N,N-Dimethyl-N'-(8-methyl-5-nitro-quinolin-4-yl)-propane-1,3-diamine | 145363-53-7

• 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,N-Dimethyl-N'-(8-methyl-5-nitro-quinolin-4-yl)-propane-1,3-diamine
• 英文别名: N',N'-dimethyl-N-(8-methyl-5-nitroquinolin-4-yl)propane-1,3-diamine
• CAS: 145363-53-7
• 化学式: C₁₅H₂₀N₄O₂
• 分子量: 288.349
• InChiKey: UQSMDQGHUADVPF-UHFFFAOYSA-N

物化性质

• 沸点：
  473.4±45.0 °C(Predicted)
• 密度：
  1.213±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  74
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N,N-Dimethyl-N'-(8-methyl-5-nitro-quinolin-4-yl)-propane-1,3-diamine 在 Chinese hamster AA₈ cells 作用下， 以 乙醇 为溶剂， 生成 N,N-Dimethyl-N'-(8-methyl-5-nitroso-quinolin-4-yl)-propane-1,3-diamine
  参考文献：
  名称：

  Efficient redox cycling of nitroquinoline bioreductive drugs due to aerobic nitroreduction in Chinese hamster cells

  摘要：

  Nitroquinoline bioreductive drugs with 4-alkylamino substituents undergo one-electron reduction in mammalian cells, resulting in futile redox cycling due to oxidation of the nitro radical anion in aerobic cultures, and eventual reduction to the corresponding amines in the absence of oxygen. Rates of drug-induced oxygen consumption (R) due to redox cycling in cyanide-treated AA8 cell cultures were determined for 17 nitroquinolines. There was a linear dependence of log R on the one-electron reduction potential at pH 7 (E(7)(1)) with a slope of 7.1 V-1, excluding compounds with substituents ortho to the nitro group. The latter had anomalously low rates of oxygen consumption relative to E(7)(1), suggesting that interaction with the active site of nitroreductases is impeded sterically for such compounds. Absolute values of R (and the observed E:dependence) were well predicted by a simple kinetic model that used rates of net nitroreduction to the amines under anoxia as a measure of the rates of one-electron reduction in aerobic cells. This indicates that redox cycling of 4-alkylaminonitroquinolines occurs at high efficiency in aerobic cells, suggesting that there are no quantitatively significant fates of nitro radical anions in cells other than their reaction with oxygen (or their spontaneous disproportionation under hypoxia).

  DOI：

  10.1016/0006-2952(95)00112-d
• 作为产物：
  描述：

  4-氯-8-甲基喹啉 在 硫酸 、 硝酸 作用下， 反应 0.08h， 生成 N,N-Dimethyl-N'-(8-methyl-5-nitro-quinolin-4-yl)-propane-1,3-diamine
  参考文献：
  名称：

  Hypoxia-selective antitumor agents. 6. 4-(Alkylamino)nitroquinolines: a new class of hypoxia-selective cytotoxins

  摘要：

  A series of isomeric 4-[[3-(dimethylamino)propyl]amino]nitroquinolines has been synthesized and evaluated as hypoxia-selective cytotoxins and as radioeensitizers of hypoxic cells. The compounds showed widely-differing hypersensitivity factors (ratios of cytotoxicity against wild-type and repair-deficient mammalian cells). Many compounds showed oxygen-sensitive bioreduction resulting in DNA alkylation, while others show oxygen-insensitive modes of action. Of the nitro isomers studied, the 5-nitro showed the greatest hypoxic selectivity. A series of ring-substituted analogues were then prepared, in an effort to lower its reduction potential of -286 mV. Structure-activity studies showed that the effects of substitution on reduction potential were complex, being mediated by electronic and steric effects on the nitro group, as well as by effects on quinoline pK(a). Two compounds of lower reduction potential, the 3- and 8-methyl analogues, showed improved selectivity (47- and 60-fold in a clonogenic assay). These two compounds also showed the highest ''in vitro therapeutic indices'' of the series as hypoxic cell radiosensitizers. Despite these favorable in vitro properties, neither compound had activity against hypoxic cells in SCCVII tumors when administered at 60% of the MTD.

  DOI：

  10.1021/jm00104a008

文献信息

• Hypoxia-selective antitumor agents. 6. 4-(Alkylamino)nitroquinolines: a new class of hypoxia-selective cytotoxins
  作者：William A. Denny、Graham J. Atwell、Peter B. Roberts、Robert F. Anderson、Maruta Boyd、Colin J. L. Lock、William R. Wilson

  DOI：10.1021/jm00104a008

  日期：1992.12

  A series of isomeric 4-[[3-(dimethylamino)propyl]amino]nitroquinolines has been synthesized and evaluated as hypoxia-selective cytotoxins and as radioeensitizers of hypoxic cells. The compounds showed widely-differing hypersensitivity factors (ratios of cytotoxicity against wild-type and repair-deficient mammalian cells). Many compounds showed oxygen-sensitive bioreduction resulting in DNA alkylation, while others show oxygen-insensitive modes of action. Of the nitro isomers studied, the 5-nitro showed the greatest hypoxic selectivity. A series of ring-substituted analogues were then prepared, in an effort to lower its reduction potential of -286 mV. Structure-activity studies showed that the effects of substitution on reduction potential were complex, being mediated by electronic and steric effects on the nitro group, as well as by effects on quinoline pK(a). Two compounds of lower reduction potential, the 3- and 8-methyl analogues, showed improved selectivity (47- and 60-fold in a clonogenic assay). These two compounds also showed the highest ''in vitro therapeutic indices'' of the series as hypoxic cell radiosensitizers. Despite these favorable in vitro properties, neither compound had activity against hypoxic cells in SCCVII tumors when administered at 60% of the MTD.
• Efficient redox cycling of nitroquinoline bioreductive drugs due to aerobic nitroreduction in Chinese hamster cells
  作者：Bronwyn G. Siim、William R. Wilson

  DOI：10.1016/0006-2952(95)00112-d

  日期：1995.6

  Nitroquinoline bioreductive drugs with 4-alkylamino substituents undergo one-electron reduction in mammalian cells, resulting in futile redox cycling due to oxidation of the nitro radical anion in aerobic cultures, and eventual reduction to the corresponding amines in the absence of oxygen. Rates of drug-induced oxygen consumption (R) due to redox cycling in cyanide-treated AA8 cell cultures were determined for 17 nitroquinolines. There was a linear dependence of log R on the one-electron reduction potential at pH 7 (E(7)(1)) with a slope of 7.1 V-1, excluding compounds with substituents ortho to the nitro group. The latter had anomalously low rates of oxygen consumption relative to E(7)(1), suggesting that interaction with the active site of nitroreductases is impeded sterically for such compounds. Absolute values of R (and the observed E:dependence) were well predicted by a simple kinetic model that used rates of net nitroreduction to the amines under anoxia as a measure of the rates of one-electron reduction in aerobic cells. This indicates that redox cycling of 4-alkylaminonitroquinolines occurs at high efficiency in aerobic cells, suggesting that there are no quantitatively significant fates of nitro radical anions in cells other than their reaction with oxygen (or their spontaneous disproportionation under hypoxia).