國家衛生研究院 NHRI:Item 3990099045/10914

NHRI > Institute of Biotechnology and Pharmaceutical Research > Jinq-Chyi Lee > Periodical Articles > Item 3990099045/10914

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/10914

Title:	Identification of an oxime-containing C-glucosylarene as a potential inhibitor of sodium-dependent glucose co-transporter 2
Authors:	Yuan, MC;Yeh, TK;Chen, CT;Song, JS;Huang, YC;Hsieh, TC;Huang, CY;Huang, YL;Wang, MH;Wu, SH;Yao, CH;Chao, YS;Lee, JC
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	Treatment of hyperglycemia with drugs that block renal glucose reabsorption via inhibition of sodium-dependent glucose cotransporter 2 (SGLT2) is a novel approach to diabetes management. In this study, twenty-seven aryl C-glycosides bearing a C=N/C−N linkage at the glucosyl C6 position were designed, synthesized and evaluated for their inhibitory activity against human SGLT2 (hSGLT2). Compounds with good hSGLT2 inhibition were further investigated to determine their selectivity over hSGLT1. Of these, five representative aryl C-glycosides were chosen for pharmacokinetic analysis. Oxime 2a was determined to have the most promising pharmacokinetic properties and was selected for in vivo glucosuria and plasma glucose level studies, which found it to exhibit comparable efficacy to dapagliflozin (1). Furthermore, 2a was not found to exhibit either significant cytotoxicity (CC50 > 50 μM) or human ether-a-go-go related gene (hERG) inhibition (2% inhibition at 10 μM). Taken together, these efforts culminated in the discovery of oxime 2a as a potential SGLT2 inhibitor
Date:	2018-01-01
Relation:	European Journal of Medicinal Chemistry. 2018 Jan 1;143:611-620.
Link to:	http://dx.doi.org/10.1016/j.ejmech.2017.11.019
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0223-5234&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000428216700051
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85036563478
Appears in Collections:	[Jinq-Chyi Lee] Periodical Articles [Yu-Sheng Chao(2002-2013)] Periodical Articles [Chiung-Tong Chen] Periodical Articles [Teng-Kuang Yeh] Periodical Articles

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