A series of novel N-(pyrimidin-4-yl)thiazol-2-amine derivatives have been synthesized and evaluated as glucokinase(GK)activators.Ethyl 2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl-amino)thiazole-5-carboxylate was found to be a potent dual-acting hypoglycemic agent activating both GK and PPARg.When given orally to normal mice,the compound demonstrated significant efficacy in decreasing the glucose level after oral glucose loading.
A new series of benzamide derivatives as glucokinase activators （GKAs） were designed and synthesized, and their activation for glucokinase were evaluated by the preliminary glucokinase activity assay. The structure-activity relationship （SAR） is discussed. The result shows that compound 12d and 12h have potent activity reference drug RO-28-1675.
