N,1'-anthracenyl-6,8-dimethoxy-1,3-dimethylisoquinolinium trifluoroacetate | 1106678-29-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: N,1'-anthracenyl-6,8-dimethoxy-1,3-dimethylisoquinolinium trifluoroacetate
• 英文别名: 2-Anthracen-1-yl-6,8-dimethoxy-1,3-dimethylisoquinolin-2-ium;2,2,2-trifluoroacetate
• CAS: 1106678-29-8
• 化学式: C₂F₃O₂*C₂₇H₂₄NO₂
• 分子量: 507.509
• InChiKey: VMIRYPJPZZXWSD-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  5.36
• 重原子数：
  37
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  62.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  6,8-dimethoxy-1,3-dimethyl-2-benzopyrilium tetrafluoroborate 、 1-氨基蒽 、 三氟乙酸 以 溶剂黄146 、 水 、 乙腈 为溶剂， 反应 8.0h， 以95%的产率得到N,1'-anthracenyl-6,8-dimethoxy-1,3-dimethylisoquinolinium trifluoroacetate
  参考文献：
  名称：

  Structure−Activity Relationship and Studies on the Molecular Mechanism of Leishmanicidal N,C-Coupled Arylisoquinolinium Salts

  摘要：

  Alternative drugs against leishmaniasis are desperately needed. Antimonials, the main chemotherapeutic tool, cause serious side effects and promote chemoresistance. We previously demonstrated that representatives of N,C-linked arylisoquinolines are promising leishmanicidal drug candidates. We now performed structure-activity relationship studies varying the aryl portion of our lead substrate. The new series of compounds show an enhanced selectivity against Leishmania mayor in comparison to their major host cell, the macrophage. Our results suggest that the arylisoquinolinium salts decrease the macrophage infection rate acting directly on the intracellular parasites. However, the activity of the 4'-i-propyl derivative might also involve the modulation of cytokine and nitric oxide production by host macrophages. Additionally, this isoquinoline acts synergistically with amphotericin B and does not interact with drug-metabolizing cytochrome P450 enzymes involved in the metabolism of antileishmanial drugs. The results demonstrate that the newly synthesized structurally simplified N,C-coupled arylisoquinolinium halts are promising candidates to be considered as leishmanicidal pharmacophores.

  DOI：

  10.1021/jm801084u

文献信息

• Structure−Activity Relationship and Studies on the Molecular Mechanism of Leishmanicidal <i>N</i>,<i>C</i>-Coupled Arylisoquinolinium Salts
  作者：Alicia Ponte-Sucre、Tanja Gulder、Annemarie Wegehaupt、Christoph Albert、Carina Rikanović、Leonhard Schaeflein、Andreas Frank、Martina Schultheis、Matthias Unger、Ulrike Holzgrabe、Gerhard Bringmann、Heidrun Moll

  DOI：10.1021/jm801084u

  日期：2009.2.12

  Alternative drugs against leishmaniasis are desperately needed. Antimonials, the main chemotherapeutic tool, cause serious side effects and promote chemoresistance. We previously demonstrated that representatives of N,C-linked arylisoquinolines are promising leishmanicidal drug candidates. We now performed structure-activity relationship studies varying the aryl portion of our lead substrate. The new series of compounds show an enhanced selectivity against Leishmania mayor in comparison to their major host cell, the macrophage. Our results suggest that the arylisoquinolinium salts decrease the macrophage infection rate acting directly on the intracellular parasites. However, the activity of the 4'-i-propyl derivative might also involve the modulation of cytokine and nitric oxide production by host macrophages. Additionally, this isoquinoline acts synergistically with amphotericin B and does not interact with drug-metabolizing cytochrome P450 enzymes involved in the metabolism of antileishmanial drugs. The results demonstrate that the newly synthesized structurally simplified N,C-coupled arylisoquinolinium halts are promising candidates to be considered as leishmanicidal pharmacophores.