(E)-N-(1-(2-(diethylamino)ethyl)-7-(trifluoromethyl)quinolin-4(1H)-ylidene)biphenyl-4-amine

• 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: (E)-N-(1-(2-(diethylamino)ethyl)-7-(trifluoromethyl)quinolin-4(1H)-ylidene)biphenyl-4-amine
• 化学式: C₂₈H₂₈F₃N₃
• 分子量: 463.546
• InChiKey: HSQUSIKNDZFDED-HMZBKAONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  34.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  20.53
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  4-氯-6-(三氟甲基)喹啉 在 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 (E)-N-(1-(2-(diethylamino)ethyl)-7-(trifluoromethyl)quinolin-4(1H)-ylidene)biphenyl-4-amine
  参考文献：
  名称：

  Structural Optimization of Quinolon-4(1H)-imines as Dual-Stage Antimalarials: Toward Increased Potency and Metabolic Stability

  摘要：

  Discovery of novel effective and safe antimalarials has been traditionally focused on targeting erythrocytic parasite stages that cause clinical symptoms. However, elimination of malaria parasites from the human population will be facilitated by intervention at different life-cycle stages of the parasite, including the obligatory developmental phase in the liver, which precedes the erythrocytic stage. We have previously reported that N-Mannich-based quinolon-4(1H)-imines are potent antiplasmodial agents but present several stability liabilities. We now report our efforts to optimize quinolon-4(1H)-imines as dual-stage antiplasmodial agents endowed with chemical and metabolic stability. We report compounds active against both the erythrocytic and exoerythrocytic forms of malaria parasites, such as the quinolon-4(1H)-imine 5p (IC50 values of 54 and 710 nM against the erythrocytic and exoerythrocytic forms), which constitute excellent starting points for further lead optimization as dual-stage antimalarials.

  DOI：

  10.1021/jm4011466

文献信息

• Structural Optimization of Quinolon-4(1<i>H</i>)-imines as Dual-Stage Antimalarials: Toward Increased Potency and Metabolic Stability
  作者：Ana S. Ressurreição、Daniel Gonçalves、Ana R. Sitoe、Inês S. Albuquerque、Jiri Gut、Ana Góis、Lídia M. Gonçalves、Maria R. Bronze、Thomas Hanscheid、Giancarlo A. Biagini、Philip J. Rosenthal、Miguel Prudêncio、Paul O’Neill、Maria M. Mota、Francisca Lopes、Rui Moreira

  DOI：10.1021/jm4011466

  日期：2013.10.10

  Discovery of novel effective and safe antimalarials has been traditionally focused on targeting erythrocytic parasite stages that cause clinical symptoms. However, elimination of malaria parasites from the human population will be facilitated by intervention at different life-cycle stages of the parasite, including the obligatory developmental phase in the liver, which precedes the erythrocytic stage. We have previously reported that N-Mannich-based quinolon-4(1H)-imines are potent antiplasmodial agents but present several stability liabilities. We now report our efforts to optimize quinolon-4(1H)-imines as dual-stage antiplasmodial agents endowed with chemical and metabolic stability. We report compounds active against both the erythrocytic and exoerythrocytic forms of malaria parasites, such as the quinolon-4(1H)-imine 5p (IC50 values of 54 and 710 nM against the erythrocytic and exoerythrocytic forms), which constitute excellent starting points for further lead optimization as dual-stage antimalarials.