Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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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)
  • Received : 2010.09.14
  • Accepted : 2010.10.25
  • Published : 2010.12.20
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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.

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