Patent Evaluation: Novel anti-androgens for the treatment of prostate cancer

Summary

Novelty: Novel thiazole derivatives useful as anti-androgens are disclosed. They are potentially useful in the treatment of androgen related disorders including prostatic cancer, benign prostatic hypertrophy and polycystic ovarian disease.

Biology: An in vitro rat prostate androgen receptor competition assay is described. The preferred compound gives a 1 h/18 h relative binding affinity ratio of 11.3. This is comparable with known anti-androgens such as flutamide and cyproterone. The same compound gives an ED₅₀ of 17 mg/kg (the dose required to inhibit testosterone propionate stimulated prostate weight gain by 50%).

Chemistry: 2′-Methylsulphonyl-5α-pregn-2-en-20-yno[3,2-d]thiazol-17β-ol is one of three compounds specifically exemplified. Full preparatory details, utilizing standard techniques, are presented.

Structure: