Patent Evaluation: Indolyl 5α-reductase inhibitors

Summary

Novelty: Novel 3-benzoyl indol-1-yl derivatives are claimed together with their methods of preparation. They are said to be steriodal 5α-reductase inhibitors and are potentially useful for the treatment of acne vulgaris, alopecia, seborrhoea, female hirsutism, benign prostate hypertrophy, male pattern baldness and human prostate adenocarcinoma.

Biology: Testosterone 5α-reductase inhibitory activity was assessed using ventral prostate tissue from male rats and tritiated testosterone. The inhibitory effect of the test compounds on the formulation of 5α-dihydro-testosterone was determined using thin layer chromatography. The most active compounds caused 50% inhibition in the range 1–5 nM.

Chemistry: The syntheses of forty-three compounds are described by standard methods and characterized by nmr and mass spectrometry. Four compounds are specifically claimed including (S)-4-(3-[4-(1-[4-(2-methylpropyl)phenyl]ethoxy)-benzoyl]indol-1-yl)butanoic acid.