RU2569056C2 - Соединения-агонисты рецептора 5-нт4 для лечения расстройств познавательной способности - Google Patents
Соединения-агонисты рецептора 5-нт4 для лечения расстройств познавательной способности Download PDFInfo
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- RU2569056C2 RU2569056C2 RU2011146032/15A RU2011146032A RU2569056C2 RU 2569056 C2 RU2569056 C2 RU 2569056C2 RU 2011146032/15 A RU2011146032/15 A RU 2011146032/15A RU 2011146032 A RU2011146032 A RU 2011146032A RU 2569056 C2 RU2569056 C2 RU 2569056C2
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| RU2776366C2 (ru) * | 2017-05-24 | 2022-07-19 | Х. Лундбекк А/С | Комбинация антагониста 5-ht6-рецептора и ингибитора ацетилхолинэстеразы для применения при лечении болезни альцгеймера у субпопуляции пациентов, которые являются носителями аллелей apoe4 |
| US11464759B2 (en) | 2017-05-24 | 2022-10-11 | H. Lundbeck A/S | 5-HT6 receptor antagonists for use in the treatment of alzheimer's disease in patient subpopulation carrying APOE4 alleles |
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| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| HUE026815T2 (en) | 2008-11-19 | 2016-07-28 | Forum Pharmaceuticals Inc | Treatment of Cognitive Disorders with (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof |
| AU2010247835A1 (en) * | 2009-05-11 | 2011-12-08 | Envivo Pharmaceuticals, Inc. | Treatment of cognitive disorders with certain alpha-7 nicotinic acid receptors in combination with acetylcholinesterase inhibitors |
| TWI519532B (zh) | 2010-05-17 | 2016-02-01 | 艾維沃製藥公司 | （Ｒ）－７－氯－Ｎ－（啶－３－基）苯並［b］噻吩－２－羧醯胺鹽酸鹽單水合物之結晶形體 |
| RU2017136693A (ru) | 2012-05-08 | 2019-02-08 | Форум Фармасьютикалз, Инк. | Способы поддержания, лечения или улучшения когнитивной функции |
| JP6009080B2 (ja) | 2012-08-16 | 2016-10-19 | ユニバーシティ−インダストリー コオペレーション グループ オブ キョン ヒ ユニバーシティＵｎｉｖｅｒｓｉｔｙ−Ｉｎｄｕｓｔｒｙ Ｃｏｏｐｅｒａｔｉｏｎ Ｇｒｏｕｐ Ｏｆ Ｋｙｕｎｇ Ｈｅｅ Ｕｎｉｖｅｒｓｉｔｙ | 老化及び認知症の予防及び／または治療活性を有する乳酸菌 |
| US10874701B2 (en) | 2012-08-16 | 2020-12-29 | University-Industry Cooperation Group Of Kyung Hee University | Lactic acid bacteria capable of preventing and/or treating senescence and dementia |
| CN116585316A (zh) | 2017-06-01 | 2023-08-15 | 卫材R&D管理有限公司 | 包含pde9抑制剂的药物组合物 |
| JP7282028B2 (ja) | 2017-06-02 | 2023-05-26 | 富士フイルム富山化学株式会社 | 脳萎縮予防または治療剤 |
| CA3069989C (en) | 2017-07-31 | 2025-05-06 | Alfasigma S.P.A. | METHODS FOR TREATING GASTROPARESIA SYMPTOMS USING VELUSETRAG |
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| WO2006108127A2 (en) * | 2005-04-06 | 2006-10-12 | Theravance, Inc. | Crystalline form of a quinolinone-carboxamide compound |
| US7375114B2 (en) * | 2004-04-07 | 2008-05-20 | Theravance, Inc. | Quinolinone-carboxamide compounds as 5-HT4 receptor agonists |
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| DE60124730T2 (de) * | 2000-03-03 | 2007-10-04 | Eisai R&D Management Co., Ltd. | Neue methoden unter verwendung von cholinesteraseinhibitoren |
| US7598265B2 (en) * | 2004-09-30 | 2009-10-06 | Epix Delaware, Inc. | Compositions and methods for treating CNS disorders |
| MY147756A (en) * | 2005-05-25 | 2013-01-15 | Theravance Inc | Benzimidazole-carboxamide compounds as 5-ht4 receptor agonists |
-
2010
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- 2010-04-12 HR HRP20180018TT patent/HRP20180018T1/hr unknown
- 2010-04-12 AU AU2010236734A patent/AU2010236734B2/en not_active Ceased
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- 2010-04-12 RU RU2011146032/15A patent/RU2569056C2/ru not_active IP Right Cessation
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- 2010-04-12 SM SM20180036T patent/SMT201800036T1/it unknown
- 2010-04-12 ES ES10713790.3T patent/ES2654930T3/es active Active
- 2010-04-12 JP JP2012504924A patent/JP2012523437A/ja active Pending
- 2010-04-12 NO NO10713790A patent/NO2419104T3/no unknown
- 2010-04-12 US US12/758,631 patent/US8404711B2/en not_active Expired - Fee Related
- 2010-04-12 CN CN2010800164976A patent/CN102395371A/zh active Pending
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- 2010-04-12 KR KR1020117026729A patent/KR20120017421A/ko not_active Ceased
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- 2010-04-12 PL PL10713790T patent/PL2419104T3/pl unknown
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7375114B2 (en) * | 2004-04-07 | 2008-05-20 | Theravance, Inc. | Quinolinone-carboxamide compounds as 5-HT4 receptor agonists |
| WO2006108127A2 (en) * | 2005-04-06 | 2006-10-12 | Theravance, Inc. | Crystalline form of a quinolinone-carboxamide compound |
Non-Patent Citations (1)
| Title |
|---|
| ДАМУЛИН И.В. "Болезнь Альцгеймера: некоторые дифференциально-диагностические и терапевтические аспекты", с.1 абзац 1// найдено[25.03.2014] найдено из Интернет: http://medi.ru/doc/a030101.htm. VAN DEN HEUVEL C. et al. Neuroprotective effects of SAAPa administration following diffuse traumatic brain injury//7-th Int. Neurotr. Symposium, Adelaide, Australia, Sept. 12-16, 2004. * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2776366C2 (ru) * | 2017-05-24 | 2022-07-19 | Х. Лундбекк А/С | Комбинация антагониста 5-ht6-рецептора и ингибитора ацетилхолинэстеразы для применения при лечении болезни альцгеймера у субпопуляции пациентов, которые являются носителями аллелей apoe4 |
| US11464759B2 (en) | 2017-05-24 | 2022-10-11 | H. Lundbeck A/S | 5-HT6 receptor antagonists for use in the treatment of alzheimer's disease in patient subpopulation carrying APOE4 alleles |
Also Published As
| Publication number | Publication date |
|---|---|
| US20140057939A1 (en) | 2014-02-27 |
| JP2012523437A (ja) | 2012-10-04 |
| CY1119800T1 (el) | 2018-06-27 |
| HRP20180018T1 (hr) | 2018-02-09 |
| BRPI1013777A2 (pt) | 2016-04-05 |
| US8404711B2 (en) | 2013-03-26 |
| KR20120017421A (ko) | 2012-02-28 |
| AU2010236734B2 (en) | 2015-06-11 |
| LT2419104T (lt) | 2018-02-12 |
| IL215660A0 (en) | 2012-01-31 |
| WO2010120695A3 (en) | 2010-12-02 |
| EP2419104B1 (en) | 2017-11-08 |
| NO2419104T3 (enExample) | 2018-04-07 |
| PT2419104T (pt) | 2018-01-31 |
| DK2419104T3 (en) | 2018-02-05 |
| AU2010236734A1 (en) | 2011-11-03 |
| WO2010120695A2 (en) | 2010-10-21 |
| BRPI1013777A8 (pt) | 2017-09-19 |
| EP2419104A2 (en) | 2012-02-22 |
| PL2419104T3 (pl) | 2018-04-30 |
| SMT201800036T1 (it) | 2018-03-08 |
| ZA201107490B (en) | 2012-06-27 |
| US20100261752A1 (en) | 2010-10-14 |
| AU2010236734A8 (en) | 2012-02-16 |
| RU2011146032A (ru) | 2013-05-20 |
| ES2654930T3 (es) | 2018-02-15 |
| CN105832735A (zh) | 2016-08-10 |
| HUE038141T2 (hu) | 2018-10-29 |
| SI2419104T1 (en) | 2018-03-30 |
| CA2758321A1 (en) | 2010-10-21 |
| MX2011010782A (es) | 2012-01-20 |
| CN102395371A (zh) | 2012-03-28 |
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