南方医科大学学报

南方医科大学学报 ›› 2014, Vol. 34 ›› Issue (12): 1830-.

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苯氧丁酸类非甾体5α-还原酶抑制剂的设计、合成及活性研究

陈凯旋，江振洲，陈文华，习保民   

  • 出版日期:2014-12-20 发布日期:2014-12-20

Design, synthesis and biological activity assessment of phenoxybutyric acid derivatives
as nonsteroidal 5α-reductase inhibitors

  • Online:2014-12-20 Published:2014-12-20

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摘要： 目的设计合成苯氧丁酸类非甾体5α-还原酶抑制剂，对其进行活性测试。方法以苯基哌嗪哒嗪酮为骨架，引入苯氧丁酸
及不同的取代基，设计8个非甾体5α-还原酶抑制剂。以不同取代的苯基哌嗪为原料，与3,6-二氯哒嗪反应制备相应苯基哌嗪哒
嗪酮，再与烷基链长度不同的苯氧丁酸乙酯中间体反应得目标化合物。结果所得目标化合物经1H-NMR、MS确认结构，并以
非那雄胺为阳性对照药，对其进行体外活性筛选，有7个化合物具有抑制活性。结论活性测试显示7个目标化合物有一定的
5α-还原酶抑制活性，其中，化合物A1和A7的抑制活性较好，在3.3×10-5 mol/L水平的抑制率分别是A（1 12.50%）、A（7 19.64%）。

Abstract: Objective To synthesize phenoxybutyric acid derivatives as 5α-reductase inhibitors and test their biological activities
in vitro. Methods Eight analogues as nonsteroidal 5α-reductase inhibitors were designed and synthesized by substitution
reaction of 6-(4-phenyl-piperazine-1-yl)-3(2H)-pyridazinone with phenoxybutyric acid derivatives. Results and Conclusion
The structures of the compounds were characterized by 1H-NMR and MS. Biological evaluation indicated that 7 out of the 8
compounds exhibited moderate 5α-reductase inhibitory activities, especially the compounds A1 and A7 with inhibition rates
reaching 12.50% and 19.64% at the concentration of 3.3×10-5 mol/L, respectively.