EA009696B1 - Замещенные нафтилиндольные производные в качестве ингибиторов ингибитора активатора плазминогена типа 1 (pai-1) - Google Patents
Замещенные нафтилиндольные производные в качестве ингибиторов ингибитора активатора плазминогена типа 1 (pai-1) Download PDFInfo
- Publication number
- EA009696B1 EA009696B1 EA200400054A EA200400054A EA009696B1 EA 009696 B1 EA009696 B1 EA 009696B1 EA 200400054 A EA200400054 A EA 200400054A EA 200400054 A EA200400054 A EA 200400054A EA 009696 B1 EA009696 B1 EA 009696B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- carbon atoms
- compound according
- pharmaceutically acceptable
- alkyl
- pentyl
- Prior art date
Links
- XEQHAEZWPZICKJ-UHFFFAOYSA-N 2-naphthalen-1-yl-1h-indole Chemical class C1=CC=C2C(C3=CC4=CC=CC=C4N3)=CC=CC2=C1 XEQHAEZWPZICKJ-UHFFFAOYSA-N 0.000 title description 5
- 239000003112 inhibitor Substances 0.000 title description 4
- 102000010752 Plasminogen Inactivators Human genes 0.000 title 1
- 108010077971 Plasminogen Inactivators Proteins 0.000 title 1
- 239000002797 plasminogen activator inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 148
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 65
- 150000003839 salts Chemical class 0.000 claims abstract description 52
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 48
- 238000000034 method Methods 0.000 claims abstract description 38
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 26
- 239000000203 mixture Substances 0.000 claims abstract description 26
- 238000011282 treatment Methods 0.000 claims abstract description 24
- 150000002148 esters Chemical group 0.000 claims abstract description 21
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 20
- 150000002367 halogens Chemical class 0.000 claims abstract description 20
- 239000002253 acid Substances 0.000 claims abstract description 17
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 13
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims abstract description 7
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 7
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims abstract description 6
- PGRHXDWITVMQBC-UHFFFAOYSA-N dehydroacetic acid Natural products CC(=O)C1C(=O)OC(C)=CC1=O PGRHXDWITVMQBC-UHFFFAOYSA-N 0.000 claims abstract description 5
- PEQJBOMPGWYIRO-UHFFFAOYSA-N n-ethyl-3,4-dimethoxyaniline Chemical compound CCNC1=CC=C(OC)C(OC)=C1 PEQJBOMPGWYIRO-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- 239000001257 hydrogen Substances 0.000 claims description 38
- 150000002431 hydrogen Chemical class 0.000 claims description 26
- -1 (2-trifluoromethyl) benzyl Chemical group 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 150000003536 tetrazoles Chemical class 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 239000003527 fibrinolytic agent Substances 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 9
- 230000003480 fibrinolytic effect Effects 0.000 claims description 9
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 8
- 208000007536 Thrombosis Diseases 0.000 claims description 8
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 208000035475 disorder Diseases 0.000 claims description 7
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 5
- SRZKBYNNCQFTFV-UHFFFAOYSA-N 1-[(4-tert-butylphenyl)methyl]-3-pentyl-2-[6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]indole Chemical compound C=1C=C(C(C)(C)C)C=CC=1CN1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C=C2OCC1=NN=NN1 SRZKBYNNCQFTFV-UHFFFAOYSA-N 0.000 claims description 4
- OPHHMFYPCBMHNT-UHFFFAOYSA-N 1-[2-[5-bromo-6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]-3-pentylindol-1-yl]ethanone Chemical compound CC(=O)N1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C(Br)=C2OCC1=NN=NN1 OPHHMFYPCBMHNT-UHFFFAOYSA-N 0.000 claims description 4
- OUFFKANICABSLH-UHFFFAOYSA-N 1-[3-pentyl-2-[6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]indol-1-yl]ethanone Chemical compound CC(=O)N1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C=C2OCC1=NN=NN1 OUFFKANICABSLH-UHFFFAOYSA-N 0.000 claims description 4
- BUMHVJNXFPVEMO-UHFFFAOYSA-N 1-methyl-3-pentyl-2-[6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]indole Chemical compound CN1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C=C2OCC1=NN=NN1 BUMHVJNXFPVEMO-UHFFFAOYSA-N 0.000 claims description 4
- XVZQHCZCEZTSKR-UHFFFAOYSA-N 2-[1-bromo-6-(1-methyl-3-pentylindol-2-yl)naphthalen-2-yl]oxyacetic acid Chemical compound CN1C2=CC=CC=C2C(CCCCC)=C1C1=CC=C(C(Br)=C(OCC(O)=O)C=C2)C2=C1 XVZQHCZCEZTSKR-UHFFFAOYSA-N 0.000 claims description 4
- AAWAZICAXDCTFO-UHFFFAOYSA-N 2-[5-bromo-6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]-1-methyl-3-pentylindole Chemical compound CN1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C(Br)=C2OCC1=NN=NN1 AAWAZICAXDCTFO-UHFFFAOYSA-N 0.000 claims description 4
- NJGPFBJGXYWQGI-UHFFFAOYSA-N 2-[5-bromo-6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]-3-pentyl-1-[[2-(trifluoromethyl)phenyl]methyl]indole Chemical compound C=1C=CC=C(C(F)(F)F)C=1CN1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C(Br)=C2OCC1=NN=NN1 NJGPFBJGXYWQGI-UHFFFAOYSA-N 0.000 claims description 4
- SJDRBMZDCCSQEB-UHFFFAOYSA-N 3-pentyl-2-[6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]-1-[[2-(trifluoromethyl)phenyl]methyl]indole Chemical compound C=1C=CC=C(C(F)(F)F)C=1CN1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C=C2OCC1=NN=NN1 SJDRBMZDCCSQEB-UHFFFAOYSA-N 0.000 claims description 4
- 230000007062 hydrolysis Effects 0.000 claims description 4
- 238000006460 hydrolysis reaction Methods 0.000 claims description 4
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 208000011580 syndromic disease Diseases 0.000 claims description 4
- BPYFWNGIPZCIAT-UHFFFAOYSA-N 1-benzyl-2-[5-bromo-6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]-3-pentylindole Chemical compound C=1C=CC=CC=1CN1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C(Br)=C2OCC1=NN=NN1 BPYFWNGIPZCIAT-UHFFFAOYSA-N 0.000 claims description 3
- BDPXZFKVHDEPIQ-UHFFFAOYSA-N 1-benzyl-3-pentyl-2-[6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]indole Chemical compound C=1C=CC=CC=1CN1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C=C2OCC=1N=NNN=1 BDPXZFKVHDEPIQ-UHFFFAOYSA-N 0.000 claims description 3
- UGVQLUVEIHRNFD-UHFFFAOYSA-N 2-[5-bromo-6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]-1-[(4-tert-butylphenyl)methyl]-3-pentylindole Chemical compound C=1C=C(C(C)(C)C)C=CC=1CN1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C(Br)=C2OCC1=NN=NN1 UGVQLUVEIHRNFD-UHFFFAOYSA-N 0.000 claims description 3
- 206010003658 Atrial Fibrillation Diseases 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
- 210000001367 artery Anatomy 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 230000015271 coagulation Effects 0.000 claims description 3
- 238000005345 coagulation Methods 0.000 claims description 3
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 3
- 206010003178 Arterial thrombosis Diseases 0.000 claims description 2
- 208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 2
- 206010008132 Cerebral thrombosis Diseases 0.000 claims description 2
- 201000001429 Intracranial Thrombosis Diseases 0.000 claims description 2
- 206010047249 Venous thrombosis Diseases 0.000 claims description 2
- 150000001540 azides Chemical class 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 208000031225 myocardial ischemia Diseases 0.000 claims description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 201000010099 disease Diseases 0.000 abstract description 19
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 abstract description 8
- 230000002401 inhibitory effect Effects 0.000 abstract description 8
- 229910052799 carbon Inorganic materials 0.000 abstract description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 1
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
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Landscapes
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US29965101P | 2001-06-20 | 2001-06-20 | |
| PCT/US2002/021113 WO2003000684A1 (en) | 2001-06-20 | 2002-06-18 | Substituted naphthyl indole derivatives as inhibitors of plasminogen activator inhibitor type-1 (pai-1) |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200400054A1 EA200400054A1 (ru) | 2004-04-29 |
| EA009696B1 true EA009696B1 (ru) | 2008-02-28 |
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| EA200400054A EA009696B1 (ru) | 2001-06-20 | 2002-06-18 | Замещенные нафтилиндольные производные в качестве ингибиторов ингибитора активатора плазминогена типа 1 (pai-1) |
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|---|---|---|---|---|
| US7291639B2 (en) * | 2001-06-20 | 2007-11-06 | Wyeth | Aryloxy-acetic acid compounds useful as inhibitors of plasminogen activator inhibitor-1 (PAI-1) |
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- 2002-06-18 MX MXPA03011522A patent/MXPA03011522A/es active IP Right Grant
- 2002-06-18 BR BR0210504-7A patent/BR0210504A/pt not_active IP Right Cessation
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- 2002-06-18 WO PCT/US2002/021113 patent/WO2003000684A1/en not_active Ceased
- 2002-06-18 CN CNB028123913A patent/CN1280288C/zh not_active Expired - Fee Related
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- 2002-06-18 UA UA2004010350A patent/UA78708C2/uk unknown
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2003
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