title: Carbocyclic prostaglandin analogs. 1. Steroid carboxylic acids.
abstract: 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.
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000731:Androstanes / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D003106:Colon / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005849:Gerbillinae; D006168:Guinea Pigs; D006914:Hydroxysteroids / Q000138:chemical synthesis / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008968:Molecular Conformation; D009119:Muscle Contraction / Q000187:drug effects; D010974:Platelet Aggregation; D011453:Prostaglandins / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000731:Androstanes; D002264:Carboxylic Acids; D006914:Hydroxysteroids; D011453:Prostaglandins; D000429:Alcohol Oxidoreductases; D000109:Acetylcholine; D001920:Bradykinin