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A novel selective androgen receptor modulator scaffoldhas beendiscovered through structural modifications of hydantoin antiandrogens.Several 4-(4-hydroxyphenyl)-N-arylhydantoins displayedpartial agonism with nanomolar in vitro potency in transactivationexperiments using androgen receptor (AR) transfected cells. In a standardcastrated male rat model, several compounds showed good anabolic activityon levator ani muscle, dissociated from the androgenic activity onventral prostate, after oral dosing at 30 mg/kg. ()-4-[3,4-Dimethyl-2,5-dioxo-4-(4-hydroxyphenyl)imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile(()-11b) displayed anabolic potency with a strong dissociationbetween levator ani muscle and ventral prostate (A50= 0.5 mg/kg vs 70 mg/kg). The binding modes of twocompounds, including ()-11b, within the AR ligand-bindingdomain have been studied by cocrystallization experiments using acoactivator-like peptide. Both compounds bound to the same site, andthe overall structures of the AR were very similar. [ABSTRACT FROM AUTHOR]