(1-Benzylinodole-3-yl)alkanoic Acids : Novel Nonsteroidal Inhibitors of Steroid 5α-Reductase (I)

Abstract

A novel series of indole-3-alkanoic acids with varied N-benzyl substituents were synthesized as nonsteroidal inhibitors of steroid 5α-reductase. The structure-activity relationship in this series were studied and the optimum carboxylic acid side chain was butyric acid. Furthermore, compounds with a diaryl substituent at the 1-position of the indole ring displayed strong inhibitory activities in vitro. Amongst these derivatives, 4-[1-(6, 6-dimethyl-6H-dibenzo[b, d]pyran-3-yl)methylindol-3-yl]butyric acid (FR119680) displayed very high inhibitory activity in vitro against rat prostatic 5α-reductase (IC₅₀=5.0 nM) and good in vivo activity in the castrated young rat model.