Hormones Department, National Research Centre, Dokki, Giza, Egypt.
Steroids. 2011 Jan;76(1-2):78-84. doi: 10.1016/j.steroids.2010.09.001. Epub 2010 Sep 16.
epi-Androsterone 1 was converted into its hydrazone derivative through the reaction with hydrazine hydrate 80%. Hydrazonoandrostane derivative 2b reacted with hydrazonoyl halides in the presence of K(2)CO(3) forming the corresponding hydrazopyridazinoandrostane derivatives 6a-d. The 3β-acetyl-17-hydrazonoandrostane derivative 2b reacted with a halogen reagent, benzoyl chloride, to form the non-cyclic 16-benzoylated hydrazone 9. On the other hand, compound 2b produced the corresponding pyridazinoandrostane derivatives 11 and 12 via its reaction with phenacyl bromide and chloroacetone respectively. Reaction of the hydrazono derivative 2b with benzaldehyde in the presence of acetic acid drops led to the formation of the benzylidenehydrazonoandrostane derivative 13. The product 14, phosphinom-ethylenehydrazonoandrostane was obtained by the reaction of the derivative 13 with trisdimethylaminophosphine in the presence of dry benzene. The reaction of compound 2b with phenyl isothiocyanate followed by boiling in chloroacetic acid or thioglycolic acid produced the pyrazoloandrostane derivatives 17 and 18 respectively. The biological activity of compounds 6a, 6d, 11, 12, and 15 was evaluated as inhibitor of growth in a human liver carcinoma cell line and doxorubicine was used for comparison. Compounds 15 and 12 showed a higher potency than the other tested compounds.
表雄酮 1 与 80%水合肼反应转化为其腙衍生物。3β-乙酰基-17-腙雄烷衍生物 2b 在 K(2)CO(3)存在下与腙酰卤反应，形成相应的 3β-乙酰基-17-腙并[4,5-d]吡唑并[1,5-a]并[1,3]二氮杂卓衍生物 6a-d。2b 与卤素试剂苯甲酰氯反应形成非环 16-苯甲酰化腙 9。另一方面，化合物 2b 分别与苯乙腈溴化物和氯乙酮反应生成相应的吡唑并[1,5-a]并[1,3]二氮杂卓衍生物 11 和 12。在醋酸存在下，腙衍生物 2b 与苯甲醛反应生成苯亚甲基腙雄烷衍生物 13。在无水苯中，用三(二甲基氨基)膦与衍生物 13 反应得到磷亚甲基腙雄烷产物 14。化合物 2b 与苯异硫氰酸酯反应，然后在氯乙酸或硫代乙醇酸中回流，分别生成吡唑并[1,5-a]并[1,3]二氮杂卓衍生物 17 和 18。化合物 6a、6d、11、12 和 15 的生物活性作为人肝癌细胞系生长抑制剂进行了评价，并用多柔比星进行了比较。化合物 15 和 12 比其他测试化合物具有更高的活性。
