JP2012508737A5 - - Google Patents
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- JP2012508737A5 JP2012508737A5 JP2011536316A JP2011536316A JP2012508737A5 JP 2012508737 A5 JP2012508737 A5 JP 2012508737A5 JP 2011536316 A JP2011536316 A JP 2011536316A JP 2011536316 A JP2011536316 A JP 2011536316A JP 2012508737 A5 JP2012508737 A5 JP 2012508737A5
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| EA201992409A1 (ru) | 2017-05-23 | 2020-03-23 | Лундбекк Ла-Хойя Рисерч Сентер, Инк. | Ингибиторы magl на основе пиразола |
| US20210069230A1 (en) * | 2018-04-13 | 2021-03-11 | The Broad Institute, Inc. | Synergistic drug combinations predicted from genomic features and single-agent response profiles |
| KR20210010475A (ko) | 2018-05-15 | 2021-01-27 | 룬드벡 라 졸라 리서치 센터 인코포레이티드 | Magl 저해제 |
| AU2019304198A1 (en) | 2018-07-19 | 2021-02-04 | Pfizer Inc. | Heterocyclic spiro compounds as MAGL inhibitors |
| TWI767148B (zh) | 2018-10-10 | 2022-06-11 | 美商弗瑪治療公司 | 抑制脂肪酸合成酶(fasn) |
| US10793554B2 (en) | 2018-10-29 | 2020-10-06 | Forma Therapeutics, Inc. | Solid forms of 4-(2-fluoro-4-(1-methyl-1H-benzo[d]imidazol-5-yl)benzoyl)piperazin-1-yl)(1-hydroxycyclopropyl)methanone |
| US11147805B2 (en) * | 2019-02-07 | 2021-10-19 | Medipure Pharmaceuticals Inc. | Cannabinoid receptor agonists and serine hydrolase enzyme inhibitor based anxiolytic therapeutic product |
| CN109750104A (zh) * | 2019-03-18 | 2019-05-14 | 南通大学附属医院 | Abhd6在非小细胞肺癌诊断、预后、治疗产品中的应用 |
| WO2021062232A1 (en) * | 2019-09-26 | 2021-04-01 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for reducing rewarding effects of morphine without affecting its analgesic effects |
| IL297470A (en) | 2020-04-21 | 2022-12-01 | H Lundbeck As | Synthesis of a monoacylglycerol lipase inhibitor |
| TW202304932A (zh) * | 2021-04-01 | 2023-02-01 | 日商小野藥品工業股份有限公司 | Abhd6拮抗劑 |
| CN113527270B (zh) * | 2021-07-16 | 2024-03-01 | 河南大学 | 一种靶向单酰基甘油脂肪酶的protac分子的医药中间体、制备方法及应用 |
| CA3242372A1 (en) | 2021-12-29 | 2023-07-06 | Psy Therapeutics, Inc. | Inhibiting monoacylglycerol lipase (magl) |
| JP7852604B2 (ja) * | 2022-09-30 | 2026-04-28 | 小野薬品工業株式会社 | Ａｂｈｄ６アンタゴニストを含有する医薬組成物 |
| EP4665718A1 (en) | 2023-02-13 | 2025-12-24 | Apogee Pharmaceuticals, Inc. | Small molecules as monoacylglycerol lipase (magl) inhibitors, compositions and use thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003262515A1 (en) | 2002-09-19 | 2004-04-08 | Nieland, John Mr | Inhibitors of the fatty acid oxidation for the prophylaxis and/or the treatment of chronic and/or atopic skin diseases |
| WO2006058088A2 (en) * | 2004-11-23 | 2006-06-01 | Ptc Therapeutics, Inc. | Carbazole, carboline and indole derivatives useful in the inhibition of vegf production |
| WO2006116773A2 (en) * | 2005-04-28 | 2006-11-02 | The Regents Of The University Of California | Methods, compositions, and compounds for modulation of monoacylglycerol lipase, pain, and stress-related disorders |
| WO2008024408A2 (en) * | 2006-08-22 | 2008-02-28 | Theraquest Biosciences, Inc. | Pharmaceutical formulations of cannabinoids for application to the skin and method of use |
| FR2915197B1 (fr) * | 2007-04-18 | 2009-06-12 | Sanofi Aventis Sa | Derives de triazolopyridine-carboxamides, leur preparation et leur application therapeutique. |
| US7989623B2 (en) * | 2007-11-21 | 2011-08-02 | Synthon Bv | Process for making n-(diphenylmethyl)piperazines |
| MX342128B (es) | 2008-12-24 | 2016-09-14 | Bial - Portela & C A S A | Compuestos farmaceuticos. |
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2009
- 2009-11-10 WO PCT/US2009/006045 patent/WO2010056309A2/en not_active Ceased
- 2009-11-10 AU AU2009314629A patent/AU2009314629B2/en not_active Ceased
- 2009-11-10 JP JP2011536316A patent/JP5576874B2/ja not_active Expired - Fee Related
- 2009-11-10 US US12/998,642 patent/US8772318B2/en not_active Expired - Fee Related
- 2009-11-10 EP EP09826412A patent/EP2373315A4/en not_active Withdrawn
- 2009-11-10 CA CA2743861A patent/CA2743861A1/en not_active Abandoned
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