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

作　　者：韩蓓[1] 环奕[1] 林紫云[1] 李鹏[1] 申竹芳[1] 尹大力[1] 黄海洪[1] 

机构地区：[1]中国医学科学院北京协和医学院药物研究所,北京100050

出　　处：《药学学报》2010年第11期1379-1384,共6页Acta Pharmaceutica Sinica

基　　金：中国医学科学院;北京协和医学院药物研究所基本科研业务费(李鹏504-基本10DPP-Ⅳ抑制剂)

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。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.

关 键 词：二肽基肽酶IV抑制剂 合成 甘氨酰胺 构效关系 

分 类 号：R916[医药卫生—药学]