Synthesis, antidiabetic and hypolipidemic activities of new diethylamine and triethoxysilyl derivatives of tolbutamide on rats.

Tolbutamide (N-[(butylamino)carbonyl]-4-methylbenzenesulfonamide, CAS 64-77-7, I) is the first generation of potassium channel blocker and sulfonylurea oral hypoglycemic drug that imparts marked blood glucose lowering effect in type 2 diabetes or non-insulin dependent diabetes mellitus (NIDDM) patients. In this study, I and its two new analogs with substituting butylamine side by 3-diethylamino-1-propylamine (3) and 3-triethoxysilyl-1-propylamine (4) were synthesized and their antidiabetic and hypolipidemic activities were evaluated applying known procedures, and compared with both I and glibenclamide (II, well known second-generation sulfonylurea antidiabetic drug). The results showed that these new drugs (III and IV) were more potent than I and II and it could be concluded that changing the amine side of I would produce more potentials in new drugs (III and IV) of the first generation, to be named as the third generation. Also investigations on hypoglycemic and lipid lowering effects of these drugs proved that IV could reduce glucose, triglyceride (TG) and a low density lipoprotein (VLDL) level in blood serum more than others (I-III), 16 days after STZ injection.