Synthesis of regioisomeric 17beta-N-phenylpyrazolyl steroid derivatives and their inhibitory effect on 17alpha-hydroxylase/C(17,20)-lyase.

The reaction of 3beta-hydroxy-21-hydroxymethylidenepregn-5-en-3beta-ol-20-one (1) with phenylhydrazine (2a) affords two regioisomers, 17beta-(1-phenyl-3-pyrazolyl)androst-3-en-3beta-ol (5a) and 17beta-(1-phenyl-5-pyrazolyl)androst-5-en-3beta-ol (6a). The direction of the ring-closure reactions of 1 with p-substituted phenylhydrazines (2b-e) depends strongly on the electronic features of the substituents. Oppenauer oxidation of 3beta-hydroxy-17beta-exo-heterocyclic steroids 5a-e and 6a-e yielded the corresponding Delta(4)-3-ketosteroids 9a-e and 10a-e. The inhibitory effects (IC(50)) of these compounds on rat testicular C(17,20)-lyase were investigated by means of an in vitro radioligand incubation technique. Copyright 2010 Elsevier Inc. All rights reserved.