Sodium glucose co-transporter 2 (SGLT2) mediates glucose reabsorption into the kidney. Inhibition of SGLT2 in vivo results in increased urinary glucose excretion and controls blood glucose levels in hyperglycemic animals. In previous studies, T-1095 was identified through optimization of the natural phenol-O-glucoside product phlorizin, producing the first orally active SGLT2 inhibitor. T-1095 enhanced urinary glucose excretion and lowered blood glucose levels independent of the action of insulin in various animal models of diabetes. We recently reported that aryl-C-glucoside analogues, including canagliflozin, are metabolically stable SGLT2 inhibitors that exhibit excellent in vivo potency. Canagliflozin has been launched in the USA. Further investigations of the structure�activity relationships of a series of C-glucosides with heteroaryl thiophene led to the identification of the fluoropyridyl thiophene derivative TA-3404 as a potent SGLT2 inhibitor. In the present study, we developed novel synthetic methods and produced pharmacological data for C-glucosides with heteroaryl thiophene and analyzed their potential as novel antihyperglycemic agents. 

<i>C</i>-Glucosides with heteroaryl thiophene as novel sodium glucose co-transporter 2 inhibitors

248th National Meeting (2014)

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C-Glucosides with heteroaryl thiophene as novel sodium glucose co-transporter 2 inhibitors