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 Diabetes

Xu, Ge; Lv, Binhua; Roberge, Jacques Y.; Xu, Baihua; Du, Jiyan; Dong, Jiajia; Chen, Yuanwei; Peng, Kun; Zhang, Lili; Tang, Xinxing; Feng, Yan; Xu, Min; Fu, Wei; Zhang, Wenbin; Zhu, Liangcheng; Deng, Zhongping; Sheng, Zelin; Welihinda, Ajith; Sun, Xun

doi:10.1021/jm401780b.s001

jm401780b_si_001.pdf (2.81 MB)

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 Diabetes

journal contribution

posted on 2014-02-27, 00:00 authored by 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

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.