The development of non-steroidal dual inhibitors of both human 5α-reductase isozymes

The design, synthesis and biological properties of homochiral non-steroidal inhibitors of both isozymes of human 5α-reductase are described. The o-hydroxy aniline moiety of the initial lead (1) can be replaced by a 3-acyl indole isostere, whilst the minimum energy conformation of the benzyl ether in the potent inhibitor (3) is mimicked by the conformationally locked benzodioxolane system in the potent non-steroidal inhibitor (7). Pharmacokinetics and oral efficacy in a rat model of BPH are presented for (3) and (7).