Cell Penetrant Inhibitors of the KDM4 and KDM5 Families of Histone Lysine Demethylases. 2. Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives

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• 作者：Susan M. Westaway ; Alex G. S. Preston ; Michael D. Barker ; Fiona Brown ; Jack A. Brown ; Matthew Campbell ; Chun-wa Chung ; Gerard Drewes ; Robert Eagle ; Neil Garton ; Laurie Gordon ; Carl Haslam ; Thomas G. Hayhow ; Philip G. Humphreys ; Gerard Joberty ; Roy Katso ; Laurens Kruidenier ; Melanie Leveridge ; Michelle Pemberton ; Inma Rioja ; Gail A. Seal ; Tracy Shipley ; Onkar Singh ; Colin J. Suckling ; Joanna Taylor ; Pamela Thomas ; David M. Wilson ; Kevin Lee ; Rab K. Prinjha
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：February 25, 2016
• 年：2016
• 卷：59
• 期：4
• 页码：1370-1387
• 全文大小：546K
• ISSN：1520-4804

文摘

Following the discovery of cell penetrant pyridine-4-carboxylate inhibitors of the KDM4 (JMJD2) and KDM5 (JARID1) families of histone lysine demethylases (e.g., 1), further optimization led to the identification of non-carboxylate inhibitors derived from pyrido[3,4-d]pyrimidin-4(3H)-one. A number of exemplars such as compound 41 possess interesting activity profiles in KDM4C and KDM5C biochemical and target-specific, cellular mechanistic assays.