Biphenyls as Surrogates of the Steroidal Backbone. Part 2: Discovery of a Novel Family of Non-steroidal 5-α-Reductase Inhibitors

Abstract A new family of non-steroidal 5-α-reductase inhibitors was designed by replacing the steroid skeleton of an inhibitor related to estrone by a biphenyl moiety. This hypothesis originated from the reported estrogenic activity of a few biphenyl compounds (see Part 1 of this paper; Lesuisse et al. Bioorg. Med. Chem. Lett . 2001 , 11 , 1709). Two compounds turned out to be potent type 2 5-α-reductase inhibitors with IC 50 's of inhibition in the nanomolar range. These are to our knowledge amongst the most potent non-steroidal 5-α-reductase inhibitors described to date.