Improvement of pharmacological properties of irreversible thyroid receptor coactivator binding inhibitors

…, F Zhu, A Kosinski, TJ Mangano, V Setola…

文献索引：Jong, Yeon Hwang; Arnold, Leggy A.; Zhu, Fangyi; Kosinski, Aaron; Mangano, Thomas J.; Setola, Vincent; Roth, Bryan L.; Guy, R. Kiplin Journal of Medicinal Chemistry, 2009 , vol. 52, # 13 p. 3892 - 3901

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被引用次数: 40

摘要

We have previously reported the discovery and preliminary structure activity relationships of a series of β-aminoketones that disrupt the binding of coactivators to TR. However, the most active compounds had moderate inhibitory potency and relatively high cytotoxicity, resulting in narrow therapeutic index. Additionally, preliminary evaluation of in vivo toxicology revealed a significant dose related cardiotoxicity. Here we describe the improvement of ...