4-([5,7-dimethoxy-3-(4-methoxyphenyl)-2-quinolinyl]oxy)butanenitrile

• 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-([5,7-dimethoxy-3-(4-methoxyphenyl)-2-quinolinyl]oxy)butanenitrile
• 英文别名: 4-[5,7-Dimethoxy-3-(4-methoxyphenyl)quinolin-2-yl]oxybutanenitrile
• 化学式: C₂₂H₂₂N₂O₄
• 分子量: 378.428
• InChiKey: PGUZPWGQRZPSJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  73.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3,5-二甲氧基苯胺 在 polyphosphoric acid trimethylsilyl ester 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.25h， 生成 4-([5,7-dimethoxy-3-(4-methoxyphenyl)-2-quinolinyl]oxy)butanenitrile
  参考文献：
  名称：

  3-Aryl-2-Quinolone Derivatives:  Synthesis and Characterization of In Vitro and In Vivo Antitumor Effects with Emphasis on a New Therapeutical Target Connected with Cell Migration

  摘要：

  Among 25 3-aryl-2-quinolone derivatives synthesized, the antitumor activity of some of them was characterized both in vitro and in vivo. In this series, no compound appeared to be cytotoxic in vitro, as was known by the colorimetric MTT assay carried out on 12 distinct human cancer cell lines obtained from the American Type Culture Collection. Indeed, the concentration values decreasing the growth of the 12 cell lines by at least 50% (IC50 index) were always higher than 10(-5) M. We then made use of a computer-assisted phase-contrast videomicroscopy system to quantitatively determine in vitro the level of migration of living MCF-7 human breast cancer cells. For example, at 10(-7) M, compounds 7, 13, 16, and 28 markedly decreased the migration level of these MCF-7 human breast cancer cells. The in vivo determination of the maximum tolerated dose showed that all compounds tested were definitively nontoxic. When the nontoxic, antimigratory compound 16 was combined with either doxorubicin or etoposide, two cytotoxic compounds routinely used in the clinic, this led to additive in vivo benefits from this treatment (as compared to individual administrations of the drugs) when the MXT mouse mammary adenocarcinoma was used. Thus, nontoxic antimigratory compounds, including the 2-quinolone derivatives synthesized here, can actually improve the efficiency of antitumor treatment when combined with conventional cytotoxic agents.

  DOI：

  10.1021/jm010978m

文献信息

• 3-Aryl-2-Quinolone Derivatives:  Synthesis and Characterization of In Vitro and In Vivo Antitumor Effects with Emphasis on a New Therapeutical Target Connected with Cell Migration
  作者：Benoît Joseph、Francis Darro、Aurélie Béhard、Brigitte Lesur、Françoise Collignon、Christine Decaestecker、Armand Frydman、Gérald Guillaumet、Robert Kiss

  DOI：10.1021/jm010978m

  日期：2002.6.1

  Among 25 3-aryl-2-quinolone derivatives synthesized, the antitumor activity of some of them was characterized both in vitro and in vivo. In this series, no compound appeared to be cytotoxic in vitro, as was known by the colorimetric MTT assay carried out on 12 distinct human cancer cell lines obtained from the American Type Culture Collection. Indeed, the concentration values decreasing the growth of the 12 cell lines by at least 50% (IC50 index) were always higher than 10(-5) M. We then made use of a computer-assisted phase-contrast videomicroscopy system to quantitatively determine in vitro the level of migration of living MCF-7 human breast cancer cells. For example, at 10(-7) M, compounds 7, 13, 16, and 28 markedly decreased the migration level of these MCF-7 human breast cancer cells. The in vivo determination of the maximum tolerated dose showed that all compounds tested were definitively nontoxic. When the nontoxic, antimigratory compound 16 was combined with either doxorubicin or etoposide, two cytotoxic compounds routinely used in the clinic, this led to additive in vivo benefits from this treatment (as compared to individual administrations of the drugs) when the MXT mouse mammary adenocarcinoma was used. Thus, nontoxic antimigratory compounds, including the 2-quinolone derivatives synthesized here, can actually improve the efficiency of antitumor treatment when combined with conventional cytotoxic agents.