SYNTHESIS AND BIOCHEMICAL EVALUATION OF (CARBAMOYLALKENYL)PHENYLOXY CARBOXYLIC-ACID DERIVATIVES AS NONSTEROIDAL 5-ALPHA-REDUCTASE INHIBITORS

Several (carbamoylalkenyl)- and (carbamoylalkenyl)phenyloxy carboxylic acids (Table 1) and some of their ethyl esters (Table 2) were synthes ized and evaluated in vitro as inhibitors of steroid 5 alpha-reductase . Inhibitors of this enzyme may be useful in treating dihydrotestoster one-related diseases such as prostate cancer and benign prostatic hype rplasia Using an enzyme preparation obtained from human prostate carci noma tissue, the inhibition values ranged from 0 to 57 % at the given dose of 100 mu M. In the series of free acids, surprisingly, the compo unds showed only modest inhibitory potency (0-26 %). By contrast, the ethyl esters displayed inhibition values up to 57 %. Structure-activit y relationships are discussed