N-{3-[6,7-dimethoxyquinazolin-4-yloxy]phenyl}-N'-phenylurea | 1188909-85-4

• 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'-phenylurea
• 英文别名: 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-phenylurea；1-[3-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-phenylurea
• CAS: 1188909-85-4
• 化学式: C₂₃H₂₀N₄O₄
• 分子量: 416.436
• InChiKey: XMINJNABOBQTEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  94.6
• 氢给体数：
  2
• 氢受体数：
  6

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'-phenylurea
  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

• RAF KINASE MODULATOR COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Abraham Sunny

  公开号：US20110118245A1

  公开（公告）日：2011-05-19

  Compounds according to formula (I), compositions and methods are provided for modulating the activity of RAF kinases, including BRAF kinase and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by RAF kinases. Formula (I): or a pharmaceutically acceptable salt, solvate, clathrate of hydrate thereof, wherein X is O or S(O) t ; R a is O or S.

  提供了按照公式(I)的化合物、组合物和方法，用于调节RAF激酶的活性，包括BRAF激酶，并用于治疗、预防或缓解由RAF激酶介导的一种或多种疾病或障碍的症状。公式(I)：或其药学上可接受的盐、溶剂化合物、包合物或水合物，其中X为O或S(O)t；R为O或S。
• RAF kinase modulator compounds and methods of use thereof
  申请人：Ambit Biosciences Corporation

  公开号：US08969587B2

  公开（公告）日：2015-03-03

  Compounds, compositions and methods are provided for modulating the activity of RAF kinases, including BRAF kinase and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by RAF kinases.

  本发明提供了用于调节RAF激酶活性的化合物、组合物和方法，包括BRAF激酶，并用于治疗、预防或改善由RAF激酶介导的一种或多种疾病或障碍的症状。
• 1-(3-(6,7-DIMETHOXYQUINAZOLIN-4-YLOXY)PHENYL)-3-(5-(1,1,1-TRIFLUORO-2-METHYLPROPAN-2-YL)ISOXAZOL-3-YL)UREA AS RAF KINASE MODULATOR IN THE TREATMENT OF CANCER DISEASES
  申请人：Ambit Biosciences Corporation

  公开号：EP2947072A1

  公开（公告）日：2015-11-25

  Compounds, compositions and methods are provided for modulating the activity of RAF kinases, including BRAF kinase and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by RAF kinases. The compound is 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)urea, having the structure or a pharmaceutically acceptable salt, solvate, clathrate or hydrate thereof.

  本发明提供了用于调节 RAF 激酶（包括 BRAF 激酶）活性以及治疗、预防或改善由 RAF 激酶介导的疾病或紊乱的一种或多种症状的化合物、组合物和方法。 该化合物为 1-(3-(6,7-二甲氧基喹唑啉-4-氧基)苯基)-3-(5-(1,1,1-三氟-2-甲基丙-2-基)异恶唑-3-基)脲，其结构为 或其药学上可接受的盐、溶液、凝胶或水合物。
• 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.
• [EN] QUINAZOLINE DERIVATIVES AS RAF KINASE MODULATORS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS QUINAZOLINE UTILES EN TANT QUE DE MODULATEURS DES KINASES RAF ET MÉTHODES D'UTILISATION DE CES DERNIERS
  申请人：AMBIT BIOSCIENCES CORP

  公开号：WO2009117080A8

  公开（公告）日：2010-11-04