基础研究苯氧丁酸类非甾体还原酶抑制剂的设计、合成及活性研究.pdfVIP

·1830 · doi 10.3969/j.issn. 1673-4254.2014.12.26 J South Med Univ, 2014, 34(12): 1830-1833 基础研究 苯氧丁酸类非甾体苯氧丁酸类非甾体55αα--还原酶抑制剂的设计还原酶抑制剂的设计、、合成及活性研究合成及活性研究 1 2 1 1 陈凯旋 ，江振洲 ，陈文华 ，习保民 1 2 南方医科大学药学院，广东 广州 510515；中国药科大学新药筛选中心，江苏 南京 210009 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 -5 5α-还原酶抑制活性，其中，化合物A 和A 的抑制活性较好，在3.3×10 mol/L 水平的抑制率分别是A （12.50%）、A （19.64%）。 1 7 1 7 关键词：良性前列腺增生；5α-还原酶抑制剂；丁酸基团 Design, synthesis and biological activity assessment of phenoxybutyric acid derivatives as nonsteroidal 5α-reductase inhibitors 1 2 1 2 CHEN Kaixuan , JIANG Zhenzhou , CHEN Wenhua , XI Baomin 1College of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, China; 2New Drug Research and Development Center, China Pharmaceutical University, Nanjing 210009, China 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