那格列奈类似物的合成与活性测定

目的合成新型那格列奈类似物,评价其对小鼠血糖的影响.方法以N-异丙基哌嗪、N-异丙基哌啶-4-羧酸、反式-4-二甲氨基环己烷-1-甲酸及各种取代苯丙氨酸为原料合成目标化合物,并通过小鼠禁食后给药、口服葡萄糖、采尾血测血糖,来确定新化合物对血糖值的影响.结果共合成43个新化合物,经元素分析、红外光谱、旋光、核磁共振氢谱和质谱确定结构;其中化合物1对小鼠血糖升高有明显的抑制作用.结论所合成的那格列奈类似物(1)有明显降糖活性,且手性中心为S构型,与对照药构型相反.

Synthesis of nateglinide analogues and their bioactivity determination

Aim To synthesize nateglinide analogues and test their biology activities by the glycemia levels in mice.Methods The new compounds were synthesized by using N isopropylpiperazine, N isopropylpiperidine 4 carboxylic acid, trans 4 dimethylaminocyclohexane 1 carboxylic acid and substituded phenylalanine as the starting materials.The biological activities of the new compounds were tested by the glycemia levels in mice via drug administration after forbiddance of food intaking and oral delivery of glucose.Results Forty three new compounds were synthesized and their structures were confirmed by elementary analysis,IR,polarimetric analysis, 1H NMR and MS.The new compound 1 showed significant control effect on glycemia of mice.Conclusion Compound 1,nateglinide analogues showed significant hypoglycaemic effect.