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http://dx.doi.org/10.5012/bkcs.2010.31.12.3760

A Novel 3-(8-Chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)phenyl Acetate Skeleton and Pharmacophore Model as Glucagon-like Peptide 1 Receptor Agonists  

Gong, Young-Dae (Innovative Drug Library Research Center, Department of Chemistry, Dongguk University-Seoul)
Cheon, Hyae-Gyeong (Department of Pharmacology, Medical School, Gachon University of Medicine and Science)
Lee, Tae-Ho (Bio-Organic Science Division, Korea Research Institute of Chemical Technology)
Kang, Nam-Sook (Bio-Organic Science Division, Korea Research Institute of Chemical Technology)
Publication Information
Bulletin of the Korean Chemical Society / v.31, no.12, 2010 , pp. 3760-3764 More about this Journal
Abstract
We screened 10,000 heterocyclic small molecules and identified a novel hit core skeleton of 3-(8-chloro-6-(trifluoromethyl) imidazo[1,2-a]pyridine-2-yl)phenyl acetate derivatives. It has been selected as a potential glucagon-like peptide 1 receptor (GLP-1R) activator and demonstrated its effects in increasing GLP-1 secretion, and thereby increasing the glucose responsiveness in both in vitro and pharmacology analyses. Further studies are currently underway to optimize the potency and selectivity of 3-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)phenyl acetate derivatives (hit compounds 2 and 8), and address their in vivo efficacy and therapeutic potential. These molecules may serve as useful evidence showing that compounds with a 3-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)phenyl acetate moiety are selective GLP-1R agonists, and have potential as anti-diabetic treatment agents.
Keywords
Imidazo[1,2-a]pyridine-2-yl-phenyl acetate; Glucagon-like peptide 1 receptor (GLP-1R); Drug-like core skeleton; Pharmacophore;
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