3-((4-((6,7-dimethoxy-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)methyl)piperidin-1-yl)methyl)-2-hydroxy-5-methylbenzaldehyde oxime

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 3-((4-((6,7-dimethoxy-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)methyl)piperidin-1-yl)methyl)-2-hydroxy-5-methylbenzaldehyde oxime
• 化学式: C₃₂H₃₉N₃O₄
• 分子量: 529.679
• InChiKey: SCRNOXGJBMVNIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.39
• 重原子数：
  39.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  77.76
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  6,7-二甲氧基-1-苯基-1,2,3,4-四氢异喹啉 在 盐酸羟胺 、 sodium acetate 、 potassium carbonate 、 三乙胺 、 三氟乙酸 、 sodium iodide 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 11.0h， 生成 3-((4-((6,7-dimethoxy-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)methyl)piperidin-1-yl)methyl)-2-hydroxy-5-methylbenzaldehyde oxime
  参考文献：
  名称：

  Conjugates of salicylaldoximes and peripheral site ligands: Novel efficient nonquaternary reactivators for nerve agent-inhibited acetylcholinesterase

  摘要：

  A new family of nonquaternary reactivators for nerve agent-inhibited human acetylcholinesterase (hAChE) were designed, synthesized and tested in this paper. It was found that salicylaldoximes were able to quickly cleave the P-S bond of organophosphate and avoid the reinhibition phenomenon in the reactivation process, but they lacked reactivating ability due to poor affinity for AChE. Based on a dual site binding strategy, different peripheral site ligands of AChE were introduced to achieve extra affinity. The in vitro reactivation experiments demonstrated that some of the yielding conjugates exhibited similar or even superior ability to reactivate sarin-, VX- or tabun-inhibited hAChE in comparison with the mono-and bis-pyridinium aldoximes currently used. Moreover, due to greatly improved lipophilicity, these nonquaternary conjugates hold promise for the development of efficient centrally activating reactivators. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.06.041

文献信息

• Conjugates of salicylaldoximes and peripheral site ligands: Novel efficient nonquaternary reactivators for nerve agent-inhibited acetylcholinesterase
  作者：Zhao Wei、Yan-qin Liu、Sheng-zheng Wang、Lin Yao、Hui-fang Nie、Yong-an Wang、Xue-Ying Liu、Zhi-bing Zheng、Song Li

  DOI：10.1016/j.bmc.2017.06.041

  日期：2017.8

  A new family of nonquaternary reactivators for nerve agent-inhibited human acetylcholinesterase (hAChE) were designed, synthesized and tested in this paper. It was found that salicylaldoximes were able to quickly cleave the P-S bond of organophosphate and avoid the reinhibition phenomenon in the reactivation process, but they lacked reactivating ability due to poor affinity for AChE. Based on a dual site binding strategy, different peripheral site ligands of AChE were introduced to achieve extra affinity. The in vitro reactivation experiments demonstrated that some of the yielding conjugates exhibited similar or even superior ability to reactivate sarin-, VX- or tabun-inhibited hAChE in comparison with the mono-and bis-pyridinium aldoximes currently used. Moreover, due to greatly improved lipophilicity, these nonquaternary conjugates hold promise for the development of efficient centrally activating reactivators. (C) 2017 Elsevier Ltd. All rights reserved.