JP4511023B2 - 神経細胞ニコチン性α７レセプタアゴニストとしてのベンジリデン−およびシンナミリデン−アナバセイン - Google Patents
神経細胞ニコチン性α７レセプタアゴニストとしてのベンジリデン−およびシンナミリデン−アナバセイン Download PDFInfo
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- JP4511023B2 JP4511023B2 JP2000507667A JP2000507667A JP4511023B2 JP 4511023 B2 JP4511023 B2 JP 4511023B2 JP 2000507667 A JP2000507667 A JP 2000507667A JP 2000507667 A JP2000507667 A JP 2000507667A JP 4511023 B2 JP4511023 B2 JP 4511023B2
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/82—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- Chemical Kinetics & Catalysis (AREA)
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/924,008 | 1997-08-29 | ||
| US08/924,008 US5977144A (en) | 1992-08-31 | 1997-08-29 | Methods of use and compositions for benzylidene- and cinnamylidene-anabaseines |
| PCT/US1998/017850 WO1999010338A2 (en) | 1997-08-29 | 1998-08-28 | Benzylidene- and cinnamylidene-anabaseines as neuronal nicotinic alpha-7 receptor agonists |
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| JP2010007505A Division JP2010116404A (ja) | 1997-08-29 | 2010-01-15 | 神経細胞ニコチン性α７レセプタアゴニストとしてのベンジリデン−およびシンナミリデン−アナバセイン |
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| JP2003524575A JP2003524575A (ja) | 2003-08-19 |
| JP2003524575A5 JP2003524575A5 (enExample) | 2006-01-05 |
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| JP2000507667A Expired - Fee Related JP4511023B2 (ja) | 1997-08-29 | 1998-08-28 | 神経細胞ニコチン性α７レセプタアゴニストとしてのベンジリデン−およびシンナミリデン−アナバセイン |
| JP2010007505A Withdrawn JP2010116404A (ja) | 1997-08-29 | 2010-01-15 | 神経細胞ニコチン性α７レセプタアゴニストとしてのベンジリデン−およびシンナミリデン−アナバセイン |
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| DE (1) | DE69814688T2 (enExample) |
| WO (1) | WO1999010338A2 (enExample) |
Families Citing this family (90)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR0012793A (pt) * | 1999-07-28 | 2002-04-30 | Univ Leland Stanford Junior | Métodos para indução de angiogênese pela administração de nicotina ou outro agonista de receptor de nicotina |
| US8914114B2 (en) | 2000-05-23 | 2014-12-16 | The Feinstein Institute For Medical Research | Inhibition of inflammatory cytokine production by cholinergic agonists and vagus nerve stimulation |
| US6492385B2 (en) | 2000-08-18 | 2002-12-10 | Pharmacia & Upjohn Company | Quinuclidine-substituted heteroaryl moieties for treatment of disease |
| US6479510B2 (en) | 2000-08-18 | 2002-11-12 | Pharmacia & Upjohn Company | Quinuclidine-substituted aryl compounds for treatment of disease |
| AU2001282873A1 (en) | 2000-08-18 | 2002-03-04 | Pharmacia And Upjohn Company | Quinuclidine-substituted aryl compounds for treatment of disease |
| AU2001284646A1 (en) | 2000-08-21 | 2002-03-04 | Pharmacia And Upjohn Company | Quinuclidine-substituted heteroaryl moieties for treatment of disease |
| US6500840B2 (en) | 2000-08-21 | 2002-12-31 | Pharmacia & Upjohn Company | Quinuclidine-substituted heteroaryl moieties for treatment of disease |
| CA2341952A1 (en) * | 2001-03-23 | 2002-09-23 | Universite Laval | Nicotinic receptor agonists for the treatment of inflammatory pulmonary diseases |
| US20050130990A1 (en) * | 2001-03-23 | 2005-06-16 | Universite Laval | Nicotinic receptor agonists for the treatment of inflammatory diseases |
| PE20021019A1 (es) | 2001-04-19 | 2002-11-13 | Upjohn Co | Grupos azabiciclicos sustituidos |
| AR036040A1 (es) | 2001-06-12 | 2004-08-04 | Upjohn Co | Compuestos de heteroarilo multiciclicos sustituidos con quinuclidinas y composiciones farmaceuticas que los contienen |
| AR036041A1 (es) * | 2001-06-12 | 2004-08-04 | Upjohn Co | Compuestos aromaticos heterociclicos sustituidos con quinuclidina y composiciones farmaceuticas que los contienen |
| US6562816B2 (en) | 2001-08-24 | 2003-05-13 | Pharmacia & Upjohn Company | Substituted-heteroaryl-7-aza[2.2.1]bicycloheptanes for the treatment of disease |
| CA2455773A1 (en) * | 2001-08-24 | 2003-03-06 | Pharmacia & Upjohn Company | Substituted-aryl 7-aza¬2.2.1|bicycloheptanes for the treatment of disease |
| BR0212477A (pt) * | 2001-09-12 | 2004-08-24 | Upjohn Co | 7-aza[2.2.1] bicicloheptanos substituìdos para o tratamento de doenças |
| MXPA04003007A (es) | 2001-10-02 | 2004-07-15 | Upjohn Co | Compuestos azabiciclico sustituidos condensados con heteroarilo para el tratamiento de enfermedades. |
| MXPA04004464A (es) * | 2001-11-08 | 2004-08-11 | Upjohn Co | Compuestos de heteroarilo sustituido con azabiciclo para el tratamiento de enfermedades. |
| WO2003042210A1 (en) | 2001-11-09 | 2003-05-22 | Pharmacia & Upjohn Company | Azabicyclic-phenyl-fused-heterocyclic compounds and their use as alpha7 nachr ligands |
| PL374384A1 (en) * | 2001-12-14 | 2005-10-17 | Targacept, Inc. | Methods and compositions for treatment of central nervous system disorders |
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| US6852741B2 (en) * | 2001-12-31 | 2005-02-08 | University Of Florida | Compositions and methods for treatment of neurological disorders |
| US6852716B2 (en) | 2002-02-15 | 2005-02-08 | Pfizer Inc | Substituted-aryl compounds for treatment of disease |
| WO2003070731A2 (en) * | 2002-02-19 | 2003-08-28 | Pharmacia & Upjohn Company | Azabicyclic compounds for the treatment of disease |
| WO2003070732A1 (en) * | 2002-02-19 | 2003-08-28 | Pharmacia & Upjohn Company | Fused bicyclic-n-bridged-heteroaromatic carboxamides for the treatment of disease |
| EP1478646A1 (en) * | 2002-02-20 | 2004-11-24 | PHARMACIA & UPJOHN COMPANY | Azabicyclic compounds with alfa7 nicotinic acetylcholine receptor activity |
| US8557804B2 (en) | 2002-03-25 | 2013-10-15 | Universite Laval | Nicotinic receptor agonists for the treatment of inflammatory diseases |
| US8039459B2 (en) * | 2004-07-15 | 2011-10-18 | Universite Laval | Nicotinic receptor agonists for the treatment of inflammatory diseases |
| US7176198B2 (en) * | 2002-08-01 | 2007-02-13 | Pfizer Inc. | 1H-pyrazole and 1H-pyrrole-azabicyclic compounds for the treatment of disease |
| EP2298759A1 (en) * | 2002-08-30 | 2011-03-23 | Memory Pharmaceuticals Corporation | Anabaseine derivatives useful in the treatment of neurodegenerative diseases |
| JP2006506395A (ja) * | 2002-11-01 | 2006-02-23 | ファルマシア・アンド・アップジョン・カンパニー・エルエルシー | ＣＮＳ疾患の治療のための、α７ニコチンアゴニスト活性及び５ＨＴ３アンタゴニスト活性を有する化合物 |
| DE10251963A1 (de) * | 2002-11-08 | 2004-05-19 | Lts Lohmann Therapie-Systeme Ag | Transmucosale pharmazeutische Darreichungsform |
| CN102657651A (zh) * | 2002-12-06 | 2012-09-12 | 范因斯坦医学研究院 | 用α 7受体结合胆碱能激动剂抑制炎症 |
| US7238715B2 (en) * | 2002-12-06 | 2007-07-03 | The Feinstein Institute For Medical Research | Treatment of pancreatitis using alpha 7 receptor-binding cholinergic agonists |
| WO2005023942A2 (en) * | 2003-02-20 | 2005-03-17 | University Of Florida | Materials and methods for inhibiting fouling of surfaces exposed to aquatic environments |
| US8580842B2 (en) * | 2003-09-30 | 2013-11-12 | Abbott Gmbh & Co. Kg | Heteroaryl-substituted 1,3-dihydroindol-2-one derivatives and medicaments containing them |
| CA2560756A1 (en) * | 2004-03-25 | 2005-10-06 | The Feinstein Institute For Medical Research | Methods and devices for reducing bleed time using vagus nerve stimulation |
| US10912712B2 (en) | 2004-03-25 | 2021-02-09 | The Feinstein Institutes For Medical Research | Treatment of bleeding by non-invasive stimulation |
| WO2005123075A2 (en) * | 2004-06-08 | 2005-12-29 | University Of Florida Research Foundation, Inc. | Controlling angiogenesis with anabaseine analogs |
| US11207518B2 (en) | 2004-12-27 | 2021-12-28 | The Feinstein Institutes For Medical Research | Treating inflammatory disorders by stimulation of the cholinergic anti-inflammatory pathway |
| DE602005025020D1 (de) | 2004-12-27 | 2011-01-05 | The Feinstein Inst Medical Res | Behandlung von entzündlichen erkrankungen durch el |
| EP1891036A4 (en) * | 2005-06-07 | 2010-08-04 | Univ Florida | SELECTIVE LIGANDS FOR ALPHA-7 NICOTINE RECEPTORS |
| US8316104B2 (en) | 2005-11-15 | 2012-11-20 | California Institute Of Technology | Method and apparatus for collaborative system |
| US7662965B2 (en) * | 2006-01-26 | 2010-02-16 | Cornerstone Therapeutics, Inc. | Anabaseine derivatives, pharmaceutical compositions and method of use thereof |
| US20080167286A1 (en) * | 2006-12-12 | 2008-07-10 | Abbott Laboratories | Pharmaceutical compositions and their methods of use |
| US8486979B2 (en) * | 2006-12-12 | 2013-07-16 | Abbvie Inc. | 1,2,4 oxadiazole compounds and methods of use thereof |
| UY30846A1 (es) | 2006-12-30 | 2008-07-31 | Abbott Gmbh & Amp | Derivados de oxindol sustituidos, medicamentos que los comprenden y uso de los mismos |
| SA08290475B1 (ar) * | 2007-08-02 | 2013-06-22 | Targacept Inc | (2s، 3r)-n-(2-((3-بيردينيل)ميثيل)-1-آزا بيسيكلو[2، 2، 2]أوكت-3-يل)بنزو فيوران-2-كربوكساميد، وصور أملاحه الجديدة وطرق استخدامه |
| US8391970B2 (en) | 2007-08-27 | 2013-03-05 | The Feinstein Institute For Medical Research | Devices and methods for inhibiting granulocyte activation by neural stimulation |
| ES2455197T3 (es) | 2007-12-07 | 2014-04-14 | Abbvie Deutschland Gmbh & Co Kg | Derivados de oxindol 5,6-disustituidos y el uso de los mismos para la preparación de un medicamento para el tratamiento de enfermedades dependientes de vasopresina |
| NZ586651A (en) * | 2007-12-07 | 2012-06-29 | Abbott Gmbh & Co Kg | 5-halogen-substituted oxindole derivatives and use thereof for treating vasopressine-dependent diseases |
| US8703775B2 (en) * | 2007-12-07 | 2014-04-22 | AbbVie Deutschland GmbH & Co. KG | Amidomethyl-substituted oxindole derivatives and the use thereof for the treatment of vasopressin-dependent illnesses |
| WO2010009775A1 (de) * | 2007-12-07 | 2010-01-28 | Abbott Gmbh & Co. Kg | Carbamat-substituierte oxindol-derivate und ihre verwendung zur behandlung von vasopressin-abhängigen erkrankungen |
| US8383657B2 (en) | 2007-12-21 | 2013-02-26 | Abbott Laboratories | Thiazolylidine urea and amide derivatives and methods of use thereof |
| US9211409B2 (en) | 2008-03-31 | 2015-12-15 | The Feinstein Institute For Medical Research | Methods and systems for reducing inflammation by neuromodulation of T-cell activity |
| US9662490B2 (en) | 2008-03-31 | 2017-05-30 | The Feinstein Institute For Medical Research | Methods and systems for reducing inflammation by neuromodulation and administration of an anti-inflammatory drug |
| US9463190B2 (en) * | 2008-03-31 | 2016-10-11 | University Of South Florida | Methods of treating disease-induced ataxia and non-ataxic imbalance |
| ES2452484T3 (es) | 2008-11-18 | 2014-04-01 | Setpoint Medical Corporation | Dispositivos para optimizar la colocación de electrodos para la estimulación antiinflamatoria |
| CN105687190A (zh) | 2008-11-19 | 2016-06-22 | 福拉姆医药股份有限公司 | 用(R)-7-氯-N-(奎宁环-3-基)苯并[b]噻吩-2-甲酰胺及其可药用盐治疗认知障碍 |
| TW201031664A (en) | 2009-01-26 | 2010-09-01 | Targacept Inc | Preparation and therapeutic applications of (2S,3R)-N-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)-3,5-difluorobenzamide |
| US9211410B2 (en) | 2009-05-01 | 2015-12-15 | Setpoint Medical Corporation | Extremely low duty-cycle activation of the cholinergic anti-inflammatory pathway to treat chronic inflammation |
| US8996116B2 (en) | 2009-10-30 | 2015-03-31 | Setpoint Medical Corporation | Modulation of the cholinergic anti-inflammatory pathway to treat pain or addiction |
| PE20120324A1 (es) * | 2009-05-11 | 2012-04-17 | Envivo Pharmaceuticals Inc | Combinacion que comprende (r)-7-cloro-n-(quinuclidin-3-il)benzo[b]tiofeno-2-carboxamida y donezepilo como moduladora de trastornos cognitivos |
| EP2435080A2 (en) | 2009-05-29 | 2012-04-04 | Abbott Laboratories | Pharmaceutical compositions for the treatment of pain |
| CN102573986B (zh) | 2009-06-09 | 2016-01-20 | 赛博恩特医疗器械公司 | 用于无导线刺激器的具有袋部的神经封套 |
| US9833621B2 (en) | 2011-09-23 | 2017-12-05 | Setpoint Medical Corporation | Modulation of sirtuins by vagus nerve stimulation |
| WO2014169145A1 (en) | 2013-04-10 | 2014-10-16 | Setpoint Medical Corporation | Closed-loop vagus nerve stimulation |
| CN102821814B (zh) | 2009-12-23 | 2015-07-15 | 赛博恩特医疗器械公司 | 用于治疗慢性炎症的神经刺激设备和系统 |
| KR20180101641A (ko) | 2010-05-17 | 2018-09-12 | 포럼 파마슈티칼즈 인크. | (R)-7-클로로-N-(퀴누클리딘-3-일)벤조[b]티오펜-2-카르복사미드 히드로클로리드 모노히드레이트의 결정질 형태 |
| US9440948B2 (en) | 2010-09-03 | 2016-09-13 | University Of Florida Research Foundation, Inc. | Nicotine compounds and analogs thereof, synthetic methods of making compounds, and methods of use |
| US12172017B2 (en) | 2011-05-09 | 2024-12-24 | Setpoint Medical Corporation | Vagus nerve stimulation to treat neurodegenerative disorders |
| WO2012154865A2 (en) | 2011-05-09 | 2012-11-15 | Setpoint Medical Corporation | Single-pulse activation of the cholinergic anti-inflammatory pathway to treat chronic inflammation |
| US9572983B2 (en) | 2012-03-26 | 2017-02-21 | Setpoint Medical Corporation | Devices and methods for modulation of bone erosion |
| EP3461481A1 (en) | 2012-05-08 | 2019-04-03 | Forum Pharmaceuticals Inc. | Methods of maintaining, treating or improving cognitive function |
| US11311725B2 (en) | 2014-10-24 | 2022-04-26 | Setpoint Medical Corporation | Systems and methods for stimulating and/or monitoring loci in the brain to treat inflammation and to enhance vagus nerve stimulation |
| WO2016126807A1 (en) | 2015-02-03 | 2016-08-11 | Setpoint Medical Corporation | Apparatus and method for reminding, prompting, or alerting a patient with an implanted stimulator |
| US10596367B2 (en) | 2016-01-13 | 2020-03-24 | Setpoint Medical Corporation | Systems and methods for establishing a nerve block |
| WO2017127758A1 (en) | 2016-01-20 | 2017-07-27 | Setpoint Medical Corporation | Implantable microstimulators and inductive charging systems |
| CN108882885A (zh) | 2016-01-20 | 2018-11-23 | 赛博恩特医疗器械公司 | 迷走神经刺激的控制 |
| US11471681B2 (en) | 2016-01-20 | 2022-10-18 | Setpoint Medical Corporation | Batteryless implantable microstimulators |
| US10583304B2 (en) | 2016-01-25 | 2020-03-10 | Setpoint Medical Corporation | Implantable neurostimulator having power control and thermal regulation and methods of use |
| US11096932B2 (en) | 2016-09-29 | 2021-08-24 | The Uab Research Foundation | Methods and compositions for increasing mucus clearance |
| WO2019036470A1 (en) | 2017-08-14 | 2019-02-21 | Setpoint Medical Corporation | TESTING TEST FOR STIMULATION OF NERVE WAVE |
| US11660443B2 (en) | 2018-04-20 | 2023-05-30 | The Feinstein Institutes For Medical Research | Methods and apparatuses for reducing bleeding via electrical trigeminal nerve stimulation |
| US20210255202A1 (en) | 2018-06-13 | 2021-08-19 | Michael R. D'Andrea | Methods and dosing regimens for preventing or delaying onset of alzheimer's disease and other forms of dementia and mild congnitive impairment |
| US11260229B2 (en) | 2018-09-25 | 2022-03-01 | The Feinstein Institutes For Medical Research | Methods and apparatuses for reducing bleeding via coordinated trigeminal and vagal nerve stimulation |
| US12343535B2 (en) | 2019-04-12 | 2025-07-01 | Setpoint Medical Corporation | Vagus nerve stimulation to treat neurodegenerative disorders |
| JP2023512447A (ja) | 2020-01-13 | 2023-03-27 | ザ ファインスタイン インスティチューツ フォー メディカル リサーチ | 脾臓への高密度集束超音波刺激による出血及び出血性疾患の治療 |
| US11938324B2 (en) | 2020-05-21 | 2024-03-26 | The Feinstein Institutes For Medical Research | Systems and methods for vagus nerve stimulation |
| AU2021286756A1 (en) * | 2020-06-09 | 2023-03-23 | Elkazaz, Mohamed, Fadly Abd El Ghany | A novel medicament for immune modulation and treating chronic or hyper inflammation |
| US12444497B2 (en) | 2021-05-17 | 2025-10-14 | Setpoint Medical Corporation | Neurostimulation parameter authentication and expiration system for neurostimulation |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3275625A (en) * | 1966-09-27 | Derivatives of | ||
| US3426130A (en) * | 1960-12-19 | 1969-02-04 | Squibb & Sons Inc | Compositions containing a benzothiadiazinesulfonamide 1,1-dioxide |
| US3247213A (en) * | 1961-04-12 | 1966-04-19 | Shell Oil Co | Heterocyclic nitrogen compounds |
| US3265573A (en) * | 1962-07-27 | 1966-08-09 | Squibb & Sons Inc | Benzothiadiazinesulfonamide-1, 1-dioxide composition |
| US4155909A (en) * | 1977-06-13 | 1979-05-22 | Philip Morris Incorporated | 2-Alkyl nicotinoids and processes for their production |
| US4195645A (en) * | 1978-03-13 | 1980-04-01 | Celanese Corporation | Tobacco-substitute smoking material |
| US4728605A (en) * | 1984-07-31 | 1988-03-01 | Fudenberg Herman H | Methods for recognizing and diagnosing subsets of Alzheimer's disease associated with immune system dysfunction, and for the in vitro testing of possible therapeutic agents for treatment of same |
| US4965074A (en) * | 1985-03-05 | 1990-10-23 | Ciba-Geigy Corporation | Method of treating memory impairment |
| US5015570A (en) * | 1988-05-13 | 1991-05-14 | Molecular Therapeutics, Inc. | Molecular diagnosis of Alzheimer Disease |
| GB8929331D0 (en) * | 1989-12-29 | 1990-02-28 | Shell Int Research | Piperidine derivatives |
| JP2657583B2 (ja) * | 1991-03-01 | 1997-09-24 | ユニバーシテイ オブ フロリダ リサーチ ファンデーション インコーポレイテッド | 神経系変性疾患の治療に対するニコチン類似体の利用 |
| US5242934A (en) * | 1992-03-02 | 1993-09-07 | R. J. Reynolds Tobacco Company | Method for treatment of neurodegenerative diseases |
| US5212188A (en) * | 1992-03-02 | 1993-05-18 | R. J. Reynolds Tabacco Company | Method for treatment of neurodegenerative diseases |
| US5242935A (en) * | 1992-03-06 | 1993-09-07 | R. J. Reynolds Tobacco Company | Method for treatment of neurodegenerative diseases |
| US5227385A (en) * | 1992-03-13 | 1993-07-13 | Wake Forest University | Method for treatment of neurodegenerative diseases |
| US5187169A (en) * | 1992-04-10 | 1993-02-16 | R. J. Reynolds Tobacco Company | Method for treatment of neurodegenerative diseases |
| US5276043A (en) * | 1992-04-10 | 1994-01-04 | R. J. Reynolds Tobacco Company | Method for treatment of neurodegenerative diseases |
| US5214060A (en) * | 1992-04-10 | 1993-05-25 | R. J. Reynolds Tobacco Company | Method for treatment of neurodegenerative diseases |
| US5227391A (en) * | 1992-04-10 | 1993-07-13 | R. J. Reynolds Tobacco Company | Method for treatment of neurodegenerative diseases |
| US5232933A (en) * | 1992-05-21 | 1993-08-03 | R. J. Reynolds Tobacco Company | Method for treatment of neurodegenerative diseases |
| US5232932A (en) * | 1992-05-21 | 1993-08-03 | R. J. Reynolds Tobacco Company | Method for treatment of neurodegenerative diseases |
| US5248690A (en) * | 1992-07-07 | 1993-09-28 | R. J. Reynolds Tobacco Company | Method for treatment of neurodegenerative diseases |
| US5242916A (en) * | 1992-07-07 | 1993-09-07 | R. J. Reynolds Tobacco Company | Method for treatment of neurodegenerative diseases |
| US5741802A (en) * | 1992-08-31 | 1998-04-21 | University Of Florida | Anabaseine derivatives useful in the treatment of degenerative diseases of the nervous system |
| US5595972A (en) * | 1993-06-29 | 1997-01-21 | University Of Utah Research Foundation | Conotoxin peptides |
| US5488049A (en) * | 1993-12-10 | 1996-01-30 | Fidia - Georgetown Institute For The Neuro-Sciences | Method of treating learning and memory disorders using benzothiadiazide derivatives as nootropic agents |
| JP3708962B2 (ja) * | 1994-08-24 | 2005-10-19 | アストラゼネカ・アクチエボラーグ | 治療に有用なスピロ−アザ二環式化合物 |
| US5703100A (en) * | 1994-11-10 | 1997-12-30 | Sibia Neurosciences, Inc. | Modulators of acetylcholine receptors |
| US6177242B1 (en) * | 1994-12-14 | 2001-01-23 | Institut Pasteur | Genomic DNA fragments containing regulatory and coding sequences for the β2-subunit of the neuronal nicotinic acetylcholine receptor and transgenic animals made using these fragments or mutated fragments |
| SE9600683D0 (sv) * | 1996-02-23 | 1996-02-23 | Astra Ab | Azabicyclic esters of carbamic acids useful in therapy |
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- 1998-08-28 JP JP2000507667A patent/JP4511023B2/ja not_active Expired - Fee Related
- 1998-08-28 DE DE69814688T patent/DE69814688T2/de not_active Expired - Lifetime
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2010
- 2010-01-15 JP JP2010007505A patent/JP2010116404A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| JP2010116404A (ja) | 2010-05-27 |
| WO1999010338A3 (en) | 1999-05-14 |
| DE69814688D1 (de) | 2003-06-18 |
| WO1999010338A2 (en) | 1999-03-04 |
| DE69814688T2 (de) | 2004-04-22 |
| US5977144A (en) | 1999-11-02 |
| EP1045842A2 (en) | 2000-10-25 |
| JP2003524575A (ja) | 2003-08-19 |
| EP1045842B1 (en) | 2003-05-14 |
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