Chemical & Pharmaceutical Bulletin 2000-11-01

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

S Igarashi, H Inami, H Hara, H Koutoku, H Oritani, T Mase

Index: Chem. Pharm. Bull. 48(11) , 1689-97, (2000)

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Abstract

While searching for novel nonsteroidal inhibitors of human and rat prostatic 5alpha-reductases, we found a new series of indoline and aniline derivatives that showed potent inhibitory activities for both enzymes. Among them, 3-chloro-4-¿[1-(4-phenoxybenzyl)indolin-5-yl]oxylbenzoic acid (2e, YM-36117) 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 dihydrotestosterone (DHT) concentration by oral administration. The synthesis and the structure-activity relationships of these indoline and aniline derivatives are presented.