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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| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| SI2889033T1 (en) | 2008-11-19 | 2018-08-31 | Forum Pharmaceuticals Inc. | Treatment of negative symptoms of schizophrenia with (R) -7-chloro-N- (chonylidin-3-yl) benzo (B) thiophene-2-carboxamide and pharmaceutically acceptable salts thereof |
| WO2010132423A1 (en) * | 2009-05-11 | 2010-11-18 | Envivo Pharmaceuticals, Inc. | Treatment of cognitive disorders with certain alpha-7 nicotinic acid receptors in combination with acetylcholinesterase inhibitors |
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| US20130197028A1 (en) * | 2010-06-25 | 2013-08-01 | Oklahoma Medical Research Foundation | nAChRalpha7 Agonists and nAChRalpha7 Antagonists for Treating Ulcerative Colitis (UC) and Crohn's Disease (CD) |
| AU2012279298A1 (en) * | 2011-07-01 | 2014-01-23 | Envivo Pharmaceuticals, Inc. | Methods of treatment of Limited Cognitive Impairment |
| CA2869143A1 (en) | 2012-04-10 | 2013-10-17 | Sumitomo Dainippon Pharma Co., Ltd. | Novel 1-substituted indazole derivative |
| AU2013259871A1 (en) | 2012-05-08 | 2014-11-20 | Forum Pharmaceuticals Inc. | Methods of maintaining, treating or improving cognitive function |
| WO2014087904A1 (ja) * | 2012-12-05 | 2014-06-12 | 国立大学法人大阪大学 | 破骨細胞が関与する疾患の予防又は治療剤 |
| JP6506248B2 (ja) | 2013-03-14 | 2019-04-24 | ゾーン・ロイヤリティズ・アンド・マイルストーンズ・エルエルシー | 二環式鎮痛化合物 |
| PT3052096T (pt) | 2013-10-03 | 2018-04-04 | Kura Oncology Inc | Inibidores de erk e métodos de utilização |
| KR102380609B1 (ko) | 2013-12-12 | 2022-03-30 | 리커리엄 아이피 홀딩스, 엘엘씨 | 바이사이클릭 알킬 화합물 및 합성 |
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| EP3166940A4 (en) | 2014-07-11 | 2018-04-25 | Alpharmagen, LLC | Quinuclidine compounds for modulating alpha7 -nicotinic acetylcholine receptor activity |
| KR20170048588A (ko) | 2014-09-17 | 2017-05-08 | 카리라 파마슈티컬스, 아이앤씨. | 바이사이클릭 화합물 |
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| EP3520803A1 (en) * | 2018-01-31 | 2019-08-07 | Zarodex Therapeutics Limited | Novel uses |
Family Cites Families (43)
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- 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 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 EP EP08835512A patent/EP2217597B1/en not_active Not-in-force
- 2008-09-30 JP JP2010527249A patent/JP5022494B2/ja not_active Expired - Fee Related
- 2008-09-30 KR KR1020107008479A patent/KR101565469B1/ko not_active Expired - Fee Related
- 2008-09-30 DE DE602008005928T patent/DE602008005928D1/de active Active
- 2008-09-30 CA CA2701126A patent/CA2701126A1/en not_active Abandoned
- 2008-09-30 AT AT08835512T patent/ATE503754T1/de active
- 2008-09-30 MX MX2010003375A patent/MX2010003375A/es active IP Right Grant
- 2008-09-30 CN CN2008801186316A patent/CN101883771A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| HK1204616A1 (en) | 2015-11-27 |
| CN104193741B (zh) | 2016-08-24 |
| JP2010540562A (ja) | 2010-12-24 |
| CN101883771A (zh) | 2010-11-10 |
| EP2217597B1 (en) | 2011-03-30 |
| JP5022494B2 (ja) | 2012-09-12 |
| KR101565469B1 (ko) | 2015-11-03 |
| US8114891B2 (en) | 2012-02-14 |
| US20090088418A1 (en) | 2009-04-02 |
| DK2217597T3 (da) | 2011-06-20 |
| CA2701126A1 (en) | 2009-04-09 |
| EP2217597A1 (en) | 2010-08-18 |
| ATE503754T1 (de) | 2011-04-15 |
| WO2009046025A1 (en) | 2009-04-09 |
| MX2010003375A (es) | 2010-05-17 |
| DE602008005928D1 (de) | 2011-05-12 |
| CN104193741A (zh) | 2014-12-10 |
| KR20100068290A (ko) | 2010-06-22 |
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