title: Synthesis and investigating hypoglycemic and hypolipidemic activities of some glibenclamide analogues in rats.
abstract: 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).
authors.forename: Abbas
authors.initials: A
authors.lastname: Ahmadi
authors.forename: Mohsen
authors.initials: M
authors.lastname: Khalili
authors.forename: Khadijeh
authors.initials: K
authors.lastname: Khatami
authors.forename: Majid
authors.initials: M
authors.lastname: Farsadrooh
authors.affiliation: Department of Chemistry, Faculty of Science, Karaj Branch, Islamic Azad University, P.O. Box: 31485-313, Karaj, Iran. a-ahmadi@kiau.ac.ir.
authors.forename: Babak
authors.initials: B
authors.lastname: Nahri-Niknafs
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D005905:Glyburide / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D005905:Glyburide