Department of Pharmaceutical Sciences, The University of Tennessee, Memphis, TN 38163, USA.
J Med Chem. 2011 Jun 9;54(11):3973-6. doi: 10.1021/jm2000097. Epub 2011 May 16.
Several new androgen receptor antagonists were synthesized and found to have varying activities across typically anti-androgen resistant mutants (Thr877 → Ala and Trp741 → Leu) and markedly improved potency over previously reported pan-antagonists. X-ray crystallography of a new anti-androgen in an androgen receptor mutant (Thr877 → 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.
几种新的雄激素受体拮抗剂被合成出来，并发现它们对通常抗雄激素耐药的突变体（Thr877→Ala 和 Trp741→Leu）具有不同的活性，并且比以前报道的泛拮抗剂具有显著提高的效力。一种新的雄激素拮抗剂在雄激素受体突变体（Thr877→Ala）中的 X 射线晶体学表明，受体可以容纳苯环到萘环取代所带来的额外体积，这对以前关于预测结合方向的报告以及在大体积 B 环拮抗剂中产生拮抗作用的原因提出了质疑。
