Unexpected Binding Orientation of Bulky-B-Ring Anti-Androgens and Implications for Future Drug Targets

详细信息    查看全文

• 作者：Charles B. Duke ; III ; Amanda Jones ; Casey E. Bohl ; James T. Dalton ; Duane D. Miller
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：June 9, 2011
• 年：2011
• 卷：54
• 期：11
• 页码：3973-3976
• 全文大小：805K
• 年卷期：v.54,no.11(June 9, 2011)
• ISSN：1520-4804

文摘

Several new androgen receptor antagonists were synthesized and found to have varying activities across typically anti-androgen resistant mutants (Thr877 鈫?Ala and Trp741 鈫?Leu) and markedly improved potency over previously reported pan-antagonists. X-ray crystallography of a new anti-androgen in an androgen receptor mutant (Thr877 鈫?Ala) shows that the receptor can accommodate the added bulk presented by phenyl to naphthyl substitution, casting doubt on previous reports of predicted binding orientation and the causes of antagonism in bulky-B-ring antagonists.