2-chloro-N-(4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine | 864291-58-7

• 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: 2-chloro-N-(4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine
• CAS: 864291-58-7
• 化学式: C₁₆H₁₃ClFN₃O₂
• 分子量: 333.75
• InChiKey: JKKDBJBENZDVMF-UHFFFAOYSA-N

物化性质

• 沸点：
  432.4±45.0 °C(Predicted)
• 密度：
  1.389±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  56.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine 、 4-吡咯烷-1-基哌啶 在 N,N-二异丙基乙胺 作用下， 以 正丁醇 为溶剂， 反应 18.0h， 以62%的产率得到N-(4-Fluorophenyl)-6,7-dimethoxy-2-(4-pyrrolidin-1-ylpiperidin-1-yl)quinazolin-4-amine
  参考文献：
  名称：

  Potent CCR4 antagonists: Synthesis, evaluation, and docking study of 2,4-diaminoquinazolines

  摘要：

  A series of CC chemokine receptor-4 (CCR4) antagonists were examined in a previous report in an attempt to improve metabolic stability in human liver microsomes. In this study, the cycloheptylamine moiety of N-cycloheptyl-6,7-dimethoxy-2-(4-pyrrolidin-1-ylpiperidin-1-yl)quinazolin-4-amine 1 was replaced with the p-chloroaniline moiety, and the resulting compound, N-(4-chlorophenyl)-6,7-dimethoxy-2-(4-pyrrolidin-1-ylpiperidin-1-yl)quinazolin-4-amine (8c), retained its potency ([S-35]GTP gamma S-binding inhibition and CCL22-induced chemotaxis in humans/mice). Based on the structure-activity relationships (SAR), a homology model was constructed for CCR4 to explain the binding mode of 8c. Overall, there was good agreement between the docking pose of the CCR4 homology model and the human [S-35] GTP gamma S assay results. Administration of 8c in a murine model of acute dermatitis showed anti-inflammatory activity (oxazolone-induced contact hypersensitivity test). (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.07.062
• 作为产物：
  描述：

  2,4-二氯-6,7-二甲氧基喹唑啉 、 4-氟苯胺 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 16.0h， 生成 2-chloro-N-(4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine
  参考文献：
  名称：

  Potent CCR4 antagonists: Synthesis, evaluation, and docking study of 2,4-diaminoquinazolines

  摘要：

  A series of CC chemokine receptor-4 (CCR4) antagonists were examined in a previous report in an attempt to improve metabolic stability in human liver microsomes. In this study, the cycloheptylamine moiety of N-cycloheptyl-6,7-dimethoxy-2-(4-pyrrolidin-1-ylpiperidin-1-yl)quinazolin-4-amine 1 was replaced with the p-chloroaniline moiety, and the resulting compound, N-(4-chlorophenyl)-6,7-dimethoxy-2-(4-pyrrolidin-1-ylpiperidin-1-yl)quinazolin-4-amine (8c), retained its potency ([S-35]GTP gamma S-binding inhibition and CCL22-induced chemotaxis in humans/mice). Based on the structure-activity relationships (SAR), a homology model was constructed for CCR4 to explain the binding mode of 8c. Overall, there was good agreement between the docking pose of the CCR4 homology model and the human [S-35] GTP gamma S assay results. Administration of 8c in a murine model of acute dermatitis showed anti-inflammatory activity (oxazolone-induced contact hypersensitivity test). (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.07.062