Simple bi- and tricyclic inhibitors of human steroid 5 alpha-reductase

A number of tricyclic thiolactams, bicyclic lactams, and bicyclic thiolacta ms have been prepared and evaluated in vitro as inhibitors of types and ? s teroid 5 alpha-reductase. The tricycles with an 8-chloro substituent in the C-ring are nM (IC50) inhibitors of type steroid 5 alpha-reductase (SR). In all the cases studied, lactams are more potent than the corresponding thio lactams. Activity against type 2 SR is greatly enhanced by a styryl (or ate ) substituent on the aryl ring of the tri- and bicycles and also a related tricyclic aryl acid. (C) 2000 Elsevier Science Ltd. All rights reserved.