4-(Benzoylindolizinyl)butyric acids; Novel nonsteroidal inhibitors of steroid 5 alpha-reductase. III.

A novel series of indolizinebutyric acids with various benzoyl substituents was synthesized to develop nonsteroidal inhibitors of steroid 5 alpha -red uctase, and the structure-activity relationships in this series were studie d. We previously reported the structure-activity relationships in a series of indolebutyric acids as well as the discovery of the novel nonsteroidal 5 alpha -reductase inhibitor, FK143, We have now made other modifications to this compound to improve in vivo inhibitory activity, By altering the hete rocyclic nucleus and changing the benzoyl substituent we have succeeded in identifying the strongly active compound, FK687, (S)-4-[1-[4-[[1-(4-isobuty lphenyl)butyl]oxy]benzoyl] indolizin-3-yl]butyric acid, which displays stro ng in vitro inhibitory activity against the human enzyme and in vivo inhibi tory activity against the castrated young rat model. This compound should b e a useful agent for the treatment of benign prostatic hyperplasia.