NO331920B1 - Arylvinylazacykloalkan-forbindelser, slike forbindelser for behandling av sykdom samt fremgangsmater for deres fremstilling - Google Patents

Arylvinylazacykloalkan-forbindelser, slike forbindelser for behandling av sykdom samt fremgangsmater for deres fremstilling Download PDF

Info

Publication number: NO331920B1
Authority: NO; Norway
Prior art keywords: compound according; compounds; disorders; ylvinyl; disorder
Prior art date: 2003-03-05

Application number

NO20054120A

Other languages

English (en)

Norwegian (no)

Other versions

NO20054120D0 (no

NO20054120L (no

Inventor

Michel Cheve

Arielle Genevois-Borella

Gary Maurice Dull

Jeffrey Daniel Schmitt

Marc Capet

Original Assignee

Targacept Inc

Priority date (The priority date 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 date listed.)

2003-03-05

Filing date

2005-09-05

Publication date

2012-04-30

2005-09-05 Application filed by Targacept Inc filed Critical Targacept Inc

2005-09-05 Publication of NO20054120D0 publication Critical patent/NO20054120D0/no

2005-10-03 Publication of NO20054120L publication Critical patent/NO20054120L/no

2012-04-30 Publication of NO331920B1 publication Critical patent/NO331920B1/no

Links

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NO20054120A 2003-03-05 2005-09-05 Arylvinylazacykloalkan-forbindelser, slike forbindelser for behandling av sykdom samt fremgangsmater for deres fremstilling NO331920B1 (no)

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Families Citing this family (19)

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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
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
PT3279195T (pt) *	2008-12-01	2020-09-29	Oyster Point Pharma Inc	Síntese e novas formas de sal de (r)-5-((e)-2-pirrolidin- 3-ilvinil)pirimidina
WO2010080757A2 (en)	2009-01-07	2010-07-15	Astrazeneca Ab	Combinations with an alpha-4beta-2 nicotinic agonist
NZ596734A (en) *	2009-06-17	2014-02-28	Targacept Inc	Reversal of l-dopa-induced dyskinesia by neuronal nicotinic receptor ligands
BR112012013765A2 (pt)	2009-12-07	2016-04-26	Targacept Inc	3,6-diazabiciclo[3.1.1] heptanos como ligantes de receptor nicotínico neuronal de acetilcolina
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
JP7090551B2 (ja)	2016-04-07	2022-06-24	オイスターポイントファーマインコーポレイテッド	眼状態の治療方法
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
WO2020014217A1 (en)	2018-07-10	2020-01-16	Oyster Point Pharma, Inc.	Methods of treating ocular conditions
TW202206078A (zh)	2020-04-28	2022-02-16	美商奧伊斯特普安生物製藥公司	局部投與菸鹼乙醯膽鹼受體促效劑用以抑制冠狀病毒感染

Family Cites Families (24)

* Cited by examiner, † Cited by third party
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 (he)	1995-06-07	2006-10-05	Abbott Lab	תרכובות 3 – פירידילאוקסי (או תיו) אלקיל הטרוציקליות הרכבים רוקחיים המכילים אותן ושימושים שלהם להכנת תרופות לשליטה בתשדורת כימית סינפטית
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
DK1027336T3 (da)	1997-10-27	2005-01-24	Neurosearch As	Heteroaryldiazacycloalkaner, deres fremstilling og anvendelse
AU5326100A (en)	1999-06-07	2000-12-28	Targacept, Inc.	Pharmaceutical compositions and methods for use
EP1212319A2 (en)	1999-09-14	2002-06-12	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
WO2003008559A2 (en)	2001-07-19	2003-01-30	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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Also Published As

Publication number	Publication date
AU2008258187B2 (en)	2010-08-05
HK1084949A1 (en)	2006-08-11
IL197889A (en)	2013-03-24
AR070569A2 (es)	2010-04-21
CY1110391T1 (el)	2015-04-29
KR101185541B1 (ko)	2012-09-24
ES2389106T3 (es)	2012-10-23
IL170155A (he)	2013-08-29
CL2004000452A1 (es)	2005-05-20
BRPI0409576A (pt)	2006-04-18
US20100267776A1 (en)	2010-10-21
PL378415A1 (pl)	2006-04-03
AR043469A1 (es)	2005-07-27
PE20040930A1 (es)	2005-02-18
KR20060006006A (ko)	2006-01-18
JP2006519868A (ja)	2006-08-31
PL1601670T3 (pl)	2008-10-31
UY28218A1 (es)	2005-06-30
KR20090021228A (ko)	2009-02-27
PT1601670E (pt)	2008-07-11
CN1756754A (zh)	2006-04-05
US8633222B2 (en)	2014-01-21
US20080293778A1 (en)	2008-11-27
US20150164894A1 (en)	2015-06-18
AU2004217903A1 (en)	2004-09-16
AU2008258187A1 (en)	2009-01-15
MXPA05009386A (es)	2005-11-04
US8063068B2 (en)	2011-11-22
NO20091888L (no)	2005-10-03
PL394600A1 (pl)	2011-07-18
EP1601670B1 (en)	2008-05-07
DE602004013553D1 (de)	2008-06-19
SI1601670T1 (sl)	2008-10-31
TWI339662B (en)	2011-04-01
NO20054120D0 (no)	2005-09-05
EA200900706A1 (ru)	2009-10-30
US7714001B2 (en)	2010-05-11
ES2385941T3 (es)	2012-08-03
EP1947100A1 (en)	2008-07-23
JP2009292825A (ja)	2009-12-17
AU2008258188A1 (en)	2009-01-15
KR20090021227A (ko)	2009-02-27
US20110152293A1 (en)	2011-06-23
JO2488B1 (en)	2009-10-05
EP2085395A1 (en)	2009-08-05
DK1601670T3 (da)	2008-08-25
NO20092231L (no)	2005-10-03
HK1116800A1 (en)	2009-01-02
JP2010001296A (ja)	2010-01-07
EA200801764A1 (ru)	2008-12-30
EA014714B1 (ru)	2011-02-28
US20100010042A1 (en)	2010-01-14
NO20054120L (no)	2005-10-03
NO332293B1 (no)	2012-08-20
EA019240B1 (ru)	2014-02-28
CN101550132B (zh)	2012-03-28
ATE517893T1 (de)	2011-08-15
US8067443B2 (en)	2011-11-29
EP2085395B1 (en)	2011-01-19
HK1130254A1 (en)	2009-12-24
US7098331B2 (en)	2006-08-29
DE602004031165D1 (de)	2011-03-03
CN101550132A (zh)	2009-10-07
IL197890A (he)	2013-11-28
KR20120014236A (ko)	2012-02-16
ZA200506790B (en)	2006-05-31
PL394604A1 (pl)	2011-07-18
AR070570A2 (es)	2010-04-21
PL2085395T3 (pl)	2011-05-31
WO2004078752A1 (en)	2004-09-16
TWI377204B (en)	2012-11-21
AU2004217903B2 (en)	2010-03-04
PA8597201A1 (es)	2004-09-28
NZ541795A (en)	2008-03-28
PL215059B1 (pl)	2013-10-31
US20040176348A1 (en)	2004-09-09
SI2085395T1 (sl)	2011-05-31
US20060094732A1 (en)	2006-05-04
JP5537084B2 (ja)	2014-07-02
PL216979B1 (pl)	2014-06-30
AU2008258188B2 (en)	2011-02-24
JP4663627B2 (ja)	2011-04-06
TW200505909A (en)	2005-02-16
ATE496046T1 (de)	2011-02-15
GT200400033A (es)	2005-05-29
EP1947100B1 (en)	2011-07-27
CA2516514C (en)	2012-02-07
DK2085395T3 (da)	2011-04-18
TW200927745A (en)	2009-07-01
TW200927746A (en)	2009-07-01
CA2516514A1 (en)	2004-09-16
KR100953150B1 (ko)	2010-04-19
CN100526308C (zh)	2009-08-12
KR101018083B1 (ko)	2011-03-02
EA010870B1 (ru)	2008-12-30
ATE394394T1 (de)	2008-05-15
JP5537085B2 (ja)	2014-07-02
US20140107164A1 (en)	2014-04-17
CN101255155A (zh)	2008-09-03
EP1601670A1 (en)	2005-12-07
EA200501425A1 (ru)	2006-02-24
PT2085395E (pt)	2011-04-20
ES2309507T3 (es)	2008-12-16
CY1111615T1 (el)	2015-10-07

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