Discovery of 2,3-Dihydro-1H-indene Derivatives as Novel GPR40 Agonists

Kyung Mi An, Chang Hee Hong, Hyun Jung Kwak, Shuolin Cui, Hyo Jung Song, Joon Tae Park, An Na Moon, Jeong Ah Kim, Ji Hun Yang, Jong Min Yoon, Myong Jae Lee, Dong Gu Jeong, Dohee Kim, Don Gil Lee, Jeong Cheol Shin, In Gyu Je, Hong Sub Lee, Soobong Park, Jae Hoon Kang, Soo Young Ko

Research output: Contribution to journalArticlepeer-review

Abstract

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-1H-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.

Original languageEnglish
Pages (from-to)861-868
Number of pages8
JournalBulletin of the Korean Chemical Society
Volume38
Issue number8
DOIs
StatePublished - Aug 2017

Keywords

  • Glucose-stimulated insulin secretion
  • GPR40
  • Hypoglycemia
  • Insulin secretagogue

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