Indole and benzimidazole derivatives as steroid 5α-reductase inhibitors in the rat prostate

Article abstract of DOI:10.1016/S0968-0896(98)80018-7

A novel series of indole and benzimidazole derivatives were synthesized and evaluated for their inhibitory activity of rat prostatic 5α-reductase. Among these compounds, 4-{2-[1-(4,4'-dipropylbenzhydryl)indole-5-carboxamido]phenoxy}butyric acid (15) and its benzimidazole analogue 25 showed potent inhibitory activities for rat prostatic 5α-reductase (IC₅₀ values of 9.6±1.0 and 13±1.5nM, respectively), with the potency very close to that of finasteride. Compound 30, in which the moiety between the benzene ring and amide bond was replaced by quinolin-4-one ring, showed almost equipotent activity (IC₅₀=19±6.2nM) with the correspondent amide derivative 13. This result was consistent with the previous observation that the coplanarity of this moiety might contribute to the potent inhibitory activity. Copyright (C) 1998 Elsevier Science Ltd.