chlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C=C1 YMVFJGSXZNNUDW-UHFFFAOYSA-N 0.000 claims description 4
- HTXAEXMSNYTRMG-UHFFFAOYSA-N 2-[bis(2,3-dihydro-1h-inden-1-yl)carbamoyl]pyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(C(=O)N(C2C3=CC=CC=C3CC2)C2C3=CC=CC=C3CC2)=C1 HTXAEXMSNYTRMG-UHFFFAOYSA-N 0.000 claims description 4
- BVSYUWQODIRJAG-UHFFFAOYSA-N 2-methoxypyridine-3,5-dicarboxylic acid Chemical compound COC1=NC=C(C(O)=O)C=C1C(O)=O BVSYUWQODIRJAG-UHFFFAOYSA-N 0.000 claims description 4
- NVKLSXWYXREKSV-UHFFFAOYSA-N 2-n,4-n-bis[2-(2-methylphenyl)ethyl]pyridine-2,4-dicarboxamide Chemical compound CC1=CC=CC=C1CCNC(=O)C1=CC=NC(C(=O)NCCC=2C(=CC=CC=2)C)=C1 NVKLSXWYXREKSV-UHFFFAOYSA-N 0.000 claims description 4
- ZHWHRNLGRUMHPN-UHFFFAOYSA-N bis(1,3-benzodioxol-5-ylmethyl) pyridine-3,5-dicarboxylate Chemical compound C1=C2OCOC2=CC(COC(=O)C=2C=NC=C(C=2)C(OCC=2C=C3OCOC3=CC=2)=O)=C1 ZHWHRNLGRUMHPN-UHFFFAOYSA-N 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 201000008482 osteoarthritis Diseases 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000000301 2-(3-chlorophenyl)ethyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- VZBPFGSAQOIJMD-UHFFFAOYSA-N 2-n,4-n-bis[2-(1h-indol-3-yl)ethyl]pyridine-2,4-dicarboxamide Chemical compound C1=CC=C2C(CCNC(=O)C=3N=CC=C(C=3)C(NCCC=3C4=CC=CC=C4NC=3)=O)=CNC2=C1 VZBPFGSAQOIJMD-UHFFFAOYSA-N 0.000 claims description 3
- JIIHDHJQMVLVEZ-UHFFFAOYSA-N 2-n,4-n-bis[[2-(difluoromethoxy)phenyl]methyl]pyridine-2,4-dicarboxamide Chemical compound FC(F)OC1=CC=CC=C1CNC(=O)C1=CC=NC(C(=O)NCC=2C(=CC=CC=2)OC(F)F)=C1 JIIHDHJQMVLVEZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 3
- 230000004054 inflammatory process Effects 0.000 claims description 3
- AQBJGAUQEJFPKZ-UHFFFAOYSA-N methyl 4-(aminomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CN)C=C1 AQBJGAUQEJFPKZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- HDOUGSFASVGDCS-UHFFFAOYSA-N pyridin-3-ylmethanamine Chemical compound NCC1=CC=CN=C1 HDOUGSFASVGDCS-UHFFFAOYSA-N 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- BJDDCGVNTJFLEF-UHFFFAOYSA-N 2-n,4-n-bis(2-phenylpropyl)pyridine-2,4-dicarboxamide Chemical compound C=1C=CC=CC=1C(C)CNC(=O)C(C=1)=CC=NC=1C(=O)NCC(C)C1=CC=CC=C1 BJDDCGVNTJFLEF-UHFFFAOYSA-N 0.000 claims description 2
- GCAVUNPGQNJZKI-UHFFFAOYSA-N 2-n,4-n-bis[(2,4-difluorophenyl)methyl]pyridine-2,4-dicarboxamide Chemical compound FC1=CC(F)=CC=C1CNC(=O)C1=CC=NC(C(=O)NCC=2C(=CC(F)=CC=2)F)=C1 GCAVUNPGQNJZKI-UHFFFAOYSA-N 0.000 claims description 2
- XQKHADAMSQKLMZ-UHFFFAOYSA-N 2-n,4-n-bis[(3,4-dimethoxyphenyl)methyl]pyridine-2,4-dicarboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CNC(=O)C1=CC=NC(C(=O)NCC=2C=C(OC)C(OC)=CC=2)=C1 XQKHADAMSQKLMZ-UHFFFAOYSA-N 0.000 claims description 2
- ILLKXKGPXGHSES-UHFFFAOYSA-N 2-n,4-n-bis[(3,5-dichlorophenyl)methyl]pyridine-2,4-dicarboxamide Chemical compound ClC1=CC(Cl)=CC(CNC(=O)C=2C=C(N=CC=2)C(=O)NCC=2C=C(Cl)C=C(Cl)C=2)=C1 ILLKXKGPXGHSES-UHFFFAOYSA-N 0.000 claims description 2
- NEDKYPPIRZFHQF-UHFFFAOYSA-N 2-n,4-n-bis[(3-chloro-4-fluorophenyl)methyl]pyridine-2,4-dicarboxamide Chemical compound C1=C(Cl)C(F)=CC=C1CNC(=O)C1=CC=NC(C(=O)NCC=2C=C(Cl)C(F)=CC=2)=C1 NEDKYPPIRZFHQF-UHFFFAOYSA-N 0.000 claims description 2
- FPRXVTIDNAOLFZ-UHFFFAOYSA-N 2-n,4-n-bis[(4-methoxyphenyl)methyl]pyridine-2,4-dicarboxamide Chemical compound C1=CC(OC)=CC=C1CNC(=O)C1=CC=NC(C(=O)NCC=2C=CC(OC)=CC=2)=C1 FPRXVTIDNAOLFZ-UHFFFAOYSA-N 0.000 claims description 2
- GVPXTABEKUFVAK-UHFFFAOYSA-N 2-n,4-n-bis[2-(2,4-dimethylphenyl)ethyl]pyridine-2,4-dicarboxamide Chemical compound CC1=CC(C)=CC=C1CCNC(=O)C1=CC=NC(C(=O)NCCC=2C(=CC(C)=CC=2)C)=C1 GVPXTABEKUFVAK-UHFFFAOYSA-N 0.000 claims description 2
- MPSZPZFGPQSHQY-UHFFFAOYSA-N 2-n,4-n-bis[2-(2-methoxyphenyl)ethyl]pyridine-2,4-dicarboxamide Chemical compound COC1=CC=CC=C1CCNC(=O)C1=CC=NC(C(=O)NCCC=2C(=CC=CC=2)OC)=C1 MPSZPZFGPQSHQY-UHFFFAOYSA-N 0.000 claims description 2
- ZFNPDLWRJZJLOD-UHFFFAOYSA-N 2-n,4-n-bis[2-(2-phenoxyphenyl)ethyl]pyridine-2,4-dicarboxamide Chemical compound C=1C=NC(C(=O)NCCC=2C(=CC=CC=2)OC=2C=CC=CC=2)=CC=1C(=O)NCCC1=CC=CC=C1OC1=CC=CC=C1 ZFNPDLWRJZJLOD-UHFFFAOYSA-N 0.000 claims description 2
- HVDQYSGHZCKAKY-UHFFFAOYSA-N 2-n,4-n-bis[2-(4-chlorophenyl)ethyl]pyridine-2,4-dicarboxamide Chemical compound C1=CC(Cl)=CC=C1CCNC(=O)C1=CC=NC(C(=O)NCCC=2C=CC(Cl)=CC=2)=C1 HVDQYSGHZCKAKY-UHFFFAOYSA-N 0.000 claims description 2
- PIUNDZHKPOHXRQ-UHFFFAOYSA-N 2-n,4-n-bis[2-(4-methylphenyl)ethyl]pyridine-2,4-dicarboxamide Chemical compound C1=CC(C)=CC=C1CCNC(=O)C1=CC=NC(C(=O)NCCC=2C=CC(C)=CC=2)=C1 PIUNDZHKPOHXRQ-UHFFFAOYSA-N 0.000 claims description 2
- LICJEJNNVAMQKV-UHFFFAOYSA-N 2-n,4-n-bis[[2-(trifluoromethoxy)phenyl]methyl]pyridine-2,4-dicarboxamide Chemical compound FC(F)(F)OC1=CC=CC=C1CNC(=O)C1=CC=NC(C(=O)NCC=2C(=CC=CC=2)OC(F)(F)F)=C1 LICJEJNNVAMQKV-UHFFFAOYSA-N 0.000 claims description 2
- FZRLOAORTKAAKY-UHFFFAOYSA-N 2-n,4-n-bis[[3,5-bis(trifluoromethyl)phenyl]methyl]pyridine-2,4-dicarboxamide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CNC(=O)C=2C=C(N=CC=2)C(=O)NCC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)=C1 FZRLOAORTKAAKY-UHFFFAOYSA-N 0.000 claims description 2
- IIKWZMRADDQRHV-UHFFFAOYSA-N 2-n,4-n-bis[[3-(difluoromethoxy)phenyl]methyl]pyridine-2,4-dicarboxamide Chemical compound FC(F)OC1=CC=CC(CNC(=O)C=2C=C(N=CC=2)C(=O)NCC=2C=C(OC(F)F)C=CC=2)=C1 IIKWZMRADDQRHV-UHFFFAOYSA-N 0.000 claims description 2
- KUCNLAWXZJVEMY-UHFFFAOYSA-N 2-n,4-n-bis[[4-(trifluoromethyl)phenyl]methyl]pyridine-2,4-dicarboxamide Chemical compound C1=CC(C(F)(F)F)=CC=C1CNC(=O)C1=CC=NC(C(=O)NCC=2C=CC(=CC=2)C(F)(F)F)=C1 KUCNLAWXZJVEMY-UHFFFAOYSA-N 0.000 claims description 2
- LRTYSEMCGJDKKB-UHFFFAOYSA-N 2-n,4-n-bis[[4-fluoro-3-(trifluoromethyl)phenyl]methyl]pyridine-2,4-dicarboxamide Chemical compound C1=C(C(F)(F)F)C(F)=CC=C1CNC(=O)C1=CC=NC(C(=O)NCC=2C=C(C(F)=CC=2)C(F)(F)F)=C1 LRTYSEMCGJDKKB-UHFFFAOYSA-N 0.000 claims description 2
- ZVSZCUXYBSFUDE-UHFFFAOYSA-N 3-n,5-n-bis(1,3-benzodioxol-5-ylmethyl)-2-ethoxypyridine-3,5-dicarboxamide Chemical compound C1=C2OCOC2=CC(CNC(=O)C2=CN=C(C(=C2)C(=O)NCC=2C=C3OCOC3=CC=2)OCC)=C1 ZVSZCUXYBSFUDE-UHFFFAOYSA-N 0.000 claims description 2
- STYVAYJUUAIJAW-UHFFFAOYSA-N 3-n,5-n-bis(1,3-benzodioxol-5-ylmethyl)-2-methoxypyridine-3,5-dicarboxamide Chemical compound C1=C2OCOC2=CC(CNC(=O)C2=CN=C(C(=C2)C(=O)NCC=2C=C3OCOC3=CC=2)OC)=C1 STYVAYJUUAIJAW-UHFFFAOYSA-N 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 claims description 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims 11
- 239000004615 ingredient Substances 0.000 claims 8
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 2
- URBXYCAJWJKVEC-UHFFFAOYSA-N 2,1,3-benzothiadiazol-5-ylmethanamine Chemical compound C1=C(CN)C=CC2=NSN=C21 URBXYCAJWJKVEC-UHFFFAOYSA-N 0.000 claims 2
- CHSSFSPKKUFJDU-UHFFFAOYSA-N 2-n,4-n-bis(1,3-benzodioxol-5-ylmethyl)pyridine-2,4-dicarboxamide Chemical compound C1=C2OCOC2=CC(CNC(=O)C=2N=CC=C(C=2)C(NCC=2C=C3OCOC3=CC=2)=O)=C1 CHSSFSPKKUFJDU-UHFFFAOYSA-N 0.000 claims 2
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims 2
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims 2
- QVSVMNXRLWSNGS-UHFFFAOYSA-N (3-fluorophenyl)methanamine Chemical compound NCC1=CC=CC(F)=C1 QVSVMNXRLWSNGS-UHFFFAOYSA-N 0.000 claims 1
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- SJBQXDAJQLKGKC-UHFFFAOYSA-N 2,1,3-benzoxadiazol-5-ylmethanamine Chemical compound C1=C(CN)C=CC2=NON=C21 SJBQXDAJQLKGKC-UHFFFAOYSA-N 0.000 claims 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 1
- BQEYDQLEDOXQGO-UHFFFAOYSA-N 2-n,4-n-bis(pyridin-4-ylmethyl)pyridine-2,4-dicarboxamide Chemical compound C=1C=NC(C(=O)NCC=2C=CN=CC=2)=CC=1C(=O)NCC1=CC=NC=C1 BQEYDQLEDOXQGO-UHFFFAOYSA-N 0.000 claims 1
- DJSOKQLPOWCLFE-UHFFFAOYSA-N 2-n,4-n-bis[(2-phenylphenyl)methyl]pyridine-2,4-dicarboxamide Chemical compound C=1C=NC(C(=O)NCC=2C(=CC=CC=2)C=2C=CC=CC=2)=CC=1C(=O)NCC1=CC=CC=C1C1=CC=CC=C1 DJSOKQLPOWCLFE-UHFFFAOYSA-N 0.000 claims 1
- URYZSOPDXRECLM-UHFFFAOYSA-N 2-n,4-n-bis[(3,5-dimethoxyphenyl)methyl]pyridine-2,4-dicarboxamide Chemical compound COC1=CC(OC)=CC(CNC(=O)C=2C=C(N=CC=2)C(=O)NCC=2C=C(OC)C=C(OC)C=2)=C1 URYZSOPDXRECLM-UHFFFAOYSA-N 0.000 claims 1
- QEYUIBBNXNRXJZ-UHFFFAOYSA-N 2-n,4-n-bis[2-(4-methoxyphenyl)ethyl]pyridine-2,4-dicarboxamide Chemical compound C1=CC(OC)=CC=C1CCNC(=O)C1=CC=NC(C(=O)NCCC=2C=CC(OC)=CC=2)=C1 QEYUIBBNXNRXJZ-UHFFFAOYSA-N 0.000 claims 1
- VNCWXQMCBRGYKQ-UHFFFAOYSA-N 2-n,4-n-bis[2-[3-(trifluoromethyl)phenyl]ethyl]pyridine-2,4-dicarboxamide Chemical compound FC(F)(F)C1=CC=CC(CCNC(=O)C=2C=C(N=CC=2)C(=O)NCCC=2C=C(C=CC=2)C(F)(F)F)=C1 VNCWXQMCBRGYKQ-UHFFFAOYSA-N 0.000 claims 1
- CGZGJLKFWQBSGF-UHFFFAOYSA-N 2-n,4-n-bis[bis(4-methoxyphenyl)methyl]pyridine-2,4-dicarboxamide Chemical compound C1=CC(OC)=CC=C1C(C=1C=CC(OC)=CC=1)NC(=O)C1=CC=NC(C(=O)NC(C=2C=CC(OC)=CC=2)C=2C=CC(OC)=CC=2)=C1 CGZGJLKFWQBSGF-UHFFFAOYSA-N 0.000 claims 1
- LUJLLMQPDBTIEF-UHFFFAOYSA-N 2-n,4-n-dibenzyl-2-n,4-n-diethylpyridine-2,4-dicarboxamide Chemical compound C=1C=NC(C(=O)N(CC)CC=2C=CC=CC=2)=CC=1C(=O)N(CC)CC1=CC=CC=C1 LUJLLMQPDBTIEF-UHFFFAOYSA-N 0.000 claims 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
- MEWCNYGSAQYEHP-UHFFFAOYSA-N 3-n,5-n-bis[(3-chlorophenyl)methyl]pyridine-3,5-dicarboxamide Chemical compound ClC1=CC=CC(CNC(=O)C=2C=C(C=NC=2)C(=O)NCC=2C=C(Cl)C=CC=2)=C1 MEWCNYGSAQYEHP-UHFFFAOYSA-N 0.000 claims 1
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- MRRUMYXKJJNBNY-UHFFFAOYSA-N 5-(dibenzylcarbamoyl)-6-oxo-1h-pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CNC(=O)C(C(=O)N(CC=2C=CC=CC=2)CC=2C=CC=CC=2)=C1 MRRUMYXKJJNBNY-UHFFFAOYSA-N 0.000 claims 1
- LPJZSLTUFDTUIZ-UHFFFAOYSA-N CCOC(C=C1)=CC=C1N.CCOC(C=C1)=CC=C1N.OC(C1=CC(C(O)=O)=NC=C1)=O Chemical compound CCOC(C=C1)=CC=C1N.CCOC(C=C1)=CC=C1N.OC(C1=CC(C(O)=O)=NC=C1)=O LPJZSLTUFDTUIZ-UHFFFAOYSA-N 0.000 claims 1
- DYKIAHXCPVUSLA-UHFFFAOYSA-N N1=C(C=C(C=C1)C(=O)O)C(=O)O.NC1=C(CNC(=O)C2=NC=CC(=C2)C(=O)NCC2=C(C=CC=C2)N)C=CC=C1 Chemical compound N1=C(C=C(C=C1)C(=O)O)C(=O)O.NC1=C(CNC(=O)C2=NC=CC(=C2)C(=O)NCC2=C(C=CC=C2)N)C=CC=C1 DYKIAHXCPVUSLA-UHFFFAOYSA-N 0.000 claims 1
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 claims 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 abstract description 16
- 150000003839 salts Chemical class 0.000 abstract description 14
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 1
- 150000003222 pyridines Chemical class 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 38
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- 238000000034 method Methods 0.000 description 22
- 239000000243 solution Substances 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 239000011347 resin Substances 0.000 description 18
- 229920005989 resin Polymers 0.000 description 18
- 150000001412 amines Chemical class 0.000 description 13
- 230000003197 catalytic effect Effects 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000011282 treatment Methods 0.000 description 12
- 229940093499 ethyl acetate Drugs 0.000 description 10
- 235000019439 ethyl acetate Nutrition 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 8
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 8
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- 239000002552 dosage form Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 102100030416 Stromelysin-1 Human genes 0.000 description 7
- 125000002252 acyl group Chemical group 0.000 description 7
- 238000000160 carbon, hydrogen and nitrogen elemental analysis Methods 0.000 description 7
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 102100030417 Matrilysin Human genes 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000003389 potentiating effect Effects 0.000 description 6
- 229940124761 MMP inhibitor Drugs 0.000 description 5
- 108090000855 Matrilysin Proteins 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 239000012458 free base Substances 0.000 description 5
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 229940086542 triethylamine Drugs 0.000 description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 4
- VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- 102100030411 Neutrophil collagenase Human genes 0.000 description 4
- 101710118230 Neutrophil collagenase Proteins 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 101710108790 Stromelysin-1 Proteins 0.000 description 4
- 102100028848 Stromelysin-2 Human genes 0.000 description 4
- 102100028847 Stromelysin-3 Human genes 0.000 description 4
- 206010003246 arthritis Diseases 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 210000002808 connective tissue Anatomy 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- FTQWRYSLUYAIRQ-UHFFFAOYSA-N n-[(octadecanoylamino)methyl]octadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NCNC(=O)CCCCCCCCCCCCCCCCC FTQWRYSLUYAIRQ-UHFFFAOYSA-N 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical class CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
- DLQPZBCWAYYHGN-UHFFFAOYSA-N 2-n,4-n-bis(3,3-diphenylpropyl)pyridine-2,4-dicarboxamide Chemical compound C=1C=NC(C(=O)NCCC(C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=1C(=O)NCCC(C=1C=CC=CC=1)C1=CC=CC=C1 DLQPZBCWAYYHGN-UHFFFAOYSA-N 0.000 description 3
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 102100031111 Disintegrin and metalloproteinase domain-containing protein 17 Human genes 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 108010016160 Matrix Metalloproteinase 3 Proteins 0.000 description 3
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 3
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- BFPSDSIWYFKGBC-UHFFFAOYSA-N chlorotrianisene Chemical compound C1=CC(OC)=CC=C1C(Cl)=C(C=1C=CC(OC)=CC=1)C1=CC=C(OC)C=C1 BFPSDSIWYFKGBC-UHFFFAOYSA-N 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 238000001647 drug administration Methods 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000007937 lozenge Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- 238000004452 microanalysis Methods 0.000 description 3
- 201000006417 multiple sclerosis Diseases 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 208000037803 restenosis Diseases 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000012265 solid product Substances 0.000 description 3
- 125000000547 substituted alkyl group Chemical group 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- PDQRQJVPEFGVRK-UHFFFAOYSA-N 2,1,3-benzothiadiazole Chemical compound C1=CC=CC2=NSN=C21 PDQRQJVPEFGVRK-UHFFFAOYSA-N 0.000 description 2
- 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 2
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 2
- ZMRGFRXKKAKALY-UHFFFAOYSA-N 2-n,4-n-bis(naphthalen-1-ylmethyl)pyridine-2,4-dicarboxamide Chemical compound C1=CC=C2C(CNC(=O)C=3N=CC=C(C=3)C(NCC=3C4=CC=CC=C4C=CC=3)=O)=CC=CC2=C1 ZMRGFRXKKAKALY-UHFFFAOYSA-N 0.000 description 2
- KFXDZJTYYNGVJG-UHFFFAOYSA-N 2-n,4-n-bis[(2-methoxyphenyl)methyl]pyridine-2,4-dicarboxamide Chemical compound COC1=CC=CC=C1CNC(=O)C1=CC=NC(C(=O)NCC=2C(=CC=CC=2)OC)=C1 KFXDZJTYYNGVJG-UHFFFAOYSA-N 0.000 description 2
- MQOOWZUPQRAHAY-UHFFFAOYSA-N 2-n,4-n-bis[(3-methoxyphenyl)methyl]pyridine-2,4-dicarboxamide Chemical compound COC1=CC=CC(CNC(=O)C=2C=C(N=CC=2)C(=O)NCC=2C=C(OC)C=CC=2)=C1 MQOOWZUPQRAHAY-UHFFFAOYSA-N 0.000 description 2
- LKLXJBMXDPMJRS-UHFFFAOYSA-N 2-n,4-n-bis[2-(5-methoxy-1h-indol-3-yl)ethyl]pyridine-2,4-dicarboxamide Chemical compound C1=C(OC)C=C2C(CCNC(=O)C=3N=CC=C(C=3)C(=O)NCCC3=CNC4=CC=C(C=C43)OC)=CNC2=C1 LKLXJBMXDPMJRS-UHFFFAOYSA-N 0.000 description 2
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 2
- 101710151806 72 kDa type IV collagenase Proteins 0.000 description 2
- 102000043279 ADAM17 Human genes 0.000 description 2
- 108091007505 ADAM17 Proteins 0.000 description 2
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 108010076497 Matrix Metalloproteinase 10 Proteins 0.000 description 2
- 108010076502 Matrix Metalloproteinase 11 Proteins 0.000 description 2
- 108010076503 Matrix Metalloproteinase 13 Proteins 0.000 description 2
- 108010076557 Matrix Metalloproteinase 14 Proteins 0.000 description 2
- 102100030216 Matrix metalloproteinase-14 Human genes 0.000 description 2
- 108090000560 Matrix metalloproteinase-15 Proteins 0.000 description 2
- 108090000561 Matrix metalloproteinase-16 Proteins 0.000 description 2
- 108090000585 Matrix metalloproteinase-17 Proteins 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 101710108792 Stromelysin-2 Proteins 0.000 description 2
- 108050005271 Stromelysin-3 Proteins 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical class [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical class [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 201000008275 breast carcinoma Diseases 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 229940110456 cocoa butter Drugs 0.000 description 2
- 235000019868 cocoa butter Nutrition 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- QQVIHTHCMHWDBS-UHFFFAOYSA-N isophthalic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 150000002829 nitrogen Chemical class 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 239000001301 oxygen Chemical class 0.000 description 2
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 229960001407 sodium bicarbonate Drugs 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 2
- 239000011593 sulfur Chemical class 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- UDJGLXREBSZBDR-UHFFFAOYSA-N tert-butyl 2-[3,5-bis(benzylcarbamoyl)pyridin-2-yl]oxyacetate Chemical compound CC(C)(C)OC(=O)COC1=NC=C(C(=O)NCC=2C=CC=CC=2)C=C1C(=O)NCC1=CC=CC=C1 UDJGLXREBSZBDR-UHFFFAOYSA-N 0.000 description 2
- 125000004001 thioalkyl group Chemical group 0.000 description 2
- 230000005747 tumor angiogenesis Effects 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- MILPTZJEXYXOLP-UHFFFAOYSA-N (4-aminobenzoyl)oxymethyl 4-aminobenzoate Chemical compound C1=CC(N)=CC=C1C(=O)OCOC(=O)C1=CC=C(N)C=C1 MILPTZJEXYXOLP-UHFFFAOYSA-N 0.000 description 1
- 125000005871 1,3-benzodioxolyl 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
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- RLFZYIUUQBHRNV-UHFFFAOYSA-N 2,5-dihydrooxadiazole Chemical compound C1ONN=C1 RLFZYIUUQBHRNV-UHFFFAOYSA-N 0.000 description 1
- HUTZJNJOJPSDMU-UHFFFAOYSA-N 2-(dibenzylcarbamoyl)pyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(C(=O)N(CC=2C=CC=CC=2)CC=2C=CC=CC=2)=C1 HUTZJNJOJPSDMU-UHFFFAOYSA-N 0.000 description 1
- UEYQJQVBUVAELZ-UHFFFAOYSA-N 2-Hydroxynicotinic acid Chemical compound OC(=O)C1=CC=CN=C1O UEYQJQVBUVAELZ-UHFFFAOYSA-N 0.000 description 1
- CLDCDJBSQNZBDO-UHFFFAOYSA-N 2-amino-3-n,5-n-bis(1,3-benzodioxol-5-ylmethyl)pyridine-3,5-dicarboxamide Chemical compound C1=C2OCOC2=CC(CNC(=O)C2=CN=C(C(=C2)C(=O)NCC=2C=C3OCOC3=CC=2)N)=C1 CLDCDJBSQNZBDO-UHFFFAOYSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- IVLPFCOWTKBYGG-UHFFFAOYSA-N 2-aminopyridine-3,5-dicarboxylic acid Chemical compound NC1=NC=C(C(O)=O)C=C1C(O)=O IVLPFCOWTKBYGG-UHFFFAOYSA-N 0.000 description 1
- WEBAPQAYOPNITC-UHFFFAOYSA-N 2-ethoxypyridine-3,5-dicarboxylic acid Chemical compound CCOC1=NC=C(C(O)=O)C=C1C(O)=O WEBAPQAYOPNITC-UHFFFAOYSA-N 0.000 description 1
- AIEJKJZLMWCFLG-UHFFFAOYSA-N 2-n,4-n-bis(1-naphthalen-1-ylethyl)pyridine-2,4-dicarboxamide Chemical compound C1=CC=C2C(C(NC(=O)C=3C=C(N=CC=3)C(=O)NC(C)C=3C4=CC=CC=C4C=CC=3)C)=CC=CC2=C1 AIEJKJZLMWCFLG-UHFFFAOYSA-N 0.000 description 1
- QHJQIDSQDBSDMS-UHFFFAOYSA-N 2-n,4-n-bis(1-phenylethyl)pyridine-2,4-dicarboxamide Chemical compound C=1C=CC=CC=1C(C)NC(=O)C(C=1)=CC=NC=1C(=O)NC(C)C1=CC=CC=C1 QHJQIDSQDBSDMS-UHFFFAOYSA-N 0.000 description 1
- WZBNWKYQAKRIBX-UHFFFAOYSA-N 2-n,4-n-bis(1-phenylpropyl)pyridine-2,4-dicarboxamide Chemical compound C=1C=CC=CC=1C(CC)NC(=O)C(C=1)=CC=NC=1C(=O)NC(CC)C1=CC=CC=C1 WZBNWKYQAKRIBX-UHFFFAOYSA-N 0.000 description 1
- OPTGLJWWQLZLGO-UHFFFAOYSA-N 2-n,4-n-bis(2-ethoxyethyl)pyridine-2,4-dicarboxamide Chemical compound CCOCCNC(=O)C1=CC=NC(C(=O)NCCOCC)=C1 OPTGLJWWQLZLGO-UHFFFAOYSA-N 0.000 description 1
- SAWNUVXTFQFNML-UHFFFAOYSA-N 2-n,4-n-bis(2-phenylethyl)pyridine-2,4-dicarboxamide Chemical compound C=1C=NC(C(=O)NCCC=2C=CC=CC=2)=CC=1C(=O)NCCC1=CC=CC=C1 SAWNUVXTFQFNML-UHFFFAOYSA-N 0.000 description 1
- RBSDMZOCSDOYPI-UHFFFAOYSA-N 2-n,4-n-bis(2-pyridin-2-ylethyl)pyridine-2,4-dicarboxamide Chemical compound C=1C=NC(C(=O)NCCC=2N=CC=CC=2)=CC=1C(=O)NCCC1=CC=CC=N1 RBSDMZOCSDOYPI-UHFFFAOYSA-N 0.000 description 1
- TWHJACRXMAINQH-UHFFFAOYSA-N 2-n,4-n-bis(2-pyridin-3-ylethyl)pyridine-2,4-dicarboxamide Chemical compound C=1C=NC(C(=O)NCCC=2C=NC=CC=2)=CC=1C(=O)NCCC1=CC=CN=C1 TWHJACRXMAINQH-UHFFFAOYSA-N 0.000 description 1
- LQWOOSRMXZTAOL-UHFFFAOYSA-N 2-n,4-n-bis(3,4-dimethoxyphenyl)pyridine-2,4-dicarboxamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)C1=CC=NC(C(=O)NC=2C=C(OC)C(OC)=CC=2)=C1 LQWOOSRMXZTAOL-UHFFFAOYSA-N 0.000 description 1
- XLJHTMIKAZOPCF-UHFFFAOYSA-N 2-n,4-n-bis(3-imidazol-1-ylpropyl)pyridine-2,4-dicarboxamide Chemical compound C=1C=NC(C(=O)NCCCN2C=NC=C2)=CC=1C(=O)NCCCN1C=CN=C1 XLJHTMIKAZOPCF-UHFFFAOYSA-N 0.000 description 1
- DPUUBDLCPMQRPZ-UHFFFAOYSA-N 2-n,4-n-bis(4-ethoxyphenyl)pyridine-2,4-dicarboxamide Chemical compound C1=CC(OCC)=CC=C1NC(=O)C1=CC=NC(C(=O)NC=2C=CC(OCC)=CC=2)=C1 DPUUBDLCPMQRPZ-UHFFFAOYSA-N 0.000 description 1
- VJJOISLUFDTWIN-UHFFFAOYSA-N 2-n,4-n-bis(4-phenylbutan-2-yl)pyridine-2,4-dicarboxamide Chemical compound C=1C=NC(C(=O)NC(C)CCC=2C=CC=CC=2)=CC=1C(=O)NC(C)CCC1=CC=CC=C1 VJJOISLUFDTWIN-UHFFFAOYSA-N 0.000 description 1
- ZRHPKORPTLMGFN-UHFFFAOYSA-N 2-n,4-n-bis(4-phenylbutyl)pyridine-2,4-dicarboxamide Chemical compound C=1C=NC(C(=O)NCCCCC=2C=CC=CC=2)=CC=1C(=O)NCCCCC1=CC=CC=C1 ZRHPKORPTLMGFN-UHFFFAOYSA-N 0.000 description 1
- SIUZKMZWIKSTEB-UHFFFAOYSA-N 2-n,4-n-bis(thiophen-2-ylmethyl)pyridine-2,4-dicarboxamide Chemical compound C=1C=NC(C(=O)NCC=2SC=CC=2)=CC=1C(=O)NCC1=CC=CS1 SIUZKMZWIKSTEB-UHFFFAOYSA-N 0.000 description 1
- PHRBAFXTMDOEHP-UHFFFAOYSA-N 2-n,4-n-bis[(2,4-dimethoxyphenyl)methyl]pyridine-2,4-dicarboxamide Chemical compound COC1=CC(OC)=CC=C1CNC(=O)C1=CC=NC(C(=O)NCC=2C(=CC(OC)=CC=2)OC)=C1 PHRBAFXTMDOEHP-UHFFFAOYSA-N 0.000 description 1
- FSEWKWJTPWFGRK-UHFFFAOYSA-N 2-n,4-n-bis[(2-aminophenyl)methyl]pyridine-2,4-dicarboxamide Chemical compound NC1=CC=CC=C1CNC(=O)C1=CC=NC(C(=O)NCC=2C(=CC=CC=2)N)=C1 FSEWKWJTPWFGRK-UHFFFAOYSA-N 0.000 description 1
- NBZPVHMKXDQMCR-UHFFFAOYSA-N 2-n,4-n-bis[(2-chlorophenyl)methyl]pyridine-2,4-dicarboxamide Chemical compound ClC1=CC=CC=C1CNC(=O)C1=CC=NC(C(=O)NCC=2C(=CC=CC=2)Cl)=C1 NBZPVHMKXDQMCR-UHFFFAOYSA-N 0.000 description 1
- FJJDOSNEGTZSLL-UHFFFAOYSA-N 2-n,4-n-bis[(3,4,5-trimethoxyphenyl)methyl]pyridine-2,4-dicarboxamide Chemical compound COC1=C(OC)C(OC)=CC(CNC(=O)C=2C=C(N=CC=2)C(=O)NCC=2C=C(OC)C(OC)=C(OC)C=2)=C1 FJJDOSNEGTZSLL-UHFFFAOYSA-N 0.000 description 1
- AWQYRHYRDMLSEB-UHFFFAOYSA-N 2-n,4-n-bis[(3-chlorophenyl)methyl]pyridine-2,4-dicarboxamide Chemical compound ClC1=CC=CC(CNC(=O)C=2C=C(N=CC=2)C(=O)NCC=2C=C(Cl)C=CC=2)=C1 AWQYRHYRDMLSEB-UHFFFAOYSA-N 0.000 description 1
- MOQATVDDGLHYKN-UHFFFAOYSA-N 2-n,4-n-bis[(4-chlorophenyl)methyl]pyridine-2,4-dicarboxamide Chemical compound C1=CC(Cl)=CC=C1CNC(=O)C1=CC=NC(C(=O)NCC=2C=CC(Cl)=CC=2)=C1 MOQATVDDGLHYKN-UHFFFAOYSA-N 0.000 description 1
- FKPZMSGBSZYRTB-UHFFFAOYSA-N 2-n,4-n-bis[(5-methylfuran-2-yl)methyl]pyridine-2,4-dicarboxamide Chemical compound O1C(C)=CC=C1CNC(=O)C1=CC=NC(C(=O)NCC=2OC(C)=CC=2)=C1 FKPZMSGBSZYRTB-UHFFFAOYSA-N 0.000 description 1
- GREFOQGWAZIDPW-UHFFFAOYSA-N 2-n,4-n-bis[2-(2-fluorophenyl)ethyl]pyridine-2,4-dicarboxamide Chemical compound FC1=CC=CC=C1CCNC(=O)C1=CC=NC(C(=O)NCCC=2C(=CC=CC=2)F)=C1 GREFOQGWAZIDPW-UHFFFAOYSA-N 0.000 description 1
- HWARXDGFAOPAIN-UHFFFAOYSA-N 2-n,4-n-bis[2-(3-chlorophenyl)ethyl]pyridine-2,4-dicarboxamide Chemical compound ClC1=CC=CC(CCNC(=O)C=2C=C(N=CC=2)C(=O)NCCC=2C=C(Cl)C=CC=2)=C1 HWARXDGFAOPAIN-UHFFFAOYSA-N 0.000 description 1
- PZHCMAROMHJVJD-UHFFFAOYSA-N 2-n,4-n-bis[2-(3-methoxyphenyl)ethyl]pyridine-2,4-dicarboxamide Chemical compound COC1=CC=CC(CCNC(=O)C=2C=C(N=CC=2)C(=O)NCCC=2C=C(OC)C=CC=2)=C1 PZHCMAROMHJVJD-UHFFFAOYSA-N 0.000 description 1
- QIWZORFXSXEUCV-UHFFFAOYSA-N 2-n,4-n-bis[2-(4-ethylphenyl)ethyl]pyridine-2,4-dicarboxamide Chemical compound C1=CC(CC)=CC=C1CCNC(=O)C1=CC=NC(C(=O)NCCC=2C=CC(CC)=CC=2)=C1 QIWZORFXSXEUCV-UHFFFAOYSA-N 0.000 description 1
- PQGSYNJKRQXVJX-UHFFFAOYSA-N 2-n,4-n-bis[[2-(trifluoromethyl)phenyl]methyl]pyridine-2,4-dicarboxamide Chemical compound FC(F)(F)C1=CC=CC=C1CNC(=O)C1=CC=NC(C(=O)NCC=2C(=CC=CC=2)C(F)(F)F)=C1 PQGSYNJKRQXVJX-UHFFFAOYSA-N 0.000 description 1
- NTLJEBHQNVXPPJ-UHFFFAOYSA-N 2-n,4-n-bis[[3-(trifluoromethoxy)phenyl]methyl]pyridine-2,4-dicarboxamide Chemical compound FC(F)(F)OC1=CC=CC(CNC(=O)C=2C=C(N=CC=2)C(=O)NCC=2C=C(OC(F)(F)F)C=CC=2)=C1 NTLJEBHQNVXPPJ-UHFFFAOYSA-N 0.000 description 1
- MPPBHQFNIPMFOL-UHFFFAOYSA-N 2-n,4-n-bis[[3-(trifluoromethyl)phenyl]methyl]pyridine-2,4-dicarboxamide Chemical compound FC(F)(F)C1=CC=CC(CNC(=O)C=2C=C(N=CC=2)C(=O)NCC=2C=C(C=CC=2)C(F)(F)F)=C1 MPPBHQFNIPMFOL-UHFFFAOYSA-N 0.000 description 1
- JVHOQLZUKPQKQQ-UHFFFAOYSA-N 2-n,4-n-diethyl-2-n,4-n-bis(pyridin-4-ylmethyl)pyridine-2,4-dicarboxamide Chemical compound C=1C=NC(C(=O)N(CC)CC=2C=CN=CC=2)=CC=1C(=O)N(CC)CC1=CC=NC=C1 JVHOQLZUKPQKQQ-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
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- ICIOTZDZYOAWSD-UHFFFAOYSA-N 3-n,5-n-bis[(4-fluorophenyl)methyl]pyridine-3,5-dicarboxamide Chemical compound C1=CC(F)=CC=C1CNC(=O)C1=CN=CC(C(=O)NCC=2C=CC(F)=CC=2)=C1 ICIOTZDZYOAWSD-UHFFFAOYSA-N 0.000 description 1
- VGVJGNBTROFAQL-UHFFFAOYSA-N 3-n,5-n-bis[(4-methoxyphenyl)methyl]pyridine-3,5-dicarboxamide Chemical compound C1=CC(OC)=CC=C1CNC(=O)C1=CN=CC(C(=O)NCC=2C=CC(OC)=CC=2)=C1 VGVJGNBTROFAQL-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 125000001054 5 membered carbocyclic group Chemical group 0.000 description 1
- UDDKNRMSZGVATE-UHFFFAOYSA-N 5-(benzylcarbamoyl)-6-oxo-1h-pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=C(O)C(C(=O)NCC=2C=CC=CC=2)=C1 UDDKNRMSZGVATE-UHFFFAOYSA-N 0.000 description 1
- GYXOTADLHQJPIP-UHFFFAOYSA-N 5-bromo-2-oxo-1h-pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC(Br)=CNC1=O GYXOTADLHQJPIP-UHFFFAOYSA-N 0.000 description 1
- GANZODCWZFAEGN-UHFFFAOYSA-N 5-mercapto-2-nitro-benzoic acid Chemical compound OC(=O)C1=CC(S)=CC=C1[N+]([O-])=O GANZODCWZFAEGN-UHFFFAOYSA-N 0.000 description 1
- ICCYUQVWGMCKJK-UHFFFAOYSA-N 5-methoxycarbonyl-2-oxo-1h-pyridine-3-carboxylic acid Chemical compound COC(=O)C1=CN=C(O)C(C(O)=O)=C1 ICCYUQVWGMCKJK-UHFFFAOYSA-N 0.000 description 1
- JTEJPPKMYBDEMY-UHFFFAOYSA-N 5-methoxytryptamine Chemical compound COC1=CC=C2NC=C(CCN)C2=C1 JTEJPPKMYBDEMY-UHFFFAOYSA-N 0.000 description 1
- 125000004008 6 membered carbocyclic group Chemical group 0.000 description 1
- DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-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
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 206010006262 Breast inflammation Diseases 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
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 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
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101000990912 Homo sapiens Matrilysin Proteins 0.000 description 1
- 101001011896 Homo sapiens Matrix metalloproteinase-19 Proteins 0.000 description 1
- 101000627854 Homo sapiens Matrix metalloproteinase-26 Proteins 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
- 229930194542 Keto Chemical group 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 102100027998 Macrophage metalloelastase Human genes 0.000 description 1
- 101710187853 Macrophage metalloelastase Proteins 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 1
- 102000004043 Matrix metalloproteinase-15 Human genes 0.000 description 1
- 102100030201 Matrix metalloproteinase-15 Human genes 0.000 description 1
- 102000004044 Matrix metalloproteinase-16 Human genes 0.000 description 1
- 102100030200 Matrix metalloproteinase-16 Human genes 0.000 description 1
- 102000004054 Matrix metalloproteinase-17 Human genes 0.000 description 1
- 102100030219 Matrix metalloproteinase-17 Human genes 0.000 description 1
- 102000004055 Matrix metalloproteinase-19 Human genes 0.000 description 1
- 102100030218 Matrix metalloproteinase-19 Human genes 0.000 description 1
- 108090000587 Matrix metalloproteinase-19 Proteins 0.000 description 1
- 102100024128 Matrix metalloproteinase-26 Human genes 0.000 description 1
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 1
- 108010088571 Membrane-Associated Matrix Metalloproteinases Proteins 0.000 description 1
- 102000008887 Membrane-Associated Matrix Metalloproteinases Human genes 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 101150101095 Mmp12 gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- FARMEEAGJWMFSZ-UHFFFAOYSA-N N-[2-[4-[[2-[(hydroxyamino)-oxomethyl]-4,6-dimethylphenyl]-(phenylmethyl)sulfamoyl]phenoxy]ethyl]-2-benzofurancarboxamide Chemical compound ONC(=O)C1=CC(C)=CC(C)=C1N(S(=O)(=O)C=1C=CC(OCCNC(=O)C=2OC3=CC=CC=C3C=2)=CC=1)CC1=CC=CC=C1 FARMEEAGJWMFSZ-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 102000056189 Neutrophil collagenases Human genes 0.000 description 1
- 108030001564 Neutrophil collagenases Proteins 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 101001011890 Xenopus laevis Matrix metalloproteinase-18 Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 description 1
- FDQSRULYDNDXQB-UHFFFAOYSA-N benzene-1,3-dicarbonyl chloride Chemical compound ClC(=O)C1=CC=CC(C(Cl)=O)=C1 FDQSRULYDNDXQB-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 125000004181 carboxyalkyl group Chemical group 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000007958 cherry flavor Substances 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical group 0.000 description 1
- KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 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
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 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
- 238000013461 design Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- AAXGWYDSLJUQLN-UHFFFAOYSA-N diphenyl(propyl)phosphane Chemical compound C=1C=CC=CC=1P(CCC)C1=CC=CC=C1 AAXGWYDSLJUQLN-UHFFFAOYSA-N 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 208000007565 gingivitis Diseases 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 208000024348 heart neoplasm Diseases 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 125000005113 hydroxyalkoxy group Chemical group 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 208000004396 mastitis Diseases 0.000 description 1
- 125000005341 metaphosphate group Chemical group 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- KKYCXCHMCFIFDJ-UHFFFAOYSA-N methyl 5-(benzylcarbamoyl)-6-oxo-1h-pyridine-3-carboxylate Chemical compound COC(=O)C1=CN=C(O)C(C(=O)NCC=2C=CC=CC=2)=C1 KKYCXCHMCFIFDJ-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 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
- 239000011812 mixed powder Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002825 nitriles Chemical group 0.000 description 1
- 239000012740 non-selective inhibitor Substances 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- XULSCZPZVQIMFM-IPZQJPLYSA-N odevixibat Chemical compound C12=CC(SC)=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C=3C=CC(O)=CC=3)C=C2S(=O)(=O)NC(CCCC)(CCCC)CN1C1=CC=CC=C1 XULSCZPZVQIMFM-IPZQJPLYSA-N 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 201000010198 papillary carcinoma Diseases 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 230000003239 periodontal effect Effects 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000001044 red dye Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229940116351 sebacate Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 108091007196 stromelysin Proteins 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 125000004426 substituted alkynyl group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-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
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 125000006000 trichloroethyl group Chemical group 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 238000013022 venting Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 230000037314 wound repair Effects 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- 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
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, 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
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US26878101P | 2001-02-14 | 2001-02-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| OA12544A true OA12544A (en) | 2006-06-05 |
Family
ID=23024446
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| OA1200300180A OA12544A (en) | 2001-02-14 | 2002-02-04 | Pyridine matrix metalloproteinase inhibitors. |
Country Status (36)
| Country | Link |
|---|---|
| US (2) | US6881743B2 (de) |
| EP (1) | EP1362033B1 (de) |
| JP (1) | JP4249981B2 (de) |
| KR (1) | KR20030075196A (de) |
| CN (1) | CN1537101A (de) |
| AP (1) | AP2003002840A0 (de) |
| AR (1) | AR035936A1 (de) |
| AT (1) | ATE358667T1 (de) |
| BG (1) | BG108089A (de) |
| BR (1) | BR0207863A (de) |
| CA (1) | CA2434982A1 (de) |
| CR (1) | CR7048A (de) |
| CZ (1) | CZ20032143A3 (de) |
| DE (1) | DE60219286T2 (de) |
| DO (1) | DOP2002000332A (de) |
| EA (1) | EA200300763A1 (de) |
| EC (1) | ECSP034691A (de) |
| EE (1) | EE200300391A (de) |
| ES (1) | ES2283540T3 (de) |
| GT (1) | GT200200014A (de) |
| HN (2) | HN2002000025A (de) |
| HU (1) | HUP0303152A2 (de) |
| IL (1) | IL156912A0 (de) |
| IS (1) | IS6871A (de) |
| MA (1) | MA26989A1 (de) |
| MX (1) | MXPA03006204A (de) |
| NO (1) | NO20033570L (de) |
| OA (1) | OA12544A (de) |
| PA (1) | PA8538201A1 (de) |
| PE (1) | PE20020995A1 (de) |
| PL (1) | PL365098A1 (de) |
| SK (1) | SK10022003A3 (de) |
| TN (1) | TNSN02012A1 (de) |
| UY (1) | UY27167A1 (de) |
| WO (1) | WO2002064568A1 (de) |
| ZA (1) | ZA200306041B (de) |
Families Citing this family (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DOP2002000333A (es) | 2001-02-14 | 2002-09-30 | Warner Lambert Co | Derivados de acido isoftalico como inhibidores de metaloproteinasas de la matriz |
| WO2002064571A1 (en) | 2001-02-14 | 2002-08-22 | Warner-Lambert Company Llc | Pyrimidine matrix metalloproteinase inhibitors |
| US6924276B2 (en) | 2001-09-10 | 2005-08-02 | Warner-Lambert Company | Diacid-substituted heteroaryl derivatives as matrix metalloproteinase inhibitors |
| JP4164028B2 (ja) | 2001-10-12 | 2008-10-08 | ワーナー−ランバート カンパニー リミテッド ライアビリティー カンパニー | アルキンマトリックスメタロプロテイナーゼ阻害剤 |
| US6962922B2 (en) | 2001-10-12 | 2005-11-08 | Warner-Lambert Company Llc | Alkynylated quinazoline compounds |
| US6933298B2 (en) | 2001-12-08 | 2005-08-23 | Aventis Pharma Deutschland Gmbh | Pyridine-2,4-dicarboxylic acid diamides and pyrimidine-4,6-dicarboxylic acid diamides and the use thereof for selectively inhibiting collagenases |
| DE10160357A1 (de) * | 2001-12-08 | 2003-06-18 | Aventis Pharma Gmbh | Verwendung von Pyridin-2,4-dicarbonsäurediamiden und Pyrimidin-4,6-dicarbonsäurediamiden zur selektiven Inhibierung von Kollagenasen |
| US6747147B2 (en) | 2002-03-08 | 2004-06-08 | Warner-Lambert Company | Oxo-azabicyclic compounds |
| US6894057B2 (en) | 2002-03-08 | 2005-05-17 | Warner-Lambert Company | Oxo-azabicyclic compounds |
| US20040006077A1 (en) * | 2002-06-25 | 2004-01-08 | Bernard Gaudilliere | Thiazine and oxazine derivatives as MMP-13 inhibitors |
| JP2006502114A (ja) * | 2002-07-17 | 2006-01-19 | ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー | マトリクスメタロプロテイナーゼ−13のアロステリックアルキン阻害薬とセレコキシブまたはバルデコキシブとの組合せ |
| AU2003247024A1 (en) * | 2002-07-17 | 2004-02-02 | Warner-Lambert Company Llc | Combination of an allosteric inhibitor of matrix metalloproteinase-13 with celecoxib or valdecoxib |
| EP1531904A1 (de) * | 2002-07-17 | 2005-05-25 | Warner-Lambert Company LLC | Pharmazeutische zusammensetzung enthaltend einen allosterischen matrix-metalloproteinase-13-inhibitor sowie einen cyclooxygenase-2-inhibitor der nicht celecoxib oder valdecoxib ist |
| MXPA05000754A (es) * | 2002-07-17 | 2005-04-19 | Warner Lambert Co | Combinacion de un inhibidor carboxilico alosterico de la metaloproteinasa de matriz-13 con celecoxib o valdecoxib. |
| PA8578101A1 (es) | 2002-08-13 | 2004-05-07 | Warner Lambert Co | Derivados de heterobiarilo como inhibidores de metaloproteinasa de la matriz |
| AU2003250475A1 (en) * | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | 5,6-fused 3,4-dihydropyrimidine-2-one derivatives as matrix metalloproteinase inhibitors |
| MXPA05001603A (es) | 2002-08-13 | 2005-04-25 | Warner Lambert Co | Derivados monociclicos como inhibidores de metaloproteinasa de matriz. |
| AU2003250466A1 (en) | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | 3-isoquinolinone derivatives as matrix metalloproteinase inhiitors |
| AU2003253165A1 (en) * | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Pyrimidine fused bicyclic metalloproteinase inhibitors |
| WO2004014866A1 (en) | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | Azaisoquinoline derivatives as matrix metalloproteinase inhibitors |
| WO2004014365A1 (en) * | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | Phthalimide derivatives as matrix metalloproteinase inhibitors |
| CA2497658A1 (en) | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | Chromone derivatives as matrix metalloproteinase inhibitors |
| MXPA05001784A (es) * | 2002-08-13 | 2005-04-25 | Warner Lambert Co | Derivados de isoquinolina como inhibidores de metaloproteinasa de matriz. |
| AU2003249540A1 (en) | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Fused bicyclic metalloproteinase inhibitors |
| AU2003249535A1 (en) * | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | 1,6-fused uracil derivatives as matrix metalloproteinase inhibitors |
| WO2004014923A1 (en) | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | Pyrimidinone fused bicyclic metalloproteinase inhibitors |
| AU2003253186A1 (en) | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Fused tetrahydropyridine derivatives as matrix metalloproteinase inhibitors |
| AU2003249539A1 (en) * | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Cyclic compounds containing zinc binding groups as matrix metalloproteinase inhibitors |
| ES2283851T3 (es) | 2002-08-13 | 2007-11-01 | Warner-Lambert Company Llc | Derivados de pirimidin-2,4-diona como inhibidores de las metaloproteinasas de matriz. |
| AU2003249477A1 (en) * | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Heterobicylcic metalloproteinase inhibitors |
| PL375044A1 (en) * | 2002-11-02 | 2005-11-14 | Sanofi-Aventis Deutschland Gmbh | Novel pyrimidine-4,6-dicarboxamides for the selective inhibition of collagenases |
| US20040142950A1 (en) * | 2003-01-17 | 2004-07-22 | Bunker Amy Mae | Amide and ester matrix metalloproteinase inhibitors |
| JP4667384B2 (ja) | 2003-10-07 | 2011-04-13 | レノビス, インコーポレイテッド | イオンチャネルリガンドとしてのアミド誘導体および薬学的組成物、ならびにこれらを使用する方法 |
| US20060247231A1 (en) * | 2003-12-18 | 2006-11-02 | Warner-Lambert Company Llc | Amide and ester matrix metalloproteinase inhibitors |
| BR122015027139B1 (pt) | 2004-01-28 | 2016-05-10 | Mitsui Chemicals Inc | compostos derivados de amida, inseticida compreendendo os mesmos e método de uso dos mesmos como inseticida |
| US7576099B2 (en) | 2005-02-28 | 2009-08-18 | Renovis, Inc. | Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same |
| US20070155738A1 (en) | 2005-05-20 | 2007-07-05 | Alantos Pharmaceuticals, Inc. | Heterobicyclic metalloprotease inhibitors |
| US20080021024A1 (en) * | 2006-06-29 | 2008-01-24 | Alantos Pharmaceuticals Holding, Inc. | Metalloprotease inhibitors |
| US20110105602A2 (en) | 2007-03-08 | 2011-05-05 | Daria Mochly-Rosen | Mitochondrial Aldehyde Dehydrogenase-2 Modulators and Methods of Use Thereof |
| CN102209541B (zh) * | 2008-09-08 | 2016-05-18 | 小利兰·斯坦福大学托管委员会 | 醛脱氢酶活性调节剂和其使用方法 |
| JP5657201B2 (ja) * | 2008-09-30 | 2015-01-21 | サンメディカル株式会社 | 酵素阻害作用または酵素阻害作用と抗菌作用とを有する歯科用組成物 |
| CN102202669A (zh) | 2008-10-28 | 2011-09-28 | 利兰·斯坦福青年大学托管委员会 | 醛脱氢酶调节剂及其使用方法 |
| AR076177A1 (es) * | 2009-04-01 | 2011-05-26 | Colgate Palmolive Co | MÉTODO PARA IDENTIFICAR UN COMPUESTO uTIL PARA TRATAR UNA ENFERMEDAD O CONDICIoN DE LA CAVIDAD ORAL |
| GB201021103D0 (en) | 2010-12-13 | 2011-01-26 | Univ Leuven Kath | New compounds for the treatment of neurodegenerative diseases |
| US10457659B2 (en) | 2011-04-29 | 2019-10-29 | The Board Of Trustees Of The Leland Stanford Junior University | Compositions and methods for increasing proliferation of adult salivary stem cells |
| CN105358531B (zh) | 2013-03-14 | 2017-11-14 | 利兰-斯坦福大学初级学院的董事会 | 线粒体醛脱氢酶‑2调节剂和其使用方法 |
| BR112018073524A2 (pt) * | 2016-05-24 | 2019-05-28 | Glaxosmithkline Ip No 2 Ltd | composto, composição farmacêutica, combinação, uso de um composto ou um sal farmaceuticamente aceitável do mesmo, e, método de tratamento de uma doença ou condição. |
| GB201703282D0 (en) * | 2017-03-01 | 2017-04-12 | Glaxosmithkline Intellectual Property (No 2) Ltd | Compounds |
| GB201908453D0 (en) | 2019-06-12 | 2019-07-24 | Enterprise Therapeutics Ltd | Compounds for treating respiratory disease |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1149356B (de) * | 1955-03-24 | 1963-05-30 | Bayer Ag | Verfahren zur Herstellung von N-substituierten Thiosaeureamiden |
| US4971986A (en) * | 1988-03-25 | 1990-11-20 | Ciba-Geigy Corporation | Arylhydrazones useful as SAMDC inhibitors |
| US5219847A (en) * | 1989-06-12 | 1993-06-15 | Shiseido Company, Ltd. | Antipruritic composition |
| DE3924093A1 (de) * | 1989-07-20 | 1991-02-07 | Hoechst Ag | N,n'-bis(alkoxy-alkyl)-pyridin-2,4-dicarbonsaeurediamide, verfahren zu deren herstellung sowie deren verwendung |
| US5425289A (en) | 1993-10-21 | 1995-06-20 | Snap-On Incorporated | Bung tool |
| DE3931432A1 (de) | 1989-09-21 | 1991-04-04 | Hoechst Ag | Pyrimidin-4,6-dicarbonsaeurediamide, verfahren zu deren herstellung sowie verwendung derselben sowie arzneimittel auf basis dieser verbindungen |
| DE4020570A1 (de) * | 1990-06-28 | 1992-01-02 | Hoechst Ag | 2,4- und 2,5-substituierte pyridin-n-oxide, verfahren zu deren herstellung sowie deren verwendung |
| US5260323A (en) * | 1990-06-28 | 1993-11-09 | Hoechst Aktiengesellschaft | 2,4- and 2,5-substituted pyridine-N-oxides, processes for their preparation and their use |
| US5716965A (en) * | 1991-05-22 | 1998-02-10 | Pfizer Inc. | Substituted 3-aminoquinuclidines |
| AU658898B2 (en) * | 1991-05-22 | 1995-05-04 | Pfizer Inc. | Substituted 3-aminoquinuclidines |
| EP0541042A1 (de) * | 1991-11-05 | 1993-05-12 | Hoechst Aktiengesellschaft | Pyridin-2,4- und 2,5-dicarbonsäureamide und deren Derivate, Verfahren zu ihrer Herstellung sowie deren Verwendung als Arzneimittel |
| US6008243A (en) * | 1996-10-24 | 1999-12-28 | Agouron Pharmaceuticals, Inc. | Metalloproteinase inhibitors, pharmaceutical compositions containing them, and their use |
| JP2001504462A (ja) * | 1996-11-12 | 2001-04-03 | ビイク グルデン ロンベルク ヒエーミツシエ フアブリーク ゲゼルシヤフト ミツト ベシユレンクテル ハフツング | ホスホジエステラーゼ阻害剤としての(2,3―ジヒドロベンゾフラニル)―チアゾール |
| NZ334897A (en) | 1996-12-09 | 2001-02-23 | Warner Lambert Co | Medicaments for treating and preventing heart failure and ventricular dilatation |
| JPH11199512A (ja) | 1997-10-24 | 1999-07-27 | Pfizer Prod Inc | 変形性関節症および他のmmp媒介疾患の治療のためのmmp−13選択的阻害剤の使用 |
| UA59453C2 (uk) | 1998-08-12 | 2003-09-15 | Пфайзер Продактс Інк. | Похідні гідроксипіпеколат гідроксамової кислоти як інгібітори матричних металопротеїназ |
| US6300341B1 (en) * | 1998-09-30 | 2001-10-09 | The Procter & Gamble Co. | 2-substituted heterocyclic sulfonamides |
| US6307049B1 (en) * | 1998-09-30 | 2001-10-23 | The Procter & Gamble Co. | Heterocyclic 2-substituted ketoamides |
| EP1165496B1 (de) * | 1999-03-31 | 2003-07-09 | Basf Aktiengesellschaft | Substituierte anilinverbindungen |
| PA8498701A1 (es) | 1999-08-12 | 2002-08-26 | Pfizer Prod Inc | Pirimidina-2,4,6-trionas inhibidores de metaloproteinasas |
| US6307490B1 (en) * | 1999-09-30 | 2001-10-23 | The Engineering Consortium, Inc. | Digital to analog converter trim apparatus and method |
| US6934639B1 (en) | 2000-02-25 | 2005-08-23 | Wyeth | Methods for designing agents that interact with MMP-13 |
| EP1138680A1 (de) | 2000-03-29 | 2001-10-04 | Pfizer Products Inc. | Gem substituierte Sulfonylhydroxamsäuren mit MMP inhibierender Wirkung |
| US6916846B2 (en) * | 2000-05-12 | 2005-07-12 | Merck & Co. Inc. | Coumermycin analogs as chemical dimerizers of chimeric proteins |
| CA2425283A1 (en) | 2000-10-26 | 2002-05-02 | Pfizer Products Inc. | Spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors |
| CA2425280A1 (en) | 2000-10-26 | 2002-05-02 | Pfizer Products Inc. | Pyrimidine-2,4,6-trione metalloproteinase inhibitors |
| DOP2002000333A (es) | 2001-02-14 | 2002-09-30 | Warner Lambert Co | Derivados de acido isoftalico como inhibidores de metaloproteinasas de la matriz |
| WO2002064571A1 (en) | 2001-02-14 | 2002-08-22 | Warner-Lambert Company Llc | Pyrimidine matrix metalloproteinase inhibitors |
| PA8539301A1 (es) | 2001-02-14 | 2002-09-30 | Warner Lambert Co | Inhibidores de la metaloproteinasa de la matriz |
| US6924276B2 (en) | 2001-09-10 | 2005-08-02 | Warner-Lambert Company | Diacid-substituted heteroaryl derivatives as matrix metalloproteinase inhibitors |
| DE10160357A1 (de) | 2001-12-08 | 2003-06-18 | Aventis Pharma Gmbh | Verwendung von Pyridin-2,4-dicarbonsäurediamiden und Pyrimidin-4,6-dicarbonsäurediamiden zur selektiven Inhibierung von Kollagenasen |
| US6933298B2 (en) | 2001-12-08 | 2005-08-23 | Aventis Pharma Deutschland Gmbh | Pyridine-2,4-dicarboxylic acid diamides and pyrimidine-4,6-dicarboxylic acid diamides and the use thereof for selectively inhibiting collagenases |
| US20050004111A1 (en) * | 2003-01-03 | 2005-01-06 | Aventis Pharma Deutschland Gmbh | Selective MMP-13 inhibitors |
-
2002
- 2002-01-24 DO DO2002000332A patent/DOP2002000332A/es unknown
- 2002-02-01 PA PA20028538201A patent/PA8538201A1/es unknown
- 2002-02-04 EA EA200300763A patent/EA200300763A1/ru unknown
- 2002-02-04 IL IL15691202A patent/IL156912A0/xx unknown
- 2002-02-04 ES ES02716263T patent/ES2283540T3/es not_active Expired - Lifetime
- 2002-02-04 EP EP02716263A patent/EP1362033B1/de not_active Expired - Lifetime
- 2002-02-04 JP JP2002564501A patent/JP4249981B2/ja not_active Expired - Fee Related
- 2002-02-04 DE DE60219286T patent/DE60219286T2/de not_active Expired - Lifetime
- 2002-02-04 OA OA1200300180A patent/OA12544A/en unknown
- 2002-02-04 CZ CZ20032143A patent/CZ20032143A3/cs unknown
- 2002-02-04 WO PCT/IB2002/000345 patent/WO2002064568A1/en not_active Ceased
- 2002-02-04 MX MXPA03006204A patent/MXPA03006204A/es active IP Right Grant
- 2002-02-04 CA CA002434982A patent/CA2434982A1/en not_active Abandoned
- 2002-02-04 AP APAP/P/2003/002840A patent/AP2003002840A0/en unknown
- 2002-02-04 BR BR0207863-5A patent/BR0207863A/pt not_active IP Right Cessation
- 2002-02-04 EE EEP200300391A patent/EE200300391A/xx unknown
- 2002-02-04 AT AT02716263T patent/ATE358667T1/de not_active IP Right Cessation
- 2002-02-04 GT GT200200014A patent/GT200200014A/es unknown
- 2002-02-04 KR KR10-2003-7010682A patent/KR20030075196A/ko not_active Ceased
- 2002-02-04 SK SK1002-2003A patent/SK10022003A3/sk unknown
- 2002-02-04 HU HU0303152A patent/HUP0303152A2/hu unknown
- 2002-02-04 CN CNA028049454A patent/CN1537101A/zh active Pending
- 2002-02-04 PL PL02365098A patent/PL365098A1/xx not_active Application Discontinuation
- 2002-02-08 US US10/071,073 patent/US6881743B2/en not_active Expired - Fee Related
- 2002-02-11 HN HN2002000025A patent/HN2002000025A/es unknown
- 2002-02-11 HN HN2002000028A patent/HN2002000028A/es unknown
- 2002-02-13 TN TNTNSN02012A patent/TNSN02012A1/fr unknown
- 2002-02-13 UY UY27167A patent/UY27167A1/es not_active Application Discontinuation
- 2002-02-13 PE PE2002000119A patent/PE20020995A1/es not_active Application Discontinuation
- 2002-02-13 AR ARP020100478A patent/AR035936A1/es unknown
-
2003
- 2003-07-10 IS IS6871A patent/IS6871A/is unknown
- 2003-07-16 EC EC2003004691A patent/ECSP034691A/es unknown
- 2003-08-05 ZA ZA200306041A patent/ZA200306041B/xx unknown
- 2003-08-05 CR CR7048A patent/CR7048A/es not_active Application Discontinuation
- 2003-08-05 MA MA27263A patent/MA26989A1/fr unknown
- 2003-08-12 NO NO20033570A patent/NO20033570L/no not_active Application Discontinuation
- 2003-08-13 BG BG108089A patent/BG108089A/xx unknown
-
2004
- 2004-05-10 US US10/842,863 patent/US7015237B2/en not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| OA12544A (en) | Pyridine matrix metalloproteinase inhibitors. | |
| EP1368323B1 (de) | Pyrimidinmatrixmetalloproteinaseinhibitoren | |
| US6995151B2 (en) | Isophthalic acid derivatives as matrix metalloproteinase inhibitors | |
| US6849648B2 (en) | Phenylene alkyne matrix metalloproteinase inhibitors | |
| US6686355B2 (en) | Biphenyl sulfonamides useful as matrix metalloproteinase inhibitors | |
| EP1233017B1 (de) | Als Matrix-Metalloproteinasehemmer verwendbare tricyclische Sulfonamide | |
| US6555535B2 (en) | Tricyclic biphenyl sulfonamide matrix metalloproteinase inhibitors | |
| AU2002226642A1 (en) | Pyridine matrix metalloproteinase inhibitors |