CAJ | 학술논문

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A1（12.50%）、A7（19.64%）。
목적：설계합성분양정산류비치체5α-환원매억제제，대기진행활성측시。방법이분기고진달진동위골가，인입분양정산급불동적취대기，설계8개비치체5α-환원매억제제。이불동취대적분기고진위원료，여3,6-이록달진반응제비상응분기고진달진동，재여완기련장도불동적분양정산을지중간체반응득목표화합물。결과소득목표화합물경1H-NMR、MS학인결구，병이비나웅알위양성대조약，대기진행체외활성사선，유7개화합물구유억제활성。결론활성측시현시7개목표화합물유일정적5α-환원매억제활성，기중，화합물A1화A7적억제활성교호，재3.3×10-5 mol/L수평적억제솔분별시A1（12.50%）、A7（19.64%）。
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.