Abstract

The present study reported the synthesis and antihyperglycemic activity of 1,4-benzothiazepines (1,4-benzothiazepine-2-one derivatives) in alloxan-induced diabetic rats. 1,4-benzothiazepines (3a-i) were synthesized via Friedel-Crafts acylation, reduction and microwave assisted S-alkylation reactions and characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance, mass and elemental analysis. In silico absorption, distribution, metabolism, excretion and toxicity parameters of synthesized compounds 3a-i were found within their acceptable limits. In acute toxicity study, none of synthesized 1,4-benzothiazepines showed any toxicity risks such as tremor, convulsion, lacrimation, sedation, increased or decreased motor activity, etc., in Wistar rats. The antihyperglycemic activity showed that synthesized 1,4-benzothiazepines (3a-i) reduced the elevated blood glucose level significantly in Wistar rats. 3f, 3h and 3i with electronegative substitution at 7 position of benzothiazepine nucleus and at 2’ position of phenyl ring, showed better antihyperglycemic activity as compared to other 1,4-benzothiazepines having weak electronegative substituent at the same position. The antihyperglycemic activity of synthesized 1,4-benzothiazepines was comparable with antihyperglycemic activity of metformin and CGP37157. The present study may be helpful in development of novel antidiabetic agents.