ES2309507T3 - Compuestos de arilvinilazacicloalcano y metodos de preparacion y uso de los mismos. - Google Patents
Compuestos de arilvinilazacicloalcano y metodos de preparacion y uso de los mismos. Download PDFInfo
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- ES2309507T3 ES2309507T3 ES04717398T ES04717398T ES2309507T3 ES 2309507 T3 ES2309507 T3 ES 2309507T3 ES 04717398 T ES04717398 T ES 04717398T ES 04717398 T ES04717398 T ES 04717398T ES 2309507 T3 ES2309507 T3 ES 2309507T3
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- Prior art keywords
- compound
- compounds
- pyrimidine
- ylvinyl
- disorders
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Landscapes
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Applications Claiming Priority (2)
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| US379868 | 1982-05-19 | ||
| US10/379,868 US7098331B2 (en) | 2003-03-05 | 2003-03-05 | Arylvinylazacycloalkane compounds and methods of preparation and use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2309507T3 true ES2309507T3 (es) | 2008-12-16 |
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| ES04717398T Expired - Lifetime ES2309507T3 (es) | 2003-03-05 | 2004-03-04 | Compuestos de arilvinilazacicloalcano y metodos de preparacion y uso de los mismos. |
| ES08075106T Expired - Lifetime ES2389106T3 (es) | 2003-03-05 | 2004-03-04 | Compuestos de arilvinilazacicloalcano y métodos de preparación y usos de ellos |
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| ES09075124T Expired - Lifetime ES2385941T3 (es) | 2003-03-05 | 2004-03-04 | Compuesto de arilvinilazacicloalcano y métodos de preparación y usos de ellos. |
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| ES08075106T Expired - Lifetime ES2389106T3 (es) | 2003-03-05 | 2004-03-04 | Compuestos de arilvinilazacicloalcano y métodos de preparación y usos de ellos |
Country Status (31)
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Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7098331B2 (en) * | 2003-03-05 | 2006-08-29 | Targacept, Inc. | Arylvinylazacycloalkane compounds and methods of preparation and use thereof |
| FR2896800B1 (fr) | 2006-01-30 | 2008-04-11 | Servier Lab | Nouveaux composes pyridinylaminoalkylene-et pyridinyloxyalkylene-cyclopropanamines polysubstitues, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
| WO2008157365A2 (en) * | 2007-06-15 | 2008-12-24 | Targacept, Inc. | Vinylazacycloalkanes for treating neuropathic pain |
| US20110098312A1 (en) * | 2008-05-12 | 2011-04-28 | Targacept ,Inc | Methods for preventing the development of retinopathy by the oral administration of nnr ligands |
| US9145396B2 (en) | 2008-12-01 | 2015-09-29 | Targacept, Inc. | Synthesis and novel salt forms of (R)-5-((E)-2-pyrrolidin-3ylvinyl)pyrimidine |
| PE20110589A1 (es) | 2008-12-01 | 2011-09-07 | Targacept Inc | Formas cristalinas del compuesto (r)-5-((e)-2-(pirrolidin-3-ilvinil)pirimidina |
| TW201024283A (en) * | 2008-12-01 | 2010-07-01 | Targacept Inc | Synthesis and novel salt forms of (R)-3-((E)-2-(pyrrolidin-3-yl)vinyl)-5-(tetrahydropyran-4-yloxy)pyridine |
| WO2010080757A2 (en) | 2009-01-07 | 2010-07-15 | Astrazeneca Ab | Combinations with an alpha-4beta-2 nicotinic agonist |
| JP2012530707A (ja) * | 2009-06-17 | 2012-12-06 | ターガセプト，インコーポレイテッド | 神経性ニコチン受容体リガンドによるｌ−ドーパ誘発性ジスキネジアの回復 |
| PH12012501068A1 (en) | 2009-12-07 | 2013-02-04 | Targacept Inc | 3,6-diazabicyclo [3.1.1] heptanes as neuronal nicotinic acetylcholine receptor ligands |
| WO2011112428A2 (en) * | 2010-03-11 | 2011-09-15 | Targacept, Inc. | Arylvinylazacycloalkane compounds for constipation |
| US20110274628A1 (en) * | 2010-05-07 | 2011-11-10 | Borschke August J | Nicotine-containing pharmaceutical compositions |
| US20140081714A1 (en) * | 2012-09-19 | 2014-03-20 | Salesforce.Com, Inc. | Systems and methods of rewarding users in an on-demand system |
| US20140278929A1 (en) * | 2013-03-15 | 2014-09-18 | Yahoo! Inc. | System and method identifying opportunities for advertising entities based on user goal achievement |
| ES2893126T3 (es) | 2016-04-07 | 2022-02-08 | Oyster Point Pharma Inc | Métodos de tratamiento de afecciones oculares |
| KR101848601B1 (ko) * | 2016-07-27 | 2018-04-12 | 송기봉 | 일회용 위생 티슈 |
| EP3820443A1 (en) | 2018-07-10 | 2021-05-19 | Oyster Point Pharma, Inc. | Combinations of positive allosteric modulators and nicotinic acetylcholine receptor agonists for treating ocular conditions |
| TW202019424A (zh) | 2018-07-10 | 2020-06-01 | 美商奧伊斯特普安生物製藥公司 | 治療眼部症狀之方法 |
| WO2021222230A1 (en) | 2020-04-28 | 2021-11-04 | Oyster Point Pharma, Inc. | Local administration of nicotinic acetylcholine receptor agonists for the inhibition of coronavirus infections |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1989000158A1 (en) | 1987-07-02 | 1989-01-12 | Pfizer Inc. | Bridged-diazabicycloalkyl quinolone carboxylic acids and esters |
| US4922901A (en) | 1988-09-08 | 1990-05-08 | R. J. Reynolds Tobacco Company | Drug delivery articles utilizing electrical energy |
| US5187166A (en) | 1990-07-31 | 1993-02-16 | Nisshin Flour Milling Co., Ltd. | Azabicyclo derivatives and their use as antiemetics |
| IL107184A (en) | 1992-10-09 | 1997-08-14 | Abbott Lab | Heterocyclic ether compounds that enhance cognitive function |
| US5852041A (en) | 1993-04-07 | 1998-12-22 | Sibia Neurosciences, Inc. | Substituted pyridines useful as modulators of acethylcholine receptors |
| IT1274018B (it) | 1994-02-23 | 1997-07-14 | Riace Ets | Derivati del 3,8-diazabiciclo(3.2.1.)ottano ad attivita' analgesica |
| GB2295387A (en) | 1994-11-23 | 1996-05-29 | Glaxo Inc | Quinazoline antagonists of alpha 1c adrenergic receptors |
| US5604231A (en) | 1995-01-06 | 1997-02-18 | Smith; Carr J. | Pharmaceutical compositions for prevention and treatment of ulcerative colitis |
| US5597919A (en) | 1995-01-06 | 1997-01-28 | Dull; Gary M. | Pyrimidinyl or Pyridinyl alkenyl amine compounds |
| US5585388A (en) | 1995-04-07 | 1996-12-17 | Sibia Neurosciences, Inc. | Substituted pyridines useful as modulators of acetylcholine receptors |
| US5583140A (en) | 1995-05-17 | 1996-12-10 | Bencherif; Merouane | Pharmaceutical compositions for the treatment of central nervous system disorders |
| IL118279A (en) | 1995-06-07 | 2006-10-05 | Abbott Lab | Compounds 3 - Pyridyloxy (or Thio) Alkyl Heterocyclic Pharmaceutical Compositions Containing Them and Their Uses for Preparing Drugs to Control Synaptic Chemical Transmission |
| US5616716A (en) | 1996-01-06 | 1997-04-01 | Dull; Gary M. | (3-(5-ethoxypyridin)yl)-alkenyl 1 amine compounds |
| AT403803B (de) | 1996-04-19 | 1998-05-25 | Sanochemia Ltd | Neue benzazepinderivate, diese enthaltende arzneimittel und verwendung derselben zum herstellen von arzneimitteln |
| US5663356A (en) | 1996-04-23 | 1997-09-02 | Ruecroft; Graham | Method for preparation of aryl substituted alefinic secondary amino compounds |
| US5629325A (en) | 1996-06-06 | 1997-05-13 | Abbott Laboratories | 3-pyridyloxymethyl heterocyclic ether compounds useful in controlling chemical synaptic transmission |
| US6437138B1 (en) | 1996-06-06 | 2002-08-20 | Abbott Laboratories | 3-pyridyloxymethyl heterocyclic ether compounds useful in controlling chemical synaptic transmission |
| ATE278670T1 (de) | 1997-10-27 | 2004-10-15 | Neurosearch As | Heteroaryl diazacycloalkane als cholinergische ligande für nikotin-acetylcholin-rezeptoren |
| WO2000075110A1 (en) | 1999-06-07 | 2000-12-14 | Targacept, Inc. | Pharmaceutical compositions and methods for use |
| WO2001019817A2 (en) | 1999-09-14 | 2001-03-22 | Abbott Laboratories | 3-pyrrolidinyloxy-3'-pyridyl ether compounds useful for controlling chemical synaptic transmission |
| JP2003513054A (ja) | 1999-11-01 | 2003-04-08 | ターガセプト，インコーポレイテッド | アリールオレフィンアザ環式化合物及びアリールアセチレンアザ環式化合物、それらを含有する薬剤組成物、及び、ニコチンコリン作動性受容体の阻害薬としてのそれらの使用 |
| US6624167B1 (en) * | 2000-08-04 | 2003-09-23 | Targacept, Inc. | Pharmaceutical compositions and methods for use |
| AU2002322562A1 (en) | 2001-07-19 | 2003-03-03 | Medical College Of Georgia Research Institute | Novel analogs of choline for neuroprotection and cognitive enhancement in neurodegenerative disorders |
| US7098331B2 (en) * | 2003-03-05 | 2006-08-29 | Targacept, Inc. | Arylvinylazacycloalkane compounds and methods of preparation and use thereof |
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