Development Of Dapagliflozin Derivatives Which Have A New Mechanism For The Pharmacotherapy Of Diabetes Mellitus

Dapagliflozin was a new kind of oral hypoglycemic drug which was developed by Bristol-Myers Squibb. It was a non-insulin-dependent drug which was mainly by inhibiting sodium-dependent glucose cotransporters (SGLT) which control the plasma glucose that is filtered in the kidney glomerulus is reabsorbed. In recent years, dapagliflozin has attracted much attention by many scientists due to its high activity, less toxic and suitable for long-term use, etc.Dapagliflozin is the phase of III clinical trials for the treatment of diabetic and will appear on the market at the near future. In this paper, we have relatively comprehensive summarized the developments and pharmacological activity of dapagliflozin and its derivatives. Meanwhile, we also obtained the significance of the experiments and the main research direction of this paper.In this work, three new derivatives of dapagliflozin were successfully synthesized by using5-bromo-2-chloro-benzoic acid and D-glucose lactone as the starting material, which were referenced by synthesis routes of dapagliflozin. The structures of the dapagliflozin derivatives were systematically investigated by’HNMR and13CNMR and MS. Moreover, the methods and reaction conditions for the preparation of dapagliflozin derivatives were also optimized, which were conducive not only to improve their yields but also to reduce costs.