A novel class of inhibitors for human steroid 5 alpha-reductase: Synthesisand biological evaluation of indole derivatives. II

In a search for novel nonsteroidal inhibitors of human prostatic 5 alpha-re ductase, ne found a new series of indole derivatives that showed potent inh ibitory activities for the human enzyme. Among them, 4-[(1-benzyl-1H-indol- 5-yl)oxy]-3-chlorobenzoic acid (2d, YM-32906) showed more potent inhibitory activity than finasteride with an IC50 value of 0.44 nM, 3-Chloro-4-{[1-(4 -phenoxybenzyl)-1H-indol-5-yl]oxy}benzoic acid (2m) showed inhibitory activ ities for both human and rat prostatic 5 alpha-reductase with IC50 values o f 2.1 and 73 nM, respectively. The synthesis and structure-activity relatio nships of these indole derivatives are presented.