N-(4-Chlorophenyl)-6,7-dimethoxy-2-[4-(2-pyrrolidin-1-ylethyl)-1,4-diazepan-1-yl]quinazolin-4-amine | 1063232-38-1

• 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-(4-Chlorophenyl)-6,7-dimethoxy-2-[4-(2-pyrrolidin-1-ylethyl)-1,4-diazepan-1-yl]quinazolin-4-amine
• CAS: 1063232-38-1
• 化学式: C₂₇H₃₅ClN₆O₂
• 分子量: 511.067
• InChiKey: YJLIDCZGFXMCEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N-(4-chlorophenyl)-2-(1,4-diazepan-1-yl)-6,7-dimethoxyquinazolin-4-amine 、 N-(2-氯乙基)吡咯烷盐酸盐 在 sodium carbonate 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 N-(4-Chlorophenyl)-6,7-dimethoxy-2-[4-(2-pyrrolidin-1-ylethyl)-1,4-diazepan-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