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Synthesis and biological evaluation of glucagon-like peptide-1 receptor agonists.

ABSTRACT: In this study, a series of fused-heterocyclic derivatives were systematically designed and synthesized using an efficient route, and evaluated in terms of GLP-1R agonist activity. We employed short synthetic steps and reactions that are tolerant of the presence of various functional groups and suitable for parallel operations to enable the rapid generation of libraries of diverse and structurally complex small molecules. Of the compounds synthesized, 3-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a] pyridin-2-yl)phenyl methanesulfonate (8e) was the most potent agonist with an EC50 of 7.89 μM, and thus is the compound with the greatest potential for application. These findings represent a valuable starting point for the design and discovery of small-molecule GLP-1R agonists that can be administered orally.

SUBMITTER: Zhang YJ

PROVIDER: S-EPMC4016675 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Synthesis and biological evaluation of glucagon-like peptide-1 receptor agonists.

Zhang Yu-Juan YJ Shen Liu-Lan LL Cheon Hyae-Gyeong HG Xu Yong-Nan YN Jeong Jin-Hyun JH

Archives of pharmacal research 20131101 5

In this study, a series of fused-heterocyclic derivatives were systematically designed and synthesized using an efficient route, and evaluated in terms of GLP-1R agonist activity. We employed short synthetic steps and reactions that are tolerant of the presence of various functional groups and suitable for parallel operations to enable the rapid generation of libraries of diverse and structurally complex small molecules. Of the compounds synthesized, 3-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a] ...[more]

PMID: 24178744

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