Design, Synthesis, and Biological Evaluation of Deuterated C-Aryl Glycoside as a Potent and Long-Acting Renal Sodium-Dependent Glucose Cotransporter 2 Inhibitor for the Treatment of Type 2 Diab

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• 作者：Ge Xu ; Binhua Lv ; Jacques Y. Roberge ; Baihua Xu ; Jiyan Du ; Jiajia Dong ; Yuanwei Chen ; Kun Peng ; Lili Zhang ; Xinxing Tang ; Yan Feng ; Min Xu ; Wei Fu ; Wenbin Zhang ; Liangcheng Zhu ; Zhongping Deng ; Zelin Sheng ; Ajith Welihinda ; Xun Sun
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：February 27, 2014
• 年：2014
• 卷：57
• 期：4
• 页码：1236-1251
• 全文大小：665K
• 年卷期：v.57,no.4(February 27, 2014)
• ISSN：1520-4804

文摘

SGLT2 inhibitors deuterated at sites susceptible to oxidative metabolism were found to have a slightly longer t_max and half-life (t_1/2), dose-dependent increase in urinary glucose excretion (UGE) in rats, and slightly superior effects on UGE in dogs while retaining similar in vitro inhibitory activities against hSGLT2. In particular, deuterated compound 41 has the potential to be a robust long-acting antidiabetic agent.