SYNTHESIS, CHARACTERIZATION AND PHARMACOLOGICAL ACTIVITY OF 3, 6-DISUBSTITUTED 2-PYRIDINECARBOXAMIDE DERIVATIVES AS GLUCOKINASE ACTIVATOR

Abstract

Glucokinase (GK) is the key enzyme expressed in β-cells of pancreas and liver hepatocytes and helps in the maintenance of blood glucose levels in normal range. Activators of GK are the novel category of drug candidates which activate GK enzyme allosterically and show their antidiabetic activity. A new series of 3, 6-disubstituted 2-pyridinecarboxamide derivatives have been synthesized and evaluated for antidiabetic activity. These compounds evaluated by IR,1H-NMR and Mass spectroscopy. Amongst the synthesized derivatives, compounds 5d, 5e showed maximum GK activation in the in vitro GK assay. Furthermore, the results of antihyperglycemic activity indicated that substitution with hydrophobic group like trifluoromethyl at position-3 of pyridine ring (5d and 5e) attached to carboxamide led to increased antidiabetic activity in OGTT assay results.