Design, synthesis and evaluation of potent G-protein coupled receptor 40 agonists  

作　　者：Jing Huang Bin Guo Wen-Jing Chu Xin Xie Yu-She Yang Xian-Li Zhou 

机构地区：[1]School of Life Science and Engineering, Southwest Jiao Tong University [2]State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences [3]CAS Key Laboratory of Receptor Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences

出　　处：《Chinese Chemical Letters》2016年第1期159-162,共4页中国化学快报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China (No. 2140222)

摘　　要：GPR40 has emerged as an attractive drug target for the treatment of type 2 diabetes due to its role in the enhancement of insulin secretion with glucose dependency. With the aim to improve the metabolic and safety profiles, a series of novel phenylpropionic acid derivatives were synthesized. Extensive structural optimization led to identification of compounds 22 g and 23 e as potent GPR40 agonists with moderate liver microsomal stability. All the discovery supported further exploration surrounding this scaffold.GPR40 has emerged as an attractive drug target for the treatment of type 2 diabetes due to its role in the enhancement of insulin secretion with glucose dependency. With the aim to improve the metabolic and safety profiles, a series of novel phenylpropionic acid derivatives were synthesized. Extensive structural optimization led to identification of compounds 22 g and 23 e as potent GPR40 agonists with moderate liver microsomal stability. All the discovery supported further exploration surrounding this scaffold.

关 键 词：GPR40 ANTI-DIABETIC Agonist Phenylpropionic acid derivative 

分 类 号：R91[医药卫生—药学] R914.5