methyl (2R)-2-[(4-{[1-(1,3-thiazol-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoate | 930606-64-7

• 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: methyl (2R)-2-[(4-{[1-(1,3-thiazol-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoate
• 英文别名: methyl (2R)-2-[4-[[1-(1,3-thiazol-2-ylmethyl)indazol-5-yl]amino]quinazolin-5-yl]oxypropanoate
• CAS: 930606-64-7
• 化学式: C₂₃H₂₀N₆O₃S
• 分子量: 460.516
• InChiKey: RYXSNMQSHFXVCD-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  132
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl (2R)-2-[(4-{[1-(1,3-thiazol-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 (2R)-2-[(4-{[1-(1,3-thiazol-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoic acid
  参考文献：
  名称：

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

  摘要：

  We have identified a new series of C- 5 substituted indazolylaminoquinazolines as potent erbB2 kinase inhibitors. The lead compound 22 showed excellent in vitro potency, good physical properties, acceptable oral pharmacokinetics in rat and dog, and low human in vitro clearance. It showed at least equivalent activity dose for dose compared to lapatinib in various erbB2- or EGFR-driven xenograft models after chronic oral administration. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.02.035
• 作为产物：
  描述：

  4-{[1-(1,3-thiazol-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-ol 、 L-乳酸甲酯 在 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 生成 methyl (2R)-2-[(4-{[1-(1,3-thiazol-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoate
  参考文献：
  名称：

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

  摘要：

  We have identified a new series of C- 5 substituted indazolylaminoquinazolines as potent erbB2 kinase inhibitors. The lead compound 22 showed excellent in vitro potency, good physical properties, acceptable oral pharmacokinetics in rat and dog, and low human in vitro clearance. It showed at least equivalent activity dose for dose compared to lapatinib in various erbB2- or EGFR-driven xenograft models after chronic oral administration. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.02.035

文献信息

• 4-(1H-INDAZOL-5-YL-AMINO)-QUINAZOLINE COMPOUNDS AS ERBB RECEPTOR TYROSINE KINASE INHIBITORS FOR THE TREATMENT OF CANCER
  申请人：Bradbury Robert Hugh

  公开号：US20090048251A1

  公开（公告）日：2009-02-19

  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.

  一种公式I的喹唑啉衍生物：其中取代基如文本中所定义，用于生产抗增殖效应，该效应在温血动物（如人）中单独或部分地通过抑制erbB2受体酪氨酸激酶而产生。
• 4-(1H-indazol-5-yl-amino)-quinazoline compounds as erbB receptor tyrosine kinase inhibitors for the treatment of cancer
  申请人：AstraZeneca AB

  公开号：US07820683B2

  公开（公告）日：2010-10-26

  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Formula I中的喹唑啉衍生物：其中取代基如文本中定义，用于制备抗增殖效应，该效应在温血动物，例如人体内产生，该效应单独或部分通过抑制erbB2受体酪氨酸激酶产生。
• Neutral 5-substituted 4-indazolylaminoquinazolines as potent, orally active inhibitors of erbB2 receptor tyrosine kinase
  作者：Bernard Barlaam、David G. Acton、Peter Ballard、Robert H. Bradbury、Darren Cross、Richard Ducray、Hervé Germain、Kevin Hudson、Teresa Klinowska、Françoise Magnien、Donald J. Ogilvie、Annie Olivier、Helen S. Ross、Robin Smith、Cath B. Trigwell、Michel Vautier、Lindsay Wright

  DOI：10.1016/j.bmcl.2008.02.035

  日期：2008.3

  We have identified a new series of C- 5 substituted indazolylaminoquinazolines as potent erbB2 kinase inhibitors. The lead compound 22 showed excellent in vitro potency, good physical properties, acceptable oral pharmacokinetics in rat and dog, and low human in vitro clearance. It showed at least equivalent activity dose for dose compared to lapatinib in various erbB2- or EGFR-driven xenograft models after chronic oral administration. (C) 2008 Elsevier Ltd. All rights reserved.