NZ583823A - Furazanes for enhancing glutamatergic synaptic responses - Google Patents
Furazanes for enhancing glutamatergic synaptic responsesInfo
- Publication number
- NZ583823A NZ583823A NZ583823A NZ58382308A NZ583823A NZ 583823 A NZ583823 A NZ 583823A NZ 583823 A NZ583823 A NZ 583823A NZ 58382308 A NZ58382308 A NZ 58382308A NZ 583823 A NZ583823 A NZ 583823A
- Authority
- NZ
- New Zealand
- Prior art keywords
- substituted
- compound according
- medicament
- branched
- treatment
- Prior art date
Links
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- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
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- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
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| US96436207P | 2007-08-10 | 2007-08-10 | |
| PCT/US2008/009508 WO2009023126A2 (en) | 2007-08-10 | 2008-08-08 | Bicyclic amides for enhancing glutamatergic synaptic responses |
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| ZA200904826B (en) | 2007-01-03 | 2010-09-29 | Cortex Pharma Inc | 3-substituted-[1,2,3]-benzotriazinone compound for enhancing glutamatergic synaptic responses |
| JP5694765B2 (ja) | 2007-05-17 | 2015-04-01 | コーテックス ファーマシューティカルズ， インコーポレイテッド | グルタミン酸作動性シナプス反応を増強するための二置換アミド |
| US8168632B2 (en) | 2007-08-10 | 2012-05-01 | Cortex Pharmaceuticals, Inc. | Bicyclic amide derivatives for the treatment of respiratory disorders |
| ES2560095T3 (es) | 2007-08-10 | 2016-02-17 | Cortex Pharmaceuticals, Inc. | Amidas bicíclicas para mejorar las respuestas sinápticas glutamatérgicas |
| WO2010087980A2 (en) * | 2009-02-02 | 2010-08-05 | Cortex Pharmaceuticals, Inc. | Bicyclic amide derivatives for the treatment of respiratory depression |
| US9440982B2 (en) | 2012-02-07 | 2016-09-13 | Eolas Therapeutics, Inc. | Substituted prolines/piperidines as orexin receptor antagonists |
| JP6346862B2 (ja) | 2012-02-07 | 2018-06-20 | エオラス セラピューティクス， インコーポレイテッド | オレキシンレセプターアンタゴニストとしての置換プロリン／ピペリジン |
| TW201613902A (en) | 2014-08-13 | 2016-04-16 | Eolas Therapeutics Inc | Difluoropyrrolidines as orexin receptor modulators |
| US9739787B2 (en) | 2015-09-01 | 2017-08-22 | Abdulmohsen Ebrahim Alterki | Method for diagnosing sleep apnea by measuring adipsin and betatrophin levels |
| US10894789B2 (en) | 2016-02-12 | 2021-01-19 | Astrazeneca Ab | Halo-substituted piperidines as orexin receptor modulators |
| EP3436021B1 (en) * | 2016-03-29 | 2026-07-29 | RespireRx Pharmaceuticals, Inc. | Compositions comprising low impact ampakines for treating attention deficit disorders |
| JP2022534704A (ja) | 2019-06-04 | 2022-08-03 | ヘイガー バイオサイエンシズ，エルエルシー | オレキシンアンタゴニストとしてのイミダゾロ誘導体、組成物、及び方法 |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3723436A (en) | 1971-02-25 | 1973-03-27 | Sun Oil Co | Process for aromatic lactams |
| FR2597103B1 (fr) | 1986-04-15 | 1988-12-16 | Provesan Sa | Procede de preparation de derives d'oxazinobenzothiazine 6,6-dioxyde |
| DE69331761T2 (de) | 1992-07-24 | 2002-09-12 | The Regents Of The University Of California, Oakland | Arzneimittel, die den durch ampa rezeptoren vermittelten synaptischen respons erhöhen |
| US20020099050A1 (en) | 1993-07-23 | 2002-07-25 | Lynch Gary S. | Drugs that enhance synaptic responses mediated by AMPA receptors |
| US5650409A (en) | 1995-06-02 | 1997-07-22 | Cortex Pharmaceuticals, Inc. | Benzoyl piperidines/pyrrolidines for enhancing synaptic response |
| US5736543A (en) | 1996-04-03 | 1998-04-07 | The Regents Of The University Of California | Benzoxazines for enhancing synaptic response |
| AU4416197A (en) | 1996-09-17 | 1998-04-14 | Regents Of The University Of California, The | Positive ampa receptor modulation to enhance brain neurotrophic factor expression |
| US6110935A (en) * | 1997-02-13 | 2000-08-29 | The Regents Of The University Of California | Benzofurazan compounds for enhancing glutamatergic synaptic responses |
| US6166008A (en) | 1997-10-27 | 2000-12-26 | Cortex Pharmaceuticals, Inc. | Treatment of schizophrenia with ampakines and neuroleptics |
| US5985871A (en) | 1997-12-24 | 1999-11-16 | Cortex Pharmaceuticals, Inc. | Benzoxazine compounds for enhancing synaptic response |
| RU2214405C2 (ru) | 1998-02-18 | 2003-10-20 | НьюроСёрч А/С | Новые соединения и их применение в качестве положительных модуляторов амра-рецепторов |
| US6713474B2 (en) | 1998-09-18 | 2004-03-30 | Abbott Gmbh & Co. Kg | Pyrrolopyrimidines as therapeutic agents |
| US6303542B1 (en) | 2000-08-18 | 2001-10-16 | Rohm And Haas Company | Herbicidal 3-substituted-phenyl-1,2,3-benzotriazin-4-ones |
| PA8535601A1 (es) * | 2000-12-21 | 2002-11-28 | Pfizer | Derivados benzimidazol y piridilimidazol como ligandos para gabaa |
| AUPS255202A0 (en) | 2002-05-27 | 2002-06-13 | Monash University | Agents and methods for the treatment of disorders associated with motor neuron degeneration |
| WO2004089416A2 (en) * | 2003-04-11 | 2004-10-21 | Novo Nordisk A/S | Combination of an 11beta-hydroxysteroid dehydrogenase type 1 inhibitor and an antihypertensive agent |
| US20050085446A1 (en) | 2003-04-14 | 2005-04-21 | Babu M.K. M. | Fluoroquinolone formulations and methods of making and using the same |
| GB0317482D0 (en) | 2003-07-25 | 2003-08-27 | Pfizer Ltd | Nicotinamide derivatives useful as pde4 inhibitors |
| CN1897950A (zh) | 2003-10-14 | 2007-01-17 | 惠氏公司 | 稠合芳基和杂芳基衍生物及其使用方法 |
| BRPI0716375A2 (pt) | 2006-08-31 | 2013-10-15 | Univ Alberta | Método para reduzir ou inibir depressão respiratória em um sujeito; método para induzir analgesia, anestesia ou sedação em um sujeito, reduzindo ou inibindo simultaneamente depressão respiratória no sujeito; e composição farmacêutica para induzir analgesia, anestesia ou sedação em um sujeito... |
| CA2674321A1 (en) | 2007-01-03 | 2008-07-17 | Cortex Pharmaceuticals, Inc. | 3-substituted-[1,2,3]benzotriazinone compounds for enhancing glutamatergic synaptic responses |
| ZA200904826B (en) | 2007-01-03 | 2010-09-29 | Cortex Pharma Inc | 3-substituted-[1,2,3]-benzotriazinone compound for enhancing glutamatergic synaptic responses |
| JP5694765B2 (ja) | 2007-05-17 | 2015-04-01 | コーテックス ファーマシューティカルズ， インコーポレイテッド | グルタミン酸作動性シナプス反応を増強するための二置換アミド |
| ES2560095T3 (es) | 2007-08-10 | 2016-02-17 | Cortex Pharmaceuticals, Inc. | Amidas bicíclicas para mejorar las respuestas sinápticas glutamatérgicas |
| NZ584098A (en) | 2007-09-20 | 2012-05-25 | Cortex Pharma Inc | 3-substituted 1,2,3-triazin-4-one's and 3-substituted 1,3-pyrimidinone's for enhancing glutamatergic synaptic responses |
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