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目的合成一类新型的以4-噻唑环为母体的二肽基肽酶Ⅳ(DPP-Ⅳ)抑制剂,测试并研究它们的降血糖活性。方法通过Hantzsch噻唑合成反应制备2-氨基4-甲基噻唑,然后用氯乙酰氯和三乙胺进行氯乙酰化,所得中间体氯乙酰胺经芳基甲胺处理得到目标物,最后,在干燥的乙醚中用氯化氢乙醚溶液处理即可得到目标物的盐酸盐。利用小鼠体内口服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21个结构新颖的化合物,结构经过1H-NMR和ESI-MS确认。结论经过活性测试,发现其中的两个目标化合物(7f、7h)具有明显的降血糖作用,其中化合物7f的活性与阳性对照药西他列汀相当,化合物7h的活性则超过阳性对照药,显示了在治疗糖尿病方面的前景。
AIM: To synthesize a novel 4-thiazolyl ring-based dipeptidyl peptidase IV (DPP-IV) inhibitor and test their hypoglycemic activity. Methods The 2-amino 4-methylthiazole was synthesized by the reaction of Hantzsch thiazole and then chloroacetylated with chloroacetyl chloride and triethylamine. The obtained intermediate chloroacetamide was treated with arylmethanamine to obtain the target compound. Finally, In ether was treated with a solution of hydrogen chloride in ether to give the desired hydrochloride. The activity of the target compound in the treatment of diabetes was determined using the oral glucose tolerance test in mice. Results Twenty-one novel compounds were synthesized and confirmed by 1H-NMR and ESI-MS. Conclusions After the activity test, two of the target compounds (7f, 7h) showed obvious hypoglycemic effect. The activity of compound 7f was comparable to that of sitagliptin, and the activity of compound 7h was higher than that of positive control The prospects for the treatment of diabetes.