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