ES2362326T3 - Derivados de 1h-indol-3-carboxilato de quinuclidin-4-ilmetilo como ligandos del receptor nicotínico alfa 7 de la acetilcolina para el tratamiento de enfermedad de alzheimer. - Google Patents
Derivados de 1h-indol-3-carboxilato de quinuclidin-4-ilmetilo como ligandos del receptor nicotínico alfa 7 de la acetilcolina para el tratamiento de enfermedad de alzheimer. Download PDFInfo
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- ES2362326T3 ES2362326T3 ES08835512T ES08835512T ES2362326T3 ES 2362326 T3 ES2362326 T3 ES 2362326T3 ES 08835512 T ES08835512 T ES 08835512T ES 08835512 T ES08835512 T ES 08835512T ES 2362326 T3 ES2362326 T3 ES 2362326T3
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- Prior art keywords
- ylmethyl
- indole
- carboxylate
- quinuclidin
- heptan
- Prior art date
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| TWI558398B (zh) | 2009-09-22 | 2016-11-21 | 諾華公司 | 菸鹼乙醯膽鹼受體α７活化劑之用途 |
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| JP6088491B2 (ja) * | 2012-04-10 | 2017-03-01 | 大日本住友製薬株式会社 | 新規１位置換インダゾール誘導体 |
| US9585877B2 (en) | 2012-05-08 | 2017-03-07 | Forum Pharmaceuticals, Inc. | Methods of maintaining, treating or improving cognitive function |
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| EA032196B1 (ru) | 2013-10-03 | 2019-04-30 | Кура Онколоджи, Инк. | Ингибиторы erk и способы применения |
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Family Cites Families (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ203861A (en) | 1982-04-14 | 1986-07-11 | Beecham Group Plc | Bicyclic heterocyclic compounds and pharmaceutical compositions containing such |
| WO1985001048A1 (en) | 1983-08-26 | 1985-03-14 | Sandoz Ag | Aromatic esters or amides of carboxylic acid and sulfonic acid |
| US4910193A (en) | 1985-12-16 | 1990-03-20 | Sandoz Ltd. | Treatment of gastrointestinal disorders |
| NL8701682A (nl) | 1986-07-30 | 1988-02-16 | Sandoz Ag | Werkwijze voor het therapeutisch toepassen van serotonine antagonisten, aktieve verbindingen en farmaceutische preparaten die deze verbindingen bevatten. |
| WO1989000158A1 (en) | 1987-07-02 | 1989-01-12 | Pfizer Inc. | Bridged-diazabicycloalkyl quinolone carboxylic acids and esters |
| US4950759A (en) | 1988-07-07 | 1990-08-21 | Duphar International Research B.V. | Substituted 1,7-annelated 1H-indazoles |
| IT1228293B (it) | 1989-02-06 | 1991-06-07 | Angeli Inst Spa | Benzoderivati di composti eterociclici contenenti azoto. |
| US5187166A (en) | 1990-07-31 | 1993-02-16 | Nisshin Flour Milling Co., Ltd. | Azabicyclo derivatives and their use as antiemetics |
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| US5190953A (en) * | 1992-03-26 | 1993-03-02 | A. H. Robins Company, Incorporated | Heterocyclic carboxylic acid amides and esters of azabicyclic compounds as gastric prokinetic, antiemetic, anxiolytic and antiarrhythmic agents |
| US5300512A (en) | 1992-06-24 | 1994-04-05 | G. D. Searle & Co. | Benzimidazole compounds |
| 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 |
| JP3235913B2 (ja) | 1993-07-30 | 2001-12-04 | エーザイ株式会社 | アミノ安息香酸誘導体 |
| US5399562A (en) | 1994-02-04 | 1995-03-21 | G. D. Searle & Co. | Indolones useful as serotonergic agents |
| 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 |
| US5712270A (en) | 1995-11-06 | 1998-01-27 | American Home Products Corporation | 2-arylamidothiazole derivatives with CNS activity |
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| AT403803B (de) | 1996-04-19 | 1998-05-25 | Sanochemia Ltd | Neue benzazepinderivate, diese enthaltende arzneimittel und verwendung derselben zum herstellen von arzneimitteln |
| AR013184A1 (es) | 1997-07-18 | 2000-12-13 | Astrazeneca Ab | Aminas heterociclicas espiroazobiciclicas, composicion farmaceutica, uso de dichas aminas para preparar medicamentos y metodo de tratamiento o profilaxis |
| ES2230723T3 (es) | 1997-10-27 | 2005-05-01 | Neurosearch A/S | Diazacicloalcanos de heteroarilo como ligandos colinergicos en recptores nicotinicos de acetilcolina. |
| AU765142B2 (en) | 1998-06-01 | 2003-09-11 | Ortho-Mcneil Pharmaceutical, Inc. | Method for treating neurodegenerative disorders |
| SE9904176D0 (sv) | 1999-11-18 | 1999-11-18 | Astra Ab | New use |
| IL153707A0 (en) | 2000-06-27 | 2003-07-06 | S A L V A T Lab Sa | Carbamates derived from arylalkylamines |
| US6486172B2 (en) | 2000-08-18 | 2002-11-26 | Pharmacia & Upjohn Company | Quinuclidine-substituted aryl compounds for treatment of disease |
| AU2001284645A1 (en) | 2000-08-18 | 2002-03-04 | Pharmacia And Upjohn Company | Quinuclidine-substituted aryl compounds for treatment of disease |
| EP1381603A2 (en) | 2000-08-18 | 2004-01-21 | PHARMACIA & UPJOHN COMPANY | Quinuclidine-substituedaryl moieties for treatment of disease ( nicotinic acetylcholine receptor ligands ) |
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| PE20020719A1 (es) | 2000-12-22 | 2002-10-11 | Almirall Prodesfarma Ag | Derivados de carbamato de quinuclidina como agentes antimuscarinicos m3 |
| CN100484937C (zh) * | 2002-09-25 | 2009-05-06 | 记忆药物公司 | 吲唑、苯并噻唑和苯并异噻唑，以及它们的制备和用途 |
| US7488737B2 (en) | 2004-04-22 | 2009-02-10 | Memory Pharmaceutical Corporation | Indoles, 1H-indazoles, 1,2-benzisoxazoles, 1,2-benzoisothiazoles, and preparation and uses thereof |
| BRPI0517494A (pt) | 2004-12-22 | 2008-10-14 | Memory Pharm Corp | composto, composição farmacêutica, método de ativação/estimulação seletiva de receptores nicotìnicos de a-7 em um paciente em que tal ativação/estimulação tem um efeito terapêutico, método de tratamento de um paciente que sofre de uma doença psicótica, uma doença neurodegenerativa que envolve uma disfunção do sistema colinérgico, e/ou uma condição de debilitação da memória e/ou da cognição, método de tratamento de um paciente que sofre de demência e/ou uma outra condição com perda da memória, método de tratamento de um paciente que sofre de debilitação da memória devido à debilitação cognitiva suave devido ao envelhecimento, mal de alzheimer, esquizofrenia, mal de parkinson, mal de huntington, mal de pick, mal de creutzfeldt-jakob, depressão, envelhecimento, trauma na cabeça, acidente vascular cerebral, hipoxia do snc, senilidade cerebral, demência de multiinfarto, hiv e/ou doença cardiovascular, método de tratamento e/ou prevenção da demência em um paciente com o mal de alzheimer, método de tratamento de um paciente para cortar o vìcio do álcool ou o tratamento de um paciente com a terapia anti-intoxicação, método de tratamento de um paciente para propiciar neuroproteção contra os danos associados com acidentes vasculares cerebrais e isquemia e excitotoxicidade induzida por glutamatos, método de tratamento de um paciente que sofre do vìcio da nicotina, dor, tontura do fuso horário, obesidade e/ou diabetes, método de indução do ato de parar fumar em um paciente, método de tratamento de um paciente que sofre de debilitação cognitiva suave (mci), demência vascular (vad), declìnio cognitivo associado com a idade (aacd), amnésia associada com a cirurgia com o coração aberto, parada cardìaca, anestesia geral, deficiências da memória devido à exposição a agentes anestésicos, debilitação cognitiva induzida pela privação do sono, sìndrome de fadiga crÈnica, narcolepsia, demência relacionada com a aids, debilitação cognitiva relacionada com a epilepsia, sìndrome de down, demência relacionada ao alcoolismo, debilitações da memória induzidas por drogas/substáncias, demência pugilìstica (sìndrome do boxeador), ou demência animal, método para o tratamento da perda da memória, método para o tratamento de um paciente que sofre de debilitação da memória, método para o tratamento ou a profilaxia de uma doença ou de uma condição resultante da disfunção da transmissão do receptor nicotìnico de acetilcolina em um paciente, método para o tratamento ou a profilaxia de uma doença ou de uma condição resultante de receptores nicotìnicos de acetilcolina defeituosos ou funcionando mal em um paciente, método para o tratamento ou a profilaxia de uma doença ou de uma condição resultante da transmissão suprimida do receptor nicotìnico de acetilcolina em um paciente, método para o tratamento ou a profilaxia de uma doença ou de uma condição resultante da perda de sinapses colinérgicas em um paciente, método para a proteção dos neurÈnios em um paciente com neurotoxicidade induzi |
-
2008
- 2008-09-30 EP EP08835512A patent/EP2217597B1/en not_active Not-in-force
- 2008-09-30 KR KR1020107008479A patent/KR101565469B1/ko not_active Expired - Fee Related
- 2008-09-30 JP JP2010527249A patent/JP5022494B2/ja not_active Expired - Fee Related
- 2008-09-30 DK DK08835512.8T patent/DK2217597T3/da active
- 2008-09-30 CN CN201410331886.8A patent/CN104193741B/zh not_active Expired - Fee Related
- 2008-09-30 AT AT08835512T patent/ATE503754T1/de active
- 2008-09-30 MX MX2010003375A patent/MX2010003375A/es active IP Right Grant
- 2008-09-30 DE DE602008005928T patent/DE602008005928D1/de active Active
- 2008-09-30 CN CN2008801186316A patent/CN101883771A/zh active Pending
- 2008-09-30 US US12/242,389 patent/US8114891B2/en not_active Expired - Fee Related
- 2008-09-30 ES ES08835512T patent/ES2362326T3/es active Active
- 2008-09-30 CA CA2701126A patent/CA2701126A1/en not_active Abandoned
- 2008-09-30 WO PCT/US2008/078320 patent/WO2009046025A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| KR101565469B1 (ko) | 2015-11-03 |
| HK1204616A1 (en) | 2015-11-27 |
| CN104193741A (zh) | 2014-12-10 |
| US20090088418A1 (en) | 2009-04-02 |
| ATE503754T1 (de) | 2011-04-15 |
| KR20100068290A (ko) | 2010-06-22 |
| US8114891B2 (en) | 2012-02-14 |
| EP2217597B1 (en) | 2011-03-30 |
| DK2217597T3 (da) | 2011-06-20 |
| MX2010003375A (es) | 2010-05-17 |
| CA2701126A1 (en) | 2009-04-09 |
| EP2217597A1 (en) | 2010-08-18 |
| JP2010540562A (ja) | 2010-12-24 |
| DE602008005928D1 (de) | 2011-05-12 |
| JP5022494B2 (ja) | 2012-09-12 |
| CN104193741B (zh) | 2016-08-24 |
| WO2009046025A1 (en) | 2009-04-09 |
| CN101883771A (zh) | 2010-11-10 |
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