Synthesis and biological evaluation of benzocyclobutane-C-glycosides as potent and orally active SGLT1/SGLT2 dual inhibitors are described. Compound 19 showed high inhibitory potency at SGLT1 (IC₅₀ = 45 nM), and excellent potency at SGLT2 (IC₅₀ = 1 nM). It also displayed excellent PK profiles in mice, rats, dogs and monkeys (F = 78–107%). In SD rats, compound 19 treatments significantly reduced blood glucose levels in a dose-dependent manner. In ZDF rats, compound 19 displayed anti-hyperglycemic effect up to 24 h. Therefore, compound 19 may serve as valuable pharmacological tool, and potential use as a treatment for metabolic syndrome.

描述了作为有效和口服活性的SGLT1 / SGLT2双重抑制剂的苯并环丁烷-C-糖苷的合成和生物学评估。化合物19在SGLT1（IC ₅₀  = 45 nM）上显示出高抑制效能，在SGLT2（IC ₅₀  = 1 nM）上显示出优异的效能。它还在小鼠，大鼠，狗和猴子中表现出出色的PK分布（F  = 78–107％）。在SD大鼠中，化合物19的治疗以剂量依赖性方式显着降低了血糖水平。在ZDF大鼠中，化合物19最多显示24小时的降血糖作用。因此，化合物19可以用作有价值的药理学工具，并且可以潜在地用作代谢综合征的治疗方法。