Synthesis of 2-[2,3-dihydro-1,4-benzodioxin-6-yl(phenylsulfonyl)amino]-N-(un/substituted-phenyl)acetamides as anti-diabetic agents

Abstract

Purpose: To synthesize a series of new 2-[2,3-dihydro-1,4-benzodioxin-6-yl(phenylsulfonyl)amino]-N-(un/substituted-phenyl) acetamides, and evaluate their anti-diabetic potentials. Methods: Synthesis of the parent compound N-(2,3-dihydro-1,4-benzodioxin-6-yl) benzenesulfonamide (3) was carried out by reacting 2,3-dihydro-1,4-benzodioxin-6-amine (1) with benzenesulfonylchloride (2) in aqueous basic medium under definite pH controls. After that 3 was further treated with various 2-bromo-N-(un/substituted-phenyl)acetamides (6a-l) to yield new compounds (7a-l) in polar aprotic solvent, DMF (dimethylformamide), using LiH as activator. The proposed structures of the synthesized compounds were confirmed using proton-nuclear magnetic resonance (1H-NMR) and infra-red spectroscopy (IR), and CHN analysis. Their anti-diabetic potential was evaluated by α-glucosidase enzyme inhibitory studies. Results: All the new compounds demonstrated weak (7a-h, 7j and 7l) to moderate (7i and 7k) inhibitory activities against α-glucosidase enzyme. IC50 (50 % inhibition concentration) values for 7i and 7k were 86.31±0.11 μM and 81.12±0.13 μM, respectively relative to acarbose (reference standard) with IC50 of 37.38±0.12 μM. Conclusion: All the synthesized compounds have weak to moderate activity against α-glucosidase enzyme. These compounds can thus be considered as possible therapeutic entrants for type-2 diabetes.