Structure–activity relationships of bioisosteric replacement of the carboxylic acid in novel androgen receptor pure antagonists

A series of 5,5-dimethylthiohydantoin derivatives were synthesized and evaluated for androgen receptor pure antagonistic activities for the treatment of hormone refractory prostate cancer. CH4933468 (32d) with a sulfonamide side chain not only exhibited antagonistic activity with no agonistic activity in the reporter gene assay but also inhibited the growth of bicalutamide-resistant cell lines. This compound also inhibited tumor growth of the LNCaP xenograft in mice dose-dependently.

We designed and synthesized novel AR pure antagonists for the treatment of hormone refractory prostate cancer. CH4933468 with a sulfonamide side chain showed higher activities than lead compound 5.Figure optionsDownload as PowerPoint slide