Premium
Discovery of 2,3‐Dihydro‐1 H ‐indene Derivatives as Novel GPR40 Agonists
Author(s) -
An KyungMi,
Hong ChangHee,
Kwak HyunJung,
Cui Shuolin,
Song HyoJung,
Park JoonTae,
Moon AnNa,
Kim JeongAh,
Yang JiHun,
Yoon JongMin,
Lee MyongJae,
Jeong DongGu,
Kim Dohee,
Lee DonGil,
Shin JeongCheol,
Je InGyu,
Lee HongSub,
Park Soobong,
Kang JaeHoon,
Ko Soo Young
Publication year - 2017
Publication title -
bulletin of the korean chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.237
H-Index - 59
ISSN - 1229-5949
DOI - 10.1002/bkcs.11185
Subject(s) - free fatty acid receptor 1 , chemistry , pharmacophore , agonist , receptor , dendrimer , moiety , carboxylic acid , pharmacology , stereochemistry , biochemistry , medicine
GPR40 (G protein‐coupled receptor 40) has become an attractive target for insulin secretagogue via glucose‐dependent mechanism with low risk of hypoglycemia. In order to overcome problems associated with previously developed GPR40 agonists, we recruited the core fragment 2,3‐dihydro‐ 1 H ‐indene to GPR40 receptor binding pharmacophore with carboxylic acid moiety, and screened various amine analogs to finally discover several hit compounds displaying GPR40 agonistic activities. Through additional in vitro ADME , pharmacokinetics, and in vivo efficacy evaluations, compound 1e was demonstrated as a potent lead GPR40 agonist.