HRP20010488A2 - 5ht1 antagonists for antidepressant therapy - Google Patents
5ht1 antagonists for antidepressant therapy Download PDFInfo
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- HRP20010488A2 HRP20010488A2 HR20010488A HRP20010488A HRP20010488A2 HR P20010488 A2 HRP20010488 A2 HR P20010488A2 HR 20010488 A HR20010488 A HR 20010488A HR P20010488 A HRP20010488 A HR P20010488A HR P20010488 A2 HRP20010488 A2 HR P20010488A2
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- fluoro
- octahydro
- pyrido
- isoxazol
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Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11395798P | 1998-12-28 | 1998-12-28 | |
| PCT/IB1999/001772 WO2000039128A1 (en) | 1998-12-28 | 1999-11-03 | 5ht1 antagonists for antidepressant therapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20010488A2 true HRP20010488A2 (en) | 2002-08-31 |
Family
ID=22352526
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20010488A HRP20010488A2 (en) | 1998-12-28 | 2001-06-28 | 5ht1 antagonists for antidepressant therapy |
Country Status (43)
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60229123D1 (de) * | 2001-02-20 | 2008-11-13 | Dinan Timothy Gerard | Behandlung von fibromyalgie mit pindolol |
| GB0203778D0 (en) * | 2002-02-18 | 2002-04-03 | Glaxo Group Ltd | Compounds |
| PL378749A1 (pl) * | 2003-03-12 | 2006-05-15 | Pfizer Products Inc. | Azabicykliczne pochodne pirydyloksymetylowe i benzoizoksazolowe |
| GB0316915D0 (en) * | 2003-07-18 | 2003-08-20 | Glaxo Group Ltd | Compounds |
| BRPI0507250A (pt) * | 2004-01-29 | 2007-06-26 | Pfizer Prod Inc | combinações para tratar desordens do snc |
| AR048112A1 (es) * | 2004-03-25 | 2006-03-29 | Solvay Pharm Bv | Derivados de 1-(2h-1-benzopiran-2-on-8-il)-piperazina para el tratamiento de dolor |
| AR049478A1 (es) | 2004-03-25 | 2006-08-09 | Solvay Pharm Bv | Un procedimiento para la preparacion de 3-amino-8-(1-piperazinil)-2h-1-benzopiran-2-ona. sales e hidratos y composiciones farmaceuticas. |
| EP1791541A2 (en) * | 2004-09-10 | 2007-06-06 | Pfizer Products Inc. | Methods of treating mood disorders using benzisoxazole containing diazabicyclic compounds |
| JP2008512441A (ja) * | 2004-09-10 | 2008-04-24 | ファイザー・プロダクツ・インク | ピリジルオキシメチル、及びベンズイソオキサゾール・アザビシクロ誘導体を使用する、認知障害の治療方法 |
| DE102005026194A1 (de) * | 2005-06-06 | 2006-12-07 | Grünenthal GmbH | Substituierte N-Benzo[d]isoxazol-3-yl-amin-Derivate und deren Verwendung zur Herstellung von Arzneimitteln |
| WO2008019431A1 (en) * | 2006-08-14 | 2008-02-21 | Brc Operations Pty Limited | Method and compositions for simultaneously regulating memory and mood |
| EP2919788A4 (en) | 2012-11-14 | 2016-05-25 | Univ Johns Hopkins | METHODS AND COMPOSITIONS FOR THE TREATMENT OF SCHIZOPHRENIA |
| WO2020183011A1 (en) | 2019-03-14 | 2020-09-17 | Institut Curie | Htr1d inhibitors and uses thereof in the treatment of cancer |
| AU2020407614A1 (en) * | 2019-12-20 | 2022-08-18 | The Jackson Laboratory | Molecular targets for addiction |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5157034A (en) * | 1991-02-27 | 1992-10-20 | Pfizer Inc. | Neuroleptic perhydro-1H-pyrido[1,2-a]pyrazines |
| GB9410512D0 (en) * | 1994-05-25 | 1994-07-13 | Smithkline Beecham Plc | Novel treatment |
| US5756496A (en) * | 1994-05-28 | 1998-05-26 | Smithkline Beecham P.L.C. | Amide derivatives having 5HT1D-antagonist activity |
| NZ500252A (en) * | 1997-04-18 | 2001-07-27 | Smithkline Beecham P | 6-(4-Methyl-piperazin-1-yl)-1H-indole derivatives useful as 5HT1A, 5HT1B and 5HT1D receptor antagonists |
| IT1293807B1 (it) * | 1997-08-01 | 1999-03-10 | Recordati Chem Pharm | Derivati 1- (n-fenilaminoalchil) piperazinici sostituiti alla posizione 2 dell'anello fenilico |
| PA8469101A1 (es) * | 1998-04-09 | 2000-09-29 | Pfizer Prod Inc | Ligandos azabiciclicos de receptores 5ht1 |
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