2,4,6-trichloro-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine | 915720-78-4

• 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: 2,4,6-trichloro-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine
• 英文别名: 2,5,6-trichloro-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine
• CAS: 915720-78-4
• 化学式: C₈H₆Cl₃N₅
• 分子量: 278.528
• InChiKey: PFCOXFMBWWZUOS-UHFFFAOYSA-N

物化性质

• 沸点：
  467.7±45.0 °C(Predicted)
• 密度：
  1.681±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 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：

  2,4,6-trichloro-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine 在 N,N-二异丙基乙胺 作用下， 以 乙醇 、 水 、 乙腈 、 正丁醇 为溶剂， 反应 48.0h， 生成 5-chloro-N2-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)-6-(morpholin-4-yl)pyrimidine-2,4-diamine trifluoroacetate
  参考文献：
  名称：

  Discovery of 5-Chloro-N²-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-N⁴-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (AZD1480) as a Novel Inhibitor of the Jak/Stat Pathway

  摘要：

  The myeloproliferative neoplasms, polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis are a heterogeneous but related group of hematological malignancies characterized by clonal expansion of one or more myeloid lineages. The discovery of the Jak2 V617F gain of function mutation highlighted Jak2 as a potential therapeutic target in the MPNs. Herein, we disclose the discovery of a series of pyrazol-3-yl pyrimidin-4-amines and the identification of 9e (AZD1480) as a potent Jak2 inhibitor. 9e inhibits signaling and proliferation of Jak2 V617F cell lines in vitro, demonstrates in vivo efficacy in a TEL-Jak2 model, has excellent physical properties and preclinical pharmacokinetics, and is currently being evaluated in Phase I clinical trials.

  DOI：

  10.1021/jm1011319
• 作为产物：
  描述：

  2,4,5,6-四氯嘧啶 、 3-氨基-5-甲基吡唑 在 三乙胺 作用下， 以 乙醇 为溶剂， 生成 2,4,6-trichloro-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine
  参考文献：
  名称：

  Discovery of 5-Chloro-N²-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-N⁴-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (AZD1480) as a Novel Inhibitor of the Jak/Stat Pathway

  摘要：

  The myeloproliferative neoplasms, polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis are a heterogeneous but related group of hematological malignancies characterized by clonal expansion of one or more myeloid lineages. The discovery of the Jak2 V617F gain of function mutation highlighted Jak2 as a potential therapeutic target in the MPNs. Herein, we disclose the discovery of a series of pyrazol-3-yl pyrimidin-4-amines and the identification of 9e (AZD1480) as a potent Jak2 inhibitor. 9e inhibits signaling and proliferation of Jak2 V617F cell lines in vitro, demonstrates in vivo efficacy in a TEL-Jak2 model, has excellent physical properties and preclinical pharmacokinetics, and is currently being evaluated in Phase I clinical trials.

  DOI：

  10.1021/jm1011319

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。
• PYRAZOLYLAMINOPYRIMIDINE DERIVATIVES USEFUL AS TYROSINE KINASE INHIBITORS
  申请人：AstraZeneca AB

  公开号：EP1899323A2

  公开（公告）日：2008-03-19
• US8114989B2
  申请人：——

  公开号：US8114989B2

  公开（公告）日：2012-02-14