1-(2'-acetamido-3',4',6'-tri-O-acetyl-2'-deoxy-β-D-glucopyranosyl)-4-((E)-3-(4-methoxybenzyloxyamino)-3-oxoprop-1-enyl)-1,2,3-triazole | 1312592-18-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(2'-acetamido-3',4',6'-tri-O-acetyl-2'-deoxy-β-D-glucopyranosyl)-4-((E)-3-(4-methoxybenzyloxyamino)-3-oxoprop-1-enyl)-1,2,3-triazole
• CAS: 1312592-18-9
• 化学式: C₂₇H₃₃N₅O₁₁
• 分子量: 603.586
• InChiKey: KWZWAOBXCDZXCP-XDRAHRNXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.38
• 重原子数：
  43.0
• 可旋转键数：
  12.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  195.5
• 氢给体数：
  2.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  1-(2'-acetamido-3',4',6'-tri-O-acetyl-2'-deoxy-β-D-glucopyranosyl)-4-((E)-3-(4-methoxybenzyloxyamino)-3-oxoprop-1-enyl)-1,2,3-triazole 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以94%的产率得到1-(2'-acetamido-2'-deoxy-β-D-glucopyranosyl)-4-((E)-3-(4-methoxybenzyloxyamino)-3-oxoprop-1-enyl)-1,2,3-triazole
  参考文献：
  名称：

  Design and synthesis of O-GlcNAcase inhibitors via ‘click chemistry’ and biological evaluations

  摘要：

  Protein O-GlcNAcylation has been shown to play an important role in a number of biological processes, including regulation of the cell cycle, DNA transcription and translation, signal transduction, and protein degradation. O-GlcNAcase (OGA) is responsible for the removal of O-linked beta-N-acetylglucosamine (O-GlcNAc) from serine or threonine residues, and thus plays a key role in O-GlcNAc metabolism. Potent OGA inhibitors are useful tools for studying the cellular processes of O-GlcNAc, and may be developed as drugs for the treatment neurodegenerative diseases. In this study, Cu(I)-catalyzed 'Click' cycloaddition reactions between glycosyl azides and alkynes were exploited to generate inhibitory candidates of OGA. Enzymatic kinetic screening revealed that compound 7 was a potent competitive inhibitor of human O-GlcNAcase (K(i) = 185.6 mu M). Molecular docking simulations of compound 7 into CpOGA (Clostridium perfringens OGA) suggested that strong pi-pi stacking interaction between the compound and W490 considerably contributed to improving the inhibitory activity. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2011.03.026
• 作为产物：
  描述：

  2-乙酰氨基-3,4,6-三-O-乙酰-2-脱氧-α-D-吡喃葡萄糖酰基氯 在 sodium azide 、 四丁基硫酸氢铵 、 碳酸氢钠 、 copper(II) sulfate 、 sodium ascorbate 作用下， 以 二氯甲烷 、 水 、 叔丁醇 为溶剂， 反应 1.0h， 生成 1-(2'-acetamido-3',4',6'-tri-O-acetyl-2'-deoxy-β-D-glucopyranosyl)-4-((E)-3-(4-methoxybenzyloxyamino)-3-oxoprop-1-enyl)-1,2,3-triazole
  参考文献：
  名称：

  Design and synthesis of O-GlcNAcase inhibitors via ‘click chemistry’ and biological evaluations

  摘要：

  Protein O-GlcNAcylation has been shown to play an important role in a number of biological processes, including regulation of the cell cycle, DNA transcription and translation, signal transduction, and protein degradation. O-GlcNAcase (OGA) is responsible for the removal of O-linked beta-N-acetylglucosamine (O-GlcNAc) from serine or threonine residues, and thus plays a key role in O-GlcNAc metabolism. Potent OGA inhibitors are useful tools for studying the cellular processes of O-GlcNAc, and may be developed as drugs for the treatment neurodegenerative diseases. In this study, Cu(I)-catalyzed 'Click' cycloaddition reactions between glycosyl azides and alkynes were exploited to generate inhibitory candidates of OGA. Enzymatic kinetic screening revealed that compound 7 was a potent competitive inhibitor of human O-GlcNAcase (K(i) = 185.6 mu M). Molecular docking simulations of compound 7 into CpOGA (Clostridium perfringens OGA) suggested that strong pi-pi stacking interaction between the compound and W490 considerably contributed to improving the inhibitory activity. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2011.03.026