Design, synthesis, and biological evaluation of deuterated C-aryl glycoside as a potent and long-acting renal sodium-dependent glucose cotransporter 2 inhibitor for …

…, JY Roberge, B Xu, J Du, J Dong, Y Chen…

Index: 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 Journal of Medicinal Chemistry, 2014 , vol. 57, # 4 p. 1236 - 1251

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Citation Number: 18

Abstract

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 h SGLT2. In particular, deuterated compound 41 has the potential to be a robust long-acting antidiabetic agent.