Design, Synthesis, and Biological Evaluation of Thioglucoside Analogues of Gliflozin as Potent New Gliflozin Drugs

Abstract

In this study, we have investigated the potential of two classes of thioglucoside analogues of gliflozins as antidiabetic drugs, one with substitutions of S-atoms in meta-positions (similar to C-glucoside SGLT2 inhibitors, TAGs A, B, and C) and the other with substitutions of S-atoms in ortho-positions (similar to Oglucoside SGLT2 inhibitors, TAGs D, E, F, and G). These TAGs were confirmed to show good stability against β-glucosidase and to have no acute toxicity to cultured cells. Most importantly, TAGs D, E, F, and G all showed high inhibitory activity against SGLT2 (IC 50 : 2.0−5.9 nM) and thus have great potential to be developed as new gliflozin drugs. Compared with the synthesis of C-glucoside gliflozins, the synthesis of TAGs is simple, efficient, and associated with low costs, high yields, and very mild reaction conditions.

Transition-metal-free glycosyl sulfonation of diaryliodonium salts with sodium glycosyl sulfinate: an efficient approach to access glycosyl aryl sulfones

“…Gratifyingly, the reactions proceeded smoothly with delightful yields even for complex substrates ( 7k ). Given that the compound 7k represents an analogue of potent antidiabetic drugs targeting SGLT2, 13 a global debenzylation reaction was suggested to produce 8 , aiming to investigate its biological activity (Scheme 3). Pleasingly, treatment of 7k in the presence of BCl 3 afforded the desired product in an acceptable yield.…”