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

Changyou Zhou; Cheng Tang; Eric Chang; Min Ge; Songnian Lin; Eric Cline; Carina P Tan; Yue Feng; Yun-Ping Zhou; George J Eiermann; Aleksandr Petrov; Gino Salituro; Peter Meinke; Ralph Mosley; Taro E Akiyama; Monica Einstein; Sanjeev Kumar; Joel Berger; Andrew D Howard; Nancy Thornberry; Sander G Mills; Lihu Yang

doi:10.1016/j.bmcl.2009.10.052

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

Bioorg Med Chem Lett. 2010 Feb 1;20(3):1298-301. doi: 10.1016/j.bmcl.2009.10.052. Epub 2009 Oct 15.

Affiliation

¹ Merck Research Laboratories, Rahway, NJ 07065, USA.

PMID: 20064714
DOI: 10.1016/j.bmcl.2009.10.052

Abstract

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.

Publication types

Comparative Study

MeSH terms

Animals
Drug Discovery / methods*
Mice
Mice, Knockout
Protein Binding / physiology
Receptors, G-Protein-Coupled / agonists*
Receptors, G-Protein-Coupled / metabolism
Structure-Activity Relationship
Thiazolidinediones / agonists
Thiazolidinediones / chemistry*
Thiazolidinediones / pharmacology

Substances

Ffar1 protein, mouse
Receptors, G-Protein-Coupled
Thiazolidinediones
2,4-thiazolidinedione