N⁴,N⁴-diethyl-N¹-(3-chloro-acridin-9-yl)-1-methyl-butanediyldiamine | 146913-10-2

• 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: N⁴,N⁴-diethyl-N¹-(3-chloro-acridin-9-yl)-1-methyl-butanediyldiamine
• 英文别名: N⁴,N⁴-Diaethyl-N¹-(3-chlor-acridin-9-yl)-1-methyl-butandiyldiamin；4-N-(3-chloroacridin-9-yl)-1-N,1-N-diethylpentane-1,4-diamine
• CAS: 146913-10-2
• 化学式: C₂₂H₂₈ClN₃
• 分子量: 369.937
• InChiKey: YDSJOXQUGFFAKB-UHFFFAOYSA-N

物化性质

• 沸点：
  528.5±40.0 °C(Predicted)
• 密度：
  1.148±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  28.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3,9-二氯吖啶 、 2-氨基-5-二乙基氨基戊烷 在 苯酚 作用下， 反应 2.0h， 生成 N⁴,N⁴-diethyl-N¹-(3-chloro-acridin-9-yl)-1-methyl-butanediyldiamine
  参考文献：
  名称：

  Inhibition of Trypanosoma cruzi Trypanothione Reductase by Acridines:  Kinetic Studies and Structure−Activity Relationships

  摘要：

  Series of 9-amino and 9-thioacridines have been synthesized and studied as inhibitors of trypanothione reductase (TR) from Trypanosoma cruzi, the causative agent; of Chagas' disease. The compounds are structural analogues of the acridine drug mepacrine (quinacrine), which is a competitive inhibitor of the parasite enzyme, but not of human glutathione reductase, the closest related host enzyme. The 9-aminoacridines yielded apparent K-i values for competitive inhibition between 5 and 43 mu M. The most effective inhibitors were those with the methoxy and chlorine substituents of mepacrine and NH2 or NHCH(CH3)(CH2)(4)N(Et)(2) at C9. Detailed kinetic analyses revealed that in the case of 9-aminoacridines more than one inhibitor molecule can bind to the enzyme. In contrast, the 9-thioacridine derivatives inhibit TR with mixed-type kinetics. The kinetic data are discussed in light of the three-dimensional structure of the TR-mepacrine complex. The conclusion that structurally very similar acridine compounds can give rise to completely different inhibition patterns renders modelling studies and quantitative structure-activity relationships difficult.

  DOI：

  10.1021/jm990386s

文献信息

• Nuclear Substituted 9-(4'-Diethylamino-1'-methylbutylamino)-acridines¹
  作者：E. R. Shepard、H. A. Shonle

  DOI：10.1021/ja01185a523

  日期：1948.5
• Inhibition of <i>Trypanosoma cruzi</i> Trypanothione Reductase by Acridines:  Kinetic Studies and Structure−Activity Relationships
  作者：Susanne Bonse、Christiane Santelli-Rouvier、Jacques Barbe、R. Luise Krauth-Siegel

  DOI：10.1021/jm990386s

  日期：1999.12.1

  Series of 9-amino and 9-thioacridines have been synthesized and studied as inhibitors of trypanothione reductase (TR) from Trypanosoma cruzi, the causative agent; of Chagas' disease. The compounds are structural analogues of the acridine drug mepacrine (quinacrine), which is a competitive inhibitor of the parasite enzyme, but not of human glutathione reductase, the closest related host enzyme. The 9-aminoacridines yielded apparent K-i values for competitive inhibition between 5 and 43 mu M. The most effective inhibitors were those with the methoxy and chlorine substituents of mepacrine and NH2 or NHCH(CH3)(CH2)(4)N(Et)(2) at C9. Detailed kinetic analyses revealed that in the case of 9-aminoacridines more than one inhibitor molecule can bind to the enzyme. In contrast, the 9-thioacridine derivatives inhibit TR with mixed-type kinetics. The kinetic data are discussed in light of the three-dimensional structure of the TR-mepacrine complex. The conclusion that structurally very similar acridine compounds can give rise to completely different inhibition patterns renders modelling studies and quantitative structure-activity relationships difficult.