New progesterone esters as 5α-reductase inhibitors

The pharmacological activity of four new progesterone derivatives: 4-bromo-17 alpha -fluorobenzoyloxy)4-pregnene-3,20-dione (7), 4-bromo-17 alpha-(p-bromobenzoyloxy)-4-pregnene-3,20-dione (8), 4-bromo-17 alpha-(p-chlorobenzoyloxy)-preguene-3,20-dione (9) and 4-bromo-17 alpha (p-toluoyloxy)-4-pregnene-3,20-dione (10) was determined. These compounds were evaluated as 5 alpha -reductase inhibitors on gonadectomized hamster seminal vesicles and flank organs. The pharmacological data of this study indicate that compounds 7 and 9 having at C-17 p-fluorobenzoyloxy and p-chlorobenzoyloxy ester functions respectively showed the highest antiandrogenic effect as measured by the reduction of the weight of the seminal vesicles. In the flank organ model, the same compounds 7 and 9 exhibited a smaller diameter, 1.8 and 1.0 mm, respectively, than the commercially available finasteride 3 (2.3 mm), thus indicating a higher inhibitory effect on 5 alpha -reductase enzyme. Steroid 7 showed a higher inhibitory activity on the conversion of T to DHT (Fig. 3) than the presently used finasteride, thus indicating a higher antiandrogenic effect. The nonsubstituted benzoyloxy ester (compound 15) showed a lower antiandrogenic activity as measured in the seminal vesicles model than the p-substituted benzoyloxy compounds.