Solid phase synthesis and SAR of small molecule agonists for the GPR40 receptor

Bioorg Med Chem Lett. 2007 Mar 15;17(6):1584-9. doi: 10.1016/j.bmcl.2006.12.084. Epub 2007 Jan 4.


The discovery, synthesis and structure-activity relationship (SAR) of novel carboxylic acid agonists for GPR40 are described. Aryl propionic acid 1, identified from a high throughput screen, was selected for chemical exploration. Compound 2 was identified as our lead molecule through efficient solid phase combinatorial array chemistry and had an attractive in vitro and in vivo pharmacokinetic profile in rat. These ligands may prove useful in establishing a role for GPR40 in insulin regulation.

MeSH terms

  • Animals
  • Biological Availability
  • CHO Cells
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / pharmacokinetics
  • Carboxylic Acids / pharmacology*
  • Chemical Phenomena
  • Chemistry, Physical
  • Cricetinae
  • Cricetulus
  • Drug Evaluation, Preclinical
  • Indicators and Reagents
  • Ligands
  • Protein Binding
  • Rats
  • Receptors, G-Protein-Coupled / agonists*
  • Structure-Activity Relationship


  • Carboxylic Acids
  • G-protein-coupled receptor 40, rat
  • Indicators and Reagents
  • Ligands
  • Receptors, G-Protein-Coupled