Discovery of an Orally-Active Nonsteroidal Androgen Receptor Pure Antagonist and the Structure–Activity Relationships of Its Derivatives

抄録

The 3-(4-cyano-3-trifluoromethylphenyl)-5,5-dimethylthiohydantoin derivatives which have carboxy-terminal side chains were synthesized and their agonistic/antagonistic activities against androgen receptor (AR) measured. Among them, compound 13b showed antagonistic activity (IC₅₀=130 nM) with no agonistic activity even at 10000 nM. This compound exhibited significant metabolic stability and oral antiandrogenic activity (ED₅₀=7 mg/kg).