The first synthetic agonists of FFA2: Discovery and SAR of phenylacetamides as allosteric modulators.

Authors: Wang Y, Jiao X, Kayser F, Liu J, Wang Z, Wanska M, Greenberg J, Weiszmann J, Ge H, Tian H, Wong S, Schwandner R, Lee T, Li Y.
Publisher/Year: Bioorg Med Chem Lett. 2010 Jan 15;20(2):493-8. Epub 2009 Nov 26.
Pub Med ID/Journal ID: PMID:20005104


Free fatty acid receptor 2 (FFA2) is a G-protein coupled receptor for which only short-chain fatty acids (SCFAs) have been reported as endogenous ligands. We describe the discovery and optimization of phenylacetamides as allosteric agonists of FFA2. These novel ligands can suppress adipocyte lipolysis in vitro and reduce plasma FFA levels in vivo, suggesting that these allosteric modulators can serve as pharmacological tools for exploring the potential function of FFA2 in various disease conditions. Copyright 2009 Elsevier Ltd. All rights reserved.