943834-02-4Relevant articles and documents
Discovery of the imidazole-derived GPR40 agonist AM-3189
Ma, Zhihua,Lin, Daniel C.-H.,Sharma, Rajiv,Liu, Jinqian,Zhu, Liusheng,Li, An-Rong,Kohn, Todd,Wang, Yingcai,Liu, Jiwen,Bartberger, Michael D.,Medina, Julio C.,Zhuang, Run,Li, Frank,Zhang, Jane,Luo, Jian,Wong, Simon,Tonn, George R.,Houze, Jonathan B.
, p. 15 - 20 (2015/12/18)
As a follow-up to the GPR40 agonist AMG 837, which was evaluated in clinical trials for the treatment of type II diabetes, further optimization led to the discovery of AM-3189 (13k). AM-3189 is representative of a new class of compounds with minimal CNS penetration, superior pharmacokinetic properties and in vivo efficacy comparable to AMG 837.
Synthesis and biological evaluation of 3-aryl-3-(4-phenoxy)-propionic acid as a novel series of G protein-coupled receptor 40 agonists
Song, Fengbin,Lu, Songfeng,Gunnet, Joe,Xu, Jun Z.,Wines, Pam,Proost, Jef,Liang, Yin,Baumann, Chris,Lenhard, Jim,Murray, William V.,Demarest, Keith T.,Kuo, Gee-Hong
, p. 2807 - 2817 (2008/02/08)
High-throughput screening of a subset of the J&J compound library containing the carboxylic acid functional group uncovered a bromophenyl derivative as a moderate potent GPR40 agonist. Chemical elaboration of this bromophenyl led to the discovery of a novel series of GPR40 agonists with submicromolar potency. Among them, 22 and 24 behaved as full agonists when compared to the endogenous GPR40 ligand linolenic acid in a functional Ca +2 flux assay in HEK cells expressing GPR40 receptor. Several GPR40 agonists have also demonstrated the ability to induce glucose-mediated insulin secretion in the mouse MIN6 pancreatic β-cell line. Our data supports the hypothesis that GPR40 may play an important role in fatty acid-mediated glucose-dependent insulin secretion. Compound 22 exhibited good pharmacokinetic profile in rat and may serve as a good candidate for in vivo study and may help to determine if GPR40 agonists would be beneficial in the treatment of type II diabetes.
