Synthesis and Evaluation of 2'-Substituted 4-(4'-Carboxy- or 4'-Carboxymethylbenzylidene)-N-Acylpiperidines: Highly Potent and In Vivo Active Steroid 5α-Reductase Type 2 Inhibitors

The study synthesized and evaluated 16 compounds for their ability to inhibit rat and human steroid 5α-reductase isozymes types 1 and 2. Among these, compounds 15, 20, and 25 showed high potency against the human type 2 isozyme, with IC(50) values of 11 nM, 6 nM, and 7 nM, respectively, compared to finasteride's 5 nM. In vivo tests demonstrated that all compounds significantly reduced prostate weights in castrated testosterone-treated rats, with compound 7 showing oral activity. Despite being a poor inhibitor of the rat enzyme, compound 15 was effective in rats, suggesting it would be highly potent in humans.