OA12554A - Use of GABA a inverse agonists in combination withnicotine receptor partial agonists, estrogen, sel ective estrogen modulators, or bitamin E for the treatment of cognitive disorders. - Google Patents

Use of GABA a inverse agonists in combination withnicotine receptor partial agonists, estrogen, sel ective estrogen modulators, or bitamin E for the treatment of cognitive disorders. Download PDF

Info

Publication number: OA12554A
Authority: OA; OAPI
Prior art keywords: triene; methano; hexahydro; pyrido; oxo
Prior art date: 2001-03-01

Application number

OA1200300213A

Other languages

English (en)

Inventor

Anabella Villalobos

Original Assignee

Pfizer Prod 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.)

2001-03-01

Filing date

2002-02-20

Publication date

2006-06-07

2002-02-20 Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc

2006-06-07 Publication of OA12554A publication Critical patent/OA12554A/en

Links

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OA1200300213A 2001-03-01 2002-02-20 Use of GABA a inverse agonists in combination withnicotine receptor partial agonists, estrogen, sel ective estrogen modulators, or bitamin E for the treatment of cognitive disorders. OA12554A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US27256601P	2001-03-01	2001-03-01

Publications (1)

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OA12554A true OA12554A (en)	2006-06-07

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OA1200300213A OA12554A (en)	2001-03-01	2002-02-20	Use of GABA a inverse agonists in combination withnicotine receptor partial agonists, estrogen, sel ective estrogen modulators, or bitamin E for the treatment of cognitive disorders.

Country Status (33)

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AP (1)	AP2002002465A0 (is)
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EA (1)	EA200300854A1 (is)
EC (1)	ECSP034759A (is)
EE (1)	EE200300422A (is)
GT (1)	GT200200039A (is)
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IL (1)	IL157465A0 (is)
IS (1)	IS6905A (is)
MA (1)	MA26999A1 (is)
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PA (1)	PA8540701A1 (is)
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Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20080004332A1 (en) *	2002-03-07	2008-01-03	Alkon Daniel L	Methods for alzheimer's disease treatment and cognitive enhancement
US6825229B2 (en)	2002-03-07	2004-11-30	Blanchette Rockefeller Neurosciences Institute	Methods for Alzheimer's Disease treatment and cognitive enhancement
US20050065205A1 (en) *	2002-03-07	2005-03-24	Daniel Alkon	Methods for Alzheimer's disease treatment and cognitive enhance
WO2005000806A2 (en)	2003-06-10	2005-01-06	Georgetown University	Ligands for nicotinic acetylcholine receptors, and methods of making and using them
TW201206425A (en)	2004-05-18	2012-02-16	Brni Neurosciences Inst	Treatment of depressive disorders
EP2682481A3 (en) *	2005-08-03	2014-09-17	The Johns-Hopkins University	Methods for characterizing and treating cognitive impairment in aging and disease
US8510055B2 (en)	2005-08-03	2013-08-13	The Johns Hopkins University	Methods for characterizing and treating cognitive impairment in aging and disease
EP2032987B1 (en) *	2006-05-22	2016-02-24	The Board of Trustees of The Leland Stanford Junior University	Pharmacological treatment of cognitive impairment
NZ576036A (en)	2006-10-16	2010-10-29	Bionomics Ltd	Naphthyridine containing compounds for treating anxiety disorders
AU2013202426B2 (en) *	2006-10-16	2015-08-06	Bionomics Limited	Novel anxiolytic compounds
US10954231B2 (en)	2006-10-16	2021-03-23	Bionomics Limited	Anxiolytic compounds
EP3332797A3 (en)	2007-02-09	2018-08-01	Blanchette Rockefeller Neurosciences Institute	Therapeutic effects of bryostatins, bryologs and other related substances on head trauma-induced memory impairment and brain injury
US8039620B2 (en) *	2008-05-22	2011-10-18	Teva Pharmaceutical Industries Ltd.	Varenicline tosylate, an intermediate in the preparation process of varenicline L-tartrate
US20090318695A1 (en) *	2008-06-19	2009-12-24	Vinod Kumar Kansal	Processes for the preparation of varenicline and intermediates thereof
WO2010005643A1 (en) *	2008-07-10	2010-01-14	Teva Pharmaceutical Industries Ltd.	Processes for purifying varenicline l-tartrate salt and preparing crystalline forms of varenicline l-tartrate salt
US10206921B2 (en) *	2009-06-03	2019-02-19	The Regents Of The University Of California	Methods and compositions for treating a subject for central nervous system (CNS) injury
EP2438054A1 (en) *	2009-06-22	2012-04-11	Teva Pharmaceutical Industries Ltd.	Solid states forms of varenicline salts and processes for preparation thereof
EP3034079B1 (en)	2010-11-15	2018-01-10	Agenebio, Inc.	Pyridazine derivatives, compositions and methods for treating cognitive impairment
US20140051701A1 (en) *	2011-03-02	2014-02-20	Bionomics Limited	Methods of treating a disease or condition of the central nervous system
US9023848B2 (en)	2011-03-02	2015-05-05	Bionomics Limited	Small-molecules as therapeutics
EP2707367B1 (en)	2011-05-12	2019-10-09	Bionomics Limited	Methods for preparing naphthyridines
NZ760341A (en)	2013-12-20	2021-12-24	Agenebio Inc	Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment
MX392119B (es)	2015-06-19	2025-03-11	Agenebio Inc	Derivados de benzodiazepina, composiciones y metodos para tratar deterioro cognitivo
US20180170941A1 (en)	2016-12-19	2018-06-21	Agenebio, Inc.	Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment
US11505555B2 (en)	2016-12-19	2022-11-22	Agenebio, Inc.	Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment
CN112601749B (zh)	2018-06-19	2024-03-26	艾吉因生物股份有限公司	用于治疗认知损害的苯并二氮杂环庚三烯衍生物，组合物和方法
CN116008442B (zh) *	2023-03-27	2023-06-30	上海赛默罗生物科技有限公司	α5-GABAA受体调节剂的合成中间体的杂质检测方法
CN116077459B (zh) *	2023-04-10	2023-07-07	上海赛默罗生物科技有限公司	α5-GABAA受体调节剂的胶囊剂及其制备方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
KR20010023313A (ko) *	1997-08-25	2001-03-26	해피 페너 ; 해리 에이치. 페너 2세	Ｇａｂａ 뇌 수용체 리간드로서의 치환된4-옥소-나프티리딘-3-카르복스아미드
WO2000071528A1 (en) *	1999-05-25	2000-11-30	Neurogen Corporation	4h-1,4-benzothiazine-2-carboxamides and their use as gaba brain receptor ligands

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Publication number	Publication date
BG108131A (en)	2004-09-30
EE200300422A (et)	2004-02-16
CN1494422A (zh)	2004-05-05
AP2002002465A0 (en)	2002-06-30
ECSP034759A (es)	2003-10-28
UY27188A1 (es)	2002-10-31
WO2002069948A1 (en)	2002-09-12
US20040082555A1 (en)	2004-04-29
CA2439581A1 (en)	2002-09-12
KR20030076717A (ko)	2003-09-26
US20020193360A1 (en)	2002-12-19
PE20020927A1 (es)	2002-10-30
IL157465A0 (en)	2004-03-28
AR033425A1 (es)	2003-12-17
HUP0303448A2 (hu)	2004-01-28
MXPA03007834A (es)	2003-12-08
PL364081A1 (en)	2004-12-13
NZ527397A (en)	2005-05-27
TNSN02018A1 (fr)	2005-12-23
EA200300854A1 (ru)	2004-02-26
PA8540701A1 (es)	2002-09-30
MA26999A1 (fr)	2004-12-20
DOP2002000345A (es)	2002-12-15
NO20033821L (no)	2003-09-10
EP1363606A1 (en)	2003-11-26
GT200200039A (es)	2002-11-21
BR0207802A (pt)	2004-03-09
ZA200306193B (en)	2004-08-11
IS6905A (is)	2003-08-07
NO20033821D0 (no)	2003-08-28
SK10752003A3 (sk)	2004-08-03
HUP0303448A3 (en)	2005-05-30
CZ20032338A3 (cs)	2004-08-18
JP2004527500A (ja)	2004-09-09
CR7059A (es)	2004-03-10

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