8-[(4-amino-1-methyl)-butyl]-amino-2,6-dimethoxy-4-methyl-5-(4-trifluoromethylphenyl)-quinoline succinate | 1260253-49-3

• 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-[(4-amino-1-methyl)-butyl]-amino-2,6-dimethoxy-4-methyl-5-(4-trifluoromethylphenyl)-quinoline succinate
• 英文别名: butanedioic acid;4-N-[2,6-dimethoxy-4-methyl-5-[4-(trifluoromethyl)phenyl]quinolin-8-yl]pentane-1,4-diamine
• CAS: 1260253-49-3
• 化学式: C₄H₆O₄*C₂₄H₂₈F₃N₃O₂
• 分子量: 565.59
• InChiKey: AAKLUKITDSVBIY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.72
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  144
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2-氯-6-甲氧基-4-甲基-喹啉 在 磺酰氯 、 四磷十氧化物 、 10% palladium on activated carbon 、 四丁基溴化铵 、 氢气 、 palladium diacetate 、 sodium carbonate 、 一水合肼 、 二异丙胺 、 三苯基膦 作用下， 以 N-甲基吡咯烷酮 、 甲醇 、 乙二醇二甲醚 、 磷酸三乙酯 、 乙醇 、 水 、 溶剂黄146 为溶剂， 20.0~80.0 ℃ 、344.75 kPa 条件下， 反应 44.75h， 生成 8-[(4-amino-1-methyl)-butyl]-amino-2,6-dimethoxy-4-methyl-5-(4-trifluoromethylphenyl)-quinoline succinate
  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