4-(1-benzoylindol-3-yl)butyric acids and FK143: Novel nonsteroidal inhibitors of steroid 5 alpha-reductase (II)

A novel series of indolebutyric acids with varying benzoyl substituents wer e synthesized to develop nonsteroidal inhibitors of steroid 5 alpha-reducta se. We previously reported the discovery of a novel nonsteroidal 5 alpha-re ductase inhibitor, FR119680, which had an IC50 value of 5.0 nM against the rat prostatic enzyme. However, this compound was not strongly active agains t the human prostatic enzyme. BS further study of the structure-activity re lationships we succeeded in producing the strongly active compound, FK143, 4-[3-[3-[bis(4-isobutylphenyl)methylamino]benzoyl]-1H-indol-1-yl]butyric ac id, with an IC50 value of 1.9 nM against the human enzyme. FK143 also has i n vivo inhibitory activity against the castrated young rat model and it sho uld therefore be an extremely useful agent for the treatment of benign pros tatic hyperplasia.