JP2006510673A5 - - Google Patents
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- JP2006510673A5 JP2006510673A5 JP2004559413A JP2004559413A JP2006510673A5 JP 2006510673 A5 JP2006510673 A5 JP 2006510673A5 JP 2004559413 A JP2004559413 A JP 2004559413A JP 2004559413 A JP2004559413 A JP 2004559413A JP 2006510673 A5 JP2006510673 A5 JP 2006510673A5
- Authority
- JP
- Japan
- Prior art keywords
- phenyl
- alkyl
- indol
- oxo
- perfluoroalkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 150000001875 compounds Chemical class 0.000 claims description 41
- 125000000217 alkyl group Chemical group 0.000 claims description 25
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical group 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 23
- -1 -CH 2 -heteroaryl Chemical group 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 14
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 12
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 12
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 6
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 6
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 150000002148 esters Chemical group 0.000 claims description 5
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- TVDZLGHJDRXSPR-UHFFFAOYSA-N 2-[1-(cyclobutylmethyl)-5-prop-2-enoxyindol-3-yl]-2-oxoacetic acid Chemical compound C12=CC=C(OCC=C)C=C2C(C(=O)C(=O)O)=CN1CC1CCC1 TVDZLGHJDRXSPR-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 2
- BHYSBKUSUMQEDF-UHFFFAOYSA-N 1-[4-[(5-ethoxycarbonylfuran-2-yl)methoxy]phenyl]-5-fluoro-2-formylindole-3-carboxylic acid Chemical compound O1C(C(=O)OCC)=CC=C1COC1=CC=C(N2C3=CC=C(F)C=C3C(C(O)=O)=C2C=O)C=C1 BHYSBKUSUMQEDF-UHFFFAOYSA-N 0.000 claims description 2
- MTIRVIPDQBZVPX-UHFFFAOYSA-N 2-(1-benzyl-5-phenylmethoxyindol-3-yl)-2-oxoacetic acid Chemical compound C12=CC=C(OCC=3C=CC=CC=3)C=C2C(C(=O)C(=O)O)=CN1CC1=CC=CC=C1 MTIRVIPDQBZVPX-UHFFFAOYSA-N 0.000 claims description 2
- DRPFVQGQDQAUQP-UHFFFAOYSA-N 2-[1,5-bis[4-(trifluoromethoxy)phenyl]indol-3-yl]-2-oxoacetic acid Chemical compound C12=CC=C(C=3C=CC(OC(F)(F)F)=CC=3)C=C2C(C(=O)C(=O)O)=CN1C1=CC=C(OC(F)(F)F)C=C1 DRPFVQGQDQAUQP-UHFFFAOYSA-N 0.000 claims description 2
- CVAKCQKTWWHSDL-UHFFFAOYSA-N 2-[1-[4-[(2,4-dichlorophenyl)methoxy]phenyl]-5-methylindol-3-yl]-2-oxoacetic acid Chemical compound C1=C(C(=O)C(O)=O)C2=CC(C)=CC=C2N1C(C=C1)=CC=C1OCC1=CC=C(Cl)C=C1Cl CVAKCQKTWWHSDL-UHFFFAOYSA-N 0.000 claims description 2
- ZJNNARNIAJBQIG-UHFFFAOYSA-N 2-[1-[4-[(3,5-dimethoxyphenyl)methoxy]phenyl]-5-fluoroindol-3-yl]-2-oxoacetic acid Chemical compound COC1=CC(OC)=CC(COC=2C=CC(=CC=2)N2C3=CC=C(F)C=C3C(C(=O)C(O)=O)=C2)=C1 ZJNNARNIAJBQIG-UHFFFAOYSA-N 0.000 claims description 2
- GNNWWHTUVNXPSE-UHFFFAOYSA-N 2-[1-[4-[(3-chlorophenyl)methoxy]phenyl]-5-methylindol-3-yl]-2-oxoacetic acid Chemical compound C1=C(C(=O)C(O)=O)C2=CC(C)=CC=C2N1C(C=C1)=CC=C1OCC1=CC=CC(Cl)=C1 GNNWWHTUVNXPSE-UHFFFAOYSA-N 0.000 claims description 2
- TZHYUUMDKOHMCF-UHFFFAOYSA-N 2-[1-[4-[(4-cyanophenyl)methoxy]phenyl]-5-fluoroindol-3-yl]-2-oxoacetic acid Chemical compound C12=CC=C(F)C=C2C(C(=O)C(=O)O)=CN1C(C=C1)=CC=C1OCC1=CC=C(C#N)C=C1 TZHYUUMDKOHMCF-UHFFFAOYSA-N 0.000 claims description 2
- ATEZGFIJQUZCGK-UHFFFAOYSA-N 2-[1-[4-[(4-cyanophenyl)methoxy]phenyl]indol-3-yl]-2-oxoacetic acid Chemical compound C12=CC=CC=C2C(C(=O)C(=O)O)=CN1C(C=C1)=CC=C1OCC1=CC=C(C#N)C=C1 ATEZGFIJQUZCGK-UHFFFAOYSA-N 0.000 claims description 2
- FNJSRAMSUGWQOE-UHFFFAOYSA-N 2-[1-[4-[(4-tert-butylphenyl)methoxy]phenyl]-5-methylindol-3-yl]-2-oxoacetic acid Chemical compound C1=C(C(=O)C(O)=O)C2=CC(C)=CC=C2N1C(C=C1)=CC=C1OCC1=CC=C(C(C)(C)C)C=C1 FNJSRAMSUGWQOE-UHFFFAOYSA-N 0.000 claims description 2
- FEGXMJMFVUACQW-UHFFFAOYSA-N 2-[1-benzyl-5-[2-chloro-4-(trifluoromethyl)phenoxy]indol-3-yl]-2-oxoacetic acid Chemical compound C12=CC=C(OC=3C(=CC(=CC=3)C(F)(F)F)Cl)C=C2C(C(=O)C(=O)O)=CN1CC1=CC=CC=C1 FEGXMJMFVUACQW-UHFFFAOYSA-N 0.000 claims description 2
- ODXJEZZYAFVFOA-UHFFFAOYSA-N 2-[5-[2-(4-fluorophenyl)ethoxy]-1-[(4-fluorophenyl)methyl]indol-3-yl]-2-oxoacetic acid Chemical compound C12=CC=C(OCCC=3C=CC(F)=CC=3)C=C2C(C(=O)C(=O)O)=CN1CC1=CC=C(F)C=C1 ODXJEZZYAFVFOA-UHFFFAOYSA-N 0.000 claims description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- YQKWTFPVGFGNJW-UHFFFAOYSA-N 5-chloro-1-[3-[(5-ethoxycarbonylfuran-2-yl)methoxy]phenyl]-2-formylindole-3-carboxylic acid Chemical compound O1C(C(=O)OCC)=CC=C1COC1=CC=CC(N2C3=CC=C(Cl)C=C3C(C(O)=O)=C2C=O)=C1 YQKWTFPVGFGNJW-UHFFFAOYSA-N 0.000 claims description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims 21
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims 4
- 229920001774 Perfluoroether Polymers 0.000 claims 4
- 208000007536 Thrombosis Diseases 0.000 claims 3
- 206010003658 Atrial Fibrillation Diseases 0.000 claims 2
- 206010051055 Deep vein thrombosis Diseases 0.000 claims 2
- 206010047249 Venous thrombosis Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 208000035475 disorder Diseases 0.000 claims 2
- 208000031225 myocardial ischemia Diseases 0.000 claims 2
- 230000002093 peripheral effect Effects 0.000 claims 2
- XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 claims 1
- UYGWFCIWPIVBJA-UHFFFAOYSA-N 2-[1-[4-[(2,6-dichloropyridin-4-yl)methoxy]phenyl]-5-methylindol-3-yl]-2-oxoacetic acid Chemical compound C1=C(C(=O)C(O)=O)C2=CC(C)=CC=C2N1C(C=C1)=CC=C1OCC1=CC(Cl)=NC(Cl)=C1 UYGWFCIWPIVBJA-UHFFFAOYSA-N 0.000 claims 1
- LSJPCRCLJHFBJP-UHFFFAOYSA-N 2-oxo-2-[1-[4-[[4-(thiadiazol-4-yl)phenyl]methoxy]phenyl]indol-3-yl]acetic acid Chemical compound C12=CC=CC=C2C(C(=O)C(=O)O)=CN1C(C=C1)=CC=C1OCC(C=C1)=CC=C1C1=CSN=N1 LSJPCRCLJHFBJP-UHFFFAOYSA-N 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- 208000031104 Arterial Occlusive disease Diseases 0.000 claims 1
- 206010003162 Arterial injury Diseases 0.000 claims 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 claims 1
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- 206010008132 Cerebral thrombosis Diseases 0.000 claims 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 201000001429 Intracranial Thrombosis Diseases 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 102000010752 Plasminogen Inactivators Human genes 0.000 claims 1
- 108010077971 Plasminogen Inactivators Proteins 0.000 claims 1
- 206010036049 Polycystic ovaries Diseases 0.000 claims 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 claims 1
- 208000021328 arterial occlusion Diseases 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 230000015271 coagulation Effects 0.000 claims 1
- 238000005345 coagulation Methods 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000020764 fibrinolysis Effects 0.000 claims 1
- 239000003527 fibrinolytic agent Substances 0.000 claims 1
- 230000003480 fibrinolytic effect Effects 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 230000007505 plaque formation Effects 0.000 claims 1
- 239000002797 plasminogen activator inhibitor Substances 0.000 claims 1
- 201000010065 polycystic ovary syndrome Diseases 0.000 claims 1
- 208000005069 pulmonary fibrosis Diseases 0.000 claims 1
- 201000002793 renal fibrosis Diseases 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 238000001356 surgical procedure Methods 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 230000009424 thromboembolic effect Effects 0.000 claims 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 1
- 239000000243 solution Substances 0.000 description 17
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 11
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 11
- 229960000187 tissue plasminogen activator Drugs 0.000 description 11
- 102000012335 Plasminogen Activator Inhibitor 1 Human genes 0.000 description 10
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 239000012043 crude product Substances 0.000 description 8
- 239000000725 suspension Substances 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- 238000003556 assay Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- 101000609255 Homo sapiens Plasminogen activator inhibitor 1 Proteins 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- 102000043283 human SERPINE1 Human genes 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- SYSZENVIJHPFNL-UHFFFAOYSA-N (alpha-D-mannosyl)7-beta-D-mannosyl-diacetylchitobiosyl-L-asparagine, isoform B (protein) Chemical compound COC1=CC=C(I)C=C1 SYSZENVIJHPFNL-UHFFFAOYSA-N 0.000 description 2
- STICGQRKPLURKK-UHFFFAOYSA-N 1,5-bis[4-(trifluoromethoxy)phenyl]indole Chemical compound C1=CC(OC(F)(F)F)=CC=C1C1=CC=C(N(C=C2)C=3C=CC(OC(F)(F)F)=CC=3)C2=C1 STICGQRKPLURKK-UHFFFAOYSA-N 0.000 description 2
- CJJDJQFZVLGJLB-UHFFFAOYSA-N 1-(4-methoxyphenyl)indole Chemical compound C1=CC(OC)=CC=C1N1C2=CC=CC=C2C=C1 CJJDJQFZVLGJLB-UHFFFAOYSA-N 0.000 description 2
- UMLFTCYAQPPZER-UHFFFAOYSA-N 4-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=C(C#N)C=C1 UMLFTCYAQPPZER-UHFFFAOYSA-N 0.000 description 2
- NCLYASZGRPCNLM-UHFFFAOYSA-N 4-indol-1-ylphenol Chemical compound C1=CC(O)=CC=C1N1C2=CC=CC=C2C=C1 NCLYASZGRPCNLM-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N methyl pentane Natural products CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- BTHIGJGJAPYFSJ-UHFFFAOYSA-N 1-(bromomethyl)-3,5-dimethoxybenzene Chemical compound COC1=CC(CBr)=CC(OC)=C1 BTHIGJGJAPYFSJ-UHFFFAOYSA-N 0.000 description 1
- ZKSOJQDNSNJIQW-UHFFFAOYSA-N 1-(bromomethyl)-3-methoxybenzene Chemical compound COC1=CC=CC(CBr)=C1 ZKSOJQDNSNJIQW-UHFFFAOYSA-N 0.000 description 1
- QZNQSIHCDAGZIA-UHFFFAOYSA-N 1-(bromomethyl)-4-tert-butylbenzene Chemical compound CC(C)(C)C1=CC=C(CBr)C=C1 QZNQSIHCDAGZIA-UHFFFAOYSA-N 0.000 description 1
- GYBMJVZOZTVDKS-UHFFFAOYSA-N 1-iodo-2-(trifluoromethoxy)benzene Chemical compound FC(F)(F)OC1=CC=CC=C1I GYBMJVZOZTVDKS-UHFFFAOYSA-N 0.000 description 1
- RSHBAGGASAJQCH-UHFFFAOYSA-N 1-iodo-3-methoxybenzene Chemical compound COC1=CC=CC(I)=C1 RSHBAGGASAJQCH-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- CTASQNRTEQOJDK-UHFFFAOYSA-N 2-(4-indol-1-ylphenoxy)-2-phenylacetonitrile Chemical compound C1=CC=C(C=C1)C(C#N)OC2=CC=C(C=C2)N3C=CC4=CC=CC=C43 CTASQNRTEQOJDK-UHFFFAOYSA-N 0.000 description 1
- AFMCAWBAQSCVIJ-UHFFFAOYSA-N 2-[5-chloro-1-[3-[(3,5-dimethoxyphenyl)methoxy]phenyl]indol-3-yl]-2-oxoacetic acid Chemical compound COC1=CC(OC)=CC(COC=2C=C(C=CC=2)N2C3=CC=C(Cl)C=C3C(C(=O)C(O)=O)=C2)=C1 AFMCAWBAQSCVIJ-UHFFFAOYSA-N 0.000 description 1
- VYWNKGPTZQDPSH-UHFFFAOYSA-N 2-[5-chloro-1-[3-[(4-cyanophenyl)methoxy]phenyl]indol-3-yl]-2-oxoacetic acid Chemical compound C12=CC=C(Cl)C=C2C(C(=O)C(=O)O)=CN1C(C=1)=CC=CC=1OCC1=CC=C(C#N)C=C1 VYWNKGPTZQDPSH-UHFFFAOYSA-N 0.000 description 1
- MBYOXHQNYRONJG-UHFFFAOYSA-N 2-[5-chloro-1-[3-[[2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl]methoxy]phenyl]indol-3-yl]-2-oxoacetic acid Chemical compound C12=CC=C(Cl)C=C2C(C(=O)C(=O)O)=CN1C(C=1)=CC=CC=1OCC1=C(F)C(F)=C(C(F)(F)F)C(F)=C1F MBYOXHQNYRONJG-UHFFFAOYSA-N 0.000 description 1
- ZTFBRYAJTSQNQE-UHFFFAOYSA-N 2-[5-chloro-1-[3-[[4-(thiadiazol-4-yl)phenyl]methoxy]phenyl]indol-3-yl]-2-oxoacetic acid Chemical compound C12=CC=C(Cl)C=C2C(C(=O)C(=O)O)=CN1C(C=1)=CC=CC=1OCC(C=C1)=CC=C1C1=CSN=N1 ZTFBRYAJTSQNQE-UHFFFAOYSA-N 0.000 description 1
- XDKGMGJZRFOZRV-UHFFFAOYSA-N 4-(bromomethyl)-2,6-dichloropyridine Chemical compound ClC1=CC(CBr)=CC(Cl)=N1 XDKGMGJZRFOZRV-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
- PCQVWCHZMARESC-UHFFFAOYSA-N 5-[4-(trifluoromethoxy)phenyl]-1h-indole Chemical compound C1=CC(OC(F)(F)F)=CC=C1C1=CC=C(NC=C2)C2=C1 PCQVWCHZMARESC-UHFFFAOYSA-N 0.000 description 1
- MYTGFBZJLDLWQG-UHFFFAOYSA-N 5-chloro-1h-indole Chemical compound ClC1=CC=C2NC=CC2=C1 MYTGFBZJLDLWQG-UHFFFAOYSA-N 0.000 description 1
- ODFFPRGJZRXNHZ-UHFFFAOYSA-N 5-fluoroindole Chemical compound FC1=CC=C2NC=CC2=C1 ODFFPRGJZRXNHZ-UHFFFAOYSA-N 0.000 description 1
- LMIQERWZRIFWNZ-UHFFFAOYSA-N 5-hydroxyindole Chemical compound OC1=CC=C2NC=CC2=C1 LMIQERWZRIFWNZ-UHFFFAOYSA-N 0.000 description 1
- YPKBCLZFIYBSHK-UHFFFAOYSA-N 5-methylindole Chemical compound CC1=CC=C2NC=CC2=C1 YPKBCLZFIYBSHK-UHFFFAOYSA-N 0.000 description 1
- CJOAAJIGYICLNT-UHFFFAOYSA-N 5-prop-2-enoxy-1h-indole Chemical compound C=CCOC1=CC=C2NC=CC2=C1 CJOAAJIGYICLNT-UHFFFAOYSA-N 0.000 description 1
- ONYNOPPOVKYGRS-UHFFFAOYSA-N 6-methylindole Natural products CC1=CC=C2C=CNC2=C1 ONYNOPPOVKYGRS-UHFFFAOYSA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 101000801481 Homo sapiens Tissue-type plasminogen activator Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
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| US7141592B2 (en) * | 2003-09-25 | 2006-11-28 | Wyeth | Substituted oxadiazolidinediones |
| US7265148B2 (en) * | 2003-09-25 | 2007-09-04 | Wyeth | Substituted pyrrole-indoles |
| US7446201B2 (en) * | 2003-09-25 | 2008-11-04 | Wyeth | Substituted heteroaryl benzofuran acids |
| US7420083B2 (en) * | 2003-09-25 | 2008-09-02 | Wyeth | Substituted aryloximes |
| US7342039B2 (en) * | 2003-09-25 | 2008-03-11 | Wyeth | Substituted indole oximes |
| US7582773B2 (en) * | 2003-09-25 | 2009-09-01 | Wyeth | Substituted phenyl indoles |
| US7351726B2 (en) * | 2003-09-25 | 2008-04-01 | Wyeth | Substituted oxadiazolidinediones |
| US7268159B2 (en) * | 2003-09-25 | 2007-09-11 | Wyeth | Substituted indoles |
| US7163954B2 (en) * | 2003-09-25 | 2007-01-16 | Wyeth | Substituted naphthyl benzothiophene acids |
| JP2007508367A (ja) | 2003-10-16 | 2007-04-05 | ファイザー・プロダクツ・インク | ３−アザビシクロ［３．１．０］ヘキサン誘導体の製造方法 |
-
2003
- 2003-12-09 DE DE60324183T patent/DE60324183D1/de not_active Expired - Lifetime
- 2003-12-09 CA CA002509191A patent/CA2509191A1/en not_active Abandoned
- 2003-12-09 WO PCT/US2003/038934 patent/WO2004052854A2/en not_active Ceased
- 2003-12-09 MX MXPA05006283A patent/MXPA05006283A/es active IP Right Grant
- 2003-12-09 EP EP03812847A patent/EP1569901B1/en not_active Expired - Lifetime
- 2003-12-09 CN CNA2003801054475A patent/CN1723198A/zh not_active Withdrawn
- 2003-12-09 AU AU2003296324A patent/AU2003296324A1/en not_active Withdrawn
- 2003-12-09 AT AT03812847T patent/ATE411288T1/de not_active IP Right Cessation
- 2003-12-09 BR BR0316585-0A patent/BR0316585A/pt not_active IP Right Cessation
- 2003-12-09 US US10/731,308 patent/US7259182B2/en not_active Expired - Fee Related
- 2003-12-09 DK DK03812847T patent/DK1569901T3/da active
- 2003-12-09 JP JP2004559413A patent/JP2006510673A/ja active Pending
- 2003-12-09 ES ES03812847T patent/ES2314289T3/es not_active Expired - Lifetime
-
2007
- 2007-07-11 US US11/827,579 patent/US7674818B2/en not_active Expired - Fee Related
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