4-<(3-bromophenyl)amino>-6,7-dimethoxy-2-methylquinazoline hydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-<(3-bromophenyl)amino>-6,7-dimethoxy-2-methylquinazoline hydrochloride
• 英文别名: 4-N-(3'-bromo-phenylamino)-6,7-dimethoxy-2-methylquinazoline hydrochloride；N-(3-bromophenyl)-6,7-dimethoxy-2-methylquinazolin-4-amine;hydrochloride
• 化学式: C₁₇H₁₆BrN₃O₂*ClH
• 分子量: 410.698
• InChiKey: YGXLGRXXJNEHEJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.88
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  56.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氨基-4,5-二甲氧基苯甲酸 在 氯化亚砜 作用下， 以 异丙醇 为溶剂， 反应 12.5h， 生成 4-<(3-bromophenyl)amino>-6,7-dimethoxy-2-methylquinazoline hydrochloride
  参考文献：
  名称：

  一些4-苯胺基喹唑啉衍生物的合成

  摘要：

  一些4-N-(3'-或4'-取代-苯基)氨基-6,7-二甲氧基喹唑啉和相应的未取代化合物由2-氨基-4,5-二甲氧基苯甲酸和适当的取代苯胺合成。还获得了其他相关的喹唑啉或其合成中间体。大量描述的喹唑啉是新化合物，而其余的则通过更有效的方法制备。合成这些化合物的主要目标是 4-苯胺基喹唑啉药效团是一个重要的单元，它存在于几种蛋白激酶的 ATP 竞争性抑制剂中。

  DOI：

  10.1055/s-2004-815949

文献信息

• Tyrosine Kinase Inhibitors. 8. An Unusually Steep Structure−Activity Relationship for Analogues of 4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a Potent Inhibitor of the Epidermal Growth Factor Receptor
  作者：Alexander J. Bridges、Hairong Zhou、Donna R. Cody、Gordon W. Rewcastle、Amy McMichael、H. D. Hollis Showalter、David W. Fry、Alan J. Kraker、William A. Denny

  DOI：10.1021/jm9503613

  日期：1996.1.1

  4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (32, PD 153035) is a very potent inhibitor (IC50 0.025 nM) of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), binding competitively at the ATP site. Structure-activity relationships for close analogues of 32 are very steep. Some derivatives have IC(50)s UP to 80-fold better than predicted from simple additive binding energy arguments, yet analogues possessing combinations of similar phenyl and quinazoline substituents do not show this ''supra-additive'' effect. Because some substituents which are mildly deactivating by themselves can be strongly activating when used in the correct combinations, it is proposed that certain substituted analogues possess the ability to induce a change in the conformation of the receptor when they bind. There is some bulk tolerance for substitution in the 6- and 7-positions of the quinazoline, so that 32 is not the optimal inhibitor for the induced conformation. The diethoxy derivative 56 [4-(3-bromoanilino)-6,7-diethoxyquinazoline] shows an IC50 Of 0.006 nM, making it the most potent inhibitor of the tyrosine kinase activity of the EGFR yet reported.
• Syntheses of Some 4-Anilinoquinazoline Derivatives
  作者：Roberto Rittner、Silvana A. Rocco、José Eduardo Barbarini

  DOI：10.1055/s-2004-815949

  日期：——

  Some 4-N-(3'- or 4'-substituted-phenyl)amino-6,7-dimethoxyquinazolines and the corresponding unsubstituted compounds were synthesized from 2-amino-4,5-dimethoxybenzoic acid and the appropriate substituted anilines. Other related quinazolines or their synthetic intermediates were also obtained. A large number of the described quinazolines are new compounds, while the remaining were prepared by a more

  一些4-N-(3'-或4'-取代-苯基)氨基-6,7-二甲氧基喹唑啉和相应的未取代化合物由2-氨基-4,5-二甲氧基苯甲酸和适当的取代苯胺合成。还获得了其他相关的喹唑啉或其合成中间体。大量描述的喹唑啉是新化合物，而其余的则通过更有效的方法制备。合成这些化合物的主要目标是 4-苯胺基喹唑啉药效团是一个重要的单元，它存在于几种蛋白激酶的 ATP 竞争性抑制剂中。