Steroidal A ring aryl carboxylic acids: a new class of steroid 5.alpha.-reductase inhibitors

A series of 17β-carbamoyl-1,3,5(10)-estratriene-3-carboxylic acids has been prepared and evaluated in vitro as inhibitors of human and rat prostatic steroid 5α-reductase (EC 1.3.1.30). Potent inhibition of the human enzyme, in particular, was observed and preliminary studies using rat enzyme suggest that the inhibition results from the formation of an enzyme-NADP + -inhibitor complex. The compounds were synthesized from estrone, generally employing a differentiated bis-triflate carbonylation strategy