CA2518740C - Pyridyloxymethyl and benzisoxazole azabicyclic derivatives - Google Patents
Pyridyloxymethyl and benzisoxazole azabicyclic derivatives Download PDFInfo
- Publication number
- CA2518740C CA2518740C CA2518740A CA2518740A CA2518740C CA 2518740 C CA2518740 C CA 2518740C CA 2518740 A CA2518740 A CA 2518740A CA 2518740 A CA2518740 A CA 2518740A CA 2518740 C CA2518740 C CA 2518740C
- Authority
- CA
- Canada
- Prior art keywords
- isoxazol
- benzo
- octahydro
- pyridin
- pyrido
- 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.)
- Expired - Fee Related
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- 150000001875 compounds Chemical class 0.000 claims abstract description 227
- 238000000034 method Methods 0.000 claims abstract description 57
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 46
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- -1 aminomethylpyridyloxymethyl Chemical group 0.000 claims abstract description 36
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 14
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Classifications
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Landscapes
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US45392503P | 2003-03-12 | 2003-03-12 | |
| US60/453,925 | 2003-03-12 | ||
| PCT/IB2004/000499 WO2004081007A1 (en) | 2003-03-12 | 2004-02-23 | Pyridyloxymethyl and benzisoxazole azabicyclic derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2518740A1 CA2518740A1 (en) | 2004-09-23 |
| CA2518740C true CA2518740C (en) | 2011-01-11 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2518740A Expired - Fee Related CA2518740C (en) | 2003-03-12 | 2004-02-23 | Pyridyloxymethyl and benzisoxazole azabicyclic derivatives |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US7345038B2 (https=) |
| EP (1) | EP1608648B1 (https=) |
| JP (2) | JP3910627B2 (https=) |
| KR (2) | KR100767854B1 (https=) |
| CN (1) | CN100389115C (https=) |
| AP (1) | AP2005003390A0 (https=) |
| AR (1) | AR043537A1 (https=) |
| AU (2) | AU2004220327B2 (https=) |
| BR (1) | BRPI0408248A (https=) |
| CA (1) | CA2518740C (https=) |
| EA (1) | EA009527B1 (https=) |
| EC (1) | ECSP056011A (https=) |
| GT (1) | GT200400041A (https=) |
| HR (1) | HRP20050798A2 (https=) |
| IL (1) | IL170290A (https=) |
| MA (1) | MA27747A1 (https=) |
| MX (1) | MXPA05009660A (https=) |
| NL (1) | NL1025710C2 (https=) |
| NO (1) | NO20054095L (https=) |
| OA (1) | OA13038A (https=) |
| PA (1) | PA8597501A1 (https=) |
| PE (1) | PE20041057A1 (https=) |
| PL (1) | PL378749A1 (https=) |
| RS (1) | RS20050692A (https=) |
| TN (1) | TNSN05224A1 (https=) |
| TW (1) | TW200502234A (https=) |
| UA (1) | UA78437C2 (https=) |
| UY (1) | UY28225A1 (https=) |
| WO (1) | WO2004081007A1 (https=) |
| ZA (1) | ZA200506373B (https=) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6994726B2 (en) * | 2004-05-25 | 2006-02-07 | Calcitec, Inc. | Dual function prosthetic bone implant and method for preparing the same |
| UA83509C2 (en) * | 2003-10-15 | 2008-07-25 | Оси Фармасьютикалз, Инк. | Imidazopyrazines as tyrosine kinase inhibitors |
| EP1715868A1 (en) * | 2004-01-29 | 2006-11-02 | Pfizer Products Incorporated | Combinations of an atypical antipsychotic and an aminomethylpyridyloxymethyl/benzisoxazole azabicyclic derivatives for treating cns disorders |
| EP2168968B1 (en) | 2004-04-02 | 2017-08-23 | OSI Pharmaceuticals, LLC | 6,6-bicyclic ring substituted heterobicyclic protein kinase inhibitors |
| TW200613306A (en) | 2004-07-20 | 2006-05-01 | Osi Pharm Inc | Imidazotriazines as protein kinase inhibitors |
| MX2007002842A (es) * | 2004-09-10 | 2007-04-30 | Pfizer Prod Inc | Metodos de tratamiento de trastornos cognitivos que usan derivados azabiciclicos de piridiloximetilo y benzoisoxazol. |
| US8575164B2 (en) * | 2005-12-19 | 2013-11-05 | OSI Pharmaceuticals, LLC | Combination cancer therapy |
| US20110046144A1 (en) * | 2008-01-18 | 2011-02-24 | Mulvihill Mark J | Imidazopyrazinol derivatives for the treatment of cancers |
| ES2396613T3 (es) * | 2008-05-19 | 2013-02-22 | OSI Pharmaceuticals, LLC | Imidazopirazinas e imidazotriazinas sustituidas |
| US8513415B2 (en) | 2009-04-20 | 2013-08-20 | OSI Pharmaceuticals, LLC | Preparation of C-pyrazine-methylamines |
| EP2427192A1 (en) * | 2009-05-07 | 2012-03-14 | OSI Pharmaceuticals, LLC | Use of osi-906 for treating adrenocortical carcinoma |
| US9394290B2 (en) * | 2010-10-21 | 2016-07-19 | Universitaet Des Saarlandes Campus Saarbruecken | Selective CYP11B1 inhibitors for the treatment of cortisol dependent diseases |
| US20140206667A1 (en) | 2012-11-14 | 2014-07-24 | Michela Gallagher | Methods and compositions for treating schizophrenia |
| WO2016115282A1 (en) * | 2015-01-13 | 2016-07-21 | Vanderbilt University | Benzoisoxazole-substituted compounds as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction |
| US9585867B2 (en) | 2015-08-06 | 2017-03-07 | Charles Everett Ankner | Cannabinod formulation for the sedation of a human or animal |
| WO2020183011A1 (en) | 2019-03-14 | 2020-09-17 | Institut Curie | Htr1d inhibitors and uses thereof in the treatment of cancer |
| WO2023083445A1 (en) | 2021-11-10 | 2023-05-19 | Symrise Ag | Compositions comprising trpm8 agonistic cooling agents |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1990008148A1 (en) * | 1989-01-23 | 1990-07-26 | Pfizer Inc. | Bis-aza-bicyclic anxiolytic agents |
| US5167034A (en) * | 1990-06-18 | 1992-11-24 | International Business Machines Corporation | Data integrity for compaction devices |
| US5157034A (en) | 1991-02-27 | 1992-10-20 | Pfizer Inc. | Neuroleptic perhydro-1H-pyrido[1,2-a]pyrazines |
| FI941377A0 (fi) * | 1991-09-25 | 1994-03-24 | Pfizer | Neuroleptisiä 2-substituoituja perhydro-1-H-pyrido/1,2-a/-pyratsiineja |
| DE69326767T2 (de) * | 1992-06-16 | 2000-03-02 | Pfizer Inc., New York | Verfahren und zwischenprodukte zur herstellung von bis-aza-bicyclischen anxiolytica |
| WO1996010570A1 (en) * | 1994-09-30 | 1996-04-11 | Pfizer Inc. | NEUROLEPTIC 2,7-DISUBSTITUTED PERHYDRO-1H-PYRIDO[1,2-a]PYRAZINES |
| KR100589872B1 (ko) | 1997-05-30 | 2006-06-15 | 뉴로서치 에이/에스 | 8-아자비사이클로(3,2,1)옥트-2-엔 유도체 및 이의 제조방법 |
| PA8469101A1 (es) * | 1998-04-09 | 2000-09-29 | Pfizer Prod Inc | Ligandos azabiciclicos de receptores 5ht1 |
| US6608084B1 (en) | 1998-08-26 | 2003-08-19 | Aventis Pharma Ltd. | Aza-bicycles which modulate the inhibition of cell adhesion |
| ID29028A (id) | 1998-09-18 | 2001-07-26 | Basf Ag | Pirolopirimidina sebagai penghambat protein kinase |
| ES2253930T3 (es) | 1998-09-18 | 2006-06-01 | ABBOTT GMBH & CO. KG | 4-aminopirrolopirimidinas como inhibidores de quinasa. |
| UA62015C2 (en) * | 1998-12-28 | 2003-12-15 | Pfizer Prod Inc | Benzoizoxazol derivatives, a pharmaceutical composition (variants) based thereon (variants) and a method for treatment (variants) |
| ATE278674T1 (de) | 1999-03-12 | 2004-10-15 | Boehringer Ingelheim Pharma | Heterocyklischer harnstoff und verwandte verbindungen als entzündungshemmende mittel |
| EP1177792A3 (en) * | 2000-07-27 | 2002-10-23 | Pfizer Products Inc. | Dopamine D4 Ligands for the treatment of novelty-seeking disorders |
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