A new class of potent and highly selective SGLT2 inhibitors is disclosed. Compound 31 (HSK0935) demonstrated excellent hSGLT2 inhibition of 1.3 nM and a high hSGLT1/hSGLT2 selectivity of 843-fold. It showed robust urinary glucose excretion in Sprague–Dawley (SD) rats and affected more urinary glucose excretion in Rhesus monkeys. Finally, an efficient synthetic route has been developed featuring a ring-closing cascade reaction to incorporate a double ketal 1-methoxy-6,8-dioxabicyclo[3.2.1]octane ring system.

中文翻译：

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发现有效的选择性肾钠依赖性葡萄糖共转运蛋白2（SGLT2）抑制剂（HSK0935），用于治疗2型糖尿病

公开了新型的有效和高度选择性的SGLT2抑制剂。化合物31（HSK0935）对hSGLT2的抑制作用为1.3 nM，对hSGLT1 / hSGLT2的选择性为843倍。它显示了Sprague-Dawley（SD）大鼠的尿糖排泄能力强，并影响了恒河猴的尿糖排泄量。最后，已开发出一种有效的合成路线，其特征在于具有闭环级联反应，以结合双缩酮1-甲氧基-6,8-二氧杂双环[3.2.1]辛烷环系统。