新型PPARα激动剂(E)-4-氯苯氧苯丙烯酸衍生物的合成及降血脂活性研究  

Synthesis and Lipid-lowering Activities of New PPARα Agonists (E)-4-Chlorophenoxy-phenylpropanoid Acid Derivatives

作　　者：陈小兵 黄丽芸 许军[2] 袁章林 凌志杰 林丽娟 彭红[2] Chen Xiaobing;Huang Liyun;Xu Jun;Yuan Zhanglin;Ling Zhijie;Lin Lijuan;Peng Hong(Gannan Health Vocational College,Ganzhou 341000,China;Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China)

机构地区：[1]赣南卫生健康职业学院,江西赣州341000 [2]江西中医药大学药学院,江西南昌330004

出　　处：《亚太传统医药》2019年第10期56-60,共5页Asia-Pacific Traditional Medicine

基　　金：赣州市科技局重大科技项目(赣市财教字[2017] 179号)

摘　　要：目的:设计合成新型PPARα激动剂(E)-4-氯苯氧苯丙烯酸衍生物,寻找比先导化合物更强降脂活性的新型PPARα激动剂。方法:由香草醛与化学降血脂药对氯苯氧异丁酸合成先导化合物对氯苯氧异丁酸甲氧基苯丙烯酸酯(1),再将先导化合物进行结构修饰,将其分别与脂肪醇、芳香醇、芳杂环醇成酯,与脂肪胺、芳香胺、芳杂环胺成酰胺;以高脂血症模型大鼠的降血脂活性考察新合成的(E)-4-氯苯氧苯丙烯酸衍生物的降血脂活性。结果:合成得到10个未见文献报道的(E)-4-氯苯氧苯丙烯酸衍生物,化合物的结构经~1HMNR、MS分析、IR及元素分析确证其结构;目标化合物2b,2e,3b,3d,3e可明显降低高脂血症模型大鼠血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)的水平(P<0.05或P<0.01)。结论:目标化合物2b,2e,3b,3d,3e对高脂血症模型大鼠有明显的降血脂活性。Objective:To design and synthesize of new PPARα agonists(E)-4-chlorophenoxy-phenylpropanoid acid derivatives and study their lipid-lowering activities,and search for the compounds that have better biological activity of lipid-lowering.Methods:The target compounds were designed and synthesized by chlorophenoxy isobutyric acid of chemical lowering blood-lipid drugs and vanillin and their biological activities were evaluated with the model of hyperlipidemia in mice.Results:Ten novel compounds were obtained and their structures were characterized by the nuclear magnetic resonance(NMR),mass spectra(MS),infrared spectra(IR) and elemental analyses.Pharmacological tests showed the target compounds 2 b,2 e,3 b,3 d,3 e were decreased significantly the serum levels of TC,TG,LDL-C and HDL-C(P<0.05 or P<0.01).Conclusion:The target compounds 2 b,2 e,3 b,3 d,3 e have significant lipid-lowering activities in hyperlipidemic model rats.

关 键 词：PPARΑ 化学合成 (E)-4-氯苯氧苯丙烯酸 衍生物 降血脂活性 

分 类 号：R285.5[医药卫生—中药学] R914.5[医药卫生—中医学]