5,6-dichloro-N2-[(1S)-1-(4-fluorophenyl)ethyl]-N4-(3-isopropoxy-1H-pyrazol-5-yl)pyrimidine-2,4-diamine

• 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-N2-[(1S)-1-(4-fluorophenyl)ethyl]-N4-(3-isopropoxy-1H-pyrazol-5-yl)pyrimidine-2,4-diamine
• 英文别名: 5,6-dichloro-2-N-[(1S)-1-(4-fluorophenyl)ethyl]-4-N-(3-propan-2-yloxy-1H-pyrazol-5-yl)pyrimidine-2,4-diamine
• 化学式: C₁₈H₁₉Cl₂FN₆O
• 分子量: 425.293
• InChiKey: HORBFMDWBCVWSA-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  87.8
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  丝氨醇 、 5,6-dichloro-N2-[(1S)-1-(4-fluorophenyl)ethyl]-N4-(3-isopropoxy-1H-pyrazol-5-yl)pyrimidine-2,4-diamine 以 正丁醇 为溶剂， 生成 2-[[5-chloro-2-[[(1S)-1-(4-fluorophenyl)ethyl]amino]-6-[(5-propan-2-yloxy-1H-pyrazol-3-yl)amino]pyrimidin-4-yl]amino]propane-1,3-diol
  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
• 作为产物：
  描述：

  (S)-(-)-1-(4-氟苯基)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-N2-[(1S)-1-(4-fluorophenyl)ethyl]-N4-(3-isopropoxy-1H-pyrazol-5-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

• EP1686999B1
  申请人：——

  公开号：EP1686999B1

  公开（公告）日：2009-07-01
• Use of Pyrazolyl-Pyrimidine Derivatives in the Treatment of Pain
  申请人：Claesson Alf

  公开号：US20090005396A1

  公开（公告）日：2009-01-01

  This invention relates to the use of a pyrazolyl-pyrimidine of the formula (I). n=0, 1, 2 or 3 (I) in the manufacture of a medicament for use in the treatment or prophylaxis of pain. and to their pharmaceutical formulations and to their methods of use.
• 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.