2. Academic Validation
  3. Discovery of novel N-β-D-xylosylindole derivatives as sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the management of hyperglycemia in diabetes

Discovery of novel N-β-D-xylosylindole derivatives as sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the management of hyperglycemia in diabetes

  • J Med Chem. 2011 Jan 13;54(1):166-78. doi: 10.1021/jm101072y.
Chun-Hsu Yao 1,  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
Affiliations

Affiliation

  • 1 Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan, ROC.
PMID: 21128592 DOI: 10.1021/jm101072y
Abstract

A novel series of N-linked β-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-(β-D-xylopyranosyl)-1H-indole 19m was found to be the most potent inhibitor, with an EC(50) value similar to that of the natural SGLT2 Inhibitor phlorizin. Further studies in Sprague-Dawley (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.

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