JP2007502253A5 - - Google Patents
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- Publication number
- JP2007502253A5 JP2007502253A5 JP2006522897A JP2006522897A JP2007502253A5 JP 2007502253 A5 JP2007502253 A5 JP 2007502253A5 JP 2006522897 A JP2006522897 A JP 2006522897A JP 2006522897 A JP2006522897 A JP 2006522897A JP 2007502253 A5 JP2007502253 A5 JP 2007502253A5
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- phenyl
- piperidin
- amide
- compound
- 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.)
- Granted
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- 150000001875 compounds Chemical class 0.000 description 124
- 150000003839 salts Chemical class 0.000 description 119
- 229910052739 hydrogen Inorganic materials 0.000 description 64
- 239000001257 hydrogen Substances 0.000 description 64
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 33
- 150000002431 hydrogen Chemical class 0.000 description 31
- 125000000304 alkynyl group Chemical group 0.000 description 26
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 22
- 125000003342 alkenyl group Chemical group 0.000 description 22
- 125000003118 aryl group Chemical group 0.000 description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- 150000001408 amides Chemical class 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 11
- 125000000392 cycloalkenyl group Chemical group 0.000 description 10
- 229910052736 halogen Inorganic materials 0.000 description 8
- 150000002367 halogens Chemical class 0.000 description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
- 125000006621 (C3-C8) cycloalkyl-(C1-C6) alkyl group Chemical group 0.000 description 7
- 125000000217 alkyl group Chemical group 0.000 description 7
- SZJIQLSCDIEJFC-UHFFFAOYSA-N 1-(4-fluorophenyl)-n-methylmethanamine Chemical compound CNCC1=CC=C(F)C=C1 SZJIQLSCDIEJFC-UHFFFAOYSA-N 0.000 description 6
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
- 125000001072 heteroaryl group Chemical group 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 6
- 125000003386 piperidinyl group Chemical group 0.000 description 6
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 5
- 125000004093 cyano group Chemical group *C#N 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 125000001153 fluoro group Chemical group F* 0.000 description 5
- -1 fluoromethylsulfonyl Chemical group 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 125000002757 morpholinyl group Chemical group 0.000 description 5
- 125000004193 piperazinyl group Chemical group 0.000 description 5
- 201000000980 schizophrenia Diseases 0.000 description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
- 206010020751 Hypersensitivity Diseases 0.000 description 4
- 208000026935 allergic disease Diseases 0.000 description 4
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- 230000009610 hypersensitivity Effects 0.000 description 4
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- RCSSHZGQHHEHPZ-QMMMGPOBSA-N (1s)-n-methyl-1-phenylethanamine Chemical compound CN[C@@H](C)C1=CC=CC=C1 RCSSHZGQHHEHPZ-QMMMGPOBSA-N 0.000 description 3
- WADCIXSZAVKQOL-RBISFHTESA-N (1s,2r)-1-(3,4-dichlorophenyl)-2-[[4-phenyl-4-(piperidine-1-carbonyl)piperidin-1-yl]methyl]cyclopropane-1-carboxylic acid Chemical compound C([C@@H]1C[C@@]1(C(=O)O)C=1C=C(Cl)C(Cl)=CC=1)N(CC1)CCC1(C=1C=CC=CC=1)C(=O)N1CCCCC1 WADCIXSZAVKQOL-RBISFHTESA-N 0.000 description 3
- QVLDRYAPMREZPR-NBGIEHNGSA-N (1s,2r)-2-[[4-[acetyl(methyl)amino]-4-phenylpiperidin-1-yl]methyl]-1-(3,4-dichlorophenyl)cyclopropane-1-carboxylic acid Chemical compound C1([C@]2(C(O)=O)C[C@H]2CN2CCC(CC2)(N(C(C)=O)C)C=2C=CC=CC=2)=CC=C(Cl)C(Cl)=C1 QVLDRYAPMREZPR-NBGIEHNGSA-N 0.000 description 3
- 125000005251 aryl acyl group Chemical group 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 3
- NFOFRWYYQMPIID-RBJSKKJNSA-N (1s,2r)-1-phenyl-2-[[4-phenyl-4-(piperidine-1-carbonyl)piperidin-1-yl]methyl]cyclopropane-1-carboxylic acid Chemical compound C([C@@H]1C[C@@]1(C(=O)O)C=1C=CC=CC=1)N(CC1)CCC1(C=1C=CC=CC=1)C(=O)N1CCCCC1 NFOFRWYYQMPIID-RBJSKKJNSA-N 0.000 description 2
- HRLBRKOUKOXSPJ-VCTRWQRLSA-N (1s,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-1-(3,4-dichlorophenyl)-n-(2-phenylpropan-2-yl)cyclopropane-1-carboxamide Chemical compound O=C([C@]1(C[C@H]1CN1CCC(CC1)(NC(=O)C)C=1C=CC=CC=1)C=1C=C(Cl)C(Cl)=CC=1)NC(C)(C)C1=CC=CC=C1 HRLBRKOUKOXSPJ-VCTRWQRLSA-N 0.000 description 2
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 2
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 description 2
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- 206010006482 Bronchospasm Diseases 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- 206010011224 Cough Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 230000007885 bronchoconstriction Effects 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 230000036461 convulsion Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 230000019948 ion homeostasis Effects 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- KNFMUJDPRXCBKF-DICHSLLOSA-N n'-[1-[[(1s,2r)-2-[(4-fluorophenyl)methyl-methylcarbamoyl]-2-phenylcyclopropyl]methyl]-4-phenylpiperidin-4-yl]oxamide Chemical compound O=C([C@]1([C@H](C1)CN1CCC(CC1)(NC(=O)C(N)=O)C=1C=CC=CC=1)C=1C=CC=CC=1)N(C)CC1=CC=C(F)C=C1 KNFMUJDPRXCBKF-DICHSLLOSA-N 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 208000020016 psychiatric disease Diseases 0.000 description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000007279 water homeostasis Effects 0.000 description 2
- ITPVLULKKKHELH-MHECFPHRSA-N (1S,2R)-1-(3,4-dichlorophenyl)-2-[[4-(methylcarbamoylamino)-4-phenylpiperidin-1-yl]methyl]cyclopropane-1-carboxylic acid Chemical compound CNC(=O)NC1(CCN(C[C@@H]2C[C@@]2(C(O)=O)c2ccc(Cl)c(Cl)c2)CC1)c1ccccc1 ITPVLULKKKHELH-MHECFPHRSA-N 0.000 description 1
- DGLDUQZIRFLLRH-UCGGBYDDSA-N (1r,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-n-benzyl-1-(3,4-dichlorophenyl)-n-methylcyclopropane-1-carboxamide Chemical compound O=C([C@]1([C@@H](C1)CN1CCC(CC1)(NC(C)=O)C=1C=CC=CC=1)C=1C=C(Cl)C(Cl)=CC=1)N(C)CC1=CC=CC=C1 DGLDUQZIRFLLRH-UCGGBYDDSA-N 0.000 description 1
- DGLDUQZIRFLLRH-ZUKKLESISA-N (1r,2s)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-n-benzyl-1-(3,4-dichlorophenyl)-n-methylcyclopropane-1-carboxamide Chemical compound O=C([C@]1([C@H](C1)CN1CCC(CC1)(NC(C)=O)C=1C=CC=CC=1)C=1C=C(Cl)C(Cl)=CC=1)N(C)CC1=CC=CC=C1 DGLDUQZIRFLLRH-ZUKKLESISA-N 0.000 description 1
- DBCVAUCXGHOPJA-MUAVYFROSA-N (1s,2r)-1-(3,4-dichlorophenyl)-n-[(3,4-dichlorophenyl)methyl]-2-[(4-phenylpiperidin-1-yl)methyl]cyclopropane-1-carboxamide Chemical compound C1=C(Cl)C(Cl)=CC=C1CNC(=O)[C@]1(C=2C=C(Cl)C(Cl)=CC=2)[C@H](CN2CCC(CC2)C=2C=CC=CC=2)C1 DBCVAUCXGHOPJA-MUAVYFROSA-N 0.000 description 1
- MBGIOCNEVBWQBE-VVFBEHOQSA-N (1s,2r)-1-(3,4-dichlorophenyl)-n-[(3,4-dimethoxyphenyl)methyl]-2-[(4-phenylpiperidin-1-yl)methyl]cyclopropane-1-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CNC(=O)[C@]1(C=2C=C(Cl)C(Cl)=CC=2)[C@H](CN2CCC(CC2)C=2C=CC=CC=2)C1 MBGIOCNEVBWQBE-VVFBEHOQSA-N 0.000 description 1
- SLQBRRXYVVAFBF-ZBWWXOROSA-N (1s,2r)-1-(3,4-dichlorophenyl)-n-methyl-n-(naphthalen-1-ylmethyl)-2-[(4-phenylpiperidin-1-yl)methyl]cyclopropane-1-carboxamide Chemical compound C([C@@H]1C[C@@]1(C(=O)N(CC=1C2=CC=CC=C2C=CC=1)C)C=1C=C(Cl)C(Cl)=CC=1)N(CC1)CCC1C1=CC=CC=C1 SLQBRRXYVVAFBF-ZBWWXOROSA-N 0.000 description 1
- MQXIFSWAEDBTTK-MUAVYFROSA-N (1s,2r)-1-(3,4-difluorophenyl)-n-methyl-2-[[4-phenyl-4-(piperidine-1-carbonyl)piperidin-1-yl]methyl]cyclopropane-1-carboxamide Chemical compound C([C@@H]1C[C@@]1(C(=O)NC)C=1C=C(F)C(F)=CC=1)N(CC1)CCC1(C=1C=CC=CC=1)C(=O)N1CCCCC1 MQXIFSWAEDBTTK-MUAVYFROSA-N 0.000 description 1
- SKDJGFHBUDMAKY-NEKDWFFYSA-N (1s,2r)-1-(4-chlorophenyl)-2-[[4-phenyl-4-(piperidine-1-carbonyl)piperidin-1-yl]methyl]cyclopropane-1-carboxylic acid Chemical compound C([C@@H]1C[C@@]1(C(=O)O)C=1C=CC(Cl)=CC=1)N(CC1)CCC1(C=1C=CC=CC=1)C(=O)N1CCCCC1 SKDJGFHBUDMAKY-NEKDWFFYSA-N 0.000 description 1
- YYXXJEARXRQGLM-RYWJPUDZSA-N (1s,2r)-1-(4-chlorophenyl)-n-[(2-chlorophenyl)methyl]-n-methyl-2-[[4-phenyl-4-(piperidine-1-carbonyl)piperidin-1-yl]methyl]cyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(C(=O)N1CCCCC1)C=1C=CC=CC=1)C=1C=CC(Cl)=CC=1)N(C)CC1=CC=CC=C1Cl YYXXJEARXRQGLM-RYWJPUDZSA-N 0.000 description 1
- GZHKAPFILJGCBZ-PWUYWRBVSA-N (1s,2r)-1-(4-chlorophenyl)-n-[(4-fluorophenyl)methyl]-n-methyl-2-[[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methyl]cyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCN(CC1)C=1C=C(C=CC=1)C(F)(F)F)C=1C=CC(Cl)=CC=1)N(C)CC1=CC=C(F)C=C1 GZHKAPFILJGCBZ-PWUYWRBVSA-N 0.000 description 1
- KIDNYKAVAWJQHD-RYWJPUDZSA-N (1s,2r)-1-(4-chlorophenyl)-n-[(4-fluorophenyl)methyl]-n-methyl-2-[[4-phenyl-4-(piperidine-1-carbonyl)piperidin-1-yl]methyl]cyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(C(=O)N1CCCCC1)C=1C=CC=CC=1)C=1C=CC(Cl)=CC=1)N(C)CC1=CC=C(F)C=C1 KIDNYKAVAWJQHD-RYWJPUDZSA-N 0.000 description 1
- JASAZPATAMVUTL-NEKDWFFYSA-N (1s,2r)-1-(4-fluorophenyl)-2-[[4-phenyl-4-(piperidine-1-carbonyl)piperidin-1-yl]methyl]cyclopropane-1-carboxylic acid Chemical compound C([C@@H]1C[C@@]1(C(=O)O)C=1C=CC(F)=CC=1)N(CC1)CCC1(C=1C=CC=CC=1)C(=O)N1CCCCC1 JASAZPATAMVUTL-NEKDWFFYSA-N 0.000 description 1
- WDKKCWLRJSMLLL-RYWJPUDZSA-N (1s,2r)-1-(4-fluorophenyl)-n-[(4-fluorophenyl)methyl]-n-methyl-2-[[4-phenyl-4-(piperidine-1-carbonyl)piperidin-1-yl]methyl]cyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(C(=O)N1CCCCC1)C=1C=CC=CC=1)C=1C=CC(F)=CC=1)N(C)CC1=CC=C(F)C=C1 WDKKCWLRJSMLLL-RYWJPUDZSA-N 0.000 description 1
- HNYNJVUGLYPLMY-QXNWPYRLSA-N (1s,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-1-(3,4-dichlorophenyl)-n-[(3,4-dichlorophenyl)methyl]cyclopropane-1-carboxamide Chemical compound O=C([C@]1(C[C@H]1CN1CCC(CC1)(NC(=O)C)C=1C=CC=CC=1)C=1C=C(Cl)C(Cl)=CC=1)NCC1=CC=C(Cl)C(Cl)=C1 HNYNJVUGLYPLMY-QXNWPYRLSA-N 0.000 description 1
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- DGWJZKUIZMZNGT-VVFBEHOQSA-N (1s,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-1-(3,4-dichlorophenyl)-n-methyl-n-phenylcyclopropane-1-carboxamide Chemical compound C([C@@H]1C[C@@]1(C(=O)N(C)C=1C=CC=CC=1)C=1C=C(Cl)C(Cl)=CC=1)N(CC1)CCC1(NC(C)=O)C1=CC=CC=C1 DGWJZKUIZMZNGT-VVFBEHOQSA-N 0.000 description 1
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- LRSHGWZKUHQQCF-YADARESESA-N (1s,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-1-(3,4-dichlorophenyl)cyclopropane-1-carboxylic acid Chemical compound C1([C@]2(C(O)=O)C[C@H]2CN2CCC(CC2)(NC(=O)C)C=2C=CC=CC=2)=CC=C(Cl)C(Cl)=C1 LRSHGWZKUHQQCF-YADARESESA-N 0.000 description 1
- DWYWNTMREHRHJA-BFGHFXMOSA-N (1s,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-1-(3,4-dimethylphenyl)-n-[(4-fluorophenyl)methyl]-n-methylcyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(NC(C)=O)C=1C=CC=CC=1)C=1C=C(C)C(C)=CC=1)N(C)CC1=CC=C(F)C=C1 DWYWNTMREHRHJA-BFGHFXMOSA-N 0.000 description 1
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- XYQWIBWAKCBKIC-ABYGYWHVSA-N (1s,2r)-n-benzyl-1-(4-chlorophenyl)-n-methyl-2-[[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methyl]cyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCN(CC1)C=1C=C(C=CC=1)C(F)(F)F)C=1C=CC(Cl)=CC=1)N(C)CC1=CC=CC=C1 XYQWIBWAKCBKIC-ABYGYWHVSA-N 0.000 description 1
- SALJSQRYLOFWPG-BHBYDHKZSA-N (1s,2r)-n-benzyl-2-[(4-benzylpiperazin-1-yl)methyl]-1-(4-chlorophenyl)-n-methylcyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCN(CC=2C=CC=CC=2)CC1)C=1C=CC(Cl)=CC=1)N(C)CC1=CC=CC=C1 SALJSQRYLOFWPG-BHBYDHKZSA-N 0.000 description 1
- JRUDUVWSHPGECD-MFMCTBQISA-N (1s,2r)-n-benzyl-2-[(4-benzylpiperazin-1-yl)methyl]-n-methyl-1-phenylcyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCN(CC=2C=CC=CC=2)CC1)C=1C=CC=CC=1)N(C)CC1=CC=CC=C1 JRUDUVWSHPGECD-MFMCTBQISA-N 0.000 description 1
- FYWXEKFVHHPBEC-VVFBEHOQSA-N (1s,2r)-n-benzyl-2-[[4-(carbamoylamino)-4-phenylpiperidin-1-yl]methyl]-1-(3,4-dichlorophenyl)-n-methylcyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(NC(N)=O)C=1C=CC=CC=1)C=1C=C(Cl)C(Cl)=CC=1)N(C)CC1=CC=CC=C1 FYWXEKFVHHPBEC-VVFBEHOQSA-N 0.000 description 1
- REZWFYJRDMQOME-LITSAYRRSA-N (1s,2r)-n-benzyl-n-methyl-1-phenyl-2-[[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methyl]cyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCN(CC1)C=1C=C(C=CC=1)C(F)(F)F)C=1C=CC=CC=1)N(C)CC1=CC=CC=C1 REZWFYJRDMQOME-LITSAYRRSA-N 0.000 description 1
- QRJAOGZMUZGLLZ-LBHUVFDKSA-N (1s,2r)-n-benzyl-n-methyl-1-phenyl-2-[[4-phenyl-4-(piperidine-1-carbonyl)piperidin-1-yl]methyl]cyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(C(=O)N1CCCCC1)C=1C=CC=CC=1)C=1C=CC=CC=1)N(C)CC1=CC=CC=C1 QRJAOGZMUZGLLZ-LBHUVFDKSA-N 0.000 description 1
- DGLDUQZIRFLLRH-WXGMZPBLSA-N (1s,2s)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-n-benzyl-1-(3,4-dichlorophenyl)-n-methylcyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@H](C1)CN1CCC(CC1)(NC(C)=O)C=1C=CC=CC=1)C=1C=C(Cl)C(Cl)=CC=1)N(C)CC1=CC=CC=C1 DGLDUQZIRFLLRH-WXGMZPBLSA-N 0.000 description 1
- DIWGZVQKFSFNLH-UHFFFAOYSA-N 1-(2-chlorophenyl)-n-methylmethanamine Chemical compound CNCC1=CC=CC=C1Cl DIWGZVQKFSFNLH-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
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- HUVHGTPPNVTGKM-CWQVRNILSA-N C[C@@H](C1=CC=CC=C1)N.CC(N(C)C1(CCN(C[C@H](C2)[C@]2(C(OC)=O)C(C=C2)=CC(F)=C2F)CC1)C1=CC=CC=C1)=O Chemical compound C[C@@H](C1=CC=CC=C1)N.CC(N(C)C1(CCN(C[C@H](C2)[C@]2(C(OC)=O)C(C=C2)=CC(F)=C2F)CC1)C1=CC=CC=C1)=O HUVHGTPPNVTGKM-CWQVRNILSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 125000005129 aryl carbonyl group Chemical group 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 150000002366 halogen compounds Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- VIFVMMJNUPMJOT-ZUKKLESISA-N methyl n-[1-[[(1s,2r)-2-[(4-fluorophenyl)methyl-methylcarbamoyl]-2-phenylcyclopropyl]methyl]-4-phenylpiperidin-4-yl]carbamate Chemical compound O=C([C@@]1(C[C@@H]1CN1CCC(CC1)(NC(=O)OC)C=1C=CC=CC=1)C=1C=CC=CC=1)N(C)CC1=CC=C(F)C=C1 VIFVMMJNUPMJOT-ZUKKLESISA-N 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- OMATZDJSJPLAIF-GOXGLGGOSA-N n'-[1-[[(1s,2r)-2-[benzyl(methyl)carbamoyl]-2-(3,4-dichlorophenyl)cyclopropyl]methyl]-4-phenylpiperidin-4-yl]oxamide Chemical compound O=C([C@]1([C@H](C1)CN1CCC(CC1)(NC(=O)C(N)=O)C=1C=CC=CC=1)C=1C=C(Cl)C(Cl)=CC=1)N(C)CC1=CC=CC=C1 OMATZDJSJPLAIF-GOXGLGGOSA-N 0.000 description 1
- MQRIUFVBEVFILS-UHFFFAOYSA-N n-methyl-1-naphthalen-1-ylmethanamine Chemical compound C1=CC=C2C(CNC)=CC=CC2=C1 MQRIUFVBEVFILS-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 125000003441 thioacyl group Chemical group 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
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| DKPA200301175 | 2003-08-15 | ||
| DKPA200301175 | 2003-08-15 | ||
| US50153503P | 2003-09-08 | 2003-09-08 | |
| US60/501,535 | 2003-09-08 | ||
| PCT/DK2004/000538 WO2005016884A1 (en) | 2003-08-15 | 2004-08-13 | Cyclopropyl derivatives as nk3 receptor antagonists |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2007502253A JP2007502253A (ja) | 2007-02-08 |
| JP2007502253A5 true JP2007502253A5 (https=) | 2007-09-20 |
| JP4713474B2 JP4713474B2 (ja) | 2011-06-29 |
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| JP2006522897A Expired - Fee Related JP4713474B2 (ja) | 2003-08-15 | 2004-08-13 | Ｎｋ３受容体アンタゴニストとしてのシクロプロピル誘導体 |
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| KR (1) | KR20060066721A (https=) |
| CN (1) | CN1867549B (https=) |
| AR (1) | AR045368A1 (https=) |
| AT (1) | ATE528291T1 (https=) |
| EA (1) | EA009477B1 (https=) |
| IS (1) | IS8278A (https=) |
| ZA (1) | ZA200601175B (https=) |
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| GB0328908D0 (en) | 2003-12-12 | 2004-01-14 | Syngenta Participations Ag | Chemical compounds |
| EP2674428B1 (en) * | 2006-04-07 | 2016-04-06 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-binding cassette transporters |
| CA2747961C (en) * | 2009-01-30 | 2016-11-08 | F. Hoffmann-La Roche Ag | Piperidine derivatives as nk3 receptor antagonists |
| US8324250B2 (en) * | 2009-03-19 | 2012-12-04 | Hoffmann-La Roche Inc. | Piperidine derivatives as NK3 receptor antagonists |
| US20110144081A1 (en) * | 2009-12-15 | 2011-06-16 | Henner Knust | Pyrrolidine derivatives |
| WO2014168262A1 (en) * | 2013-04-11 | 2014-10-16 | D.D.P. Corporation | Kinase inhibitors containing cyclopropane skeleton |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2508035A1 (fr) * | 1981-06-23 | 1982-12-24 | Fabre Sa Pierre | Derives d'aryl-1-aminomethyl-2 cyclopropanes carboxamides (z), leur preparation et leur application en tant que medicaments utiles dans le traitement des troubles du systeme nerveux central |
| FR2719311B1 (fr) * | 1994-03-18 | 1998-06-26 | Sanofi Sa | Composés antagonistes sélectifs du récepteur NK3 humain et leur utilisation comme médicaments et outils de diagnostic. |
| US5434158A (en) * | 1994-04-26 | 1995-07-18 | Merck & Co., Inc. | Spiro-substituted azacycles as neurokinin-3 antagonists |
| FR2738819B1 (fr) * | 1995-09-14 | 1997-12-05 | Sanofi Sa | Nouveaux composes antagonistes selectifs du recepteur nk3 humain, procede pour leur obtention et compositions pharmaceutiques les contenant |
| WO2002069973A1 (en) * | 2001-03-02 | 2002-09-12 | Sepracor, Inc. | Piperidine-piperazine ligand for neurotransmitter receptors |
| IL162310A0 (en) * | 2001-12-19 | 2005-11-20 | Lundbeck & Co As H | 3,4-Dihydro-1h-isoquinoloin-2-yl-derivatives |
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2004
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- 2004-08-13 KR KR1020067002995A patent/KR20060066721A/ko not_active Ceased
- 2004-08-13 ZA ZA200601175A patent/ZA200601175B/en unknown
- 2004-08-13 EA EA200600416A patent/EA009477B1/ru not_active IP Right Cessation
- 2004-08-13 AT AT04739035T patent/ATE528291T1/de not_active IP Right Cessation
- 2004-08-13 JP JP2006522897A patent/JP4713474B2/ja not_active Expired - Fee Related
- 2004-08-13 CN CN2004800296912A patent/CN1867549B/zh not_active Expired - Fee Related
-
2006
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