N-(3-tert-butyl-1H-pyrazol-5-yl)-2,5-dichloropyrimidin-4-amine | 543712-87-4

• 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: N-(3-tert-butyl-1H-pyrazol-5-yl)-2,5-dichloropyrimidin-4-amine
• 英文别名: n-(3-Tert-butyl-1h-pyrazol-5-yl)-2,5-dichloropyrimidin-4-amine；N-(5-tert-butyl-1H-pyrazol-3-yl)-2,5-dichloropyrimidin-4-amine
• CAS: 543712-87-4
• 化学式: C₁₁H₁₃Cl₂N₅
• 分子量: 286.164
• InChiKey: INFUQHBUJVHGNV-UHFFFAOYSA-N

物化性质

• 沸点：
  477.6±45.0 °C(Predicted)
• 密度：
  1.402±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  66.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-(-)-1-(4-氟苯基)乙胺 、 N-(3-tert-butyl-1H-pyrazol-5-yl)-2,5-dichloropyrimidin-4-amine 在 N,N-二异丙基乙胺 作用下， 以 正丁醇 为溶剂， 生成 N4-(5-tert-butyl-1H-pyrazol-3-yl)-5-chloro-N2-[(1S)-1-(4-fluorophenyl)ethyl]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
• 作为产物：
  描述：

  2,4,5-三氯嘧啶 、 3-叔丁基-吡唑-5-胺 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 10.0h， 生成 N-(3-tert-butyl-1H-pyrazol-5-yl)-2,5-dichloropyrimidin-4-amine
  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

• [EN] 4-(PYRAZOL-3-YLAMINO) PYRIMIDINE DERIVATIVES FOR USE IN THE TREATMENT OF CANCER<br/>[FR] DERIVES DE 4-(PYRAZOL-3-YLAMINO) PYRIMIDINE QUI S'UTILISENT DANS LE TRAITEMENT DU CANCER
  申请人：ASTRAZENECA AB

  公开号：WO2005040159A1

  公开（公告）日：2005-05-06

  A compound of Formula (I); wherein the substituents are as defined in the text for use in modulating insulin-like growth factor 1 receptor activity in a warm blooded animal such as man.

  一种化合物，其化学式为（I）；其中取代基如文本中定义的那样，用于调节类胰岛素生长因子1受体在温血动物（如人类）中的活性。
• Pyrimidine derivatives as modulators of insulin-like growth factor-1 receptor (igf-i)
  申请人：Barlaam Bernard

  公开号：US20050054638A1

  公开（公告）日：2005-03-10

  The invention provides compounds of formula in which R 1 , R 2 , R 3 and R 4 have the meanings defined in the specification; processes for the preparation; pharmaceutical compositions containing them; a process for preparing the pharmaceutical compositions; and their use in therapy.

  该发明提供了公式中R1，R2，R3和R4具有规范中定义的含义的化合物；制备过程；包含它们的制药组合物；制备制药组合物的过程；以及它们在治疗中的使用。
• 4-(Pyrazol-3-ylamino) pyrimidine derivatives for use in the treatment of cancer
  申请人：Nowak Thorsten

  公开号：US20070037888A1

  公开（公告）日：2007-02-15

  A compound of Formula (I); wherein the substituents are as defined in the text for use in modulating insulin-like growth factor 1 receptor activity in a warm blooded animal such as man.

  化合物公式（I）中的取代基如文本中所定义，用于调节温血动物（如人）中胰岛素样生长因子1受体的活性。
• NOVEL COMPOUNDS
  申请人：Barlaam Bernard

  公开号：US20120095011A1

  公开（公告）日：2012-04-19

  The invention provides compounds of formula in which R 1 , R 2 , R 3 and R 4 have the meanings defined in the specification; processes for their preparation; pharmaceutical compositions containing them; a process for preparing the pharmaceutical compositions; and their use in therapy.

  本发明提供的化合物具有公式，其中R1，R2，R3和R4具有规范中定义的含义；制备它们的过程；包含它们的制药组合物；制备制药组合物的过程；以及它们在治疗中的使用。
• PYRIMIDINE DERIVATIVES AS MODULATORS OF INSULINE-LIKE GROWTH FACTOR-1 RECEPTOR (IGF-I)
  申请人：AstraZeneca AB

  公开号：EP1456182B1

  公开（公告）日：2009-03-11