JP7293129B2 - Ｐｄｅ９阻害剤を含む医薬組成物 - Google Patents
Ｐｄｅ９阻害剤を含む医薬組成物 Download PDFInfo
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| RU2019135834A (ru) | 2017-06-01 | 2021-07-13 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Терапевтическое средство для лечения деменции, представляющее собой комбинацию производного пиразолохинолина и донепезила |
| BR112019023552A2 (pt) | 2017-06-01 | 2020-06-02 | Eisai R&D Management Co., Ltd. | Agente terapêutico para a demência com corpos de lewy contendo derivado de pirazoloquinolina |
| WO2023064857A1 (en) | 2021-10-14 | 2023-04-20 | Incyte Corporation | Quinoline compounds as inhibitors of kras |
| CN120897742A (zh) * | 2022-11-15 | 2025-11-04 | 福睿德姆生物科学公司 | 通过抑制9型磷酸二酯酶增强血清素能致幻药物在治疗或预防某些神经精神障碍中的功效 |
| CN119302958B (zh) * | 2023-12-01 | 2025-10-21 | 郑州大学第一附属医院 | 含有bay 73-6691或其衍生物的药物制剂在制备治疗脑损伤疾病药物中的应用 |
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Family Cites Families (34)
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|---|---|---|---|---|
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| JPH05132484A (ja) | 1991-04-26 | 1993-05-28 | Otsuka Pharmaceut Factory Inc | ピラゾロキノリン及びピラゾロナフチリジン誘導体 |
| DK0760819T3 (da) | 1994-05-24 | 2000-10-09 | Hoffmann La Roche | Tricykliske dicarbonylderivater |
| DE19642591A1 (de) | 1996-10-15 | 1998-04-16 | Basf Ag | Neue Piperidin-Ketocarbonsäure-Derivate, deren Herstellung und Anwendung |
| HN2002000317A (es) | 2001-11-02 | 2003-05-21 | Pfizer | Inhibidores de pde9 para tratamiento de trastornos cardiovasculares |
| BR0313262A (pt) | 2002-08-07 | 2005-07-12 | Mitsubishi Pharma Corp | Compostos de dihidropirazolpiridina |
| DE10238722A1 (de) * | 2002-08-23 | 2004-03-11 | Bayer Ag | Selektive Phosphodiesterase 9A-Inhibitoren als Arzneimittel zur Verbesserung kognitiver Prozesse |
| DE102004004142A1 (de) | 2003-05-09 | 2004-11-25 | Bayer Healthcare Ag | 6-Cyclylmethyl- und 6-Alkylmethyl-substituierte Pyrazolopyrimidine |
| RU2426734C2 (ru) | 2003-10-03 | 2011-08-20 | Зм Инновейтив Пропертиз Компани | Пиразолопиридины и их аналоги |
| WO2005118583A1 (en) | 2004-05-28 | 2005-12-15 | Millennium Pharmaceuticals, Inc. | 2, 5-dihydro-pyrazolo`4, 3-c!quinolin-4-ones as chk-1 inhibitors |
| JP2006045118A (ja) | 2004-08-04 | 2006-02-16 | Mochida Pharmaceut Co Ltd | 新規ピラゾロキノロン誘導体 |
| CA2622605A1 (en) | 2005-09-15 | 2007-03-22 | Aska Pharmaceutical Co., Ltd. | Heterocycle compound, and production process and application thereof |
| CN101466365A (zh) | 2006-06-09 | 2009-06-24 | 惠氏公司 | 增强认知功能的方法 |
| TW200808741A (en) | 2006-06-09 | 2008-02-16 | Wyeth Corp | 6-methoxy-8-[4-(1-(5-fluoro)-quinolin-8-yl-piperidin-4-yl)-piperazin-1-yl]-quinoline hydrochloric acid salts |
| WO2008072778A1 (ja) | 2006-12-13 | 2008-06-19 | Aska Pharmaceutical Co., Ltd. | 尿路系疾患の処置剤 |
| CA2671980C (en) | 2006-12-13 | 2015-05-05 | Aska Pharmaceutical Co., Ltd. | Quinoxaline derivatives |
| PT2152712E (pt) | 2007-05-11 | 2012-02-29 | Pfizer | Compostos amino-heterocíclicos |
| UA105362C2 (en) | 2008-04-02 | 2014-05-12 | Бьорингер Ингельхайм Интернациональ Гмбх | 1-heterocyclyl-1, 5-dihydro-pyrazolo [3, 4-d] pyrimidin-4-one derivatives and their use as pde9a modulators |
| JP5453431B2 (ja) | 2008-09-08 | 2014-03-26 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ピラゾロピリミジン及びｃｎｓ障害の治療のためのそれらの使用 |
| TWI404721B (zh) | 2009-01-26 | 2013-08-11 | Pfizer | 胺基－雜環化合物 |
| WO2010101230A1 (ja) | 2009-03-05 | 2010-09-10 | アステラス製薬株式会社 | キノキサリン化合物 |
| PE20120505A1 (es) | 2009-03-31 | 2012-05-09 | Boehringer Ingelheim Int | Derivados de 1-heterociclil-1,5-dihidro-pirazolo[3,4-d]pirimidin-4-ona como moduladores de pde9a |
| SMT201800036T1 (it) | 2009-04-13 | 2018-03-08 | Theravance Biopharma R&D Ip Llc | Combinazioni di agonisti di recettore 5-ht4 e inibitori di acetilcolinesterasi per il trattamento di disturbi cognitivi |
| US8880976B2 (en) | 2009-09-25 | 2014-11-04 | Stmicroelectronics, Inc. | Method and apparatus for encoding LBA information into the parity of a LDPC system |
| AP2012006631A0 (en) | 2010-08-12 | 2012-12-31 | Boehringer Ingelheim Int | 6-Cycloalkyl-1, 5-dihydro-pyrazolo[3,4-D] pyrimidin-4-one derivatives and their use as PDE9A inhibitors |
| RS54834B1 (sr) | 2010-09-07 | 2016-10-31 | Astellas Pharma Inc | Jedinjenja pirazolokvinolina |
| US20130040971A1 (en) | 2011-02-14 | 2013-02-14 | Boehringer Ingelheim International Gmbh | 6-cycloalkyl-pyrazolopyrimidinones for the treatment of cns disorders |
| PT2573073E (pt) | 2011-09-26 | 2015-02-05 | Sanofi Sa | Derivados de pirazoloquinolinona, sua preparação e sua utilização terapêutica |
| JP6042060B2 (ja) | 2011-09-26 | 2016-12-14 | サノフイ | ピラゾロキノリノン誘導体、その調製および治療上の使用 |
| JP5938299B2 (ja) | 2011-10-05 | 2016-06-22 | ダイセルポリマー株式会社 | 繊維強化樹脂組成物 |
| CN107847499A (zh) | 2015-05-07 | 2018-03-27 | 阿速万科学有限责任公司 | 治疗神经退行性疾病的方法 |
| BR112019023552A2 (pt) | 2017-06-01 | 2020-06-02 | Eisai R&D Management Co., Ltd. | Agente terapêutico para a demência com corpos de lewy contendo derivado de pirazoloquinolina |
| RU2019135834A (ru) | 2017-06-01 | 2021-07-13 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Терапевтическое средство для лечения деменции, представляющее собой комбинацию производного пиразолохинолина и донепезила |
| WO2018221550A1 (ja) | 2017-06-01 | 2018-12-06 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ピラゾロキノリン誘導体とメマンチンの併用による認知症治療剤 |
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2018
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- 2018-05-30 US US16/609,514 patent/US11484502B2/en active Active
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- 2018-05-30 JP JP2019559117A patent/JP7293129B2/ja active Active
- 2018-05-30 SG SG11201909359Y patent/SG11201909359YA/en unknown
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- 2018-05-30 MX MX2019013198A patent/MX2019013198A/es unknown
- 2018-05-30 AU AU2018276566A patent/AU2018276566A1/en not_active Abandoned
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013051639A1 (ja) | 2011-10-07 | 2013-04-11 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ピラゾロキノリン誘導体 |
| WO2014163147A1 (ja) | 2013-04-05 | 2014-10-09 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ピラゾロキノリン誘導体の塩およびその結晶 |
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|---|---|
| WO2018221546A1 (en) | 2018-12-06 |
| CN116585316A (zh) | 2023-08-15 |
| SG11201909359YA (en) | 2019-11-28 |
| KR20200010211A (ko) | 2020-01-30 |
| RU2019135261A (ru) | 2021-07-09 |
| CA3059539A1 (en) | 2018-12-06 |
| EP3630113A4 (en) | 2021-02-24 |
| JP2020521726A (ja) | 2020-07-27 |
| RU2019135261A3 (https=) | 2021-09-08 |
| CN110545812A (zh) | 2019-12-06 |
| US11484502B2 (en) | 2022-11-01 |
| AU2018276566A1 (en) | 2019-11-07 |
| BR112019023557A2 (pt) | 2020-06-02 |
| US20220378706A1 (en) | 2022-12-01 |
| MX2019013198A (es) | 2020-01-20 |
| US20200078306A1 (en) | 2020-03-12 |
| EP3630113A1 (en) | 2020-04-08 |
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