甲基9-(3-二甲基氨基丙基氨基)-1-硝基吖啶-4-羧酸酯 | 116374-64-2

• 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
• 中文名称: 甲基9-(3-二甲基氨基丙基氨基)-1-硝基吖啶-4-羧酸酯
• 英文名称: 4-(methoxycarbonyl)-9-<<3-(dimethylamino)propyl>amino>-1-nitroacridine
• 英文别名: 9-((3-(Dimethylamino)propyl)amino)-1-nitro-4-acridinecarboxylic acid methyl ester；methyl 9-[3-(dimethylamino)propylamino]-1-nitroacridine-4-carboxylate
• CAS: 116374-64-2
• 化学式: C₂₀H₂₂N₄O₄
• 分子量: 382.419
• InChiKey: LJNIDEWFUGGGMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  甲基9-(3-二甲基氨基丙基氨基)-1-硝基吖啶-4-羧酸酯 在 水 作用下， 生成 1-Nitro-9-oxo-9,10-dihydro-acridine-4-carboxylic acid methyl ester
  参考文献：
  名称：

  O'Connor, Charmian J.; McLennan, Duncan J.; Denny, William A., Journal of the Chemical Society. Perkin transactions II, 1990, # 9, p. 1637 - 1641

  摘要：

  DOI：
• 作为产物：
  描述：

  2-[2-(3-Dimethylamino-propylcarbamoyl)-phenylamino]-4-nitro-benzoic acid methyl ester 在 polyphosphate ester 作用下， 反应 100.0h， 生成 甲基9-(3-二甲基氨基丙基氨基)-1-硝基吖啶-4-羧酸酯
  参考文献：
  名称：

  Hypoxia-selective antitumor agents. 1. Relationships between structure, redox properties and hypoxia-selective cytotoxicity for 4-substituted derivatives of nitracrine

  摘要：

  The nitroacridine derivative 9-[[3-(dimethylamino)propyl]amino]-1-nitroacridine (nitracrine) is selectively cytotoxic to hypoxic tumor cells in culture. However, the compound undergoes reductive metabolism too rapidly, with the reduction not being sufficiently inhibited by molecular oxygen in aerobic tissues, for it to demonstrate the same activity in vivo. In a search for derivatives with lower reduction potentials, we have synthesized and evaluated a series of derivatives bearing 4-substituents with a wide range of electronic properties. The one-electron reduction potentials (E(1] of these compounds, when compared under conditions of equivalent ionization, were highly correlated with sigma p values. However, at pH 7 the influence of substituent electronic properties was modified by prototrophic equilibria, with the basic nature of the acridine limiting the extent to which ring substituent electronic effects can be used to modulate reduction potential of the 1-nitro group. Nevertheless, comparison of the kinetics of the killing of AA8 cells under hypoxia suggests that some metabolic stabilization of the compounds can be achieved by the use of electron-donating substituents, with such compounds retaining the hypoxia-selective toxicity of nitracrine in cell culture. However, the 4-substituted nitracrines show no clear relationship between E(1) and cytotoxic potency, in distinct contrast to simpler nitroheterocycles such as nitroimidazoles.

  DOI：

  10.1021/jm00121a006

文献信息

• OCONNOR, CHARMIAN J.;MCLENNAN, DUNCAN J.;DENNY, WILLIAM A.;SUTTON, BRIDGE+, J. CHEM. SOC. PT 2. PERKIN TRANS. ,(1990) N, C. 1634-1641
  作者：OCONNOR, CHARMIAN J.、MCLENNAN, DUNCAN J.、DENNY, WILLIAM A.、SUTTON, BRIDGE+

  DOI：——

  日期：——
• Hypoxia-selective antitumor agents. 1. Relationships between structure, redox properties and hypoxia-selective cytotoxicity for 4-substituted derivatives of nitracrine
  作者：William R. Wilson、Robert F. Anderson、William A. Denny

  DOI：10.1021/jm00121a006

  日期：1989.1

  The nitroacridine derivative 9-[[3-(dimethylamino)propyl]amino]-1-nitroacridine (nitracrine) is selectively cytotoxic to hypoxic tumor cells in culture. However, the compound undergoes reductive metabolism too rapidly, with the reduction not being sufficiently inhibited by molecular oxygen in aerobic tissues, for it to demonstrate the same activity in vivo. In a search for derivatives with lower reduction potentials, we have synthesized and evaluated a series of derivatives bearing 4-substituents with a wide range of electronic properties. The one-electron reduction potentials (E(1] of these compounds, when compared under conditions of equivalent ionization, were highly correlated with sigma p values. However, at pH 7 the influence of substituent electronic properties was modified by prototrophic equilibria, with the basic nature of the acridine limiting the extent to which ring substituent electronic effects can be used to modulate reduction potential of the 1-nitro group. Nevertheless, comparison of the kinetics of the killing of AA8 cells under hypoxia suggests that some metabolic stabilization of the compounds can be achieved by the use of electron-donating substituents, with such compounds retaining the hypoxia-selective toxicity of nitracrine in cell culture. However, the 4-substituted nitracrines show no clear relationship between E(1) and cytotoxic potency, in distinct contrast to simpler nitroheterocycles such as nitroimidazoles.
• O'Connor, Charmian J.; McLennan, Duncan J.; Denny, William A., Journal of the Chemical Society. Perkin transactions II, 1990, # 9, p. 1637 - 1641
  作者：O'Connor, Charmian J.、McLennan, Duncan J.、Denny, William A.、Sutton, Bridget M.

  DOI：——

  日期：——