Synthesis and Anti-hyperglycemic Activity of New C-Glucoside SGLT2 Inhibitors

A series of new trans- l -{4-methoxy-3-[(4-substituted cyclohexyl) methyl]phenyl}-1-deoxy-beta-D-glucopyranoses (12a-12d) was synthesized. The structures of synthesized compounds were confirmed by H-1 NMR and HR-MS data. The synthesis of compounds bearing larger alkyl groups was studied and the synthetic method of SGLT2 inhibitors was further optimized. To evaluate the hypoglycemic effects of these molecules, oral glucose tolerance test was performed. The compounds 12a-12d were found to possess potent anti-hyperglycemic activities. Moreover, complete Structure-Activity Relationship analysis for 12a-12d was carried out and a good Structure-Activity Relationship was obtained. The newly designed molecules 12a-12d, as SGLT2 inhibitors, put forth promising anti-hyperglycemic activities.