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Discovery of a Potent, Selective Renal Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitor (HSK0935) for the Treatment of Type 2 Diabetes
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2017-04-27 00:00:00 , DOI: 10.1021/acs.jmedchem.6b01818
Yao Li 1 , Zongjun Shi 1 , Lei Chen 1 , Suxin Zheng 1 , Sheng Li 1 , Bo Xu 1 , Zhenhong Liu 1 , Jianyu Liu 1 , Chongyang Deng 1 , Fei Ye 1
Affiliation  

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:

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。
更新日期:2017-05-06
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