N-{3-[6,7-dimethoxyquinazolin-4-yloxy]phenyl}-N'-(4-methoxyphenyl)urea | 1256394-34-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-{3-[6,7-dimethoxyquinazolin-4-yloxy]phenyl}-N'-(4-methoxyphenyl)urea
• 英文别名: 1-(3-(6,7-Dimethoxyquinazolin-4-yloxy)phenyl)-3-(4-methoxyphenyl)urea；1-[3-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-(4-methoxyphenyl)urea
• CAS: 1256394-34-9
• 化学式: C₂₄H₂₂N₄O₅
• 分子量: 446.462
• InChiKey: MRACQFYZGWSBCK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-氯-6,7-二甲氧基喹唑啉 在 四丁基溴化铵 、 三乙胺 、 sodium hydroxide 作用下， 以 氯仿 、 水 、 丁酮 为溶剂， 生成 N-{3-[6,7-dimethoxyquinazolin-4-yloxy]phenyl}-N'-(4-methoxyphenyl)urea
  参考文献：
  名称：

  Impact of aryloxy-linked quinazolines: A novel series of selective VEGFR-2 receptor tyrosine kinase inhibitors

  摘要：

  Three series of 6,7-dimethoxyquinazoline derivatives substituted in the 4-position by aniline, N-methylaniline and aryloxy entities, targeting EGFR and VEGFR-2 tyrosine kinases, were designed and synthesized. Pharmacological activities of these compounds have been evaluated for their enzymatic inhibition of VEGFR-2 and EGFR and for their antiproliferative activities on various cancer cell lines. We have studied the impact of the variation in the 4-position substitution of the quinazoline core. Substitution by aryloxy groups led to new compounds which are selective inhibitors of VEGFR-2 enzyme with IC50 values in the nanomolar range in vitro. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.137

文献信息

• Design, Synthesis, and DNA-Binding of <i>N</i>-Alkyl(anilino)quinazoline Derivatives
  作者：Antonio Garofalo、Laurence Goossens、Brigitte Baldeyrou、Amélie Lemoine、Séverine Ravez、Perrine Six、Marie-Hélène David-Cordonnier、Jean-Paul Bonte、Patrick Depreux、Amélie Lansiaux、Jean-François Goossens

  DOI：10.1021/jm1009605

  日期：2010.11.25

  New N-alkylanilinoquinazoline derivatives 5, 12, 20, and 22 have been prepared Crow 4-chloro-6, 7-dimethoxyquinazoline 3, 4-chloro-6,7-methylenedioxyquinazoline 19, and commercially available anilines. Differents classes of compounds substituted by an aryloxygroup (6a-c. 16a,b, and 17a,b). (aminophenyl)ureas (12a,b and 13a-f), anilines (4a-m, 20a,b), N-alkyl(aniline) (5a-m, 21a,b. 22a,d). and N-aminoalkyl(aniline) (22e-g) have been synthesized. These molecules were evaluated for then. cytotoxic activities and as potential DNA intercalating agents. We studied the strength and mode of binding to DNA of these molecules by DNA melting temperature measurements, fluorescence emission. and circular dichroism. The results of various spectral and gel electrophoresis techniques obtained with the different compounds, in particular compounds 5g and 22f, revealed significant DNA interaction. These experiments confirm that the N-aminoalkyl(anilino)-6,7-dimethoxyquinazoline nucleus is an efficient pharmacophore to trigger binding to DNA, via an intercalative binding process.
• Impact of aryloxy-linked quinazolines: A novel series of selective VEGFR-2 receptor tyrosine kinase inhibitors
  作者：Antonio Garofalo、Laurence Goossens、Perrine Six、Amélie Lemoine、Séverine Ravez、Amaury Farce、Patrick Depreux

  DOI：10.1016/j.bmcl.2011.01.137

  日期：2011.4

  Three series of 6,7-dimethoxyquinazoline derivatives substituted in the 4-position by aniline, N-methylaniline and aryloxy entities, targeting EGFR and VEGFR-2 tyrosine kinases, were designed and synthesized. Pharmacological activities of these compounds have been evaluated for their enzymatic inhibition of VEGFR-2 and EGFR and for their antiproliferative activities on various cancer cell lines. We have studied the impact of the variation in the 4-position substitution of the quinazoline core. Substitution by aryloxy groups led to new compounds which are selective inhibitors of VEGFR-2 enzyme with IC50 values in the nanomolar range in vitro. (C) 2011 Elsevier Ltd. All rights reserved.