Discovery of potent and selective agonists for the free fatty acid receptor 1 (FFA(1)/GPR40), a potential target for the treatment of type II diabetes

J Med Chem. 2008 Nov 27;51(22):7061-4. doi: 10.1021/jm8010178.

Abstract

A series of 4-phenethynyldihydrocinnamic acid agonists of the free fatty acid receptor 1 (FFA(1)) has been discovered and explored. The preferred compound 20 (TUG-424, EC(50) = 32 nM) significantly increased glucose-stimulated insulin secretion at 100 nM and may serve to explore the role of FFA(1) in metabolic diseases such as diabetes or obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cinnamates / chemical synthesis
  • Cinnamates / chemistry
  • Cinnamates / pharmacology*
  • Crystallography, X-Ray
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Glucose / antagonists & inhibitors
  • Glucose / pharmacology
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Rats
  • Receptors, G-Protein-Coupled / agonists*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Time Factors

Substances

  • Cinnamates
  • FFAR1 protein, human
  • Ffar1 protein, mouse
  • G-protein-coupled receptor 40, rat
  • Insulin
  • Receptors, G-Protein-Coupled
  • Glucose