N-[(2R)-2-({4-[3-chloro-4-hydroxyanilino]quinazolin-5-yl}oxy)propyl]-2-hydroxy-N-methylacetamide | 853001-94-2

• 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-[(2R)-2-({4-[3-chloro-4-hydroxyanilino]quinazolin-5-yl}oxy)propyl]-2-hydroxy-N-methylacetamide
• 英文别名: N-[(2R)-2-[4-(3-chloro-4-hydroxyanilino)quinazolin-5-yl]oxypropyl]-2-hydroxy-N-methylacetamide
• CAS: 853001-94-2
• 化学式: C₂₀H₂₁ClN₄O₄
• 分子量: 416.864
• InChiKey: URHVCPCFHYADSE-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-[(2R)-2-({4-[3-chloro-4-hydroxyanilino]quinazolin-5-yl}oxy)propyl]-2-hydroxy-N-methylacetamide 、 2-氯甲基吡啶盐酸盐 在 18-冠醚-6 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-{(2R)-2-[(4-{3-chloro-4-(pyridin-2-ylmethoxy)anilino}quinazolin-5-yl)oxy]propyl}-2-hydroxy-N-methylacetamide
  参考文献：
  名称：

  Neutral 5-substituted 4-anilinoquinazolines as potent, orally active inhibitors of erbB2 receptor tyrosine kinase

  摘要：

  Neutral 5-substituted 4-anilinoquinazolines addressed high in vivo clearance and phospholipidosis associated with previous basic compounds. A representative compound 8a inhibited tumor growth in a mouse xenograft model when co-administered with the cytochrome P450 inhibitor 1-aminobenzotriazole (ABT), and data are consistent with pharmacology primarily reflecting inhibition of erbB2 receptor tyrosine kinase. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.08.073
• 作为产物：
  描述：

  2-chloro-4-({5-[(1R)-1-methyl-2-(methylamino)ethoxy]quinazolin-4-yl}amino)phenol 、 羟基乙酸 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-[(2R)-2-({4-[3-chloro-4-hydroxyanilino]quinazolin-5-yl}oxy)propyl]-2-hydroxy-N-methylacetamide
  参考文献：
  名称：

  Neutral 5-substituted 4-anilinoquinazolines as potent, orally active inhibitors of erbB2 receptor tyrosine kinase

  摘要：

  Neutral 5-substituted 4-anilinoquinazolines addressed high in vivo clearance and phospholipidosis associated with previous basic compounds. A representative compound 8a inhibited tumor growth in a mouse xenograft model when co-administered with the cytochrome P450 inhibitor 1-aminobenzotriazole (ABT), and data are consistent with pharmacology primarily reflecting inhibition of erbB2 receptor tyrosine kinase. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.08.073
• 作为试剂：
  描述：

  2-chloro-4-({5-[(1R)-1-methyl-2-(methylamino)ethoxy]quinazolin-4-yl}amino)phenol 、 羟基乙酸 、 2-hydroxy-N-[2-({4-[4-hydroxy-3-methylanilino]quinazolin-5-yl}oxy)ethyl]-N-methylacetamide 在 N-[(2R)-2-({4-[3-chloro-4-hydroxyanilino]quinazolin-5-yl}oxy)propyl]-2-hydroxy-N-methylacetamide 作用下， 以to give N-[(2R)-2-({4-[3-chloro-4-hydroxyanilino]quinazolin-5-yl}oxy)propyl]-2-hydroxy-N-methylacetamide in 57% yield的产率得到N-[(2R)-2-({4-[3-chloro-4-hydroxyanilino]quinazolin-5-yl}oxy)propyl]-2-hydroxy-N-methylacetamide
  参考文献：
  名称：

  Quinazoline Derivatives

  摘要：

  一种喹唑啉衍生物，化学式为（I），其中取代基如文本中所定义，用于制备抗增殖效应，该效应仅或部分通过抑制温血动物（例如人）中的erbB2受体酪氨酸激酶产生。

  公开号：

  US20070244136A1

文献信息

• [EN] QUINAZOLINE DERIVATIVES<br/>[FR] DERIVES DE QUINAZOLINE
  申请人：ASTRAZENECA AB

  公开号：WO2005051923A1

  公开（公告）日：2005-06-09

  A quinazoline derivative of the Formula (I): wherein the substituents are as defined in the text for use in the production of an anti proliferative effect which effect is produced alone or in part by inhibiting erbB2 receptor tyrosine kinase in a warm-blooded animal such as man.

  Formula (I)的喹唑啉衍生物：其中取代基如文本中定义的那样，用于生产抗增殖效应，该效应通过在诸如人类等恒温动物中抑制erbB2受体酪氨酸激酶而产生。
• Quinazoline derivatives
  申请人：AstraZeneca AB

  公开号：US07625908B2

  公开（公告）日：2009-12-01

  A quinazoline derivative of the Formula (I): wherein the substituents are as defined in the text for use in the production of an anti proliferative effect which effect is produced alone or in part by inhibiting erbB2 receptor tyrosine kinase in a warm-blooded animal such as man.

  一种喹唑啉衍生物，化学式为（I），其中取代基如文本所定义，用于制备抗增殖效应，该效应由于在温血动物（如人）中抑制erbB2受体酪氨酸激酶而产生。
• QUINAZOLINE DERIVATIVES
  申请人：AstraZeneca AB

  公开号：EP1685116A1

  公开（公告）日：2006-08-02
• US7625908B2
  申请人：——

  公开号：US7625908B2

  公开（公告）日：2009-12-01
• Neutral 5-substituted 4-anilinoquinazolines as potent, orally active inhibitors of erbB2 receptor tyrosine kinase
  作者：Peter Ballard、Bernard C. Barlaam、Robert H. Bradbury、Allan Dishington、Laurent F.A. Hennequin、D. Mark Hickinson、Ian M. Hollingsworth、Jason G. Kettle、Teresa Klinowska、Donald J. Ogilvie、Stuart E. Pearson、James S. Scott、Abid Suleman、Robin Whittaker、Emma J. Williams、Robin Wood、Lindsay Wright

  DOI：10.1016/j.bmcl.2007.08.073

  日期：2007.11

  Neutral 5-substituted 4-anilinoquinazolines addressed high in vivo clearance and phospholipidosis associated with previous basic compounds. A representative compound 8a inhibited tumor growth in a mouse xenograft model when co-administered with the cytochrome P450 inhibitor 1-aminobenzotriazole (ABT), and data are consistent with pharmacology primarily reflecting inhibition of erbB2 receptor tyrosine kinase. (C) 2007 Elsevier Ltd. All rights reserved.