Cabeza M, Quiroz A, Bratoeff E, Murillo M E, Ramírez E, Flores G
Department of Biological Systems, Metropolitan University of Mexico, Mexico, D.F. Mexico.
Chem Pharm Bull (Tokyo). 1999 Sep;47(9):1232-6. doi: 10.1248/cpb.47.1232.
The pharmacological activity of eight pregnane derivatives 17-alpha acetoxyprogesterone 9, 17-alpha acetoxy-4, 5-epoxypregnan-3, 20-dione 10, 17-alpha acetoxy-4-chloro-4-pregnene-3, 20-dione 11, 17-alpha acetoxy-4-bromo-4-pregnene-3, 20-dione 12, 17-alpha hydroxy-4-bromo-4-pregnene-3, 20-dione 13, 4-chloro-17-alpha hydroxy-4-pregnene-3, 20-dione 14, 17-alpha benzoyloxy-4-bromo-4-pregnene-3, 20-dione 15 and 17-alpha benzoyloxy-4-chloro-4-pregnene-3, 20-dione 16 was determined. These compounds were evaluated as antiandrogens on gonadectomized hamster seminal vesicles. The pharmacological data in this study indicate that compounds 15 and 16 having a C-17 benzoyloxy moiety showed the highest antiandrogenic activity as measured by the reduction of the weight of the seminal vesicles, followed by the steroids 11 and 12 (17-alpha acetoxy group). The free alcohols 13 and 14 exhibited a lower antiandrogenic activity. Apparently, the ester moiety at C-17 is a necessary requirement for the presence of high antiandrogenic activity. Shows the inhibitory effect on the conversion of testosterone (T) to DHT, of the above described steroids as measured by the amount of produced DHT 2 expressed as pmoles of DHT/g of protein/h. Steroids 11, 12 and 16 showed a much higher inhibitory activity on the conversion of testosterone (T) to dihydrotestosterone (DHT) than presently used finasteride 3.
测定了8种孕烷衍生物17-α-乙酰氧基孕酮9、17-α-乙酰氧基-4,5-环氧孕烷-3,20-二酮10、17-α-乙酰氧基-4-氯-4-孕烯-3,20-二酮11、17-α-乙酰氧基-4-溴-4-孕烯-3,20-二酮12、17-α-羟基-4-溴-4-孕烯-3,20-二酮13、4-氯-17-α-羟基-4-孕烯-3,20-二酮14、17-α-苯甲酰氧基-4-溴-4-孕烯-3,20-二酮15和17-α-苯甲酰氧基-4-氯-4-孕烯-3,20-二酮16的药理活性。这些化合物在去性腺仓鼠精囊上被评估为抗雄激素。本研究中的药理数据表明，具有C-17苯甲酰氧基部分的化合物15和16表现出最高的抗雄激素活性，通过精囊重量减轻来衡量，其次是甾体11和12（17-α-乙酰氧基）。游离醇13和14表现出较低的抗雄激素活性。显然，C-17处的酯部分是高抗雄激素活性存在的必要条件。通过以每克蛋白质每小时产生的DHT 2的皮摩尔数表示的产生的DHT量，显示了上述甾体对睾酮（T）向双氢睾酮（DHT）转化的抑制作用。甾体11、12和16对睾酮（T）向双氢睾酮（DHT）的转化表现出比目前使用的非那雄胺3更高的抑制活性。
