Optimization of 3-aryl-3-ethoxypropanoic acids and discovery of the potent GPR40 agonist DS-1558.
Basic Information
ID: ALA3603738
Journal: Bioorg Med Chem
Title: Optimization of 3-aryl-3-ethoxypropanoic acids and discovery of the potent GPR40 agonist DS-1558.
Authors: Takano R, Yoshida M, Inoue M, Honda T, Nakashima R, Matsumoto K, Yano T, Ogata T, Watanabe N, Hirouchi M, Kimura T, Toda N.
Abstract: GPR40 agonists stimulate insulin secretion only under the presence of high glucose concentration. Based on this mechanism, GPR40 agonists are believed to be promising novel insulin secretagogues with low risk of hypoglycemia. The optimizations of 3-aryl-3-ethoxypropanoic acids were performed to improve in vitro activity. We discovered compound 29r (DS-1558), (3S)-3-ethoxy-3-(4-{[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]oxy}phenyl)propanoic acid, which was confirmed to have an enhancing effect on glucose-dependent insulin secretion after intravenous glucose injection in SD rats.
CiteXplore: 26234904
DOI: 10.1016/j.bmc.2015.07.028
Patent ID: ┄