Document Report Card

ID: ALA1773039

Journal: ACS Med Chem Lett

Title: Structure-Activity Study of Dihydrocinnamic Acids and Discovery of the Potent FFA1 (GPR40) Agonist TUG-469.

Authors: Christiansen E, Due-Hansen ME, Urban C, Merten N, Pfleiderer M, Karlsen KK, Rasmussen SS, Steensgaard M, Hamacher A, Schmidt J, Drewke C, Petersen RK, Kristiansen K, Ullrich S, Kostenis E, Kassack MU, Ulven T.

Abstract: The free fatty acid 1 receptor (FFA1 or GPR40), which is highly expressed on pancreatic β-cells and amplifies glucose-stimulated insulin secretion, has emerged as an attractive target for the treatment of type 2 diabetes. Several FFA1 agonists containing the para-substituted dihydrocinnamic acid moiety are known. We here present a structure-activity relationship study of this compound family suggesting that the central methyleneoxy linker is preferable for the smaller compounds, whereas the central methyleneamine linker gives higher potency to the larger compounds. The study resulted in the discovery of the potent and selective full FFA1 agonist TUG-469 (29).

CiteXplore: 24900217

DOI: 10.1021/ml100106c