3-chloro-6,7,10,11-tetrahydro-9-methyl-12-{{12-[(1,2,3,4-tetrahydroacridin-9-yl)amino]dodecyl}amino}-7,11-methanocycloocta[b]quinoline

• 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: 3-chloro-6,7,10,11-tetrahydro-9-methyl-12-{{12-[(1,2,3,4-tetrahydroacridin-9-yl)amino]dodecyl}amino}-7,11-methanocycloocta[b]quinoline
• 英文别名: N'-(7-chloro-15-methyl-10-azatetracyclo[11.3.1.02,11.04,9]heptadeca-2,4(9),5,7,10,14-hexaen-3-yl)-N-(1,2,3,4-tetrahydroacridin-9-yl)dodecane-1,12-diamine
• 化学式: C₄₂H₅₃ClN₄
• 分子量: 649.363
• InChiKey: VBPYUDBSLYCEMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.2
• 重原子数：
  47
• 可旋转键数：
  15
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  49.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-chloro-6,7,10,11-tetrahydro-9-methyl-12-{{12-[(1,2,3,4-tetrahydroacridin-9-yl)amino]dodecyl}amino}-7,11-methanocycloocta[b]quinoline 在 盐酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 以362 mg的产率得到
  参考文献：
  名称：

  Synthesis, biological profiling and mechanistic studies of 4-aminoquinoline-based heterodimeric compounds with dual trypanocidal–antiplasmodial activity

  摘要：

  Dual submicromolar trypanocidal-antiplasmodial compounds have been identified by screening and chemical synthesis of 4-aminoquinoline-based heterodimeric compounds of three different structural classes. In Trypanosoma brucei, inhibition of the enzyme trypanothione reductase seems to be involved in the potent trypanocidal activity of these heterodimers, although it is probably not the main biological target. Regarding antiplasmodial activity, the heterodimers seem to share the mode of action of the antimalarial drug chloroquine, which involves inhibition of the haem detoxification process. Interestingly, all of these heterodimers display good brain permeabilities, thereby being potentially useful for late stage human African trypanosomiasis. Future optimization of these compounds should focus mainly on decreasing cytotoxicity and acetylcholinesterase inhibitory activity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.01.031
• 作为产物：
  描述：

  9-胺-1,2,3,4-四氢盐酸氯酯 在 potassium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 100.0h， 生成 3-chloro-6,7,10,11-tetrahydro-9-methyl-12-{{12-[(1,2,3,4-tetrahydroacridin-9-yl)amino]dodecyl}amino}-7,11-methanocycloocta[b]quinoline
  参考文献：
  名称：

  Synthesis, biological profiling and mechanistic studies of 4-aminoquinoline-based heterodimeric compounds with dual trypanocidal–antiplasmodial activity

  摘要：

  Dual submicromolar trypanocidal-antiplasmodial compounds have been identified by screening and chemical synthesis of 4-aminoquinoline-based heterodimeric compounds of three different structural classes. In Trypanosoma brucei, inhibition of the enzyme trypanothione reductase seems to be involved in the potent trypanocidal activity of these heterodimers, although it is probably not the main biological target. Regarding antiplasmodial activity, the heterodimers seem to share the mode of action of the antimalarial drug chloroquine, which involves inhibition of the haem detoxification process. Interestingly, all of these heterodimers display good brain permeabilities, thereby being potentially useful for late stage human African trypanosomiasis. Future optimization of these compounds should focus mainly on decreasing cytotoxicity and acetylcholinesterase inhibitory activity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.01.031

文献信息

• Synthesis, biological profiling and mechanistic studies of 4-aminoquinoline-based heterodimeric compounds with dual trypanocidal–antiplasmodial activity
  作者：Irene Sola、Sílvia Castellà、Elisabet Viayna、Carles Galdeano、Martin C. Taylor、Stephen Y. Gbedema、Belén Pérez、M. Victòria Clos、Deuan C. Jones、Alan H. Fairlamb、Colin W. Wright、John M. Kelly、Diego Muñoz-Torrero

  DOI：10.1016/j.bmc.2015.01.031

  日期：2015.8

  Dual submicromolar trypanocidal-antiplasmodial compounds have been identified by screening and chemical synthesis of 4-aminoquinoline-based heterodimeric compounds of three different structural classes. In Trypanosoma brucei, inhibition of the enzyme trypanothione reductase seems to be involved in the potent trypanocidal activity of these heterodimers, although it is probably not the main biological target. Regarding antiplasmodial activity, the heterodimers seem to share the mode of action of the antimalarial drug chloroquine, which involves inhibition of the haem detoxification process. Interestingly, all of these heterodimers display good brain permeabilities, thereby being potentially useful for late stage human African trypanosomiasis. Future optimization of these compounds should focus mainly on decreasing cytotoxicity and acetylcholinesterase inhibitory activity. (C) 2015 Elsevier Ltd. All rights reserved.