Synthesis of 17β- N-Substituted 19-Nor-10-azasteroids as Inhibitors of Human 5α-Reductases I and II

Abstract

The synthesis of 17β-[ N-(phenyl)methyl/phenyl-amido] substituted 10-azasteroids has been accomplished by either the TiCl 4- or TMSOTf-catalysed reaction of carbamates 11 and 12 with Danishefsky's diene. The reaction provided 5α-H isomers 3a– 5a and 5β-H isomers 3b– 5b depending on the reaction conditions. Both epimers of each compound were tested against human 5α-reductase types I and II. Unexpectedly, 5β-H compounds were found more active than their 5α-H counterparts, the best inhibitors being 3b (IC 50=279 and 2000 nM toward isoenzyme I and II, respectively) and 5b (IC 50=913 and 247 nM toward isoenzymes I and II, respectively).