Discovery of 5-aryloxy-2,4-thiazolidinediones as potent GPR40 agonists

Systematic structure-activity relationship (SAR) studies of a screening lead led to the discovery of a series of thiazolidinediones (TZDs) as potent GPR40 agonists. Among them, compound C demonstrated an acute mechanism-based glucose-lowering in an intraperitoneal glucose tolerance test (IPGTT) in lean mice, while no effects were observed in GPR40 knock-out mice. (C) 2010 Elsevier Ltd. All rights reserved.