5,6-dichloro-N-[(1S)-1-(5-fluoropyridin-2-yl)ethyl]-N'-(5-propan-2-yloxy-1H-pyrazol-3-yl)pyrimidine-2,4-diamine | 915720-45-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5,6-dichloro-N-[(1S)-1-(5-fluoropyridin-2-yl)ethyl]-N'-(5-propan-2-yloxy-1H-pyrazol-3-yl)pyrimidine-2,4-diamine
• 英文别名: (S)-5,6-dichloro-N2-(1-(5-fluoropyridin-2-yl)ethyl)-N4-(5-isopropoxy-1H-pyrazol-3-yl)pyrimidine-2,4-diamine；(S)-5,6-Dichloro-N2-(1-(5-fluoropyridin-2-yl)ethyl)-N4-(5-isopropoxy-1H-pyrazol-3-yl)pyrimidine-2,4-diamine；5,6-dichloro-2-N-[(1S)-1-(5-fluoropyridin-2-yl)ethyl]-4-N-(3-propan-2-yloxy-1H-pyrazol-5-yl)pyrimidine-2,4-diamine
• CAS: 915720-45-5
• 化学式: C₁₇H₁₈Cl₂FN₇O
• 分子量: 426.281
• InChiKey: WEOLCOKAMULSEM-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5,6-dichloro-N-[(1S)-1-(5-fluoropyridin-2-yl)ethyl]-N'-(5-propan-2-yloxy-1H-pyrazol-3-yl)pyrimidine-2,4-diamine 在 氨 作用下， 以 水 、 正丁醇 为溶剂， 反应 48.0h， 以24%的产率得到(S)-5-chloro-N2-(1-(5-fluoropyridin-2-yl)ethyl)-N4-(5-isopropoxy-1H-pyrazol-3-yl)pyrimidine-2,4,6-triamine
  参考文献：
  名称：

  WO2006/123113

  摘要：

  公开号：
• 作为产物：
  描述：

  (S)-1-(5-氟吡啶-2-基)乙胺 、 2,5,6-trichloro-N-(5-propan-2-yloxy-1H-pyrazol-3-yl)pyrimidin-4-amine 在 N,N-二异丙基乙胺 作用下， 以 正丁醇 为溶剂， 生成 5,6-dichloro-N-[(1S)-1-(5-fluoropyridin-2-yl)ethyl]-N'-(5-propan-2-yloxy-1H-pyrazol-3-yl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  Identification of 4-Aminopyrazolylpyrimidines as Potent Inhibitors of Trk Kinases

  摘要：

  The design, synthesis and biological evaluation of a series of 4-aminopyrazolylpyrimidines as potent Trk kinase inhibitors is reported. High-throughput screening identified a promising hit in the 4-aminopyrazolylpyrimidine chemotype. Initial optimization of the series led to more potent Trk inhibitors. Further optimization using two strategies resulted in significant improvement of physical properties and led to the discovery of IN (AZ-23), a potent, orally bioavailable Trk A/B inhibitor. The compound offers the potential to test the hypothesis that modulation of Trk activity will be of benefit in the treatment of cancer and other indications in vivo.

  DOI：

  10.1021/jm800343j

文献信息

• Pyrazolylaminopyrimidine Derivatives Useful as Tyrosine Kinase Inhibitors
  申请人：Wang Bin

  公开号：US20080287437A1

  公开（公告）日：2008-11-20

  This invention relates to novel compounds having the formula (I): and to their pharmaceutical compositions and to their methods of use. These novel compounds provide a treatment for cancer.

  本发明涉及具有以下公式（I）的新化合物，以及它们的药物组合物和使用方法。这些新化合物提供了治疗癌症的方法。
• PYRAZOLYLAMINOPYRIMIDINE DERIVATIVES USEFUL AS TYROSINE KINASE INHIBITORS
  申请人：Wang Bin

  公开号：US20100210648A1

  公开（公告）日：2010-08-19

  This invention relates to novel compounds having the formula (I): and to their pharmaceutical compositions and to their methods of use. These novel compounds provide a treatment for cancer.

  这项发明涉及具有以下公式（I）的新化合物，以及它们的药物组合物和使用方法。这些新化合物可提供一种治疗癌症的方法。
• Pyrazolylaminopyrimidine derivatives useful as tyrosine kinase inhibitors
  申请人：AstraZeneca AB

  公开号：US08114989B2

  公开（公告）日：2012-02-14

  This invention relates to novel compounds having the formula (I): and to their pharmaceutical compositions and to their methods of use. These novel compounds provide a treatment for cancer.

  本发明涉及具有以下式子（I）的新化合物，以及它们的药物组成物和使用方法。这些新化合物为癌症提供了治疗。
• US8114989B2
  申请人：——

  公开号：US8114989B2

  公开（公告）日：2012-02-14
• Identification of 4-Aminopyrazolylpyrimidines as Potent Inhibitors of Trk Kinases
  作者：Tao Wang、Michelle L. Lamb、David A. Scott、Haixia Wang、Michael H. Block、Paul D. Lyne、John W. Lee、Audrey M. Davies、Hai-Jun Zhang、Yanyi Zhu、Fei Gu、Yongxin Han、Bin Wang、Peter J. Mohr、Robert J. Kaus、John A. Josey、Ethan Hoffmann、Ken Thress、Terry MacIntyre、Haiyun Wang、Charles A. Omer、Dingwei Yu

  DOI：10.1021/jm800343j

  日期：2008.8.1

  The design, synthesis and biological evaluation of a series of 4-aminopyrazolylpyrimidines as potent Trk kinase inhibitors is reported. High-throughput screening identified a promising hit in the 4-aminopyrazolylpyrimidine chemotype. Initial optimization of the series led to more potent Trk inhibitors. Further optimization using two strategies resulted in significant improvement of physical properties and led to the discovery of IN (AZ-23), a potent, orally bioavailable Trk A/B inhibitor. The compound offers the potential to test the hypothesis that modulation of Trk activity will be of benefit in the treatment of cancer and other indications in vivo.