9-benzylsulfanyl-6-chloro-2-methoxyacridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 9-benzylsulfanyl-6-chloro-2-methoxyacridine
• 英文别名: 9-benzylmercapto-6-chloro-2-methoxy-acridine；9-Benzylmercapto-6-chlor-2-methoxy-acridin
• 化学式: C₂₁H₁₆ClNOS
• 分子量: 365.883
• InChiKey: POALDGQGMVKUNX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  47.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N'-(6-氯-2-甲氧基吖啶-9-基)-N,N-二乙基戊烷-1,4-二胺盐酸盐 、 苄硫醇 以 aq. phosphate buffer 为溶剂， 反应 23.0h， 以98%的产率得到9-benzylsulfanyl-6-chloro-2-methoxyacridine
  参考文献：
  名称：

  Quinacrine reactivity with prion proteins and prion-derived peptides

  摘要：

  Quinacrine is a drug that is known to heal neuronal cell culture infected with prions, which are the causative agents of neurodegenerative diseases called transmissible spongiform encephalopathies. However, the drug fails when it is applied in vivo. In this work, we analyzed the reason for this failure. The drug was suggested to "covalently" modify the prion protein via an acridinyl exchange reaction. To investigate this hypothesis more closely, the acridine moiety of quinacrine was covalently attached to the thiol groups of cysteines belonging to prion-derived peptides and to the full-length prion protein. The labeled compounds were conveniently monitored by fluorescence and absorption spectroscopy in the ultraviolet and visible spectral regions. The acridine moiety demonstrated characteristic UV-vis spectrum, depending on the substituent at the C-9 position of the acridine ring. These results confirm that quinacrine almost exclusively reacts with the thiol groups present in proteins and peptides. The chemical reaction alters the prion properties and increases the concentration of the acridine moiety in the prion protein.

  DOI：

  10.1007/s00726-013-1460-x

文献信息

• Dependence of the Reactivity of Acridine on Its Substituents: A Computational and Kinetic Study
  作者：Zbigniew Zawada、Jaroslav Šebestík、Martin Šafařík、Petr Bouř

  DOI：10.1002/ejoc.201101017

  日期：2011.12

  competition experiment. The theoretical predictions correlate well with the observations. The computed reaction path confirms that the thiol group attacks the aromatic core activated by the nitrogen heteroatom and replaces halogen or amino substituents via a well-defined Meisenheimer transition state. The reaction barrier is strongly influenced by both the solvent and substituents on the aromatic system.

  吖啶的 C9 碳上的芳香亲核取代在多种生物和医学应用中起着重要作用。关键反应的速率很大程度上取决于环境和吖啶取代基。在这项研究中，对影响反应机理的因素进行了理论研究，并针对简化系统进行了实验验证。密度泛函理论用于计算。模型衍生物的活化能是根据动力学研究通过实验确定的。此外，通过竞争实验验证了所选化合物的相对反应性。理论预测与观察结果密切相关。计算出的反应路径证实硫醇基团攻击由氮杂原子激活的芳香核，并通过明确定义的迈森海默过渡态取代卤素或氨基取代基。反应屏障受溶剂和芳烃系统上的取代基的强烈影响。提出了氨基吖啶反应的多步机制，其中水性溶剂参与反应。观察到反应能和几何参数之间的强相关性，可用于使吖啶药物的设计合理化以及避免过渡态的冗长计算。提出了氨基吖啶反应的多步机制，其中水性溶剂参与反应。观察到反应能和几何参数之间的强相关性，可用于使吖啶药物的设计合理化以及避免过渡态的冗长计算。提出了氨基吖啶
• Kitani, Nippon Kagaku Zasshi, 1954, vol. 75, p. 475,476
  作者：Kitani

  DOI：——

  日期：——
• Quinacrine reactivity with prion proteins and prion-derived peptides
  作者：Zbigniew Zawada、Martin Šafařík、Eva Dvořáková、Olga Janoušková、Anna Březinová、Ivan Stibor、Karel Holada、Petr Bouř、Jan Hlaváček、Jaroslav Šebestík

  DOI：10.1007/s00726-013-1460-x

  日期：2013.5

  Quinacrine is a drug that is known to heal neuronal cell culture infected with prions, which are the causative agents of neurodegenerative diseases called transmissible spongiform encephalopathies. However, the drug fails when it is applied in vivo. In this work, we analyzed the reason for this failure. The drug was suggested to "covalently" modify the prion protein via an acridinyl exchange reaction. To investigate this hypothesis more closely, the acridine moiety of quinacrine was covalently attached to the thiol groups of cysteines belonging to prion-derived peptides and to the full-length prion protein. The labeled compounds were conveniently monitored by fluorescence and absorption spectroscopy in the ultraviolet and visible spectral regions. The acridine moiety demonstrated characteristic UV-vis spectrum, depending on the substituent at the C-9 position of the acridine ring. These results confirm that quinacrine almost exclusively reacts with the thiol groups present in proteins and peptides. The chemical reaction alters the prion properties and increases the concentration of the acridine moiety in the prion protein.