CA2499326A1 - Heterocyclic substituted piperazines for the treatment of schizophrenia - Google Patents
Heterocyclic substituted piperazines for the treatment of schizophrenia Download PDFInfo
- Publication number
- CA2499326A1 CA2499326A1 CA002499326A CA2499326A CA2499326A1 CA 2499326 A1 CA2499326 A1 CA 2499326A1 CA 002499326 A CA002499326 A CA 002499326A CA 2499326 A CA2499326 A CA 2499326A CA 2499326 A1 CA2499326 A1 CA 2499326A1
- Authority
- CA
- Canada
- Prior art keywords
- disorder
- disorders
- dihydro
- quinolin
- piperazin
- 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.)
- Abandoned
Links
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- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
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- C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
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- 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
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- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
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Applications Claiming Priority (5)
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| US41147502P | 2002-09-17 | 2002-09-17 | |
| US60/411,475 | 2002-09-17 | ||
| US41635502P | 2002-10-04 | 2002-10-04 | |
| US60/416,355 | 2002-10-04 | ||
| PCT/IB2003/003902 WO2004026864A1 (en) | 2002-09-17 | 2003-09-05 | Heterocyclic substituted piperazines for the treatment of schizophrenia |
Publications (1)
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| CA2499326A1 true CA2499326A1 (en) | 2004-04-01 |
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| Application Number | Title | Priority Date | Filing Date |
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| CA002499326A Abandoned CA2499326A1 (en) | 2002-09-17 | 2003-09-05 | Heterocyclic substituted piperazines for the treatment of schizophrenia |
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| CA2505397A1 (en) * | 2002-11-08 | 2004-05-21 | Warner-Lambert Company Llc | Phenylalkyl and pyridylalkyl piperazine derivatives |
| BRPI0416739A (pt) * | 2003-12-08 | 2007-01-16 | Warner Lambert Co | derivados de indano substituìdo heterocìclico e compostos afins para o tratamento de esquizofrenia |
| MXPA06007654A (es) * | 2003-12-31 | 2006-09-04 | Warner Lambert Co | Derivados de piperidina n-sustituidos. |
| US20050256118A1 (en) * | 2004-05-12 | 2005-11-17 | Altenbach Robert J | Bicyclic-substituted amines having cyclic-substituted monocyclic substituents |
| US7098222B2 (en) | 2004-05-12 | 2006-08-29 | Abbott Laboratories | Bicyclic-substituted amines having cyclic-substituted monocyclic substituents |
| WO2006090273A2 (en) * | 2005-02-22 | 2006-08-31 | Warner-Lambert Company Llc | [1,8]naphthyridin-2-ones and related compounds with keto or hydroxyl linkers for the treatment of schizophrenia |
| TWI320783B (en) | 2005-04-14 | 2010-02-21 | Otsuka Pharma Co Ltd | Heterocyclic compound |
| JP4315393B2 (ja) * | 2005-04-14 | 2009-08-19 | 大塚製薬株式会社 | 複素環化合物 |
| TWI329641B (en) | 2005-08-31 | 2010-09-01 | Otsuka Pharma Co Ltd | (benzo[b]thiophen-4-yl)piperazine compounds, pharmaceutical compositions comprising the same, uses of the same and processes for preparing the same |
| WO2008015516A1 (en) * | 2006-07-28 | 2008-02-07 | Pfizer Products Inc. | Fused tricyclic heterocycles for the treatment of schizophrenia |
| JP4540700B2 (ja) * | 2006-10-13 | 2010-09-08 | 大塚製薬株式会社 | 医薬 |
| AR063302A1 (es) * | 2006-10-13 | 2009-01-21 | Otsuka Pharma Co Ltd | Derivados de 4-benzo[b]tiofen-4-il-piperazin-1-il con accion antagonista del receptor 5-ht2a de serotonina y receptor de adrenalina alfa1 y agonista parcial del receptor d2, una composicion farmaceutica que lo comprende y un proceso para producirla. |
| JP4785881B2 (ja) * | 2007-02-27 | 2011-10-05 | 大塚製薬株式会社 | 医薬 |
| RU2497819C2 (ru) * | 2007-05-21 | 2013-11-10 | Ривайва Фармасьютикалс, Инк. | Композиции, синтез и способы применения атипичных нейролептиков на основе хинолина |
| CA2723775A1 (en) | 2008-05-08 | 2009-11-12 | Allergan, Inc. | Therapeutically useful substituted 1,7-diphenyl-1,2,3,5,6,7-hexahydropyrido[3,2,1-ij]quinoline compounds |
| US20090281322A1 (en) * | 2008-05-08 | 2009-11-12 | Allergan, Inc. | THERAPEUTICALLY USEFUL SUBSTITUTED 1,7-DIPHENYL-1,2,3,5,6,7-HEXAHYDROPYRIDO[3,2,1-Ij]QUINOLINE COMPOUNDS |
| JP2011529090A (ja) * | 2008-07-28 | 2011-12-01 | 江蘇国華投資有限公司 | アラルキルピペリジン(又はピペラジン)誘導体及びその統合失調症治療のための使用 |
| CN102159557A (zh) | 2008-09-22 | 2011-08-17 | 弗·哈夫曼-拉罗切有限公司 | 哌嗪d3和5-ht2a受体调节剂 |
| CA2736724A1 (en) * | 2008-09-23 | 2010-04-01 | F.Hoffmann-La Roche Ag | Benzo[d]isoxazol-3-yl-piperazin derivatives useful as modulators of dopamine d3 receptors |
| AU2014265021B2 (en) * | 2009-06-25 | 2016-07-21 | Alkermes Pharma Ireland Limited | Prodrugs of nh-acidic compounds |
| PT2445502T (pt) * | 2009-06-25 | 2017-09-22 | Alkermes Pharma Ireland Ltd | Compostos heterocíclicos para o tratamento de distúrbios neurológicos e psicológicos |
| JP5732453B2 (ja) | 2009-06-25 | 2015-06-10 | アルカーメス ファーマ アイルランド リミテッド | Nh酸性化合物のプロドラッグ |
| TWI503323B (zh) * | 2010-03-29 | 2015-10-11 | Oncotherapy Science Inc | 三環化合物以及含此化合物之pbk抑制劑 |
| US8877778B2 (en) | 2010-12-15 | 2014-11-04 | Hoffmann-La Roche Inc. | Benzofurane compounds |
| ES2972387T3 (es) | 2011-03-18 | 2024-06-12 | Alkermes Pharma Ireland Ltd | Composiciones farmacéuticas que comprenden ésteres de sorbitán |
| US8921397B2 (en) | 2011-05-04 | 2014-12-30 | Hoffmann-La Roche Inc. | Benzofurane-piperidine compounds |
| ES2601457T3 (es) | 2011-07-28 | 2017-02-15 | Otsuka Pharmaceutical Co., Ltd. | Método para producir compuestos de benzo[b]tiofeno |
| JO3227B1 (ar) * | 2011-09-08 | 2018-03-08 | Otsuka Pharma Co Ltd | مشتقات بنزو ثيوفين بها استبدال ببرازين كعوامل مضادة للذهان |
| WO2013088255A1 (en) | 2011-12-15 | 2013-06-20 | Alkermes Pharma Ireland Limited | Prodrugs of secondary amine compounds |
| WO2013142202A1 (en) | 2012-03-19 | 2013-09-26 | Alkermes Pharma Ireland Limited | Pharmaceutical compositions comprising glycerol esters |
| US9999670B2 (en) | 2012-03-19 | 2018-06-19 | Alkermes Pharma Ireland Limited | Pharmaceutical compositions comprising benzyl alcohol |
| CA2867121C (en) | 2012-03-19 | 2021-05-25 | Alkermes Pharma Ireland Limited | Pharmaceutical compositions comprising fatty acid esters |
| JP6654042B2 (ja) | 2012-09-19 | 2020-02-26 | アルカームス ファーマ アイルランド リミテッド | 貯蔵安定性が改善された医薬組成物 |
| AU2015231278B2 (en) | 2014-03-20 | 2020-01-23 | Alkermes Pharma Ireland Limited | Aripiprazole formulations having increased injection speeds |
| JP5714152B2 (ja) * | 2014-03-26 | 2015-05-07 | 江蘇恒誼薬業有限公司 | アラルキルピペリジン(又はピペラジン)誘導体及びその統合失調症治療のための使用 |
| CN106608875A (zh) * | 2015-10-26 | 2017-05-03 | 江苏恩华药业股份有限公司 | 一种稠和杂环类衍生物合成及其应用 |
| CN106749219A (zh) * | 2015-11-20 | 2017-05-31 | 江苏恩华药业股份有限公司 | 一种内酰胺类衍生物及其应用 |
| AU2019230014B2 (en) | 2018-03-05 | 2024-11-28 | Alkermes Pharma Ireland Limited | Aripiprazole dosing strategy |
| JPWO2020230802A1 (enExample) * | 2019-05-14 | 2020-11-19 | ||
| WO2021098737A1 (zh) * | 2019-11-18 | 2021-05-27 | 上海枢境生物科技有限公司 | 稠和杂环类衍生物及其应用 |
| EP4382521A4 (en) * | 2021-08-05 | 2025-01-01 | Shujing Biopharma Co., Ltd | Regulator containing tricyclic derivative, preparation method therefor and application thereof |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3706427A1 (de) * | 1987-02-27 | 1988-09-08 | Boehringer Mannheim Gmbh | Neue substituierte 3h-indole, zwischenprodukte, verfahren zu ihrer herstellung sowie arzneimittel |
| GB8723763D0 (en) * | 1987-10-09 | 1987-11-11 | Hydro Tech Ltd | Liquid flow control device |
| US4831031A (en) * | 1988-01-22 | 1989-05-16 | Pfizer Inc. | Aryl piperazinyl-(C2 or C4) alkylene heterocyclic compounds having neuroleptic activity |
| US5776963A (en) * | 1989-05-19 | 1998-07-07 | Hoechst Marion Roussel, Inc. | 3-(heteroaryl)-1- (2,3-dihydro-1h-isoindol-2-yl)alkyl!pyrrolidines and 3-(heteroaryl)-1- (2,3-dihydro-1h-indol-1-yl)alkyl!pyrrolidines and related compounds and their therapeutic untility |
| US5364866A (en) * | 1989-05-19 | 1994-11-15 | Hoechst-Roussel Pharmaceuticals, Inc. | Heteroarylpiperidines, pyrrolidines and piperazines and their use as antipsychotics and analetics |
| ES2076253T3 (es) * | 1989-05-19 | 1995-11-01 | Hoechst Roussel Pharma | N-(ariloxialquil)-heteroarilpiperidinas y -heteroarilpiperazinas, un procedimiento para su preparacion y su uso como medicamentos. |
| JP2768981B2 (ja) * | 1989-06-22 | 1998-06-25 | シャープ株式会社 | 光メモリ素子 |
| WO1991000863A1 (en) * | 1989-07-07 | 1991-01-24 | Pfizer Inc. | Heteroaryl piperazine antipsychotic agents |
| US5350747A (en) * | 1989-07-07 | 1994-09-27 | Pfizer Inc | Heteroaryl piperazine antipsychotic agents |
| US5147881A (en) * | 1990-11-14 | 1992-09-15 | Pfizer Inc | 4-(1,2-benzisoxazolyl)piperidine antipsychotic agents |
| US5143923B1 (en) * | 1991-04-29 | 1993-11-02 | Hoechst-Roussel Pharmaceuticals Incorporated | Benzoisothiazole-and benzisoxazole-3-carboxamides |
| MX9201991A (es) * | 1991-05-02 | 1992-11-01 | Jonh Wyeth & Brother Limited | Derivados de piperazina y procedimiento para su preparacion. |
| IT1251144B (it) * | 1991-07-30 | 1995-05-04 | Boehringer Ingelheim Italia | Derivati del benzimidazolone |
| TW300219B (enExample) * | 1991-09-14 | 1997-03-11 | Hoechst Ag | |
| US5206366A (en) * | 1992-08-26 | 1993-04-27 | Pfizer Inc. | Process for preparing aryl piperazinyl-heterocyclic compounds |
| UA57734C2 (uk) * | 1996-05-07 | 2003-07-15 | Пфайзер Інк. | Комплекси включення арилгетероциклічних солей |
| IL125951A (en) * | 1997-09-05 | 2003-09-17 | Pfizer Prod Inc | A pharmaceutical composition comprising a piperazinyl-heterocyclic compound for treating tourette's syndrome, obsessive compulsive disorder, chronic motor or vocal tic disorder in a mammal |
| DE19746612A1 (de) * | 1997-10-22 | 1999-04-29 | Basf Ag | 2-Substituierte 1,2-Benzisothiazol-Derivate, ihre Herstellung und Verwendung |
| IL127497A (en) * | 1997-12-18 | 2002-07-25 | Pfizer Prod Inc | Medicinal products containing piperazinyl-heterocyclic compounds for the treatment of psychiatric disorders |
| US6387904B2 (en) * | 1998-05-18 | 2002-05-14 | Pfizer Inc | Method of treating glaucoma and ischemic retinopathy |
| HK1047582B (zh) * | 1999-06-23 | 2005-03-04 | 萨诺费-阿文蒂斯德国有限公司 | 取代的苯並咪唑 |
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2003
- 2003-09-05 EA EA200500342A patent/EA200500342A1/ru unknown
- 2003-09-05 EP EP03797433A patent/EP1546143A1/en not_active Withdrawn
- 2003-09-05 JP JP2004568902A patent/JP2006503106A/ja active Pending
- 2003-09-05 PL PL03375981A patent/PL375981A1/xx not_active Application Discontinuation
- 2003-09-05 BR BR0314393-7A patent/BR0314393A/pt not_active IP Right Cessation
- 2003-09-05 AU AU2003263413A patent/AU2003263413A1/en not_active Abandoned
- 2003-09-05 CA CA002499326A patent/CA2499326A1/en not_active Abandoned
- 2003-09-05 MX MXPA05002007A patent/MXPA05002007A/es unknown
- 2003-09-05 WO PCT/IB2003/003902 patent/WO2004026864A1/en not_active Ceased
- 2003-09-05 OA OA1200500072A patent/OA12923A/en unknown
- 2003-09-05 HR HR20050248A patent/HRP20050248A2/hr not_active Application Discontinuation
- 2003-09-05 KR KR1020057004592A patent/KR20050057404A/ko not_active Abandoned
- 2003-09-05 AP AP2005003250A patent/AP2005003250A0/xx unknown
- 2003-09-05 RS YUP-2005/0195A patent/RS20050195A/sr unknown
- 2003-09-12 PE PE2003000930A patent/PE20050132A1/es not_active Application Discontinuation
- 2003-09-12 US US10/660,908 patent/US20040138230A1/en not_active Abandoned
- 2003-09-15 AR ARP030103336A patent/AR041260A1/es unknown
- 2003-09-15 UY UY27976A patent/UY27976A1/es not_active Application Discontinuation
- 2003-09-15 PA PA20038582601A patent/PA8582601A1/es unknown
- 2003-09-16 TW TW092125508A patent/TW200409771A/zh unknown
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- 2005-02-24 IS IS7710A patent/IS7710A/is unknown
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- 2005-03-17 MA MA28152A patent/MA27438A1/fr unknown
- 2005-03-18 CO CO05025665A patent/CO5550472A2/es not_active Application Discontinuation
- 2005-04-15 NO NO20051826A patent/NO20051826L/no not_active Application Discontinuation
Also Published As
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|---|---|
| BR0314393A (pt) | 2005-07-19 |
| UY27976A1 (es) | 2004-04-30 |
| PA8582601A1 (es) | 2004-05-26 |
| AU2003263413A1 (en) | 2004-04-08 |
| TW200409771A (en) | 2004-06-16 |
| WO2004026864A1 (en) | 2004-04-01 |
| NO20051826L (no) | 2005-04-15 |
| EA200500342A1 (ru) | 2005-08-25 |
| PE20050132A1 (es) | 2005-03-21 |
| RS20050195A (sr) | 2007-08-03 |
| PL375981A1 (en) | 2005-12-12 |
| CO5550472A2 (es) | 2005-08-31 |
| KR20050057404A (ko) | 2005-06-16 |
| IS7710A (is) | 2005-02-24 |
| MXPA05002007A (es) | 2005-04-28 |
| ECSP055676A (es) | 2005-07-06 |
| AR041260A1 (es) | 2005-05-11 |
| OA12923A (en) | 2006-10-13 |
| EP1546143A1 (en) | 2005-06-29 |
| HRP20050248A2 (en) | 2005-10-31 |
| AP2005003250A0 (en) | 2005-03-31 |
| US20040138230A1 (en) | 2004-07-15 |
| MA27438A1 (fr) | 2005-07-01 |
| JP2006503106A (ja) | 2006-01-26 |
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