Biphenyls as surrogates of the steroidal backbone. Part 2: Discovery of a novel family of non-steroidal 5-alpha-reductase inhibitors

A new family of non-steroidal 5-alpha -reductase inhibitors was designed by replacing the steroid skeleton of an inhibitor related to estrone by a bip henyl moiety. This hypothesis originated from the reported estrogenic activ ity of a few biphenyl compounds (see Part of this paper: Lesuisse et al. Bi oorg. Med. Chem. Lett. 2001, 11. 1709). Two compounds turned out to be pote nt type 2 5-alpha -reductase inhibitors with IC50's of inhibition in the na nomolar range. These are to our knowledge amongst the most potent non-stero idal 5-alpha -reductase inhibitors described to date. (C) 2001 Elsevier Sci ence Ltd. All rights reserved.