Exploration of SAR regarding glucose moiety in novel C-aryl glucoside inhibitors of SGLT2

In order to investigate SAR regarding glucose moiety in novel C-aryl glucoside SGLT2 inhibitors containing a thiazole motif, a series of chemical modifications on glucose was conducted to explore potential utility as a suitable replacement of glucose per se. Among the compounds prepared, deshydroxy 29 (IC50 = 7.01 nM) demonstrated the best in vitro inhibitory activity against SGLT2 in this series to date. But, none of the compounds were better than the parent molecule 5 (IC50 = 1.75 nM).

A variety of modifications at the C-6 position on glucose were conducted in the present study to establish SAR on carbohydrate pharmacophore based on structure of potent thiazole 5. Among the compounds tested, deshydroxy 29 demonstrated the best in vitro inhibitory activity against hSGLT2 in this series to date.Figure optionsDownload as PowerPoint slide