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

Bulletin of the Korean chemical society

Jia Li¹  Cui Li¹  Li Sheng¹  Sando Fahnbulleh¹  Xiao Peng He¹  Min Hu¹  Yun Tang¹  Guo Rong Chen¹  Li Xin Gao¹  Yan Hui Tang¹ 

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

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 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.

【 授权许可】

Unknown