A novel class of inhibitors for human and rat steroid 5 alpha-reductases: Synthesis and biological evaluation of indoline and aniline derivatives. III

While searching for novel nonsteroidal inhibitors of human and rat prostati c 5 alpha -reductases, we found a new series of indoline and aniline deriva tives that showed potent inhibitory activities for both enzymes. Among them , 3-chloro-4-{[1-(4-phenosybenzyl)indolin-5-yl]oxy}benzoic acid (2e, YM-361 17) showed a more potent inhibitory activity for the human enzyme than ONO- 3805 with an IC50 value of 5.3 nM and a reduced rat prostatic dihydrotestos terone (DHT) concentration by oral administration. The synthesis and the st ructure-activity relationships of these indoline and aniline derivatives ar e presented.