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

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

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 acti...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of medicinal chemistry 2014-02, Vol.57 (4), p.1236-1251
Hauptverfasser: 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
Format: Artikel
Sprache:eng
Schlagworte:
Animals
Diabetes Mellitus, Type 2 - drug therapy
Glycosides - chemical synthesis
Glycosides - chemistry
Glycosides - pharmacology
Magnetic Resonance Spectroscopy
Rats
Rats, Sprague-Dawley
Sodium-Glucose Transporter 2 - antagonists & inhibitors
Spectrometry, Mass, Electrospray Ionization
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm401780b