(1-BENZYLINDOLE-3-YL)ALKANOIC ACIDS - NOVEL NONSTEROIDAL INHIBITORS OF STEROID 5-ALPHA-REDUCTASE (I)

A novel series of indole-3-alkanoic acids with varied N-benzyl substit uents were synthesized as nonsteroidal inhibitors of steroid 5 alpha-r eductase. The structure-activity relationships in this series were stu died and the optimum carboxylic acid side chain was butyric acid, Furt hermore, compounds with a diaryl substituent at the 1-position of the indole ring displayed strong inhibitory activities in vitro. Amongst t hese derivatives, 6H-dibenzo[b,d]pyran-3-yl)methylindol-3-yl]butyric a cid (FR119680) displayed very high inhibitory activity in vitro agains t rat prostatic 5 alpha-reductase (IC50=5.0 nM) and good in vivo activ ity in the castrated young rat model.