Design, synthesis, characterization and biological evaluation of some novel 3, 6-disubstituted-2-pyridinecarboxamide derivatives as antidiabetic agents

Abstract

Glucokinase catalyzes the phosphorylation of glucose to glucose-6-phosphate and is predominantly expressed in
liver and pancreatic β-cells. GK acts as a glucose sensor regulating hepatic glucose metabolism and glucosedependent insulin secretion. At present a lot of anti-hyperglycemic agents are available in market but they exhibits
single mode of action so, select the other targets having multiple action to fulfill the needs to treat type II diabetes,
for that we have synthesized some compounds by using moiety 3, 6-disubstituted 2-pyridinecarboxamide through
structure activity relationship. Such newly synthesized compounds are elucidated by IR, 1H-NMR and Mass
spectroscopy. These synthesized compounds were evaluated for their anti-diabetic activity. Comeouts of in vivo
antihyperglycemic activity specified that substitution of pyridine ring at 3rd position with hydrophobic group like
methyl group enhances the antihyperglycemic activity shown in compound 5g, 5h and 5i. The replacement of H
from the 4th postion of 1,3-thiazol-2-yl amide nucleus by methyl and ethyl group led to decreased antidiabetic
activity. It means that increase the carbon chain on such position decreased antidiabetic activity which can be seen in
compounds of 5g, 5h and 5i, and in compounds 5j, 5k and 5l respectively.