Novel macrocyclic C-aryl glucoside SGLT2 inhibitors as potential antidiabetic agents

Novel macrocyclic C-aryl glucoside SGLT2 inhibitors were designed and synthesized. Two different synthetic routes of macrocyclization were adopted to prepare novel macrocyclic SGLT2 inhibitors. Among the compounds tested, [1,7]dioxacyclopentadecine macrocycles possessing ethylphenyl at the distal ring 42 or ethoxyphenyl at the distal ring 33 showed the best in vitro inhibitory activity in this series to date (42, IC50 = 0.778 nM and 33, IC50 = 0.899 nM) against hSGLT2.