8-[(1-methyl-4-phthalimido)-butyl]-amino-6-methoxy-4-methyl-2-trifluoromethyl-5-(3-trifluoromethylphenyl)-quinoline | 1260253-92-6

• 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: 8-[(1-methyl-4-phthalimido)-butyl]-amino-6-methoxy-4-methyl-2-trifluoromethyl-5-(3-trifluoromethylphenyl)-quinoline
• 英文别名: 2-[4-[[6-Methoxy-4-methyl-2-(trifluoromethyl)-5-[3-(trifluoromethyl)phenyl]quinolin-8-yl]amino]pentyl]isoindole-1,3-dione
• CAS: 1260253-92-6
• 化学式: C₃₂H₂₇F₆N₃O₃
• 分子量: 615.575
• InChiKey: QFCAGCJKBZFBKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  44
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  71.5
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  8-[(1-methyl-4-phthalimido)-butyl]-amino-6-methoxy-4-methyl-2-trifluoromethyl-5-(3-trifluoromethylphenyl)-quinoline 在 一水合肼 作用下， 以 乙醇 为溶剂， 以76%的产率得到8-[(4-amino-1-methyl)-butyl]-amino-6-methoxy-4-methyl-2-trifluoromethyl-5-(3-trifluoromethylphenyl)-quinoline
  参考文献：
  名称：

  Antimalarial Activity of Novel 5-Aryl-8-Aminoquinoline Derivatives

  摘要：

  In an attempt to separate the antimalarial activity of tafenoquine (3) from its hemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficiency patients, a series of 5-aryl-8-aminoquinoline derivative, was prepared and assessed for antimalarial activities The new compounds were found metabolically stable in human and mouse microsomal preparations, with t(1/2) > 60 mm, and were equal to or more potent than primaquine (2) and 3 against Plasmodium falciparum cell growth The new agents were more active against the chloroquine (CQ) resistant clone than to the CQ-sensitive clone Analogues with electron donating groups showed better activity than those with electron withdrawing substituents Compounds 4bc, 4bd, and 4be showed comparable therapeutic index (TI) to that of 2 and 3, with TI ranging from 5 to 8 based on IC50 data The new compounds showed no significant causal prophylactic activity in mice infected with Plasmodium berghei sporozoites, but are substantially less toxic than 2 and 3 in mouse tests

  DOI：

  10.1021/jm100911f
• 作为产物：
  描述：

  1,1,1-trifluoromethyl-2,4-pentanedione 在 磺酰氯 、 吡啶硼烷 、 四磷十氧化物 、 10% palladium on activated carbon 、 四丁基溴化铵 、 氢气 、 palladium diacetate 、 sodium carbonate 、 溶剂黄146 、 三苯基膦 作用下， 以 乙二醇二甲醚 、 磷酸三乙酯 、 水 、 溶剂黄146 、 乙酸乙酯 为溶剂， 反应 60.0h， 生成 8-[(1-methyl-4-phthalimido)-butyl]-amino-6-methoxy-4-methyl-2-trifluoromethyl-5-(3-trifluoromethylphenyl)-quinoline
  参考文献：
  名称：

  Antimalarial Activity of Novel 5-Aryl-8-Aminoquinoline Derivatives

  摘要：

  In an attempt to separate the antimalarial activity of tafenoquine (3) from its hemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficiency patients, a series of 5-aryl-8-aminoquinoline derivative, was prepared and assessed for antimalarial activities The new compounds were found metabolically stable in human and mouse microsomal preparations, with t(1/2) > 60 mm, and were equal to or more potent than primaquine (2) and 3 against Plasmodium falciparum cell growth The new agents were more active against the chloroquine (CQ) resistant clone than to the CQ-sensitive clone Analogues with electron donating groups showed better activity than those with electron withdrawing substituents Compounds 4bc, 4bd, and 4be showed comparable therapeutic index (TI) to that of 2 and 3, with TI ranging from 5 to 8 based on IC50 data The new compounds showed no significant causal prophylactic activity in mice infected with Plasmodium berghei sporozoites, but are substantially less toxic than 2 and 3 in mouse tests

  DOI：

  10.1021/jm100911f

文献信息

• Antimalarial Activity of Novel 5-Aryl-8-Aminoquinoline Derivatives
  作者：Hiroaki Shiraki、Michael P. Kozar、Victor Melendez、Thomas H. Hudson、Colin Ohrt、Alan J. Magill、Ai J. Lin

  DOI：10.1021/jm100911f

  日期：2011.1.13

  In an attempt to separate the antimalarial activity of tafenoquine (3) from its hemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficiency patients, a series of 5-aryl-8-aminoquinoline derivative, was prepared and assessed for antimalarial activities The new compounds were found metabolically stable in human and mouse microsomal preparations, with t(1/2) > 60 mm, and were equal to or more potent than primaquine (2) and 3 against Plasmodium falciparum cell growth The new agents were more active against the chloroquine (CQ) resistant clone than to the CQ-sensitive clone Analogues with electron donating groups showed better activity than those with electron withdrawing substituents Compounds 4bc, 4bd, and 4be showed comparable therapeutic index (TI) to that of 2 and 3, with TI ranging from 5 to 8 based on IC50 data The new compounds showed no significant causal prophylactic activity in mice infected with Plasmodium berghei sporozoites, but are substantially less toxic than 2 and 3 in mouse tests