苯氧乙酸类化合物的合成及其降脂活性

Synthesis and Lipid-Lowering Activity of Phenoxy Acetic Acid Derivatives

目的 寻找更好的苯氧乙酸类降脂药。方法 以苯扎贝特为先导化合物 ,利用生物电子等排和前药原理 ,设计并合成了 10个未见报道的苯氧乙酸类化合物 ,其结构经 IR,1 HNMR,MS及元素分析确证。结果 初步的药理实验表明 ,化合物 1 、 2 、 3显示降脂活性 , 1 活性优于阳性对照药苯扎贝特 , 2 、 3的个别指标优于苯扎贝特。结论 设计思想与实验结果相符 。

AIM The purpose is to search for potent lipid-lowering agents with structures of phenoxy acetic acid. METHODS Selecting bezafibrate as leading compound, we designed and synthesized ten phenoxy acetic acid compounds according to the principle of isosterism and prodrug. Their structures were determined by means of spectra and elemental analysis. RESULTS Compounds Ⅱ 1?Ⅱ 2 and Ⅱ 3 showed significant anti-hypolipidemic activities compared to high-fatted group. Among them, the activities of Ⅱ 1 and a few of items of Ⅱ 2 and Ⅱ 3 are better than those of positive drug (bezafibrate). CONCLUSION The experimental results were accordant with initial thought and provided useful information for designing and optimizing this kind of compounds.