2-[(1-{4-[(4-Chlorophenyl)amino]-6,7-dimethoxyquinazolin-2-yl}piperidin-4-yl)(methyl)amino] ethanol | 1063232-28-9

• 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-[(1-{4-[(4-Chlorophenyl)amino]-6,7-dimethoxyquinazolin-2-yl}piperidin-4-yl)(methyl)amino] ethanol
• 英文别名: 2-[[1-[4-(4-chloroanilino)-6,7-dimethoxyquinazolin-2-yl]piperidin-4-yl]-methylamino]ethanol
• CAS: 1063232-28-9
• 化学式: C₂₄H₃₀ClN₅O₃
• 分子量: 471.987
• InChiKey: PZEJODHBRWCCMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  83
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-(甲基哌啶-4-基-氨基)-乙醇 、 2-chloro-N-(4-chlorophenyl)-6,7-dimethoxyquinazolin-4-amine 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 正丁醇 为溶剂， 反应 18.0h， 生成 2-[(1-{4-[(4-Chlorophenyl)amino]-6,7-dimethoxyquinazolin-2-yl}piperidin-4-yl)(methyl)amino] ethanol
  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

文献信息

• Potent CCR4 antagonists: Synthesis, evaluation, and docking study of 2,4-diaminoquinazolines
  作者：Kazuhiro Yokoyama、Noriko Ishikawa、Susumu Igarashi、Noriyuki Kawano、Naoyuki Masuda、Kazuyuki Hattori、Takahiro Miyazaki、Shin-ichi Ogino、Masaya Orita、Yuzo Matsumoto、Makoto Takeuchi、Mitsuaki Ohta

  DOI：10.1016/j.bmc.2008.07.062

  日期：2008.9

  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.