Synthesis and biochemical evaluation of (carbamoylalkenyl)phenyloxy carboxylic acid derivatives as non-steroidal 5α-reductase inhibitors

Article abstract of DOI:10.1002/ardp.19953280307

Several (carbamoylalkenyl)- and (carbamoylalkenyl)phenyloxy carboxylic acids and some of their ethyl esters were synthesized and evaluated in vitro as inhibitors of steroid 5α-reductase. Inhibitors of this enzyme may be useful in treating dihydrotestosterone-related diseases such as prostate cancer and benign prostatic hyperplasia. Using an enzyme preparation obtained from human prostate carcinoma tissue, the inhibition values ranged from 0 to 57% at the given dose of 100 μM. In the series of free acids, surprisingly, the compounds showed only modest inhibitory potency (0-26%). By contrast, the ethyl esters displayed inhibition values up to 57%. Sttructure-activity relationships are discussed.