2,5-dichloro-N-[5-(methylthio)-1H-pyrazol-3-yl]pyrimidin-4-amine | 852443-77-7

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2,5-dichloro-N-[5-(methylthio)-1H-pyrazol-3-yl]pyrimidin-4-amine
• 英文别名: 2,5-dichloro-N-[5-(methvlthio)-1H-pyrazol-3-yl]pyrimidin-4-amine；2,5-Dichloro-N-[5-(methylthio)-1H-pyrazol-3-yl]pyrimidin-4-amine；2,5-dichloro-N-(3-methylsulfanyl-1H-pyrazol-5-yl)pyrimidin-4-amine
• CAS: 852443-77-7
• 化学式: C₈H₇Cl₂N₅S
• 分子量: 276.149
• InChiKey: DOXKYLJBORZBAL-UHFFFAOYSA-N

物化性质

• 沸点：
  534.2±50.0 °C(Predicted)
• 密度：
  1.63±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  91.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-2-氨基-2-(4-氟苯基)乙醇 、 2,5-dichloro-N-[5-(methylthio)-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 (2R)-2-[{5-chloro-4-[(5-(methylthio)-1H-pyrazol-3-yl)amino]pyrimidin-2-yl}amino]-2-(4-fluorophenyl)ethanol
  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：

  5-(甲硫基)-1H-吡唑-3-胺 、 2,4,5-三氯嘧啶 在 三乙胺 作用下， 以 乙醇 为溶剂， 生成 2,5-dichloro-N-[5-(methylthio)-1H-pyrazol-3-yl]pyrimidin-4-amine
  参考文献：
  名称：

  [EN] PYRAZOLE DERIVATIVES AS INHIBITORS OF RECEPTOR TYROSYNE KINASES
  [FR] DERIVES DE PYRAZOLE EN TANT QU'INHIBITEURS DE RECEPTEUR TYROSINE KINASES

  摘要：

  化合物的化学式（I）及其在抑制Trk活性中的应用被描述。

  公开号：

  WO2005049033A1

文献信息

• [EN] PYRAZOLE DERIVATIVES AS INHIBITORS OF RECEPTOR TYROSYNE KINASES<br/>[FR] DERIVES DE PYRAZOLE EN TANT QU'INHIBITEURS DE RECEPTEUR TYROSINE KINASES
  申请人：ASTRAZENECA AB

  公开号：WO2005049033A1

  公开（公告）日：2005-06-02

  Compounds of formula (I): and their use in the inhibition of Trk activity are described.

  化合物的化学式（I）及其在抑制Trk活性中的应用被描述。
• Pyrazole derivatives as inhibitors of receptor tyrosone kinases
  申请人：Block Howard Michael

  公开号：US20070142413A1

  公开（公告）日：2007-06-21

  Compounds of formula (I): and their use in the inhibition of Trk activity are described.

  描述了式(I)的化合物及其在抑制Trk活性方面的用途。
• PYRAZOLE DERIVATIVES AS INHIBITORS OF RECEPTOR TYROSINE KINASES
  申请人：Block Michael Howard

  公开号：US20100152219A1

  公开（公告）日：2010-06-17

  Compounds of formula (I): and their use in the inhibition of Trk activity are described.

  描述了式(I)的化合物及其在抑制Trk活性方面的应用。
• EP1686999B1
  申请人：——

  公开号：EP1686999B1

  公开（公告）日：2009-07-01
• 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.