Synthesis And Sar Of Benzisothiazole- And Indolizine-Beta-D-Glucopyranoside Inhibitors Of Sglt2

A series of benzisothiazole- and indolizine-beta-D-glucopyranoside inhibitors of human SGLT2 are described. The synthesis of the Clinked heterocyclic glucosides took advantage of a palladium-catalyzed cross-coupling reaction between a glucal boronate and the corresponding bromo heterocycle. The compounds have been evaluated for their human SGLT2 inhibition potential using cell-based functional transporter assays, and their structure activity relationships have been described Benzisothiazole-C-glucoside 16d was found to be an inhibitor of SGLT2 with an IC50 of 10 nM