4-chloro-6,8-dimethoxyquinoline | 148018-31-9

• 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: 4-chloro-6,8-dimethoxyquinoline
• CAS: 148018-31-9
• 化学式: C₁₁H₁₀ClNO₂
• 分子量: 223.659
• InChiKey: ILKMTLUKSJFQPX-UHFFFAOYSA-N

物化性质

• 沸点：
  345.1±37.0 °C(Predicted)
• 密度：
  1.265±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  31.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-chloro-6,8-dimethoxyquinoline 在 硫酸 、 硝酸 、 苯酚 作用下， 反应 0.08h， 生成 4-((3-(Dimethylamino)propyl)amino)-5-(hydroxy(oxido)amino)-6,8-dimethoxyquinoline hydrochloride
  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：

  6,8-二甲氧基喹啉 在 三氯氧磷 作用下， 反应 3.0h， 生成 4-chloro-6,8-dimethoxyquinoline
  参考文献：
  名称：

  Synthesis of ring-substituted 4-aminoquinolines and evaluation of their antimalarial activities

  摘要：

  A simple two-step synthesis method was used to make 51 B-ring-substituted 4-hydroxyquinolines allowing analysis of the effect of ring substitutions on inhibition of growth of chloroquine sensitive and resistant strains of Plasmodium falciparum, the dominant cause of malaria morbidity. Substituted quinoline rings other than the 7-chloroquinoline ring found in chloroquine were found to have significant activity against the drug-resistant strain of P. falciparum W2. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.12.037

文献信息

• Quinoline derivatives as immunostimulants
  申请人：Pfizer Inc.

  公开号：US05506235A1

  公开（公告）日：1996-04-09

  This invention relates to compounds of the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are as defined hereinbelow that exhibit activity as immunostimulants.

  这项发明涉及公式##STR1##中R.sup.1、R.sup.2、R.sup.3、R.sup.4、R.sup.5、R.sup.6和R.sup.7的化合物，这些化合物作为免疫刺激剂表现出活性。
• QUINOLINE DERIVATIVES AS IMMUNOSTIMULANTS
  申请人：PFIZER INC.

  公开号：EP0597003A1

  公开（公告）日：1994-05-18
• US5506235A
  申请人：——

  公开号：US5506235A

  公开（公告）日：1996-04-09
• [EN] QUINOLINE DERIVATIVES AS IMMUNOSTIMULANTS
  申请人：——

  公开号：WO1993003030A1

  公开（公告）日：1993-02-18

  [EN] This invention relates to compounds of formula (I) wherein R<1>, R<2>, R<3>, R<4>, R<5>, R<6> and R<7> are as defined. These compounds exhibit activity as immunostimulants.
  [FR] Cette invention concerne des composés de formule (I), dans laquelle R1, R2, R3, R4, R5, R6 et R7 sont définis. Ces composés présentent une activité en tant qu'immunostimulants.
• Synthesis of ring-substituted 4-aminoquinolines and evaluation of their antimalarial activities
  作者：Peter B. Madrid、John Sherrill、Ally P. Liou、Jennifer L. Weisman、Joseph L. DeRisi、R. Kiplin Guy

  DOI：10.1016/j.bmcl.2004.12.037

  日期：2005.2

  A simple two-step synthesis method was used to make 51 B-ring-substituted 4-hydroxyquinolines allowing analysis of the effect of ring substitutions on inhibition of growth of chloroquine sensitive and resistant strains of Plasmodium falciparum, the dominant cause of malaria morbidity. Substituted quinoline rings other than the 7-chloroquinoline ring found in chloroquine were found to have significant activity against the drug-resistant strain of P. falciparum W2. (C) 2004 Elsevier Ltd. All rights reserved.