KR20060015556A - 에스트로겐 수용체 리간드로서의3-(1-나프틸)-2-시아노프로판산 유도체 - Google Patents
에스트로겐 수용체 리간드로서의3-(1-나프틸)-2-시아노프로판산 유도체 Download PDFInfo
- Publication number
- KR20060015556A KR20060015556A KR1020057020599A KR20057020599A KR20060015556A KR 20060015556 A KR20060015556 A KR 20060015556A KR 1020057020599 A KR1020057020599 A KR 1020057020599A KR 20057020599 A KR20057020599 A KR 20057020599A KR 20060015556 A KR20060015556 A KR 20060015556A
- Authority
- KR
- South Korea
- Prior art keywords
- methyl
- naphthyl
- methoxyphenyl
- cyano
- propanoate
- 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.)
- Withdrawn
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- 108010038795 estrogen receptors Proteins 0.000 title description 11
- 102000015694 estrogen receptors Human genes 0.000 title description 11
- 239000003446 ligand Substances 0.000 title description 6
- NUSBDSQULWMBEU-UHFFFAOYSA-N 2-cyano-3-naphthalen-1-ylpropanoic acid Chemical class C1=CC=C2C(CC(C(=O)O)C#N)=CC=CC2=C1 NUSBDSQULWMBEU-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 380
- 150000003839 salts Chemical class 0.000 claims abstract description 42
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 15
- 201000010099 disease Diseases 0.000 claims abstract description 12
- 208000010125 myocardial infarction Diseases 0.000 claims abstract description 11
- 206010007559 Cardiac failure congestive Diseases 0.000 claims abstract description 10
- 206010019280 Heart failures Diseases 0.000 claims abstract description 10
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 10
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 9
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 9
- 206010003246 arthritis Diseases 0.000 claims abstract description 9
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims abstract description 8
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 8
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 7
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 227
- -1 2,5-dimethoxyphenyl Chemical group 0.000 claims description 129
- 125000004432 carbon atom Chemical group C* 0.000 claims description 93
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 92
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 78
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 75
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 62
- 125000000217 alkyl group Chemical group 0.000 claims description 58
- 229910052757 nitrogen Inorganic materials 0.000 claims description 58
- 229910052717 sulfur Inorganic materials 0.000 claims description 46
- PHRABVHYUHIYGY-UHFFFAOYSA-N 1-methylnaphthalene Chemical group C1=CC=C2C([CH2])=CC=CC2=C1 PHRABVHYUHIYGY-UHFFFAOYSA-N 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 36
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 36
- 125000003118 aryl group Chemical group 0.000 claims description 34
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 29
- 229910052786 argon Inorganic materials 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 239000000126 substance Substances 0.000 claims description 24
- 150000002431 hydrogen Chemical class 0.000 claims description 22
- 229920006395 saturated elastomer Polymers 0.000 claims description 22
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 14
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 14
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 150000001412 amines Chemical class 0.000 claims description 11
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 11
- 125000004001 thioalkyl group Chemical group 0.000 claims description 11
- 125000004122 cyclic group Chemical group 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 9
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 9
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 claims description 8
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 8
- RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 claims description 8
- 229940126062 Compound A Drugs 0.000 claims description 7
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 7
- 235000010290 biphenyl Nutrition 0.000 claims description 7
- 125000004990 dihydroxyalkyl group Chemical group 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 6
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical class C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 claims description 6
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 claims description 5
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
- 229960002179 ephedrine Drugs 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- FNNBTMYOIIUTFI-UHFFFAOYSA-N tert-butyl 2-cyano-3-(2-methoxyphenyl)-3-naphthalen-1-ylpropanoate Chemical compound COC1=CC=CC=C1C(C(C#N)C(=O)OC(C)(C)C)C1=CC=CC2=CC=CC=C12 FNNBTMYOIIUTFI-UHFFFAOYSA-N 0.000 claims description 5
- 125000006280 2-bromobenzyl group Chemical group [H]C1=C([H])C(Br)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000005127 aryl alkoxy alkyl group Chemical group 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- CNKCDDUMEAKBMY-UHFFFAOYSA-N ethyl 2-cyano-3-(2,4-dimethoxyphenyl)-3-naphthalen-1-ylpropanoate Chemical compound C=1C=CC2=CC=CC=C2C=1C(C(C#N)C(=O)OCC)C1=CC=C(OC)C=C1OC CNKCDDUMEAKBMY-UHFFFAOYSA-N 0.000 claims description 4
- BCMHUBAKWXCWES-UHFFFAOYSA-N ethyl 2-cyano-3-(2-methoxyphenyl)-3-naphthalen-1-ylpropanoate Chemical compound C=1C=CC2=CC=CC=C2C=1C(C(C#N)C(=O)OCC)C1=CC=CC=C1OC BCMHUBAKWXCWES-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- IVXQBCUBSIPQGU-UHFFFAOYSA-N piperazine-1-carboxamide Chemical compound NC(=O)N1CCNCC1 IVXQBCUBSIPQGU-UHFFFAOYSA-N 0.000 claims description 4
- NOFLSPNCSWNKMK-UHFFFAOYSA-N tert-butyl 2-cyano-3-(2,6-dimethylphenyl)-3-naphthalen-1-ylpropanoate Chemical compound CC1=CC=CC(C)=C1C(C(C#N)C(=O)OC(C)(C)C)C1=CC=CC2=CC=CC=C12 NOFLSPNCSWNKMK-UHFFFAOYSA-N 0.000 claims description 4
- IYZKSQINJIJKKF-UHFFFAOYSA-N tert-butyl 2-cyano-3-naphthalen-1-yl-3-(2-propan-2-ylphenyl)propanoate Chemical compound CC(C)C1=CC=CC=C1C(C(C#N)C(=O)OC(C)(C)C)C1=CC=CC2=CC=CC=C12 IYZKSQINJIJKKF-UHFFFAOYSA-N 0.000 claims description 4
- YQLLYZBVSCXIAA-VTIYRKAUSA-N (2r)-2-[(r)-(2-methoxyphenyl)-naphthalen-1-ylmethyl]-2-methyl-3-[4-(2-methylphenyl)piperazin-1-yl]-3-oxopropanenitrile Chemical compound COC1=CC=CC=C1[C@H]([C@](C)(C#N)C(=O)N1CCN(CC1)C=1C(=CC=CC=1)C)C1=CC=CC2=CC=CC=C12 YQLLYZBVSCXIAA-VTIYRKAUSA-N 0.000 claims description 3
- RPFNBMZGDHKJOY-PUDHBBIYSA-N (2s)-2-[(s)-(2-methoxyphenyl)-naphthalen-1-ylmethyl]-2-methyl-3-(4-naphthalen-1-ylpiperazin-1-yl)-3-oxopropanenitrile Chemical compound COC1=CC=CC=C1[C@@H]([C@@](C)(C#N)C(=O)N1CCN(CC1)C=1C2=CC=CC=C2C=CC=1)C1=CC=CC2=CC=CC=C12 RPFNBMZGDHKJOY-PUDHBBIYSA-N 0.000 claims description 3
- MEONWHRRZKGBQZ-CQTOTRCISA-N (2s)-2-[(s)-(2-methoxyphenyl)-naphthalen-1-ylmethyl]-2-methyl-3-[4-(3-methylphenyl)piperazin-1-yl]-3-oxopropanenitrile Chemical compound COC1=CC=CC=C1[C@@H]([C@@](C)(C#N)C(=O)N1CCN(CC1)C=1C=C(C)C=CC=1)C1=CC=CC2=CC=CC=C12 MEONWHRRZKGBQZ-CQTOTRCISA-N 0.000 claims description 3
- JZPONCMNBSEYQW-CQTOTRCISA-N (2s)-2-[(s)-(2-methoxyphenyl)-naphthalen-1-ylmethyl]-2-methyl-3-oxo-3-[4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]propanenitrile Chemical compound COC1=CC=CC=C1[C@@H]([C@@](C)(C#N)C(=O)N1CCC(CC1)C=1C=C(C=CC=1)C(F)(F)F)C1=CC=CC2=CC=CC=C12 JZPONCMNBSEYQW-CQTOTRCISA-N 0.000 claims description 3
- DCCPNFFQPPRMAK-BHDXBOSCSA-N (2s,3s)-2-[4-(2,3-dichlorophenyl)piperazine-1-carbonyl]-3-(2-methoxyphenyl)-2-methyl-3-naphthalen-1-ylpropanenitrile Chemical compound COC1=CC=CC=C1[C@@H]([C@@](C)(C#N)C(=O)N1CCN(CC1)C=1C(=C(Cl)C=CC=1)Cl)C1=CC=CC2=CC=CC=C12 DCCPNFFQPPRMAK-BHDXBOSCSA-N 0.000 claims description 3
- SSHPWBDOIDZSCP-UZNNEEJFSA-N (2s,3s)-2-[4-(2,3-dimethylphenyl)piperazine-1-carbonyl]-3-(2-methoxyphenyl)-2-methyl-3-naphthalen-1-ylpropanenitrile Chemical compound COC1=CC=CC=C1[C@@H]([C@@](C)(C#N)C(=O)N1CCN(CC1)C=1C(=C(C)C=CC=1)C)C1=CC=CC2=CC=CC=C12 SSHPWBDOIDZSCP-UZNNEEJFSA-N 0.000 claims description 3
- DUAHHJADGMHDAK-XDFJSJKPSA-N (2s,3s)-2-[4-(2-chlorophenyl)piperazine-1-carbonyl]-3-(2-methoxyphenyl)-2-methyl-3-naphthalen-1-ylpropanenitrile Chemical compound COC1=CC=CC=C1[C@@H]([C@@](C)(C#N)C(=O)N1CCN(CC1)C=1C(=CC=CC=1)Cl)C1=CC=CC2=CC=CC=C12 DUAHHJADGMHDAK-XDFJSJKPSA-N 0.000 claims description 3
- YDPHVMLWKVJBQE-XDFJSJKPSA-N (2s,3s)-2-[4-(2-fluorophenyl)piperazine-1-carbonyl]-3-(2-methoxyphenyl)-2-methyl-3-naphthalen-1-ylpropanenitrile Chemical compound COC1=CC=CC=C1[C@@H]([C@@](C)(C#N)C(=O)N1CCN(CC1)C=1C(=CC=CC=1)F)C1=CC=CC2=CC=CC=C12 YDPHVMLWKVJBQE-XDFJSJKPSA-N 0.000 claims description 3
- JKPJSOHGSKFXIK-UZNNEEJFSA-N (2s,3s)-2-[4-(3,4-dimethylphenyl)piperazine-1-carbonyl]-3-(2-methoxyphenyl)-2-methyl-3-naphthalen-1-ylpropanenitrile Chemical compound COC1=CC=CC=C1[C@@H]([C@@](C)(C#N)C(=O)N1CCN(CC1)C=1C=C(C)C(C)=CC=1)C1=CC=CC2=CC=CC=C12 JKPJSOHGSKFXIK-UZNNEEJFSA-N 0.000 claims description 3
- RDYVLJXNUNCGGT-UZNNEEJFSA-N (2s,3s)-2-[4-(3,5-dimethoxyphenyl)piperazine-1-carbonyl]-3-(2-methoxyphenyl)-2-methyl-3-naphthalen-1-ylpropanenitrile Chemical compound COC1=CC(OC)=CC(N2CCN(CC2)C(=O)[C@](C)(C#N)[C@H](C=2C(=CC=CC=2)OC)C=2C3=CC=CC=C3C=CC=2)=C1 RDYVLJXNUNCGGT-UZNNEEJFSA-N 0.000 claims description 3
- NEYGOQHEACXZQW-XDFJSJKPSA-N (2s,3s)-2-[4-(4-chlorophenyl)piperazine-1-carbonyl]-3-(2-methoxyphenyl)-2-methyl-3-naphthalen-1-ylpropanenitrile Chemical compound COC1=CC=CC=C1[C@@H]([C@@](C)(C#N)C(=O)N1CCN(CC1)C=1C=CC(Cl)=CC=1)C1=CC=CC2=CC=CC=C12 NEYGOQHEACXZQW-XDFJSJKPSA-N 0.000 claims description 3
- UBVIGVSCRZJWOE-CQTOTRCISA-N (2s,3s)-2-[4-[4-chloro-3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine-1-carbonyl]-3-(2-methoxyphenyl)-2-methyl-3-naphthalen-1-ylpropanenitrile Chemical compound COC1=CC=CC=C1[C@@H]([C@@](C)(C#N)C(=O)N1CC=C(CC1)C=1C=C(C(Cl)=CC=1)C(F)(F)F)C1=CC=CC2=CC=CC=C12 UBVIGVSCRZJWOE-CQTOTRCISA-N 0.000 claims description 3
- QLYQQJLNIFDUNH-CQTOTRCISA-N (2s,3s)-2-[4-[4-chloro-3-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-3-(2-methoxyphenyl)-2-methyl-3-naphthalen-1-ylpropanenitrile Chemical compound COC1=CC=CC=C1[C@@H]([C@@](C)(C#N)C(=O)N1CCC(CC1)C=1C=C(C(Cl)=CC=1)C(F)(F)F)C1=CC=CC2=CC=CC=C12 QLYQQJLNIFDUNH-CQTOTRCISA-N 0.000 claims description 3
- PYUXCEVGIQTTRI-UHFFFAOYSA-N 2-[4-(3-chloro-2-methylphenyl)piperazine-1-carbonyl]-3-(2-methoxyphenyl)-2-methyl-3-naphthalen-1-ylpropanenitrile Chemical compound COC1=CC=CC=C1C(C(C)(C#N)C(=O)N1CCN(CC1)C=1C(=C(Cl)C=CC=1)C)C1=CC=CC2=CC=CC=C12 PYUXCEVGIQTTRI-UHFFFAOYSA-N 0.000 claims description 3
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- HTWKSMOAZUVCLC-UHFFFAOYSA-N 2-cyano-2-methyl-3-naphthalen-1-yl-3-[2-(trifluoromethyl)phenyl]propanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1C(C(C#N)(C)C(O)=O)C1=CC=CC=C1C(F)(F)F HTWKSMOAZUVCLC-UHFFFAOYSA-N 0.000 claims description 3
- 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims description 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- JLESPOKBPILILK-UHFFFAOYSA-N [O-][N+](=O)[C]C#N Chemical compound [O-][N+](=O)[C]C#N JLESPOKBPILILK-UHFFFAOYSA-N 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 claims description 3
- KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 claims description 3
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 3
- HAWZLUYUKKDNQT-UHFFFAOYSA-N ethyl 2-cyano-3-(2,6-dichlorophenyl)-3-naphthalen-1-ylpropanoate Chemical compound C=1C=CC2=CC=CC=C2C=1C(C(C#N)C(=O)OCC)C1=C(Cl)C=CC=C1Cl HAWZLUYUKKDNQT-UHFFFAOYSA-N 0.000 claims description 3
- FTSXTKLDGMGCEN-UHFFFAOYSA-N ethyl 2-cyano-3-(2,6-dimethoxyphenyl)-3-naphthalen-1-ylpropanoate Chemical compound C=1C=CC2=CC=CC=C2C=1C(C(C#N)C(=O)OCC)C1=C(OC)C=CC=C1OC FTSXTKLDGMGCEN-UHFFFAOYSA-N 0.000 claims description 3
- XEJUPNISYVEWOR-UHFFFAOYSA-N ethyl 2-cyano-3-naphthalen-1-yl-3-(2-propan-2-ylphenyl)propanoate Chemical compound C=1C=CC2=CC=CC=C2C=1C(C(C#N)C(=O)OCC)C1=CC=CC=C1C(C)C XEJUPNISYVEWOR-UHFFFAOYSA-N 0.000 claims description 3
- QSQIOLZIBXSXMS-UHFFFAOYSA-N ethyl 2-cyano-3-naphthalen-1-yl-3-[2-(trifluoromethyl)phenyl]propanoate Chemical compound C=1C=CC2=CC=CC=C2C=1C(C(C#N)C(=O)OCC)C1=CC=CC=C1C(F)(F)F QSQIOLZIBXSXMS-UHFFFAOYSA-N 0.000 claims description 3
- 150000004678 hydrides Chemical class 0.000 claims description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
- CEXMYXRLKBMHFX-UHFFFAOYSA-N n-naphthalen-1-ylpropanamide Chemical compound C1=CC=C2C(NC(=O)CC)=CC=CC2=C1 CEXMYXRLKBMHFX-UHFFFAOYSA-N 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000006413 ring segment Chemical group 0.000 claims description 3
- IIWQXKLEVDCXJI-UHFFFAOYSA-N 2-[(2-methoxyphenyl)-quinolin-3-ylmethyl]-2-methyl-3-oxo-3-[4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]propanenitrile Chemical compound COC1=CC=CC=C1C(C(C)(C#N)C(=O)N1CCC(CC1)C=1C=C(C=CC=1)C(F)(F)F)C1=CN=C(C=CC=C2)C2=C1 IIWQXKLEVDCXJI-UHFFFAOYSA-N 0.000 claims description 2
- 239000002168 alkylating agent Substances 0.000 claims description 2
- 229940100198 alkylating agent Drugs 0.000 claims description 2
- 230000029936 alkylation Effects 0.000 claims description 2
- 238000005804 alkylation reaction Methods 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical class OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 348
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 327
- 239000007787 solid Substances 0.000 description 194
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 173
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- C07C2601/14—The ring being saturated
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Applications Claiming Priority (4)
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| US46656703P | 2003-04-30 | 2003-04-30 | |
| US60/466,567 | 2003-04-30 | ||
| US10/833,678 | 2004-04-28 | ||
| US10/833,678 US20050004164A1 (en) | 2003-04-30 | 2004-04-28 | 2-Cyanopropanoic acid amide and ester derivatives and methods of their use |
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| KR20060015556A true KR20060015556A (ko) | 2006-02-17 |
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Family Applications (1)
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| JP (1) | JP2006526630A (https=) |
| KR (1) | KR20060015556A (https=) |
| AR (1) | AR044762A1 (https=) |
| AT (1) | ATE418335T1 (https=) |
| AU (1) | AU2004236216A1 (https=) |
| BR (1) | BRPI0409921A (https=) |
| CA (1) | CA2523235A1 (https=) |
| CO (1) | CO5700755A2 (https=) |
| CR (1) | CR8041A (https=) |
| DE (1) | DE602004018629D1 (https=) |
| MX (1) | MXPA05011581A (https=) |
| NO (1) | NO20054969L (https=) |
| RU (1) | RU2005137175A (https=) |
| TW (1) | TW200508217A (https=) |
| WO (1) | WO2004099150A2 (https=) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
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| SE9904723D0 (sv) | 1999-12-22 | 1999-12-22 | Carlsson A Research Ab | New modulators of dopamine neurotransmission II |
| SE9904724D0 (sv) | 1999-12-22 | 1999-12-22 | Carlsson A Research Ab | New modulators of dopamine neurotransmission I |
| USRE46117E1 (en) | 1999-12-22 | 2016-08-23 | Teva Pharmaceuticals International Gmbh | Modulators of dopamine neurotransmission |
| US7544350B2 (en) | 2002-11-22 | 2009-06-09 | Hallstar Innovations Corp. | Method of decreasing the UV light degradation of polymers |
| JP2008501749A (ja) * | 2004-06-08 | 2008-01-24 | ニューロサーチ スウェーデン アクチボラゲット | ドーパミン及びセロトニン神経伝達のモジュレーターとしての新規なジ置換フェニルピペリジン |
| DE602005021641D1 (de) | 2004-06-08 | 2010-07-15 | Nsab, Filial Af Neurosearch Sweden Ab | Neue disubstituierte phenylpiperidine und piperazine als modulatoren der dopamin-neurotransmission |
| US7851629B2 (en) | 2004-06-08 | 2010-12-14 | Nsab, Filial Af Neurosearch Sweden Ab, Sverige | Disubstituted phenylpiperidines as modulators of dopamine and serotonin neurotransmission |
| WO2005123663A1 (en) * | 2004-06-14 | 2005-12-29 | Wyeth | Processes for the preparation of 2-cyano-3-naphthalene-1-yl-3-phenyl-propionic acid alkyl or benzyl esters |
| EP2248524A3 (en) | 2004-08-25 | 2011-03-09 | Takeda Pharmaceutical Company Limited | Preventives/remedies for stress urinary incontinence and method of screening the same |
| CA2584831C (en) | 2004-10-13 | 2013-09-17 | Neurosearch Sweden Ab | Process for the synthesis of 4-(3-methanesulfonylphenyl)-1-n-propyl-piperidine |
| CN100562514C (zh) * | 2005-07-22 | 2009-11-25 | 中国科学院上海药物研究所 | 一类取代丙酰胺衍生物、其制备方法和用途 |
| SE529246C2 (sv) | 2005-10-13 | 2007-06-12 | Neurosearch Sweden Ab | Nya disubstituerade fenyl-piperidiner som modulatorer för dopaminneurotransmission |
| RU2303597C1 (ru) * | 2006-05-12 | 2007-07-27 | Иващенко Андрей Александрович | Фармацевтическая композиция, способы ее получения и применения |
| EP2742936A1 (en) | 2006-05-16 | 2014-06-18 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compound and use thereof |
| EP2089355A2 (en) * | 2006-11-01 | 2009-08-19 | Brystol-Myers Squibb Company | Modulators of glucocorticoid receptor, ap-1, and/or nf- kappa b activity and use thereof |
| EP2789338A3 (en) | 2007-11-15 | 2015-01-14 | Takeda Pharmaceutical Company Limited | Condensed pyridine derivate and use thereof |
| JPWO2011071136A1 (ja) | 2009-12-11 | 2013-04-22 | アステラス製薬株式会社 | 線維筋痛症治療剤 |
| WO2011094426A1 (en) | 2010-01-29 | 2011-08-04 | The United State Of America, As Represented By The Secretary, Department Of Health & Human Services | Caspase inhibitors |
| ES2703176T3 (es) * | 2010-03-11 | 2019-03-07 | Univ New York | Compuestos amido como moduladores de RORgammat y usos de los mismos |
| BR112014005268A2 (pt) * | 2011-09-09 | 2017-03-28 | Univ New York | compostos de amido como moduladores de ror t e usos dos mesmos |
| MX347209B (es) | 2011-12-08 | 2017-04-19 | Teva Pharmaceuticals Int Gmbh | La sal de bromhidrato de pridopidina. |
| HK1206297A1 (en) | 2012-04-04 | 2016-01-08 | Teva Pharmaceuticals International Gmbh | Pharmaceutical compositions for combination therapy |
| IN2014DN09937A (https=) | 2012-05-30 | 2015-08-14 | Clariant Int Ltd | |
| ES2599504T3 (es) | 2012-05-30 | 2017-02-02 | Clariant International Ltd | Utilización de N-metil-N-acil-glucaminas como agentes solubilizantes |
| DE102012021647A1 (de) | 2012-11-03 | 2014-05-08 | Clariant International Ltd. | Wässrige Adjuvant-Zusammensetzungen |
| TWI653235B (zh) | 2013-05-28 | 2019-03-11 | 阿斯特捷利康公司 | 作為抗癌劑之吲哚衍生物 |
| DE202014008418U1 (de) | 2014-02-19 | 2014-11-14 | Clariant International Ltd. | Schaumarme agrochemische Zusammensetzungen |
| DE102014005771A1 (de) | 2014-04-23 | 2015-10-29 | Clariant International Ltd. | Verwendung von wässrigen driftreduzierenden Zusammensetzungen |
| DE102015219651A1 (de) | 2015-10-09 | 2017-04-13 | Clariant International Ltd. | Zusammensetzungen enthaltend Zuckeramin und Fettsäure |
| DE102015219608B4 (de) | 2015-10-09 | 2018-05-03 | Clariant International Ltd | Universelle Pigmentdispersionen auf Basis von N-Alkylglukaminen |
| DE102016207877A1 (de) | 2016-05-09 | 2017-11-09 | Clariant International Ltd | Stabilisatoren für Silikatfarben |
| KR101828240B1 (ko) | 2016-10-17 | 2018-02-13 | (주)네오팜 | 항염용 조성물 |
| KR101828241B1 (ko) * | 2016-10-17 | 2018-02-13 | (주)네오팜 | 항염용 조성물 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US6451817B1 (en) * | 1995-03-10 | 2002-09-17 | Eli Lilly And Company | Alpha-substituted-1-benzyl-napthyls |
| RU2188819C2 (ru) * | 1996-08-12 | 2002-09-10 | Селджин Корпорейшн | НОВЫЕ ИММУНОТЕРАПЕВТИЧЕСКИЕ СОЕДИНЕНИЯ, СОДЕРЖАЩАЯ ИХ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ СНИЖЕНИЯ УРОВНЕЙ ФДЭ, TNFα И NFκB |
| US6271199B2 (en) * | 1997-02-15 | 2001-08-07 | Millennium Pharmaceuticals, Inc. | Treatment of infarcts |
| JP2001513501A (ja) * | 1997-08-07 | 2001-09-04 | イーライ・リリー・アンド・カンパニー | エストロゲン阻害活性を有する1−[4−(置換アルコキシ)ベンジル]ナフタレン化合物 |
| JPH11295383A (ja) * | 1998-04-15 | 1999-10-29 | Mitsubishi Electric Corp | マイクロ波帯域用半導体トランジスタのバーンイン方法、バーンイン装置及びバーンインした半導体装置 |
| HUP0102782A3 (en) * | 1998-06-19 | 2002-12-28 | Smithkline Beecham Corp | Salycilanilide as inhibitors of transcription factor nf-kb |
| SI1194425T1 (sl) * | 1999-06-23 | 2005-12-31 | Sanofi Aventis Deutschland | Substituirani benzimidazoli |
| DE19951360A1 (de) * | 1999-10-26 | 2001-05-03 | Aventis Pharma Gmbh | Substituierte Indole |
| WO2005039581A1 (en) * | 2003-09-24 | 2005-05-06 | Wyeth | Use of estrogen receptor ligands for the treatment of inflammatory bowel disease |
| WO2005039582A1 (en) * | 2003-09-24 | 2005-05-06 | Wyeth | METHODS OF TREATING ATHEROSCLEROSIS USING NF-kB INHIBITORS |
| AU2003278955A1 (en) * | 2003-09-24 | 2005-05-11 | Wyeth | METHOD OF TREATING RHEUMATOID ARTHRITIS USING NF-kB INHIBITORS |
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- 2004-04-29 TW TW093111996A patent/TW200508217A/zh unknown
- 2004-04-30 MX MXPA05011581A patent/MXPA05011581A/es not_active Application Discontinuation
- 2004-04-30 EP EP04750987A patent/EP1620102B1/en not_active Expired - Lifetime
- 2004-04-30 KR KR1020057020599A patent/KR20060015556A/ko not_active Withdrawn
- 2004-04-30 WO PCT/US2004/013360 patent/WO2004099150A2/en not_active Ceased
- 2004-04-30 AT AT04750987T patent/ATE418335T1/de not_active IP Right Cessation
- 2004-04-30 JP JP2006514164A patent/JP2006526630A/ja active Pending
- 2004-04-30 BR BRPI0409921-4A patent/BRPI0409921A/pt not_active IP Right Cessation
- 2004-04-30 RU RU2005137175/04A patent/RU2005137175A/ru not_active Application Discontinuation
- 2004-04-30 AR ARP040101492A patent/AR044762A1/es unknown
- 2004-04-30 DE DE602004018629T patent/DE602004018629D1/de not_active Expired - Fee Related
- 2004-04-30 CA CA002523235A patent/CA2523235A1/en not_active Abandoned
- 2004-04-30 AU AU2004236216A patent/AU2004236216A1/en not_active Abandoned
-
2005
- 2005-10-12 CR CR8041A patent/CR8041A/es not_active Application Discontinuation
- 2005-10-26 NO NO20054969A patent/NO20054969L/no not_active Application Discontinuation
- 2005-10-26 CO CO05109228A patent/CO5700755A2/es not_active Application Discontinuation
-
2007
- 2007-07-31 US US11/831,375 patent/US20070299105A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CA2523235A1 (en) | 2004-11-18 |
| NO20054969D0 (no) | 2005-10-26 |
| NO20054969L (no) | 2005-11-22 |
| AR044762A1 (es) | 2005-10-05 |
| TW200508217A (en) | 2005-03-01 |
| WO2004099150A2 (en) | 2004-11-18 |
| DE602004018629D1 (de) | 2009-02-05 |
| CR8041A (es) | 2006-05-30 |
| EP1620102A2 (en) | 2006-02-01 |
| RU2005137175A (ru) | 2006-05-27 |
| US20070299105A1 (en) | 2007-12-27 |
| ATE418335T1 (de) | 2009-01-15 |
| WO2004099150A3 (en) | 2004-12-23 |
| MXPA05011581A (es) | 2005-12-14 |
| EP1620102B1 (en) | 2008-12-24 |
| JP2006526630A (ja) | 2006-11-24 |
| AU2004236216A1 (en) | 2004-11-18 |
| BRPI0409921A (pt) | 2006-04-25 |
| CO5700755A2 (es) | 2006-11-30 |
| US20050004164A1 (en) | 2005-01-06 |
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