Unwalla Ray, Mousseau James J, Fadeyi Olugbeminiyi O, Choi Chulho, Parris Kevin, Hu Baihua, Kenney Thomas, Chippari Susan, McNally Christopher, Vishwanathan Karthick, Kilbourne Edward, Thompson Catherine, Nagpal Sunil, Wrobel Jay, Yudt Matthew, Morris Carl A, Powell Dennis, Gilbert Adam M, Chekler Eugene L Piatnitski
Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.
J Med Chem. 2017 Jul 27;60(14):6451-6457. doi: 10.1021/acs.jmedchem.7b00373. Epub 2017 Jul 11.
In an effort to find new and safer treatments for osteoporosis and frailty, we describe a novel series of selective androgen receptor modulators (SARMs). Using a structure-based approach, we identified compound 7, a potent AR (ARE EC = 0.34 nM) and selective (N/C interaction EC = 1206 nM) modulator. In vivo data, an AR LBD X-ray structure of 7, and further insights from modeling studies of ligand receptor interactions are also presented.
为了寻找治疗骨质疏松症和虚弱症的新型且更安全的疗法，我们描述了一系列新型的选择性雄激素受体调节剂（SARMs）。采用基于结构的方法，我们确定了化合物7，它是一种强效的雄激素受体（ARE EC = 0.34 nM）且具有选择性（N/C相互作用EC = 1206 nM）的调节剂。本文还展示了体内数据、化合物7的雄激素受体配体结合域X射线结构以及配体-受体相互作用建模研究的进一步见解。
