Synthesis of potent and tissue-selective androgen receptor modulators (SARMs): 2-(2,2,2)-Trifluoroethyl-benzimidazole scaffold

The synthesis and in vivo SAR of 2-(2,2,2)-trifluoroethyl-benzimidazoles are described. Prostate antagonism and/or levator am agonism can be modulated by varying the substitution at the 2-position of 5,6-dichloro-benzimidazoles. Potent androgen agonists on the muscle were discovered that strongly bind to the androgen receptor (2-17 nM) and show potent in vivo efficacy (0.03-0.11 mg/day). True SARMs showing both prostate antagonism and levator am agonism were revealed. (c) 2006 Elsevier Ltd. All rights reserved.