N-{3-[(7-chloroquinolin-4-yl)amino]propyl}-4-[(1E)-3-(5-methylfuran-2-yl)-3-oxoprop-1-en-1-yl]benzamide | 1547266-20-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: N-{3-[(7-chloroquinolin-4-yl)amino]propyl}-4-[(1E)-3-(5-methylfuran-2-yl)-3-oxoprop-1-en-1-yl]benzamide
• 英文别名: N-[3-[(7-chloroquinolin-4-yl)amino]propyl]-4-[(E)-3-(5-methylfuran-2-yl)-3-oxoprop-1-enyl]benzamide
• CAS: 1547266-20-5
• 化学式: C₂₇H₂₄ClN₃O₃
• 分子量: 473.959
• InChiKey: KQAGNCPPBJGDMB-IZZDOVSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  84.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-甲基-2-乙酰基呋喃 在 N,N'-羰基二咪唑 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 39.0h， 生成 N-{3-[(7-chloroquinolin-4-yl)amino]propyl}-4-[(1E)-3-(5-methylfuran-2-yl)-3-oxoprop-1-en-1-yl]benzamide
  参考文献：
  名称：

  Synthesis, in vitro antimalarial activity and cytotoxicity of novel 4-aminoquinolinyl-chalcone amides

  摘要：

  A series of 4-aminoquinolinyl-chalcone amides 11-19 were synthesized through condensation of carboxylic acid-functionalized chalcone with aminoquinolines, using 1,1'-carbonyldiimidazole as coupling agent. These compounds were screened against the chloroquine sensitive (3D7) and chloroquine resistant (W2) strains of Plasmodium falciparum. Their cytotoxicity towards the WI-38 cell line of normal human fetal lung fibroblast was determined. All compounds were found active, with IC50 values ranging between 0.04-0.5 mu M and 0.07-1.8 mu M against 3D7 and W2, respectively. They demonstrated moderate to high selective activity towards the parasitic cells in the presence of mammalian cells. However, amide 15, featuring the 1,6-diaminohexane linker, despite possessing predicted unfavourable aqueous solubility and absorption properties, was the most active of all the amides tested. It was found to be as potent as CQ against 3D7, while it displayed a two-fold higher activity than CQ against the W2 strain, with good selective antimalarial activity (SI = 435) towards the parasitic cells. During this study, amide 15 was thus identified as the best drug-candidate to for further investigation as a potential drug in search for new, safe and effective antimalarial drugs. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.12.032

文献信息

• Synthesis, in vitro antimalarial activity and cytotoxicity of novel 4-aminoquinolinyl-chalcone amides
  作者：Frans J. Smit、David D. N’Da

  DOI：10.1016/j.bmc.2013.12.032

  日期：2014.2

  A series of 4-aminoquinolinyl-chalcone amides 11-19 were synthesized through condensation of carboxylic acid-functionalized chalcone with aminoquinolines, using 1,1'-carbonyldiimidazole as coupling agent. These compounds were screened against the chloroquine sensitive (3D7) and chloroquine resistant (W2) strains of Plasmodium falciparum. Their cytotoxicity towards the WI-38 cell line of normal human fetal lung fibroblast was determined. All compounds were found active, with IC50 values ranging between 0.04-0.5 mu M and 0.07-1.8 mu M against 3D7 and W2, respectively. They demonstrated moderate to high selective activity towards the parasitic cells in the presence of mammalian cells. However, amide 15, featuring the 1,6-diaminohexane linker, despite possessing predicted unfavourable aqueous solubility and absorption properties, was the most active of all the amides tested. It was found to be as potent as CQ against 3D7, while it displayed a two-fold higher activity than CQ against the W2 strain, with good selective antimalarial activity (SI = 435) towards the parasitic cells. During this study, amide 15 was thus identified as the best drug-candidate to for further investigation as a potential drug in search for new, safe and effective antimalarial drugs. (C) 2013 Elsevier Ltd. All rights reserved.