N-(5-substituted thiazol-2-yl)-2-aryl-3-(tetrahydro-2H-pyran-4-yl) propanamides as glucokinase activators

A series of novel arylacetamides were designed to further explore the GK binding property at the aminothiazole C5 position. The C5-amide substituted aminothiazoles 7a-f generally displayed decreased potency, whereas most of the C5-triazole substituted aminothiazoles retained good GK potency. Triazole 15 with a hydroxyethyl side chain was the most potent among the current series possessing an EC₅₀ value of 0.18 μM. Its R-enantiomer R-15 showed similar potency (0.22 μM) that deserves for further evaluation.