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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- 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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Families Citing this family (20)
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| US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| EP3964507A1 (en) | 2013-10-04 | 2022-03-09 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| WO2015051241A1 (en) | 2013-10-04 | 2015-04-09 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| JP2017508798A (ja) | 2014-03-07 | 2017-03-30 | ザ ジョンズ ホプキンス ユニバーシティ | ヒストンリジン特異的デメチラーゼ（ｌｓｄ１）およびヒストンデアセチラーゼ（ｈｄａｃ）の阻害剤 |
| CN106456628A (zh) | 2014-03-19 | 2017-02-22 | 无限药品股份有限公司 | 用于治疗PI3K‑γ介导的障碍的杂环化合物 |
| US10807944B2 (en) | 2014-04-04 | 2020-10-20 | University Of Florida Research Foundation, Inc. | HDAC inhibitor compounds and methods of treatment |
| WO2016054491A1 (en) | 2014-10-03 | 2016-04-07 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| CN114230571B (zh) | 2015-09-14 | 2025-07-08 | 无限药品股份有限公司 | 异喹啉酮的固体形式、其制备方法、包含其的组合物及其使用方法 |
| WO2017161116A1 (en) | 2016-03-17 | 2017-09-21 | 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 |
| JP7254028B2 (ja) * | 2017-05-16 | 2023-04-07 | アンジー ファーマスーティカル シーオー．，エルティーディー． | ヒストンデアセチラーゼ（ｈｄａｃｓ）阻害剤 |
| 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 |
| MX2022015532A (es) * | 2020-06-08 | 2023-04-04 | Annji Pharm Co Ltd | Inhibidores selectivos de hdac6 y usos de los mismos. |
| WO2023159155A1 (en) * | 2022-02-18 | 2023-08-24 | Pivalent Therapeutics, Inc. | Inhibitors of phosphoinositide 3-kinase (pi3k) and uses thereof |
| IL326137A (en) | 2023-07-28 | 2026-03-01 | Cogent Biosciences Inc | PI3K inhibitors |
| CN120379970A (zh) * | 2023-10-18 | 2025-07-25 | 太溪生技新药股份有限公司 | 用于hdac抑制的喹唑啉酮衍生物 |
| WO2026099248A1 (en) * | 2024-11-06 | 2026-05-15 | Janssen Pharmaceutica Nv | N-phenyl-2-(4-oxo-quinazolin-3(4h)-yl)propanamide derivatives as tmem175 modulators for reducing alpha-synuclein aggregation for the treatment of parkinson's disease |
Citations (1)
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| 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 |
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| EP1524262A1 (en) | 2000-03-24 | 2005-04-20 | Methylgene, Inc. | Inhibitors of histone deacetylase |
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| ITMI20041869A1 (it) | 2004-10-01 | 2005-01-01 | Dac Srl | Nuovi inibitori delle istone deacetilasi |
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| EA018698B1 (ru) | 2005-09-21 | 2013-10-30 | 4Сц Аг | Сульфонилпирролгидрохлориды как ингибиторы гистондезацетилазы |
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| CA2700857C (en) | 2007-10-01 | 2016-08-02 | John S. Kovach | Hdac inhibitors |
| JP5838157B2 (ja) | 2009-07-22 | 2015-12-24 | ザ・ボード・オブ・トラスティーズ・オブ・ザ・ユニバーシティ・オブ・イリノイＴｈｅ Ｂｏａｒｄ Ｏｆ Ｔｒｕｓｔｅｅｓ Ｏｆ Ｔｈｅ Ｕｎｉｖｅｒｓｉｔｙ Ｏｆ Ｉｌｌｉｎｏｉｓ | Ｈｄａｃ阻害剤およびそれを用いる治療法 |
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