Bulletin of the Korean Chemical Society

  • 제31권12호
  • /
  • Pages.3760-3764
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  • 2010
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  • 0253-2964(pISSN)
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  • 1229-5949(eISSN)
대한화학회 (Korean Chemical Society)
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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)
  • 투고 : 2010.09.14
  • 심사 : 2010.10.25
  • 발행 : 2010.12.20
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초록

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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피인용 문헌

  1. ChemInform Abstract: 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. vol.42, pp.15, 2011, https://doi.org/10.1002/chin.201115159
  2. Peptide Scaffolds: Flexible Molecular Structures With Diverse Therapeutic Potentials vol.18, pp.2, 2012, https://doi.org/10.1007/s10989-011-9286-4
  3. A continued saga of Boc5, the first non-peptidic glucagon-like peptide-1 receptor agonist with in vivo activities vol.33, pp.2, 2012, https://doi.org/10.1038/aps.2011.169
  4. Fluorescent property of 3-hydroxymethyl imidazo[1,2-a]pyridine and pyrimidine derivatives vol.6, pp.1, 2012, https://doi.org/10.1186/1752-153X-6-83
  5. A β-Peptide Agonist of the GLP-1 Receptor, a Class B GPCR vol.15, pp.20, 2013, https://doi.org/10.1021/ol402568j
  6. Glucagon-like Peptide-1 (GLP-1) Analogs: Recent Advances, New Possibilities, and Therapeutic Implications vol.58, pp.3, 2015, https://doi.org/10.1021/jm500810s
  7. Positive Allosteric Modulation of the Glucagon-like Peptide-1 Receptor by Diverse Electrophiles vol.291, pp.20, 2016, https://doi.org/10.1074/jbc.M115.696039
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