Bioorganic and Medicinal Chemistry p. 5546 - 5565 (2015)
Update date:2022-08-03
Topics:
Takano, Rieko
Yoshida, Masao
Inoue, Masahiro
Honda, Takeshi
Nakashima, Ryutaro
Matsumoto, Koji
Yano, Tatsuya
Ogata, Tsuneaki
Watanabe, Nobuaki
Hirouchi, Masakazu
Kimura, Takako
Toda, Narihiro
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.
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