文献类型：期刊文献

英文题名：Monosaccharide as a Central Scaffold Toward the Construction of Salicylate-Based Bidentate PTP1B Inhibitors via Click Chemistry

作者：Tang, Yan-Hui[1,2,3];Hu, Min[1,2,3];He, Xiao-Peng[1,2,3];Fahnbulleh, Sando[1,2,3];Li, Cui[1,2,3];Gao, Li-Xin[4];Sheng, Li[4];Tang, Yun[1,2,3];Li, Jia[4];Chen, Guo-Rong[1,2,3]

机构：[1]E China Univ Sci & Technol, Key Lab Adv Mat, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Inst Fine Chem, Shanghai 200237, Peoples R China;[3]E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China;[4]Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening,State Key Lab Drug Res, Shanghai 201203, Peoples R China

年份：2011

卷号：32

期号：3

起止页码：1000

外文期刊名：BULLETIN OF THE KOREAN CHEMICAL SOCIETY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000288832700044)】；

基金：Project supported by National Natural Science Foundation of China (Grant No. 20876045, No. 30801405), National Basic Research Program of China (No. 2007CB914201), National Science & Technology Major Project of China "Key New Drug Creation and Manufacturing Program" (No. 2009ZX09302-001), Shanghai Science and Technology Community (No. 10410702700, 09DZ2291200), Chinese Academy of Sciences (No. KSCX2-YW-R-168) and the Fundamental Research Funds for the Central Universities (No. WK1013002). X.-P. He also gratefully acknowledges the French Embassy in Beijing, China for a co-tutored doctorate fellowship.

语种：英文

外文关键词：Monosaccharide; Structural preference; Click chemistry; Protein tyrosine phosphatase 1B (PTP1B) inhibitor

摘要：The discovery of carbohydrate-based bioactive compounds has recently received considerable interest in the drug development. This paper stresses on the application of 1-methoxy-O-glucoside as the central scaffold, whereas salicylic pharmacophores were introduced with diverse spatial orientations probing into the structural preference of an enzymatic target, i.e. protein tyrosine phosphatase 1B (PTP1B). By employing regioselective protection and deprotection strategy, 2,6-, 3,4-, 4,6- and 2,3-di-O-propynyl 1-methoxy-O-glucosides were previously synthesized and then coupled with azido salicylate via click chemistry in forming the desired bidentate salicylic glucosides with high yields. The inhibitory assay of the obtained triazolyl derivatives leads to the identification of the 2,3-disubstituted salicylic 1-methoxy-O-glucoside as the structurally privileged PTP1B inhibitor among this bidentate compound series with micromole-ranged IC50 value and reasonable selectivity over other homologous PTPs tested. In addition, docking simulation was conducted to propose a plausible binding mode of this authorized inhibitor with PTP1B. This research might furnish new insight toward the construction of structurally different bioactive compounds based on the monosaccharide scaffold.