4-(3-chloro-2-fluoroanilino)-7-methoxy-6-(piperidin-3-yloxy)quinazoline | 612501-51-6

• 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: 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-(piperidin-3-yloxy)quinazoline
• 英文别名: 4-(3-Chloro-2-fluoroanilino)-6-(piperidin-3-yloxy)-7-methoxyquinazoline；N-(3-chloro-2-fluorophenyl)-7-methoxy-6-piperidin-3-yloxyquinazolin-4-amine
• CAS: 612501-51-6
• 化学式: C₂₀H₂₀ClFN₄O₂
• 分子量: 402.856
• InChiKey: MORFQDRARBOZSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  68.3
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(3-chloro-2-fluoroanilino)-7-methoxy-6-(piperidin-3-yloxy)quinazoline 、 2-氯-N-甲基乙酰胺 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 1.0h， 以68%的产率得到4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[1-(N-methylcarbamoylmethyl)piperidin-3-yl]oxy}quinazoline
  参考文献：
  名称：

  Discovery of AZD8931, an Equipotent, Reversible Inhibitor of Signaling by EGFR, HER2, and HER3 Receptors

  摘要：

  Deregulation of HER family signaling promotes proliferation and tumor cell survival and has been described in many human cancers. Simultaneous, equipotent inhibition of EGFR-, HER2-, and HER3-mediated signaling may be of clinical utility in cancer settings where the selective EGFR or HER2 therapeutic agents are ineffective or only modestly active. We describe the discovery of AZD8931 (2), an equipotent, reversible inhibitor of EGFR-, HER2-, and HER3-mediated signaling and the structure-activity relationships within this series. Docking studies based on a model of the HER2 kinase domain helped rationalize the increased HER2 activity seen with the methyl acetamide side chain present in AZD8931. AZD8931 exhibited good pharmacokinetics in preclinical species and showed superior activity in the LoVo tumor growth efficacy model compared to dose analogues. AZD8931 is currently being evaluated in human clinical trials for the treatment of cancer.

  DOI：

  10.1021/ml400146c
• 作为产物：
  描述：

  4-氯-7-甲氧基喹唑啉-6-醇 在 盐酸 、 氨 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 5.0h， 生成 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-(piperidin-3-yloxy)quinazoline
  参考文献：
  名称：

  Discovery of AZD8931, an Equipotent, Reversible Inhibitor of Signaling by EGFR, HER2, and HER3 Receptors

  摘要：

  Deregulation of HER family signaling promotes proliferation and tumor cell survival and has been described in many human cancers. Simultaneous, equipotent inhibition of EGFR-, HER2-, and HER3-mediated signaling may be of clinical utility in cancer settings where the selective EGFR or HER2 therapeutic agents are ineffective or only modestly active. We describe the discovery of AZD8931 (2), an equipotent, reversible inhibitor of EGFR-, HER2-, and HER3-mediated signaling and the structure-activity relationships within this series. Docking studies based on a model of the HER2 kinase domain helped rationalize the increased HER2 activity seen with the methyl acetamide side chain present in AZD8931. AZD8931 exhibited good pharmacokinetics in preclinical species and showed superior activity in the LoVo tumor growth efficacy model compared to dose analogues. AZD8931 is currently being evaluated in human clinical trials for the treatment of cancer.

  DOI：

  10.1021/ml400146c

文献信息

• [EN] 4-ANILINO QUINAZOLINE DERIVATIVES AS ANTIPROLIFERATIVE AGENTS<br/>[FR] DERIVES DE 4-ANILINO QUINAZOLINE UTILISES EN TANT QU'AGENTS ANTIPROLIFERATIFS
  申请人：ASTRAZENECA AB

  公开号：WO2003082831A1

  公开（公告）日：2003-10-09

  The invention concerns quinazoline derivatives of Formula (I) wherein each of Q1, Z, R1 and Q2 have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours which are sensitive to inhibition of erbB receptor tyrosine kinases.

  该发明涉及式（I）的喹唑啉衍生物，其中Q1、Z、R1和Q2中的每一个具有描述中定义的任何含义；其制备方法，含有它们的药物组合物以及它们在制备用作抗增殖剂的药物中的使用，用于预防或治疗对erbB受体酪氨酸激酶抑制敏感的肿瘤。
• 4-anilino quinazoline derivatives as antiproliferative agents
  申请人：Bradbury Hugh Robert

  公开号：US20050215574A1

  公开（公告）日：2005-09-29

  The invention concerns quinazoline derivatives of Formula (I) wherein each of Q 1 , Z, R 1 and Q 2 have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours which are sensitive to inhibition of erbB receptor tyrosine kinases.

  本发明涉及公式(I)中的喹唑啉衍生物，其中Q1、Z、R1和Q2中的每一个具有在说明书中定义的任何含义；制备它们的过程，含有它们的制药组合物以及它们在制造用作erbB受体酪氨酸激酶抑制剂的药物中作为抗增殖剂预防或治疗对erbB受体酪氨酸激酶抑制敏感的肿瘤的用途。
• 4-ANILINO QUINAZOLINE DERIVATIVES AS ANTIPROLIFERATIVE AGENTS
  申请人：Bradbury Robert Hugh

  公开号：US20080269487A1

  公开（公告）日：2008-10-30

  The invention concerns quinazoline derivatives of Formula (I) wherein each of Q 1 , Z, R 1 and Q 2 have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours which are sensitive to inhibition of erbB receptor tyrosine kinases.

  本发明涉及式（I）的喹唑啉衍生物，其中Q1、Z、R1和Q2中的每一个具有在说明中定义的任何含义；它们的制备过程，含有它们的制药组合物以及它们在制造用作erbB受体酪氨酸激酶抑制剂的药物的预防或治疗对erbB受体酪氨酸激酶抑制敏感的肿瘤中的使用。
• QUINAZOLINE DERIVATIVES
  申请人：BRADBURY Robert Hugh

  公开号：US20130005727A1

  公开（公告）日：2013-01-03

  The invention concerns quinazoline derivatives of Formula I wherein each of Q 1 , Z, R 1 and Q 2 have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours which are sensitive to inhibition of erbB receptor tyrosine kinases.

  本发明涉及公式I的喹唑啉衍生物，其中Q1、Z、R1和Q2中的每一个都具有描述中定义的任何含义；其制备方法，包含它们的制药组合物以及它们在制造用作erbB受体酪氨酸激酶抑制剂的药物中用于预防或治疗对erbB受体酪氨酸激酶抑制剂敏感的肿瘤的用途。
• US8399667B2
  申请人：——

  公开号：US8399667B2

  公开（公告）日：2013-03-19