Design, synthesis and biological evaluation of novel imidazopyridines as potential antidiabetic GSK3I2 inhibitors

Design, synthesis and biological evaluation of the imidazopyridine analogs as novel GSK3I2 inhibitors for treatment of type 2 diabetes mellitus are described. Most of the analogs exhibited excellent inhibitory activities (IC50 < 44 nM) against glycogen synthase kinase 3I2 (GSK3I2). The structure-...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2012-07, Vol.22 (13), p.4221-4224
Main Authors: Lee, Seung-Chul, Kim, Hyun Tae, Park, Choul-Hong, Lee, Do Young, Chang, Ho-Jin, Park, Soobong, Cho, Joong Myung, Ro, Sunggu, Suh, Young-Ger
Format: Article
Language:English
Subjects:
Blood
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Summary:Design, synthesis and biological evaluation of the imidazopyridine analogs as novel GSK3I2 inhibitors for treatment of type 2 diabetes mellitus are described. Most of the analogs exhibited excellent inhibitory activities (IC50 < 44 nM) against glycogen synthase kinase 3I2 (GSK3I2). The structure-activity relationship (SAR) of the imidazopyridine analogs and the binding mode of analog 23 in the catalytic domain of GSK3I2, based on our X-ray crystallography study, are described. In particular, analog 28, which was selected as a potential drug candidate for treatment of type 2 diabetes mellitus, exhibited excellent GSK3I2 inhibition, pharmacokinetic profiles and blood glucose lowering effect in mouse.
ISSN:0960-894X
DOI:10.1016/j.bmcl.2012.05.060