Synthesis and SAR of Thiazolylmethylphenyl Glucoside as Novel C-Aryl Glucoside SGLT2 Inhibitors

摘要

Novel C-aryl glucoside SGLT2 inhibitors containing the thiazole motif were designed and synthesized for biological evaluation. Among the compounds assayed, thiazole containing furanyl moiety >14v and thiophenyl moiety >14y demonstrated the best in vitro inhibitory activity against SGLT2 in this series to date (IC50 = 0.720 nM for >14v and IC50 = 0.772 nM for >14y). Both of these compounds have been further evaluated on a urinary glucose excretion test and the urine volumes excreted.