新型降糖药用化合物甘氨酸衍生物的合成及其对PPARs的作用研究  

Novel Hypoglycemic Compounds-synthesis of Glycine Derivatives and Research on the Role of PPARs

作　　者：薛阳[1,2] 刘兰祥[3] 叶清泉[3] 李俊明[3] 丁国华[3] 赵砚瑾[1] 刘永学[1] 李庶心[1,4] 

机构地区：[1]军事医学科学院放射与辐射医学研究所,北京100850 [2]总后管理局第二门诊部,北京100071 [3]江西中医学院,江西南昌330006 [4]首都师范大学,北京100048

出　　处：《解放军药学学报》2009年第1期5-10,共6页Pharmaceutical Journal of Chinese People's Liberation Army

摘　　要：目的合成5个新型甘氨酸类降血糖药物,并对其对PPARs的作用进行研究。方法以3-[(4-苯氧基)苯氧基]丙醇,2-[(4-苯氧基)苯氧基]乙醇,苯并咪唑的衍生物等为起始原料,先与对羟基苯甲醛反应,再经过醛氨缩合,接着与氯甲酸对甲氧苯酯反应,最后水解四步反应得到最终目标物,随后我们测定目标物对PPARs的激活作用。结果合成了5个未见文献报道的新化合物,并利用1HNMR确证了结构;目标物显示不同程度的激活PPARs的作用。结论5个目标化合物(6a、6b、6c、6′a、6′b)均有激活PPARs的作用,其中6a,6b,6c对PPARα/γ的作用尤其明显,可做为改善胰岛素抵抗及降血糖的良好候选药物。Aim To synthesize five novel hypolipidemic glycine-type drugs and research the role of PPARs. Methods The synthesis started with the reaction between 4-hydroxybenzaldehyde and 3-[ （4-phenoxy） phenoxy ] propanol, 2-（4-phenoxyphenoxy）ethanol, benzimidazole derivatives. The resulting compounds were condensed with proper aldehyde to give Schiff bases. The imine derivatives reacted with 4-methoxyphenyl carbonochloridate, followed by hydrolysis, to give the desired glyeine analogs. The target＇s role in the activation of PPARs was determined. Results 5 novel compounds were synthesized and characterized by ^1HNMR. Targets show varying degrees of activation of PPARs. Conclusion Bioassay indicated that five target compounds 6a, 6b, 6c, 6＇a, 6＇b were capable of activating PPARs. Among them, 6a, 6b, 6c are more effective. They can be good candidates for the therapy of insulin resistance and high blood sugar.

关 键 词：3-[(4-苯氧基)苯氧基]丙醇 甘氨酸 降血糖药 PPARα/γ 

分 类 号：R914[医药卫生—药物化学]