Evaluation of new pregnane derivatives as 5α-reductase inhibitor
Evaluation of new pregnane derivatives as 5α-reductase inhibitor
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DOI：
10.1248/cpb.49.525
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发表时间：
2001-05-01
影响因子：
1.7
通讯作者：
Martínez, R
中科院分区：
文献类型：
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作者：
Cabeza, M;Heuze, I;Martínez, R
以市售的16-脱氢孕烯醇酮醋酸酯为原料(7)，合成了两种新的甾体化合物：17 β -羟基-17 β -甲基-16 β -苯基-d -homoandrosta-1,4,6-三烯-3,20-二酮（18）和17(x)；乙酰氧基-17 β -甲基-16 β -苯基-d -homoandrosta-1,4,6-三烯-3,20-二酮（19）。新化合物18和19与先前合成的中间体7、8、13、16和17在三种不同的模型中测定了5 α -还原酶的抑制作用：性腺去角质的仓鼠侧腹器官直径大小，[1,2- c -14]乙酸钠与Rank器官脂质结合，以及甲壳青霉将[H-3]睾酮(T)转化为[H-3]双氢睾酮（DHT）。对这些类固醇的评价采用三种不同的对照：一组用载体治疗，第二组用T治疗，第三组用T加非那雄胺治疗。本工作的药理学结果表明，T显著增加Rank器官上色素斑的直径(p
The objective of this study was to synthesize several new pregnane derivatives and evaluate them as antiandrogens, From the commercially available 16-dehhyropregnenolone acetate (7), two new steroidal compounds were synthesized: 17 beta -hydroxy-17 beta -methyl-16 beta -phenyl-D-homoandrosta-1,4,6-triene-3,20-dione (18) and 17(x; acetoxy-17 beta -methyl-16 beta -phenyl-D-homoandrosta-1,4,6-triene-3,20-dione , (19). The 5 alpha -reductase inhibitory effect of the new compounds 18 and 19 together with the previously synthesized intermediates 7, 8, 13, 16, and 17 was determined in three different models: gonadectomized hamster flank organs diameter size, incorporation of [1,2-C-14]sodium acetate into lipids in Rank organs and conversion of [H-3]testosterone (T) to [H-3]dihydrotestosterone (DHT) by Penicillium crustosum. The evaluation of these steroids was carried out with three different controls: one group was treated with vehicle, the second with T and the third group with T plus finasteride. The pharmacological results from this work demonstrated that T significantly increases the diameter of the pigmented spot on the Rank organs (p