BG107258A - Циклохексиламинови производни като подвид-селективни антагонисти на рецептора на n-метил - d-аспартат - Google Patents
Циклохексиламинови производни като подвид-селективни антагонисти на рецептора на n-метил - d-аспартат Download PDFInfo
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- BG107258A BG107258A BG107258A BG10725802A BG107258A BG 107258 A BG107258 A BG 107258A BG 107258 A BG107258 A BG 107258A BG 10725802 A BG10725802 A BG 10725802A BG 107258 A BG107258 A BG 107258A
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- Bulgaria
- Prior art keywords
- cyclohexyl
- phenol
- alkyl
- group
- hydrogen
- Prior art date
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- 229940127523 NMDA Receptor Antagonists Drugs 0.000 title description 2
- 150000003946 cyclohexylamines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 71
- 150000003839 salts Chemical class 0.000 claims abstract description 32
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- 201000006474 Brain Ischemia Diseases 0.000 claims abstract description 5
- 206010008120 Cerebral ischaemia Diseases 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 100
- -1 [4- (5-phenylpentylamino) cyclohexyl] phenol Chemical compound 0.000 claims description 96
- 229910052739 hydrogen Inorganic materials 0.000 claims description 77
- 125000000217 alkyl group Chemical group 0.000 claims description 76
- 239000001257 hydrogen Substances 0.000 claims description 69
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 53
- 239000000203 mixture Substances 0.000 claims description 51
- 125000001424 substituent group Chemical group 0.000 claims description 34
- 125000000623 heterocyclic group Chemical group 0.000 claims description 32
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 25
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 23
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 20
- 150000001408 amides Chemical class 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 150000002431 hydrogen Chemical class 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 18
- 125000001188 haloalkyl group Chemical group 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 15
- 125000005647 linker group Chemical group 0.000 claims description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
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- 125000004429 atom Chemical group 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 9
- MFZGWTAJGYWBEU-UHFFFAOYSA-N 4-[4-(3-phenylpropylamino)cyclohexyl]phenol Chemical compound C1=CC(O)=CC=C1C1CCC(NCCCC=2C=CC=CC=2)CC1 MFZGWTAJGYWBEU-UHFFFAOYSA-N 0.000 claims description 8
- 208000035475 disorder Diseases 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
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- 125000004001 thioalkyl group Chemical group 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 7
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- 108020003175 receptors Proteins 0.000 claims description 7
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- AFKFAJNGQSSQIZ-UHFFFAOYSA-N 2-(aminomethyl)-4-[4-[ethyl(3-phenylpropyl)amino]cyclohexyl]phenol Chemical compound C1CC(C=2C=C(CN)C(O)=CC=2)CCC1N(CC)CCCC1=CC=CC=C1 AFKFAJNGQSSQIZ-UHFFFAOYSA-N 0.000 claims description 4
- FFZAFMWWOKKINB-UHFFFAOYSA-N 4-[4-(3-phenylprop-2-ynylamino)cyclohexyl]phenol Chemical compound C1=CC(O)=CC=C1C1CCC(NCC#CC=2C=CC=CC=2)CC1 FFZAFMWWOKKINB-UHFFFAOYSA-N 0.000 claims description 4
- GPWBMSVTMPQJQL-UHFFFAOYSA-N 4-[4-[methyl(2-phenoxyethyl)amino]cyclohexyl]phenol Chemical compound C1CC(C=2C=CC(O)=CC=2)CCC1N(C)CCOC1=CC=CC=C1 GPWBMSVTMPQJQL-UHFFFAOYSA-N 0.000 claims description 4
- QPXQQOWQDOGSAY-UHFFFAOYSA-N 4-[4-[methyl(3-phenylpropyl)amino]cyclohexyl]phenol Chemical compound C1CC(C=2C=CC(O)=CC=2)CCC1N(C)CCCC1=CC=CC=C1 QPXQQOWQDOGSAY-UHFFFAOYSA-N 0.000 claims description 4
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- ZSCFHZMQBFWBIC-UHFFFAOYSA-N 4-[4-(2-anilinoethylamino)cyclohexyl]phenol Chemical compound C1=CC(O)=CC=C1C1CCC(NCCNC=2C=CC=CC=2)CC1 ZSCFHZMQBFWBIC-UHFFFAOYSA-N 0.000 claims description 3
- VLQMXBLFVHRNAT-UHFFFAOYSA-N 4-[4-(2-phenylethylamino)cyclohexyl]phenol Chemical compound C1=CC(O)=CC=C1C1CCC(NCCC=2C=CC=CC=2)CC1 VLQMXBLFVHRNAT-UHFFFAOYSA-N 0.000 claims description 3
- ZYCLAUOWJSDGTO-UHFFFAOYSA-N 4-[4-[benzyl(3-phenylpropyl)amino]cyclohexyl]phenol Chemical compound C1=CC(O)=CC=C1C1CCC(N(CCCC=2C=CC=CC=2)CC=2C=CC=CC=2)CC1 ZYCLAUOWJSDGTO-UHFFFAOYSA-N 0.000 claims description 3
- MMPGKIULWGETNC-UHFFFAOYSA-N 4-[4-[ethyl(3-phenylpropyl)amino]cyclohexyl]phenol Chemical compound C1CC(C=2C=CC(O)=CC=2)CCC1N(CC)CCCC1=CC=CC=C1 MMPGKIULWGETNC-UHFFFAOYSA-N 0.000 claims description 3
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- LHPSNJNPZAFCLK-UHFFFAOYSA-N 4-[4-(2-phenylsulfanylethylamino)cyclohexyl]phenol Chemical compound C1=CC(O)=CC=C1C1CCC(NCCSC=2C=CC=CC=2)CC1 LHPSNJNPZAFCLK-UHFFFAOYSA-N 0.000 claims description 2
- WMTXHOHVQJBPEK-UHFFFAOYSA-N 4-[4-[3-(4-methoxyphenyl)propylamino]cyclohexyl]phenol Chemical compound C1=CC(OC)=CC=C1CCCNC1CCC(C=2C=CC(O)=CC=2)CC1 WMTXHOHVQJBPEK-UHFFFAOYSA-N 0.000 claims description 2
- RQCPNEISYJHKDD-UHFFFAOYSA-N 4-[4-[3-phenylpropyl(propan-2-yl)amino]cyclohexyl]phenol Chemical compound C1CC(C=2C=CC(O)=CC=2)CCC1N(C(C)C)CCCC1=CC=CC=C1 RQCPNEISYJHKDD-UHFFFAOYSA-N 0.000 claims description 2
- CEFQMIDTRSQENZ-VQSBYGRUSA-N 4-[4-[[(2s)-1-phenylpropan-2-yl]amino]cyclohexyl]phenol Chemical compound C([C@H](C)NC1CCC(CC1)C=1C=CC(O)=CC=1)C1=CC=CC=C1 CEFQMIDTRSQENZ-VQSBYGRUSA-N 0.000 claims description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/24—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/25—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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| US19976200P | 2000-04-26 | 2000-04-26 | |
| PCT/US2001/013176 WO2001081295A1 (fr) | 2000-04-26 | 2001-04-24 | Derives cyclohexylamines utiles en tant qu'antagonistes selectifs de sous-types de recepteurs nmda |
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| US7064211B2 (en) * | 2002-03-22 | 2006-06-20 | Eisai Co., Ltd. | Hemiasterlin derivatives and uses thereof |
| AU2003303042A1 (en) * | 2002-12-17 | 2004-07-09 | Pfizer Inc. | 2-pyridyl and 2-pyrimidyl cycloalkylene amide compounds as nr2b receptor antagonists |
| US7732162B2 (en) | 2003-05-05 | 2010-06-08 | Probiodrug Ag | Inhibitors of glutaminyl cyclase for treating neurodegenerative diseases |
| US8071624B2 (en) | 2004-06-24 | 2011-12-06 | Incyte Corporation | N-substituted piperidines and their use as pharmaceuticals |
| CA2584502A1 (fr) * | 2004-06-24 | 2006-01-05 | Incyte Corporation | 2-methylpropanamides et leur utilisation comme produits pharmaceutiques |
| AU2005273986A1 (en) * | 2004-08-10 | 2006-02-23 | Incyte Corporation | Amido compounds and their use as pharmaceuticals |
| US8278345B2 (en) | 2006-11-09 | 2012-10-02 | Probiodrug Ag | Inhibitors of glutaminyl cyclase |
| ATE554085T1 (de) | 2006-11-30 | 2012-05-15 | Probiodrug Ag | Neue inhibitoren von glutaminylcyclase |
| JP5930573B2 (ja) | 2007-03-01 | 2016-06-15 | プロビオドルグ エージー | グルタミニルシクラーゼ阻害剤の新規使用 |
| EP2142514B1 (fr) | 2007-04-18 | 2014-12-24 | Probiodrug AG | Dérivés de thio-urée utilisés comme inhibiteurs de la glutaminyl cyclase |
| RU2446794C2 (ru) * | 2007-09-12 | 2012-04-10 | Мерц Фарма Гмбх Унд Ко. Кгаа | Терапия с интервалами для лечения тиннитуса |
| EP2548552B1 (fr) * | 2007-09-12 | 2015-11-18 | Merz Pharma GmbH & Co. KGaA | Ensemble de titration pour 1-amino-alkylcyclohexanes |
| WO2010021351A1 (fr) * | 2008-08-22 | 2010-02-25 | 第一三共株式会社 | Dérivé de cycloalkylamine |
| JP5934645B2 (ja) | 2009-09-11 | 2016-06-15 | プロビオドルグ エージー | グルタミニルシクラーゼ阻害剤としてのヘテロ環式誘導体 |
| JP6026284B2 (ja) | 2010-03-03 | 2016-11-16 | プロビオドルグ エージー | グルタミニルシクラーゼの阻害剤 |
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| EP2686313B1 (fr) | 2011-03-16 | 2016-02-03 | Probiodrug AG | Dérivés de benzimidazole en tant qu'inhibiteurs de la glutaminyl cyclase |
| CA2931313C (fr) | 2013-11-21 | 2022-04-05 | Marquette University | Composes substitues de (4'-hydroxyphenyl)cycloalkane et leurs utilisations en tant qu'agonistes selectifs de l'isoforme beta du recepteur d'oestrogenes |
| US9221796B2 (en) * | 2014-01-09 | 2015-12-29 | Bristol-Myers Squibb Company | Selective NR2B antagonists |
| US9187506B2 (en) | 2014-01-09 | 2015-11-17 | Bristol-Myers Squibb Company | (R)-3-((3S,4S)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one and its prodrugs for the treatment of psychiatric disorders |
| KR20190004743A (ko) * | 2016-05-04 | 2019-01-14 | 브리스톨-마이어스 스큅 컴퍼니 | 인돌아민 2,3-디옥시게나제의 억제제 및 그의 사용 방법 |
| ES2812698T3 (es) | 2017-09-29 | 2021-03-18 | Probiodrug Ag | Inhibidores de glutaminil ciclasa |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW209868B (fr) | 1991-04-04 | 1993-07-21 | Yoshitomi Pharmaceutical | |
| CA2091204C (fr) * | 1992-03-11 | 1997-04-08 | Ronald J. Mattson | Piperazinyl- et piperidinylcyclohexanes contre l'ischemie |
| DE4438020A1 (de) | 1994-10-25 | 1996-05-02 | Thomae Gmbh Dr K | N-substituierte Arylcyclohexylacylamine, ihre Salze mit physiologisch verträglichen organischen oder anorganischen Säuren, Verfahren zur Herstellung dieser Verbindungen und diese enthaltende Arzneimittel |
| WO1997015549A1 (fr) * | 1995-10-26 | 1997-05-01 | Tokyo Tanabe Company Limited | COMPOSES DE PHENYLETHANOLAMINE UTILES EN TANT QUE β3 AGONISTES, LEURS PROCEDE ET INTERMEDIAIRES DE PRODUCTION |
| PE20000728A1 (es) * | 1998-06-26 | 2000-08-21 | Cocensys Inc | Heterociclos 4-bencil piperidina alquilsulfoxido y su uso como antagonistas receptores subtipo-selectivo nmda |
| EP0982026B1 (fr) | 1998-08-18 | 2006-05-17 | F. Hoffmann-La Roche Ag | Utilisation de dérivés d'aryl-cyclohexylamine dans la fabrication d'agents bloquants du récepteur NMDA |
-
2001
- 2001-04-24 MX MXPA02009659A patent/MXPA02009659A/es active IP Right Grant
- 2001-04-24 DE DE60122495T patent/DE60122495T2/de not_active Expired - Fee Related
- 2001-04-24 KR KR1020027014329A patent/KR20020093950A/ko not_active Withdrawn
- 2001-04-24 IL IL15242401A patent/IL152424A0/xx unknown
- 2001-04-24 CZ CZ20023479A patent/CZ20023479A3/cs unknown
- 2001-04-24 WO PCT/US2001/013176 patent/WO2001081295A1/fr not_active Ceased
- 2001-04-24 SK SK1515-2002A patent/SK15152002A3/sk unknown
- 2001-04-24 ES ES01928803T patent/ES2267759T3/es not_active Expired - Lifetime
- 2001-04-24 AP APAP/P/2002/002664A patent/AP2002002664A0/en unknown
- 2001-04-24 EA EA200200952A patent/EA200200952A1/ru unknown
- 2001-04-24 JP JP2001578392A patent/JP2003531187A/ja active Pending
- 2001-04-24 BR BR0110247-8A patent/BR0110247A/pt not_active IP Right Cessation
- 2001-04-24 AT AT01928803T patent/ATE337292T1/de not_active IP Right Cessation
- 2001-04-24 AU AU2001255620A patent/AU2001255620A1/en not_active Abandoned
- 2001-04-24 CN CN01808644A patent/CN1441773A/zh active Pending
- 2001-04-24 EP EP01928803A patent/EP1278716B1/fr not_active Expired - Lifetime
- 2001-04-24 OA OA1200200326A patent/OA12253A/en unknown
- 2001-04-24 PL PL01358584A patent/PL358584A1/xx not_active Application Discontinuation
- 2001-04-24 HU HU0300600A patent/HUP0300600A2/hu unknown
- 2001-04-24 EE EEP200200612A patent/EE200200612A/xx unknown
- 2001-04-24 CA CA002406272A patent/CA2406272A1/fr not_active Abandoned
- 2001-04-24 US US10/258,721 patent/US6919377B2/en not_active Expired - Fee Related
-
2002
- 2002-09-27 IS IS6569A patent/IS6569A/is unknown
- 2002-10-10 ZA ZA200208177A patent/ZA200208177B/en unknown
- 2002-10-17 MA MA26873A patent/MA26895A1/fr unknown
- 2002-10-25 NO NO20025136A patent/NO20025136L/no not_active Application Discontinuation
- 2002-11-08 BG BG107258A patent/BG107258A/bg unknown
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| Publication number | Publication date |
|---|---|
| EE200200612A (et) | 2004-06-15 |
| PL358584A1 (en) | 2004-08-09 |
| KR20020093950A (ko) | 2002-12-16 |
| US6919377B2 (en) | 2005-07-19 |
| AP2002002664A0 (en) | 2002-12-31 |
| BR0110247A (pt) | 2003-03-05 |
| MXPA02009659A (es) | 2003-03-10 |
| ZA200208177B (en) | 2004-02-11 |
| SK15152002A3 (sk) | 2003-05-02 |
| NO20025136D0 (no) | 2002-10-25 |
| ATE337292T1 (de) | 2006-09-15 |
| EP1278716A1 (fr) | 2003-01-29 |
| NO20025136L (no) | 2002-12-20 |
| EP1278716B1 (fr) | 2006-08-23 |
| CN1441773A (zh) | 2003-09-10 |
| EA200200952A1 (ru) | 2003-02-27 |
| WO2001081295A1 (fr) | 2001-11-01 |
| ES2267759T3 (es) | 2007-03-16 |
| HUP0300600A2 (hu) | 2003-08-28 |
| AU2001255620A1 (en) | 2001-11-07 |
| JP2003531187A (ja) | 2003-10-21 |
| IS6569A (is) | 2002-09-27 |
| OA12253A (en) | 2006-05-11 |
| DE60122495T2 (de) | 2007-03-29 |
| US20030236286A1 (en) | 2003-12-25 |
| DE60122495D1 (de) | 2006-10-05 |
| CA2406272A1 (fr) | 2001-11-01 |
| CZ20023479A3 (cs) | 2003-04-16 |
| IL152424A0 (en) | 2003-05-29 |
| MA26895A1 (fr) | 2004-12-20 |
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