Biological Activity of Novel Progesterone Derivatives Having Bulky Ester Side Chains at C-3

In a 2008 study, researchers explored the antiandrogenic activity of four novel progesterone derivatives (9a-9d) with bulky ester side chains at C-3. They found that the lipophilicity, measured as logP, of these compounds was strongly correlated with their ability to bind to androgen receptors and exert antiandrogenic effects. The compound with the highest lipophilicity, 9d (logP of 4.17), showed the greatest relative binding affinity and significantly reduced the weight of the prostate and seminal vesicles in castrated hamsters treated with dihydrotestosterone. These findings suggest that the lipophilic nature of these steroids is key to their effectiveness in targeting androgen receptors, which could be beneficial for treating androgen-dependent conditions.