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目的合成一类新型的以噻唑环为母体的二肽基肽酶Ⅳ(DPP-Ⅳ)抑制剂,并测试它们在治疗糖尿病方面的活性。方法通过Hantzsch噻唑合成反应制备各种2-氨基噻唑,用氯乙酰氯和三乙胺进行氯乙酰化,乙酰化产物经芳基甲胺处理得到相应的仲胺,仲胺在干燥的乙醚中用氯化氢乙醚溶液处理即可得到目标化合物。利用小鼠体内葡萄糖耐受量法测定目标化合物在治疗糖尿病方面的活性。结果合成了20个结构新颖的化合物,其结构经过1H-NMR、13C-NMR和ESI-MS谱确证。结论活性测试结果显示,有3个化合物具有明显的降血糖作用,其中化合物6l的活性与阳性对照药格列齐特和格列喹酮相当,另外两化合物6d、6n的降血糖作用比阳性对照药强,显示出在治疗糖尿病方面的价值。
AIM: To synthesize a novel dipeptidyl peptidase IV (DPP-IV) inhibitor with thiazole ring as its precursor and test its activity in the treatment of diabetes. Methods A variety of 2-aminothiazoles were synthesized by the reaction of Hantzsch thiazole with chloroacetyl chloride and triethylamine. The acetylated products were treated with arylmethylamine to give the corresponding secondary amines. The secondary amines were treated with dry diethyl ether Hydrogen chloride diethyl ether solution to give the target compound. The in vivo glucose tolerance assay was used to determine the activity of the target compound in the treatment of diabetes. Results Twenty new compounds were synthesized and their structures were confirmed by 1H-NMR, 13C-NMR and ESI-MS spectra. Conclusion The results of the activity test showed that three compounds had obvious hypoglycemic effect. The activity of compound 6l was comparable to the positive control drug gliclazide and gliquidone. The other two compounds 6d and 6n had lower hypoglycemic effect than the positive control Strong medicine, showing the value in the treatment of diabetes.