Discovery of Potent, Orally-Active, and Muscle-Selective Androgen Receptor Modulators Based on an N-Aryl-hydroxybicyclohydantoin Scaffold
Journal of Medicinal Chemistry2006Vol. 49(26), pp. 7596–7599
Citations Over TimeTop 10% of 2006 papers
Chong‐Qing 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, Yongmi An, Mary F. Malley, John S. Sack, Mark Salvati, Gary J. Grover, Jacek Ostrowski, Lawrence G. Hamann
Abstract
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-selective agonist of the androgen receptor. After oral dosing in a rat atrophied levator ani muscle model, (7R,7aS)-10b demonstrated efficacy at restoring levator ani muscle mass to that of intact controls and exhibited >50-fold selectivity for muscle over prostate.
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