TWI481597B - 組蛋白去乙醯酶（ｈｄａｃｓ）抑制劑 - Google Patents
組蛋白去乙醯酶（ｈｄａｃｓ）抑制劑 Download PDFInfo
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- TWI481597B TWI481597B TW102112723A TW102112723A TWI481597B TW I481597 B TWI481597 B TW I481597B TW 102112723 A TW102112723 A TW 102112723A TW 102112723 A TW102112723 A TW 102112723A TW I481597 B TWI481597 B TW I481597B
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- ethyl
- dihydro
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- hydrogen
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- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
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| Publication number | Priority date | Publication date | Assignee | Title |
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Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| PE20160685A1 (es) | 2013-10-04 | 2016-07-23 | Infinity Pharmaceuticals Inc | Compuestos heterociclicos y usos de los mismos |
| US9751888B2 (en) | 2013-10-04 | 2017-09-05 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| US20170029366A1 (en) * | 2014-03-07 | 2017-02-02 | The Johns Hopkins University | Inhibitors of histone lysine specific demethylase (lsd1) and histone deacetylases (hdacs) |
| EA201691872A1 (ru) | 2014-03-19 | 2017-04-28 | Инфинити Фармасьютикалз, Инк. | Гетероциклические соединения для применения в лечении pi3k-гамма-опосредованных расстройств |
| US10807944B2 (en) | 2014-04-04 | 2020-10-20 | University Of Florida Research Foundation, Inc. | HDAC inhibitor compounds and methods of treatment |
| US9708348B2 (en) | 2014-10-03 | 2017-07-18 | Infinity Pharmaceuticals, Inc. | Trisubstituted bicyclic heterocyclic compounds with kinase activities and uses thereof |
| MX390633B (es) | 2015-09-14 | 2025-03-04 | Infinity Pharmaceuticals Inc | Formas solidas de derivados de isoquinolinona, proceso de fabricacion, composiciones que las contienen y metodos de uso de las mismas. |
| US10759806B2 (en) | 2016-03-17 | 2020-09-01 | Infinity Pharmaceuticals, Inc. | Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as PI3K kinase inhibitors |
| US10919914B2 (en) | 2016-06-08 | 2021-02-16 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| EP3624804B1 (en) * | 2017-05-16 | 2022-02-16 | Annji Pharmaceutical Co., Ltd. | Histone deacetylases (hdacs) inhibitors |
| GB201820450D0 (en) | 2018-12-14 | 2019-01-30 | Z Factor Ltd | Compound and its use for the treatment of alpha1-antitryspin deficiency |
| GB201918404D0 (en) * | 2019-12-13 | 2020-01-29 | Z Factor Ltd | Compounds and their use for the treatment of aplha1-antitrypsin deficiency |
| KR20210116830A (ko) * | 2020-03-17 | 2021-09-28 | 충북대학교 산학협력단 | 신규한 4-옥소퀴나졸린-기반 n-하이드록시프로펜아미드 및 이의 용도 |
| CN111517977B (zh) * | 2020-05-28 | 2023-05-23 | 爱斯特（成都）生物制药股份有限公司 | 一种合成2,4-二氟-3-三甲基乙酰胺基苯甲酸的方法 |
| TWI864293B (zh) * | 2020-06-08 | 2024-12-01 | 安基生技新藥股份有限公司 | 選擇性hdac6抑制劑及其用途 |
| WO2023159155A1 (en) * | 2022-02-18 | 2023-08-24 | Pivalent Therapeutics, Inc. | Inhibitors of phosphoinositide 3-kinase (pi3k) and uses thereof |
| WO2025029683A1 (en) | 2023-07-28 | 2025-02-06 | Cogent Biosciences, Inc. | Pi3k inhibitors |
| WO2025085669A1 (en) * | 2023-10-18 | 2025-04-24 | Gilva Therapeutics Co., Ltd. | Quinazolinone derivatives for hdac inhibition |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060052345A1 (en) * | 2002-11-04 | 2006-03-09 | Nps Pharmaceuticals, Inc. | Quinazolinone compounds as calcilytics |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH464935A (de) * | 1965-05-12 | 1968-11-15 | Sumitomo Chemical Co | Verfahren zur Herstellung neuer Chinazolinonderivate |
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| ZA705270B (en) * | 1969-08-02 | 1971-04-28 | Sumitomo Chemical Co | Novel quinazolinone derivatives and a process for production thereof |
| US4054658A (en) * | 1974-02-06 | 1977-10-18 | William H. Rorer, Inc. | Therapeutic compositions containing methaqualone |
| NZ192392A (en) * | 1978-12-19 | 1983-02-15 | M Ishikawa | 3-(substituted (phenyl or pyridyl)) -3,4-dihydroquinazolin-4-ones |
| JP3488890B2 (ja) * | 1993-11-09 | 2004-01-19 | アグロカネショウ株式会社 | ３−ｎ−置換キナゾリノン誘導体、その製造法および該化合物を含有する除草剤 |
| EP1524262A1 (en) | 2000-03-24 | 2005-04-20 | Methylgene, Inc. | Inhibitors of histone deacetylase |
| US7288567B2 (en) * | 2000-03-24 | 2007-10-30 | Methylgene Inc. | Inhibitors of histone deacetylase |
| ITMI20041869A1 (it) | 2004-10-01 | 2005-01-01 | Dac Srl | Nuovi inibitori delle istone deacetilasi |
| WO2007011623A1 (en) * | 2005-07-15 | 2007-01-25 | Schering Corporation | Quinazoline derivatives useful in cancer treatment |
| NZ566073A (en) | 2005-09-21 | 2011-08-26 | 4Sc Ag | Sulphonylpyrrole hydrochloride salts as histone deacetylases inhibitors |
| GB0525068D0 (en) * | 2005-12-08 | 2006-01-18 | Novartis Ag | Organic compounds |
| GB0619753D0 (en) | 2006-10-06 | 2006-11-15 | Chroma Therapeutics Ltd | Enzyme inhibitors |
| GB0624187D0 (en) | 2006-12-04 | 2007-01-10 | Jackson William P | HDAC inhibitors |
| WO2008087514A2 (en) | 2007-01-17 | 2008-07-24 | Orchid Research Laboratories Limited | Hdac inhibitors |
| CA2695452A1 (en) | 2007-08-21 | 2009-02-26 | Arqule, Inc. | Hdac inhibitors |
| WO2009045440A1 (en) | 2007-10-01 | 2009-04-09 | Lixte Biotechnology Holdings, Inc. | Hdac inhibitors |
| CA2768466C (en) | 2009-07-22 | 2018-08-14 | The Board Of Trustees Of The University Of Illinois | Hdac inhibitors and therapeutic methods using the same |
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| US9387209B2 (en) | 2016-07-12 |
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| AU2013246278A1 (en) | 2014-11-13 |
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| CN104364237B (zh) | 2016-08-24 |
| AU2013246278B2 (en) | 2016-11-03 |
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