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Bioorg Med Chem Lett. 2013 Apr 1;23(7):2166-71. doi: 10.1016/j.bmcl.2013.01.093. Epub 2013 Feb 4.

Design, synthesis and SAR of novel glucokinase activators.

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  • 1Takeda California, 10410 Science Center Drive, San Diego, CA 92121, USA.


Guided by co-crystal structures of compounds 15, 22 and 30, an SBDD approach led to the discovery of the 6-methyl pyridone series as a novel class of GKAs that potently activate GK in enzyme and cell assays. Anti-diabetic OGTT efficacy was demonstrated with 54 in a mouse model of type 2 diabetes.

Copyright © 2013 Elsevier Ltd. All rights reserved.

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