A series of novel C-aryl glucosides with various substituents at the distal aryl ring have been synthesized and evaluated for hypoglycemic effect in normal and diabetic mice and in type 2 diabetic rats. The results indicated that introduction of electron-donating group at the distal aryl ring could improve glucose tolerance in normal mice, whereas introduction of electron-withdrawing group at this position could deteriorate. The urinary glucose excretion was significantly increased after glucose (3 g/kg) administration in normal mice with the treatment of 13c. Moreover, compound 13c could reduce fed blood glucose levels in a dose-dependent manner in type 2 diabetic rats, showed a remarkable antihyperglycemic effect with 2 weeks of treatment in diabetic mice, and might be a promising drug candidate for the treatment of diabetes mellitus.
Keywords: C-aryl glucosides; diabetes mellitus type 2; sodium-glucose cotransporters.
© 2014 John Wiley & Sons A/S.