CN103788089A - 作为血清素受体调节剂的稠合杂环化合物 - Google Patents
作为血清素受体调节剂的稠合杂环化合物 Download PDFInfo
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- CN103788089A CN103788089A CN201410027820.XA CN201410027820A CN103788089A CN 103788089 A CN103788089 A CN 103788089A CN 201410027820 A CN201410027820 A CN 201410027820A CN 103788089 A CN103788089 A CN 103788089A
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- Prior art keywords
- phenyl
- tri
- azepines
- azulene
- hydrogen
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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| WO2005079845A1 (ja) * | 2004-02-20 | 2005-09-01 | Astellas Pharma Inc. | 片頭痛予防薬 |
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| KR102037494B1 (ko) | 2017-12-11 | 2019-10-28 | 씨제이헬스케어 주식회사 | 광학활성을 갖는 피페리딘 유도체의 중간체 및 이의 제조방법 |
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| US20230067461A1 (en) * | 2020-01-13 | 2023-03-02 | Aptabio Therapeutics Inc. | Novel pyrazole derivative |
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| IL322686A (en) | 2023-02-16 | 2025-10-01 | Gasherbrum Bio Inc | Heterocyclic glp-1 agonists |
Family Cites Families (94)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1197466B (de) * | 1962-03-22 | 1965-07-29 | Thomae Gmbh Dr K | Verfahren zur Herstellung von neuen 5, 6, 7, 8-Tetrahydropyrido-[4, 3-d]pyrimidinen |
| US3312716A (en) * | 1964-08-11 | 1967-04-04 | Aldrich Chem Co Inc | 4-hydroxy-3-pyrrolidinemethanols |
| GB1422263A (en) * | 1973-01-30 | 1976-01-21 | Ferrosan As | 4-phenyl-piperidine compounds |
| US4314081A (en) * | 1974-01-10 | 1982-02-02 | Eli Lilly And Company | Arloxyphenylpropylamines |
| GB1484140A (en) * | 1974-04-24 | 1977-08-24 | Wyeth John & Brother Ltd | Pyrrolopyridine derivatives |
| US3969355A (en) * | 1974-11-01 | 1976-07-13 | Morton-Norwich Products, Inc. | 5-Aminoethyl-2,4-diphenylpyrimidine dihydrobromide |
| GB1526331A (en) * | 1976-01-14 | 1978-09-27 | Kefalas As | Phthalanes |
| US4536518A (en) * | 1979-11-01 | 1985-08-20 | Pfizer Inc. | Antidepressant derivatives of cis-4-phenyl-1,2,3,4-tetrahydro-1-naphthalenamine |
| DK27383A (da) * | 1982-02-17 | 1983-08-18 | Lepetit Spa | Fremgangsmaade til fremstilling af pyrazol(4,3-c)pyridiner |
| US4673405A (en) * | 1983-03-04 | 1987-06-16 | Alza Corporation | Osmotic system with instant drug availability |
| US4576604A (en) * | 1983-03-04 | 1986-03-18 | Alza Corporation | Osmotic system with instant drug availability |
| US4857330A (en) * | 1986-04-17 | 1989-08-15 | Alza Corporation | Chlorpheniramine therapy |
| JPH03148265A (ja) | 1989-11-01 | 1991-06-25 | Sumitomo Chem Co Ltd | 5,7―ジフェニル―4,6―ジアザインダン誘導体、その製造法およびそれを有効成分とする除草剤 |
| US5137890A (en) * | 1990-02-14 | 1992-08-11 | Ortho Pharmaceutical Corporation | 4-phenyl tetrahydropyrido(4,3-d)pyrimidines |
| US5053508A (en) | 1990-03-09 | 1991-10-01 | American Home Products Corporation | Fused heterotricyclic imides with psychotropic activity and intermedrates thereof |
| US5648352A (en) * | 1991-09-13 | 1997-07-15 | Merck & Co., Inc. | Piperazinylcamphorsulfonyl oxytocin antagonists |
| US5612356A (en) | 1992-12-28 | 1997-03-18 | Eisai Co., Ltd. | Heterocycle-containing carbonic acid derivatives |
| US6677310B1 (en) * | 1999-04-21 | 2004-01-13 | Nabi | Ring-expanded nucleosides and nucleotides |
| US5843912A (en) * | 1994-07-06 | 1998-12-01 | Universy Of Maryland | Ring-expanded nucleosides and nucleotides |
| US5405848A (en) * | 1993-12-22 | 1995-04-11 | Ortho Pharmaceutical Corporation | Substituted thiazolylaminotetrahydropyridopyrimidines derivatives useful as platelet aggregation inhibitors |
| US5663178A (en) * | 1995-02-06 | 1997-09-02 | Eli Lilly And Company | Tetrahydro-beta carbolines |
| JP3004728B2 (ja) | 1994-04-29 | 2000-01-31 | ファイザー インク. | 神経伝達物質放出増強薬としての新規な非環式および環式アミド類 |
| AU5317996A (en) | 1995-04-18 | 1996-11-07 | Eli Lilly And Company | Method for using ergoline compounds to effect physiological and pathological functions at the 5-ht7 receptor |
| WO1997029097A1 (en) | 1996-02-09 | 1997-08-14 | Smithkline Beecham Plc | Sulfonamide derivatives as 5ht7 receptor antagonists |
| TW470745B (en) * | 1996-05-23 | 2002-01-01 | Janssen Pharmaceutica Nv | Hexahydro-pyrido[4,3-b]indole derivatives |
| AU2980797A (en) | 1996-06-11 | 1998-01-07 | Yoshitomi Pharmaceutical Industries, Ltd. | Fused heterocyclic compounds and medicinal uses thereof |
| GB9612884D0 (en) | 1996-06-20 | 1996-08-21 | Smithkline Beecham Plc | Novel compounds |
| JP2000512646A (ja) | 1996-06-25 | 2000-09-26 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | 5ht7受容体アンタゴニストとしてのスルホンアミド誘導体 |
| US6355642B1 (en) * | 1996-06-28 | 2002-03-12 | Meiji Seika Kaisha, Ltd. | Tetrahydrobenzindole compounds |
| GB9700899D0 (en) | 1997-01-17 | 1997-03-05 | Smithkline Beecham Plc | Novel treatment |
| JP2001514631A (ja) | 1997-03-07 | 2001-09-11 | ノボ ノルディスク アクティーゼルスカブ | 4,5,6,7−テトラヒドロ−チエノ[3,2−c]ピリジン誘導体類、それらの製造方法及び使用 |
| US6177443B1 (en) * | 1997-03-07 | 2001-01-23 | Novo Nordisk A/S | 4,5,6,7-tetrahydro-thieno[3, 2-C]pyridine derivatives, their preparation and use |
| EP0905136A1 (en) * | 1997-09-08 | 1999-03-31 | Janssen Pharmaceutica N.V. | Tetrahydro gamma-carbolines |
| US5951518A (en) | 1997-10-31 | 1999-09-14 | Teleflex, Incorporated | Introducing device with flared sheath end |
| WO1999024022A2 (en) | 1997-11-10 | 1999-05-20 | F. Hoffmann-La Roche Ag | Isoquinoline derivatives for treating disorders associated with 5ht7 receptors |
| US6407112B1 (en) * | 1998-04-22 | 2002-06-18 | Meiji Seika Kaisha, Ltd. | Optically active tetrahydrobenzindole derivative |
| JP2002516282A (ja) | 1998-05-22 | 2002-06-04 | イーライ・リリー・アンド・カンパニー | 難治性鬱病の処置のための組合せ治療 |
| US5997905A (en) * | 1998-09-04 | 1999-12-07 | Mcneil-Ppc | Preparation of pharmaceutically active particles |
| AU1321900A (en) | 1998-10-23 | 2000-05-15 | Sepracor, Inc. | Compositions and methods employing r(-) fluoxetine and other active ingredients |
| US6245785B1 (en) | 1998-11-30 | 2001-06-12 | Warner Lambert Company | Dissolution of triprolidine hydrochloride |
| GB9828004D0 (en) | 1998-12-18 | 1999-02-10 | Smithkline Beecham Plc | Use |
| GB9906624D0 (en) | 1999-03-23 | 1999-05-19 | Smithkline Beecham Plc | Novel compounds |
| CA2366858A1 (en) * | 1999-04-01 | 2000-10-12 | Margaret Yuhua Chu-Moyer | Sorbitol dehydrogenase inhibitors |
| GB9912701D0 (en) | 1999-06-01 | 1999-08-04 | Smithkline Beecham Plc | Novel compounds |
| US6806230B1 (en) | 1999-09-09 | 2004-10-19 | Kumiai Chemical Industry Co., Ltd. | Pyrimidine derivatives and herbicides containing them |
| EP1222185A1 (en) | 1999-10-18 | 2002-07-17 | Smithkline Beecham Plc | Tetrahydrobenzindolone derivatives, their preparation and their use as 5-ht7 receptor antagonists |
| UA77650C2 (en) | 1999-12-06 | 2007-01-15 | Lundbeck & Co As H | Use of serotonin reuptake inhibitor in combination with deramcyclane |
| CA2399545A1 (en) | 2000-02-04 | 2001-08-09 | Michael Gerard Kelly | Pyrrolo-isoquinoline and tetrahydropyrrolo-isoquinoline derivatives and their use as mediators of the 5-ht7 receptor |
| AU2001241128A1 (en) | 2000-03-14 | 2001-09-24 | Fujisawa Pharmaceutical Co. Ltd. | Novel amide compounds |
| US6586469B2 (en) | 2000-07-25 | 2003-07-01 | Medpointe Healthcare Inc. | Antihistaminic/antitussive compositions |
| EP1309591B1 (en) | 2000-08-14 | 2007-01-24 | Ortho-McNeil Pharmaceutical, Inc. | Substituted pyrazoles |
| AU8870601A (en) * | 2000-09-06 | 2002-03-22 | Ortho Mcneil Pharm Inc | A method for treating allergies using substituted pyrazoles |
| US20040267010A1 (en) | 2001-02-02 | 2004-12-30 | Forbes Ian Thomson | Sulfonamide compounds, their preparation and use |
| HUP0303270A3 (en) * | 2001-02-21 | 2007-03-28 | Janssen Pharmaceutica Nv | Isoxazoline derivatives as anti-depressants, process for their preparation and pharmaceutical compositions containing them |
| US20020183519A1 (en) * | 2001-03-13 | 2002-12-05 | Herbert Nar | Antithrombotic carboxylic acid amides |
| DE10111842A1 (de) | 2001-03-13 | 2002-09-19 | Boehringer Ingelheim Pharma | Antithrombotische Carbonsäureamide, deren Herstellung und deren Verwendung als Arzneimittel |
| US6559174B2 (en) * | 2001-03-20 | 2003-05-06 | Merck & Co., Inc. | N-arylsulfonyl aryl aza-bicyclic derivatives as potent cell adhesion inhibitors |
| US6806380B2 (en) * | 2001-10-02 | 2004-10-19 | Lexicon Pharmaceuticals, Inc. | Modified safe and efficient process for the environmentally friendly synthesis of imidoesters |
| IL161576A0 (en) * | 2001-10-26 | 2004-09-27 | Aventis Pharma Inc | Benzimidazoles and analogues and their use as protein kinases inhibitors |
| US6806279B2 (en) | 2001-12-17 | 2004-10-19 | Sunesis Pharmaceuticals, Inc. | Small-molecule inhibitors of interleukin-2 |
| SE0104340D0 (sv) | 2001-12-20 | 2001-12-20 | Astrazeneca Ab | New compounds |
| US20030199542A1 (en) * | 2002-04-18 | 2003-10-23 | Woods Keith W. | Farnesyltransferase inhibitors |
| US20030199544A1 (en) * | 2002-04-18 | 2003-10-23 | Woods Keith W. | Farnesyltransferase inhibitors |
| HRP20020452A2 (en) | 2002-05-23 | 2004-02-29 | Pliva D D | 1,2-diaza-dibenzoazulen as inhibitor of production of tumor necrosis factors and intermediates for preparation thereof |
| KR20050013562A (ko) * | 2002-05-30 | 2005-02-04 | 버텍스 파마슈티칼스 인코포레이티드 | Jak 및 cdk2 프로테인 키나아제의 억제제 |
| EP1545552B1 (en) * | 2002-06-20 | 2007-03-28 | H. Lundbeck A/S | Combination therapy wherein a serotonin reuptake inhibitor is used |
| AU2003244649A1 (en) | 2002-07-25 | 2004-02-23 | Pharmacia Italia Spa | Bicyclo-pyrazoles active as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them |
| CA2493625A1 (en) | 2002-07-25 | 2004-02-19 | Pharmacia Italia S.P.A. | Bicyclo-pyrazoles active as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them |
| WO2004011467A1 (ja) | 2002-07-29 | 2004-02-05 | Hokko Chemical Industry Co., Ltd. | トリアゾロピリミジン誘導体および農園芸用殺菌剤 |
| US20040132826A1 (en) | 2002-10-25 | 2004-07-08 | Collegium Pharmaceutical, Inc. | Modified release compositions of milnacipran |
| AU2003274050A1 (en) | 2002-10-30 | 2004-05-25 | Ciba Specialty Chemicals Holding Inc. | Electroluminescent device |
| MXPA05008137A (es) * | 2003-01-31 | 2005-09-30 | Pfizer Prod Inc | Antagonistas y agonistas de 5ht7. |
| GB0308208D0 (en) | 2003-04-09 | 2003-05-14 | Glaxo Group Ltd | Chemical compounds |
| US7145012B2 (en) * | 2003-04-23 | 2006-12-05 | Pfizer Inc. | Cannabinoid receptor ligands and uses thereof |
| GB0316128D0 (en) | 2003-07-10 | 2003-08-13 | Univ Aston | Novel sulfonamide compounds |
| BRPI0412262A (pt) | 2003-07-23 | 2006-09-19 | X Ceptor Therapeutics Inc | derivados de azepina como agentes farmacêuticos |
| AU2004283196B2 (en) | 2003-09-17 | 2011-08-25 | Janssen Pharmaceutica, N.V. | Fused heterocyclic compounds |
| WO2005030776A1 (en) * | 2003-09-23 | 2005-04-07 | Vertex Pharmaceuticals Incorporated | Pyrazolopyrrole derivatives as protein kinase inhibitors |
| AU2004275777A1 (en) | 2003-09-24 | 2005-04-07 | Combinatorx, Incorporated | Therapeutic regimens for administering drug combinations |
| WO2005056056A2 (en) | 2003-12-15 | 2005-06-23 | H. Lundbeck A/S | The combination of a serotonin reuptake inhibitor and a histamine 3 receptor antagonist, inverse agonist or partial agonist |
| US20050232986A1 (en) * | 2003-12-17 | 2005-10-20 | David Brown | Dosage form containing promethazine and another drug |
| US20090227562A1 (en) | 2004-08-10 | 2009-09-10 | Pfizer Inc. | Combination of a Selective Noradrenaline Reuptake Unhibitor and a PDEV Inhibitor |
| US20060037652A1 (en) | 2004-08-23 | 2006-02-23 | Ranco Incorporated Of Delaware | Reversing valve assembly with improved pilot valve mounting structure |
| ATE496892T1 (de) * | 2004-12-17 | 2011-02-15 | Janssen Pharmaceutica Nv | Tetrahydroisochinolinverbindungen zur behandlung von zns-erkrankungen |
| PL1899334T3 (pl) * | 2005-06-17 | 2009-04-30 | Janssen Pharmaceutica Nv | Związki naftyrydynowe |
| AU2006259257A1 (en) * | 2005-06-17 | 2006-12-28 | Janssen Pharmaceutica N.V. | Hexahydro-pyrrolo-isoquinoline compounds for the treatment of CNS disorders |
| NZ565334A (en) | 2005-08-04 | 2010-12-24 | Janssen Pharmaceutica Nv | Pyrimidine compounds as serotonin receptor modulators |
| US7598255B2 (en) * | 2005-08-04 | 2009-10-06 | Janssen Pharmaceutica Nv | Pyrimidine compounds as serotonin receptor modulators |
| KR20080109841A (ko) * | 2006-03-10 | 2008-12-17 | 뉴로젠 코포레이션 | 피페라지닐 옥소알킬 테트라히드로이소퀴놀린 및 관련유사체 |
| CN101479252B (zh) * | 2006-05-05 | 2014-01-29 | 詹森药业有限公司 | 用于制备含吡唑的化合物的方法 |
| AU2007265239A1 (en) * | 2006-06-29 | 2008-01-03 | Janssen Pharmaceutica N.V. | Butyl and butynyl benzyl amine compounds |
| CN101511790A (zh) * | 2006-06-29 | 2009-08-19 | 詹森药业有限公司 | 取代的氨基甲基苯甲酰胺化合物 |
| EP2049473A2 (en) * | 2006-06-29 | 2009-04-22 | Janssen Pharmaceutica N.V. | Substituted benzyl amine compounds |
| WO2008064036A1 (en) * | 2006-11-16 | 2008-05-29 | Janssen Pharmaceutica N.V. | Substituted phenyl propyl amines as histamine h3 receptor and serotonin transporter modulators |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105503647A (zh) * | 2015-12-10 | 2016-04-20 | 苏州昊帆生物科技有限公司 | 环丙基肼盐酸盐的制备方法 |
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