Glibenclamide (5-chloro-N-(4-[N-(cyclohexylcarbamoyl) sulfamoyl] phenethyl)-2-methoxybenzamide,
Glyburide, E) is a well-known and potent second-generation of sulfonylurea oral
hypoglycemic drug which is most widely used in
type 2 diabetes recently. It acts upon pancreatic β-cells by stimulating insulin secretion in
glucose and
lipid-lowering activities. So far, many derivatives of E have been synthesized by adding new structural moieties to its structure while preserving its binding affinity to the receptor before their anti-hyperglycemic and anti hyperlipidemic activities being evaluated. In this study, new analogues of E after changing lipophilic side chain (5-chloro-2-methoxy benzamide) with 4- bromo-3, 5-dimethoxy
benzamide and 2, 4-dichloro
benzamide were synthesized. Also, their
glucose and
lipid-lowering activities were evaluated and compared to E and
Tolbutamide (a famous first-generation of sulfonylurea oral
hypoglycemic drug) by the known procedures. Findings showed that
chloride substitution on lipophilic side chain of
Glibenclamide could possibly increase the affinity of drug for receptor/or its half life time that resulted in more lasting anti-hyperglycemic and anti lipidemic activities in diabetic rats. However,
bromide substitution with additional methoxy groups in
benzamide ring could slightly improve the anti-hyperglycemic potency of the new drug compared to the root drug (E).