甘氨酰胺类DPP-IV抑制剂的设计、合成及体外活性研究

Design, synthesis and in vitro activity of glycinamide-bearing compounds as DPP-IV inhibitors

摘要:
以P32/98和化合物A为先导化合物, 对其进行结构改造。在羧基端引入含氮杂环形成酰胺, 在羰基α-位引入不同取代基, 设计合成了19个以甘氨酰胺为基本骨架的二肽基肽酶IV (dipeptidyl peptidase IV, DPP-IV) 抑制剂。利用¹H NMR和HRMS确证了它们的结构, 并对其进行酶水平的体外药理活性筛选, 测试了它们对DPP-IV的抑制作用, 获得了初步的构效关系结果。

Abstract:
To research the structure-activity relationship (SAR) of glycinamide-bearing compounds that used as inhibitors of dipeptidyl peptidase IV (DPP-IV), P32/98 and compound A were chosen as the leading compounds, heterocycles containing nitrogen atom were introduced to form amide, and different residues on α-position of carbonyl were designed. The nineteen designed compounds were synthesized by a simple route and were evaluated as inhibitors of DPP-IV. All of the structures were characterized by ¹H NMR and HRMS. The preliminary SAR result was obtained.