Carbocyclic prostaglandin analogs. 1. Steroid carboxylic acids

Certain structural similarities between prostaglandins with close-packed side chains and the perhydrocyclopentanophenanthrene nucleus of steroids prompted the synthesis and biological evaluation of 6beta, 17 beta-dihydroxy-5alpha-androstane-2alpha-carboxylic acid (30), its 6-deoxy derivative 28, and the corresponding 6-deoxy-2beta derivative 29 in an attempt to evaluate carbocyclic acids as potential prostaglandin analogs. Preliminary in vitro studies on isolated guinea pig ileum have shown weakly specific, prostaglandin-stimulated smooth muscle antagonism for 28 when compared with antagonism of bradykinin- and acetylcholine-induced contractions. Complete dose-response curves for 28 on prostaglandin-stimulated guinea pig ileum have shown a reduction in the maxium response and a decrease in the slope of the curve, indicating a noncompetitive type of inhibition for this type of derivative.