Discovery of Novel N-尾-d-Xylosylindole Derivatives as Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitors for the Management of Hyperglycemia in Diabetes

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• 作者：Chun-Hsu Yao ; Jen-Shin Song ; Chiung-Tong Chen ; Teng-Kuang Yeh ; Ming-Shiu Hung ; Chih-Chun Chang ; Yu-Wei Liu ; Mao-Chia Yuan ; Chieh-Jui Hsieh ; Chung-Yu Huang ; Min-Hsien Wang ; Ching-Hui Chiu ; Tsung-Chih Hsieh ; Szu-Huei Wu ; Wen-Chi Hsiao ; Kuang-Feng Chu ; Chi-Hui Tsai ; Yu-Sheng Chao ; Jinq-Chyi Lee
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：January 13, 2011
• 年：2011
• 卷：54
• 期：1
• 页码：166-178
• 全文大小：1063K
• 年卷期：v.54,no.1(January 13, 2011)
• ISSN：1520-4804

文摘

A novel series of N-linked 尾-d-xylosides were synthesized and evaluated for inhibitory activity against sodium-dependent glucose cotransporter 2 (SGLT2) in a cell-based assay. Of these, the 4-chloro-3-(4-cyclopropylbenzyl)-1-(尾-d-xylopyranosyl)-1H-indole 19m was found to be the most potent inhibitor, with an EC₅₀ value similar to that of the natural SGLT2 inhibitor phlorizin. Further studies in Sprague鈭扗awley (SD) rats indicated that 19m significantly increased urine glucose excretion in a dose-dependent manner with oral administration. The antihyperglycemic effect of 19m was also observed in streptozotocin (STZ) induced diabetic SD rats. These results described here are a good starting point for further investigations into N-glycoside SGLT2 inhibitors.