Citation: Jing Huang, Bin Guo, Wen-Jing Chu, Xin Xie, Yu-She Yang, Xian-Li Zhou. Design, synthesis and evaluation of potent G-protein coupled receptor 40 agonists[J]. Chinese Chemical Letters, ;2016, 27(01): 159-162. doi: 10.1016/j.cclet.2015.09.002 shu

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

Jing Huang ^a ,
Bin Guo ^b ,
Wen-Jing Chu ^b ,
Xin Xie ^c ,
Yu-She Yang ^b,, ,
Xian-Li Zhou ^a,,

1.
a School of Life Science and Engineering, Southwest Jiao Tong University, Chengdu 610031, China;
2.
b State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
3.
c CAS Key Laboratory of Receptor Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

Corresponding author: Yu-She Yang, Xian-Li Zhou,
Received Date: 11 February 2015
Available Online: 10 May 2015
Fund Project: This work was supported by grants from the National Natural Science Foundation of China(No. 2140222). (No. 2140222)

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 22g and 23e as potent GPR40 agonists with moderate liver microsomal stability. All the discovery supported further exploration surrounding this scaffold.
- GPR40,
- Anti-diabetic,
- Agonist,
- Phenylpropionic acid derivative
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