N'-(7-chloroquinolin-4-yl)-N-[(1,4-dimethoxy-3-methylnaphthalen-2-yl)methyl]ethane-1,2-diamine | 1013022-82-6

• 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: N'-(7-chloroquinolin-4-yl)-N-[(1,4-dimethoxy-3-methylnaphthalen-2-yl)methyl]ethane-1,2-diamine
• CAS: 1013022-82-6
• 化学式: C₂₅H₂₆ClN₃O₂
• 分子量: 435.953
• InChiKey: AUAQIGHRSQAUOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  55.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N'-(7-chloroquinolin-4-yl)-N-[(1,4-dimethoxy-3-methylnaphthalen-2-yl)methyl]ethane-1,2-diamine 、 丙酮 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 反应 68.5h， 以80%的产率得到N-(7-chloroquinolin-4-yl)-N'-[(1,4-dimethoxy-3-methylnaphthalen-2-yl)methyl]-N'-propan-2-ylethane-1,2-diamine
  参考文献：
  名称：

  Antimalarial Dual Drugs Based on Potent Inhibitors of Glutathione Reductase from Plasmodium falciparum

  摘要：

  Plasmodium parasites are exposed to higher fluxes of reactive oxygen species and need high activities of intracellular antioxidant systems providing a steady glutathione flux. As a future generation of dual drugs, 18 naphthoquinones and phenols (or their reduced forms) containing three different linkers between the 4-aminoquinoline core and the redox active component were synthesized. Their antimalarial effects have been characterized in parasite assays using chloroquine-sensitive and -resistant strains of Plasmodium, alone or in drug combination, and in the Plasmodium berghei rodent model. In particular, two tertiary amides 34 and 36 showed potent antimalarial activity in the low nanomolar range against CQ-resistant parasites. The ability to compete both for (Fe-III)protoporphyrin and for chloroquine transporter was determined. The data are consistent with the presence of a carrier for uptake of the short chloroquine analogue 2 but not for the potent antimalarial amide 34, suggesting a mode of action distinct from chloroquine mechanism.

  DOI：

  10.1021/jm7009292
• 作为产物：
  描述：

  4-(2-氨基乙基)氨基-7-氯喹啉 、 1,4-dimethoxy-3-methylnaphthalene-2-carbaldehyde 在 三乙酰氧基硼氢化钠 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 26.0h， 以90%的产率得到N'-(7-chloroquinolin-4-yl)-N-[(1,4-dimethoxy-3-methylnaphthalen-2-yl)methyl]ethane-1,2-diamine
  参考文献：
  名称：

  Antimalarial Dual Drugs Based on Potent Inhibitors of Glutathione Reductase from Plasmodium falciparum

  摘要：

  Plasmodium parasites are exposed to higher fluxes of reactive oxygen species and need high activities of intracellular antioxidant systems providing a steady glutathione flux. As a future generation of dual drugs, 18 naphthoquinones and phenols (or their reduced forms) containing three different linkers between the 4-aminoquinoline core and the redox active component were synthesized. Their antimalarial effects have been characterized in parasite assays using chloroquine-sensitive and -resistant strains of Plasmodium, alone or in drug combination, and in the Plasmodium berghei rodent model. In particular, two tertiary amides 34 and 36 showed potent antimalarial activity in the low nanomolar range against CQ-resistant parasites. The ability to compete both for (Fe-III)protoporphyrin and for chloroquine transporter was determined. The data are consistent with the presence of a carrier for uptake of the short chloroquine analogue 2 but not for the potent antimalarial amide 34, suggesting a mode of action distinct from chloroquine mechanism.

  DOI：

  10.1021/jm7009292

文献信息

• Antimalarial Dual Drugs Based on Potent Inhibitors of Glutathione Reductase from <i>Plasmodium falciparum</i>
  作者：Wolfgang Friebolin、Beate Jannack、Nicole Wenzel、Julien Furrer、Thomas Oeser、Cecilia P. Sanchez、Michael Lanzer、Vanessa Yardley、Katja Becker、Elisabeth Davioud-Charvet

  DOI：10.1021/jm7009292

  日期：2008.3.13

  Plasmodium parasites are exposed to higher fluxes of reactive oxygen species and need high activities of intracellular antioxidant systems providing a steady glutathione flux. As a future generation of dual drugs, 18 naphthoquinones and phenols (or their reduced forms) containing three different linkers between the 4-aminoquinoline core and the redox active component were synthesized. Their antimalarial effects have been characterized in parasite assays using chloroquine-sensitive and -resistant strains of Plasmodium, alone or in drug combination, and in the Plasmodium berghei rodent model. In particular, two tertiary amides 34 and 36 showed potent antimalarial activity in the low nanomolar range against CQ-resistant parasites. The ability to compete both for (Fe-III)protoporphyrin and for chloroquine transporter was determined. The data are consistent with the presence of a carrier for uptake of the short chloroquine analogue 2 but not for the potent antimalarial amide 34, suggesting a mode of action distinct from chloroquine mechanism.