THE DEVELOPMENT OF NONSTEROIDAL DUAL INHIBITORS OF BOTH HUMAN 5-ALPHA-REDUCTASE ISOZYMES

The design, synthesis and biological properties of homochiral non-ster oidal inhibitors of both isozymes of human 5 alpha-reductase are descr ibed. The o-hydroxy aniline moiety of the initial lead (1) can be repl aced by a 3-acyl indole isostere, whilst the minimum energy conformati on of the benzyl ether in the potent inhibitor (3) is mimicked by the conformationally locked benzodioxolane system in the potent non-steroi dal inhibitor (7). Pharmacokinetics and oral efficacy in a rat model o f BPH are presented for (3) and (7). Copyright (C) 1996 Elsevier Scien ce Ltd