Design, synthesis and SAR of novel glucokinase activators.

Abstract 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.