2-(benzylaminocarbonyloxy)-5-O-(o-nitro-benzoyl)-1,4:3,6-dianhydro-D-glucitol | 1207563-71-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(benzylaminocarbonyloxy)-5-O-(o-nitro-benzoyl)-1,4:3,6-dianhydro-D-glucitol
• 英文别名: 2-(benzylaminocarbonyl)-5-O-(o-nitro-benzoyl)-1,4:3,6-dianhydro-D-glucitol；[(3R,3aR,6S,6aR)-6-(benzylcarbamoyloxy)-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-yl] 2-nitrobenzoate
• CAS: 1207563-71-0
• 化学式: C₂₁H₂₀N₂O₈
• 分子量: 428.398
• InChiKey: IXCZMWQATLZRCH-FCGDIQPGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(benzylaminocarbonyloxy)-5-O-(o-nitro-benzoyl)-1,4:3,6-dianhydro-D-glucitol 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 24.0h， 以45%的产率得到2-(benzylaminocarbonyloxy)-5-O-(o-amino-benzoyl)-1,4:3,6-dianhydro-D-glucitol
  参考文献：
  名称：

  Isosorbide-2-benzyl Carbamate-5-salicylate, A Peripheral Anionic Site Binding Subnanomolar Selective Butyrylcholinesterase Inhibitor

  摘要：

  Isosorbide-2-benzyl carbamate-5-benzoate is a highly potent and selective BuChE inhibitor. Meanwhile, isosorbide-2-aspirinate-5-salicylate is a highly effective aspirin prodrug that relies on the salicylate portion to interact productively with human BuChE. By integrating the salicylate group into the carbamate design, we have produced isosorbide-2-benzyl carbamate-5-salicylate, an inhibitor of high potency (150 pM) and selectivity for human BuChE over AChE (666000) and CES2 (23000). Modeling and mutant studies indicate that it achieves its exceptional potency because of an interaction with the polar D70/Y332 cluster in the PAS of BuChE in addition to pseudosubstrate interactions with the active site.

  DOI：

  10.1021/jm9014845
• 作为产物：
  描述：

  isosorbide-2-benzylcarbamate 、 2-硝基苯甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以85.6%的产率得到2-(benzylaminocarbonyloxy)-5-O-(o-nitro-benzoyl)-1,4:3,6-dianhydro-D-glucitol
  参考文献：
  名称：

  Isosorbide-2-benzyl Carbamate-5-salicylate, A Peripheral Anionic Site Binding Subnanomolar Selective Butyrylcholinesterase Inhibitor

  摘要：

  Isosorbide-2-benzyl carbamate-5-benzoate is a highly potent and selective BuChE inhibitor. Meanwhile, isosorbide-2-aspirinate-5-salicylate is a highly effective aspirin prodrug that relies on the salicylate portion to interact productively with human BuChE. By integrating the salicylate group into the carbamate design, we have produced isosorbide-2-benzyl carbamate-5-salicylate, an inhibitor of high potency (150 pM) and selectivity for human BuChE over AChE (666000) and CES2 (23000). Modeling and mutant studies indicate that it achieves its exceptional potency because of an interaction with the polar D70/Y332 cluster in the PAS of BuChE in addition to pseudosubstrate interactions with the active site.

  DOI：

  10.1021/jm9014845

文献信息

• Isosorbide-2-benzyl Carbamate-5-salicylate, A Peripheral Anionic Site Binding Subnanomolar Selective Butyrylcholinesterase Inhibitor
  作者：Ciaran G. Carolan、Gerald P. Dillon、Denise Khan、Sheila A. Ryder、Joanne M. Gaynor、Sean Reidy、Juan F. Marquez、Mike Jones、Valerie Holland、John F. Gilmer

  DOI：10.1021/jm9014845

  日期：2010.2.11

  Isosorbide-2-benzyl carbamate-5-benzoate is a highly potent and selective BuChE inhibitor. Meanwhile, isosorbide-2-aspirinate-5-salicylate is a highly effective aspirin prodrug that relies on the salicylate portion to interact productively with human BuChE. By integrating the salicylate group into the carbamate design, we have produced isosorbide-2-benzyl carbamate-5-salicylate, an inhibitor of high potency (150 pM) and selectivity for human BuChE over AChE (666000) and CES2 (23000). Modeling and mutant studies indicate that it achieves its exceptional potency because of an interaction with the polar D70/Y332 cluster in the PAS of BuChE in addition to pseudosubstrate interactions with the active site.