文献类型：期刊文献

英文题名：Preparation of triazole-linked glycosylated α-ketocarboxylic acid derivatives as new PTP1B inhibitors

作者：Song, Zhuo[2];He, Xiao-Peng[1,4];Li, Cui[4];Gao, Li-Xin[3];Wang, Zhao-Xia[2];Tang, Yun[4];Xie, Juan[1];Li, Jia[3];Chen, Guo-Rong[2]

机构：[1]CNRS, Inst Alembert, PPSM, ENS Cachan,UMR 8531, F-94235 Cachan, France;[2]E China Univ Sci & Technol, Key Lab Adv Mat & Fine Chem, Shanghai 200237, Peoples R China;[3]Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China;[4]E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China

年份：2011

卷号：346

期号：1

起止页码：140

外文期刊名：CARBOHYDRATE RESEARCH

收录：;EI(收录号：20105113502498);WOS:【SCI-EXPANDED(收录号:WOS:000286715700018)】；

基金：This work was supported by the National Natural Science Foundation of China (Grant No. 20876045), the National Science & Technology Major Project of China 'Key New Drug Creation and Manufacturing Program' (No. 2009ZX09302-001), Shanghai Science and Technology Community (No. 10410702700, 08DZ2291300), and the Chinese Academy of Sciences (No. KSCX2-YW-R-168). X.-P.H. also thanks French Embassy in Beijing, China for a doctoral fellowship.

语种：英文

外文关键词：alpha-Ketocarboxylic acid; Glycoconjugate; Click reaction; PTP1B inhibitor

摘要：The synthesis of triazole-linked glycosyl acetophenone, benzoic acid, and alpha-ketocarboxylic acid derivatives was readily achieved via Cu(I)-catalyzed azide-alkyne cycloaddition ('click' reaction) in excellent yields of 93-97%. Among the synthesized glycoconjugates, the triazolyl alpha-ketocarboxylic acids were identified as the most potent protein tyrosine phosphatase 1B (FTP1B) inhibitors with micromole-ranged IC50 values and moderate-to-good selectivity over a panel of homologous PTPs including TCPTP (4.6-fold), LAR (>30-fold), SHP-1 (>30-fold) and SHP-2 (>30-fold). Moreover, a docking simulation was conducted to propose a plausible binding mode of the glucosyl alpha-ketocarboxylic acid triazole with the enzymatic target. (C) 2010 Elsevier Ltd. All rights reserved.