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Pure androgen receptor (AR) full antagonists are candidates to treat anti-androgen refractory prostate cancers. We previously developed a carborane-containing AR antagonist, 3-(12-hydroxymethyl-1,12-dicarba-closo-dodecaborane-1-yl)benzonitrile (BA341), which was more potent than hydroxyflutamide (4) but acted as an agonist toward LNCaP prostate cancer cells expressing T877A AR mutant. Here, we designed and synthesized novel AR full antagonists structurally based upon the clinically used AR full antagonist (R)-bicalutamide (5) to test our hypothesis that the carborane cage is suitable as a hydrophobic pharmacophore for AR ligands. Compounds 7band 8bshowed good biological profiles in AR binding and transactivation assays and dose-dependently inhibited the testosterone-induced proliferation of LNCaP cells, as well as SC-3 cells. The IC50values of compounds 7band 8bwere 3.8 × 10−7and 4.2 × 10−7M, respectively [5, 8.7 × 10−7M]. Since compounds 7band 8bdid not show any agonistic activity in functional assays, they seem to be pure AR full antagonists and are therefore candidates for treatment of anti-androgen withdrawal syndrome. [ABSTRACT FROM AUTHOR]