3-(6,7-dimethoxyquinazolin-4-ylamino)benzonitrile hydrochloride | 1348975-84-7

• 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: 3-(6,7-dimethoxyquinazolin-4-ylamino)benzonitrile hydrochloride
• CAS: 1348975-84-7
• 化学式: C₁₇H₁₄N₄O₂*ClH
• 分子量: 342.785
• InChiKey: QANFZRKODUUXQH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.68
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  80.06
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  4-chloro-6,7-dimethoxylquinazoline hydrochloride 、 间氨基苯甲腈 以 异丙醇 为溶剂， 反应 4.0h， 以61%的产率得到3-(6,7-dimethoxyquinazolin-4-ylamino)benzonitrile hydrochloride
  参考文献：
  名称：

  Synthesis, characterization, screening and docking analysis of 4-anilinoquinazoline derivatives as tyrosine kinase inhibitors

  摘要：

  We report here the design and synthesis of a series of 4-anilinoquinazoline derivatives, of which 7 compounds were crystallographically characterized, as epidermal growth factor receptor (EGFR) inhibitors by modifications on the aniline ring or at the 6-alkoxy site of the 6,7-dimethoxy-4-anilinoquinazoline pharmacophore. The relative inhibition efficiency on EGFR of all as-prepared compounds were measured and ordered, and the IC50 values of nine highly active compounds were determined by ELISA. Docking studies indicated that all 4-anilinoquinazoline derivatives could be inserted into the ATP-binding pocket of the EGFR via indirect docking, and that the modifications at the 3'-position of the anilino group and 6-alkoxy site of the quinazoline ring have little interference with the formation of the two essential H-bonds between the N3 of the quinazoline ring and Thr766 through a water molecule, and the N1 of the quinazoline ring and N-H of Met769. The displacing of the phenyl at 4-position with pyridinyl dramatically reduces the activity of the quinazoline pharmacophore, the resulting derivative (10) being the least active compound. The docking results also showed that the formation of new H-bonds between the N-H of the ethylenediamine group linked to the 6-alkoxy site and Asp776/Cys773 in the binding pocket of EGFR makes compounds 19 (IC50= 12.1 +/- 1.6 nM) and 20 (IC50 = 13.6 +/- 0.8 nM) the most potent EGFR inhibitors in this class and worthy of further modification to obtain more potent anticancer compounds. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.07.036