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J Med Chem. 2014 Feb 27;57(4):1236-51. doi: 10.1021/jm401780b. Epub 2014 Feb 12.

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.

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School of Pharmacy, Fudan University , 826 Zhangheng Road, Pudong New Area, Shanghai 201203, P. R. China.


SGLT2 inhibitors deuterated at sites susceptible to oxidative metabolism were found to have a slightly longer tmax and half-life (t1/2), 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.

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