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Synthesis of potent and tissue-selective androgen receptor modulators (SARMs): 2-(2,2,2)-Trifluoroethyl-benzimidazole scaffold.
Bioorganic & Medicinal Chemistry Letters 2007 March 16
The synthesis and in vivo SAR of 2-(2,2,2)-trifluoroethyl-benzimidazoles are described. Prostate antagonism and/or levator ani 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 ani agonism were revealed.
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