Discovery of Potent, Orally-Active, and Muscle-Selective Androgen Receptor Modulators Based on an N-Aryl-hydroxybicyclohydantoin Scaffold

详细信息    查看全文

• 作者：Chongqing Sun ; Jeffrey A. Robl ; Tammy C. Wang ; Yanting Huang ; Joyce E. Kuhns ; John A. Lupisella ; Blake C. Beehler ; Rajasree Golla ; Paul G. Sleph ; Ramakrishna Seethala ; Aberra Fura ; Stanley R. Krystek
• 刊名：Journal of Medicinal Chemistry
• 出版年：2006
• 出版时间：December 28, 2006
• 年：2006
• 卷：49
• 期：26
• 页码：7596 - 7599
• 全文大小：167K
• 年卷期：v.49,no.26(December 28, 2006)
• ISSN：1520-4804

文摘

A novel, N-aryl-bicyclohydantoin selective androgen receptor modulator scaffold was discovered through structure-guided modifications of androgen receptor antagonists. A prototype compound(7R,7aS)-10b from this series is a potent and highly tissue-selectiveagonist of the androgen receptor. After oral dosing in a rat atrophiedlevator ani muscle model, (7R,7aS)-10b demonstrated efficacy atrestoring levator ani muscle mass to that of intact controls and exhibited>50-fold selectivity for muscle over prostate.