4-氯-3,6-二甲基喹啉 | 188758-88-5

• 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: 4-氯-3,6-二甲基喹啉
• 英文名称: 4-chloro-3,6-dimethylquinoline
• 英文别名: 4-chloro-3,6-dimethyl-quinoline；4-Chlor-3,6-dimethyl-chinolin；Quinoline, 4-chloro-3,6-dimethyl-
• CAS: 188758-88-5
• 化学式: C₁₁H₁₀ClN
• 分子量: 191.66
• InChiKey: XDAPMXLMSNIMCG-UHFFFAOYSA-N

物化性质

• 沸点：
  295.4±35.0 °C(Predicted)
• 密度：
  1.188±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-氯-3,6-二甲基喹啉 在 硫酸 、 硝酸 作用下， 反应 8.33h， 生成 N'-(3,6-Dimethyl-5-nitro-quinolin-4-yl)-N,N-dimethyl-propane-1,3-diamine
  参考文献：
  名称：

  Hypoxia-Selective Antitumor Agents. 15. Modification of Rate of Nitroreduction and Extent of Lysosomal Uptake by Polysubstitution of 4-(Alkylamino)-5-nitroquinoline Bioreductive Drugs

  摘要：

  Studies have shown that 4-(alkylamino)-5-nitroquinolines possess high selectivity (20-60-fold) for hypoxic tumor cells in vitro, but are not active as hypoxia-selective cytotoxins (HSCs) in vivo. The compounds show inadequate rates of extravascular diffusion, likely due both to sequestration of the bisbasic compounds into lysosomes and rapid nitroreduction. A further series of analogues, designed to counteract these limitations, has been synthesized and evaluated. Analogues bearing one to three electron-donating substituents on the quinoline have one-electron reduction potentials up to 100 mV lower than that of the unsubstituted compound (5), but do not have improved biological activity. The relationship between hypoxic selectivity and rates of metabolic reduction suggests at least two mechanisms of cytotoxicity for this series of 5-nitroquinolines. Compounds with high rates of reduction are toxic via oxygen-sensitive net bioreduction, while compounds which are poor substrates for nitroreduction are toxic through an oxygen-insensitive non-bioreductive mechanism. As rates of metabolic reduction are lowered, the non-bioreductive mechanism of toxicity becomes dominant and hypoxic selectivity is lost. A small series of analogues bearing hydrophilic but neutral side chains were also prepared. Compounds with a dihydroxypropyl side chain retained cytotoxic potency and hypoxic cell selectivity in cell culture assays, and had lowered uptake into lysosomes, but none of three analogues evaluated against KHT tumors in mice showed activity as an HSC in vivo.

  DOI：

  10.1021/jm9607865
• 作为产物：
  描述：

  3,6-dimethyl-quinolin-4-ol 在 三氯氧磷 作用下， 生成 4-氯-3,6-二甲基喹啉
  参考文献：
  名称：

  喹啉; 合成8-取代的3-甲基-4-（1'-甲基-4'-二乙基氨基丁基氨基）-喹啉。

  摘要：

  DOI：

  10.1021/ja01205a042

文献信息

• Some Dialkylaminoalkyl Sulfides and Ethers Derived from Quinoline and Acridine Heterocycles
  作者：R. O. Clinton、C. M. Suter

  DOI：10.1021/ja01182a017

  日期：1948.2
• Hypoxia-Selective Antitumor Agents. 15. Modification of Rate of Nitroreduction and Extent of Lysosomal Uptake by Polysubstitution of 4-(Alkylamino)-5-nitroquinoline Bioreductive Drugs
  作者：Bronwyn G. Siim、Graham J. Atwell、Robert F. Anderson、Peter Wardman、Susan M. Pullen、William R. Wilson、William A. Denny

  DOI：10.1021/jm9607865

  日期：1997.4.1

  Studies have shown that 4-(alkylamino)-5-nitroquinolines possess high selectivity (20-60-fold) for hypoxic tumor cells in vitro, but are not active as hypoxia-selective cytotoxins (HSCs) in vivo. The compounds show inadequate rates of extravascular diffusion, likely due both to sequestration of the bisbasic compounds into lysosomes and rapid nitroreduction. A further series of analogues, designed to counteract these limitations, has been synthesized and evaluated. Analogues bearing one to three electron-donating substituents on the quinoline have one-electron reduction potentials up to 100 mV lower than that of the unsubstituted compound (5), but do not have improved biological activity. The relationship between hypoxic selectivity and rates of metabolic reduction suggests at least two mechanisms of cytotoxicity for this series of 5-nitroquinolines. Compounds with high rates of reduction are toxic via oxygen-sensitive net bioreduction, while compounds which are poor substrates for nitroreduction are toxic through an oxygen-insensitive non-bioreductive mechanism. As rates of metabolic reduction are lowered, the non-bioreductive mechanism of toxicity becomes dominant and hypoxic selectivity is lost. A small series of analogues bearing hydrophilic but neutral side chains were also prepared. Compounds with a dihydroxypropyl side chain retained cytotoxic potency and hypoxic cell selectivity in cell culture assays, and had lowered uptake into lysosomes, but none of three analogues evaluated against KHT tumors in mice showed activity as an HSC in vivo.
• Quinolines. II. The Synthesis of 8-Substituted 3-Methyl-4-(1'-methyl-4'-diethyl-aminobutylamino)-quinolines
  作者：Edgar A. Steck、Louis L. Hallock、Arnold J. Holland

  DOI：10.1021/ja01205a042

  日期：1946.1