New Progesterone Esters as 5α-Reductase Inhibitors

概要

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The pharmacological activity of four new progesterone derivatives: 4-bromo-17α-(p-fluorobenzoyloxy)-4-pregnene-3, 20-dione (7), 4-bromo-17α-(p-bromobenzoyloxy)-4-pregnene-3, 20-dione (8), 4-bromo-17α-(p-chlorobenzoyloxy)-pregnene-3, 20-dione (9) and 4-bromo-17α-(p-toluoyloxy)-4-pregnene-3, 20-dione (10) was determined. These compounds were evaluated as 5α-reductase inhibitors on gonadectomized hamster seminal vesicles and Hank organs. The pharmacological data of this study indicate that compounds 7 and 9 having at C-17p-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 1.0mm, respectively, than the commercially available finasteride 3 (2.3mm), thus indicating a higher inhibitory effect on 5α-reductase enzyme. Steroid 7 showed a higher inhibitory activity on the conversion of I to DHT (Fig. 3) than the presently used dinasteride, 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.
公益社団法人日本薬学会の論文
2001-09-01