N-(1H-benzo[d]imidazol-5-yl)-6,7-dimethoxyquinazolin-4-amine hydrochloride | 1428015-56-8

• 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: N-(1H-benzo[d]imidazol-5-yl)-6,7-dimethoxyquinazolin-4-amine hydrochloride
• CAS: 1428015-56-8
• 化学式: C₁₇H₁₅N₅O₂*ClH
• 分子量: 357.799
• InChiKey: RFNQDCUDBLIUMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.69
• 重原子数：
  25.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  84.95
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  [(DMSO)₂H][trans-Ru(DMSO)₂Cl₄] 、 N-(1H-benzo[d]imidazol-5-yl)-6,7-dimethoxyquinazolin-4-amine hydrochloride 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 24.08h， 以43%的产率得到Ru^IIICl4(DMSO)(H-(4-(3'-chloro-4'-fluoroanilino)-6-(2-(1H-imidazol-1-yl)ethoxy)-7-methoxyquinazoline))
  参考文献：
  名称：

  与4-苯胺基喹唑啉衍生物连接的新型钌配合物：合成，表征和生物活性的初步评价。

  摘要：

  钌DMSO配合物顺式-Ru II C1 2（DMSO）4和[（DMSO）2 H] [反式-Ru III Cl 4（DMSO）2 ]与4-（3'-chloro-4'-fluoroanilino）-反应6-（2-（2-氨基乙基）氨基乙氧基）-7-甲氧基喹唑啉（L1），4-（3'-氯-4'-氟苯胺基）-6-（2-（1H-咪唑-1-基）乙氧基） -7-甲氧基喹唑啉（L2），N-（苯并[ d ]咪唑-4-基）-6,7-二甲氧基喹唑啉-4-胺盐酸盐（L3），5-（6,7-二甲氧基喹唑啉-4-基氨基）分别用喹啉8-醇盐酸盐（L4）制成[Ru II Cl 2（DMSO）2（L1）]（1），[RuIII Cl 3（DMSO）（L1）]（2），[Ru III Cl 4（DMSO）（H-L2）]（3），[Ru III Cl 4（DMSO）（H-L3）]（4），和[Ru III Cl 3（DMSO）（H-L4）]

  DOI：

  10.1016/j.ejmech.2014.02.062
• 作为产物：
  描述：

  4-硝基邻苯二胺 在 盐酸 、 palladium on activated charcoal 、 一水合肼 作用下， 以 乙醇 、 水 、 异丙醇 为溶剂， 反应 32.0h， 生成 N-(1H-benzo[d]imidazol-5-yl)-6,7-dimethoxyquinazolin-4-amine 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