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

Abstract 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 ).