含噻唑环的二肽基肽酶IV抑制剂的设计、合成和降血糖活性研究

Design,Synthesis and Anti-diabetic Activities of Thiazole-Bearing Compounds as Dipeptidyl Peptidase IV Inhibitors

设计并合成了16个含噻唑环的二肽基肽酶IV(DPP-IV)抑制剂,利用IR,1HNMR,13CNMR和HR-MS表征了它们的结构.通过小鼠口服糖耐量实验测试了它们的降血糖作用,结果显示其中两个化合物具有很强的降血糖作用,一个与格列齐特相当,另一个强于格列齐特,显示了在治疗II型糖尿病方面的前景.构效关系研究发现,这16个化合物的构效关系呈现出明显的规律.

Sixteen thiazole-bearing compounds were designed and synthesized as dipeptidyl peptidase IV （DPP-IV） inhibitors, and characterized by IR, 1H NMR, 13C NMR and HR-MS techniques. Their activities to decrease blood glucose level were determined through a rat oral glucose tolerance test （OGTT） and the result showed that two compounds exhibited potent activities to decrease the blood glucose level, with one being comparable with and the other being more potent than gliclazide, which indicates that these two compounds are promising for the treatment of type Ⅱ diabetes. Careful examination led to the establishment of a regular structure-activity relationship （SAR）.