2-chloro-5-fluoro-N-(5-methyl-1H-pyrazol-3-yl)-6-(morpholin-4-yl)pyrimidin-4-amine | 935667-42-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-chloro-5-fluoro-N-(5-methyl-1H-pyrazol-3-yl)-6-(morpholin-4-yl)pyrimidin-4-amine
• 英文别名: 2-chloro-5-fluoro-N-(5-methyl-1H-pyrazol-3-yl)-6-morpholin-4-ylpyrimidin-4-amine
• CAS: 935667-42-8
• 化学式: C₁₂H₁₄ClFN₆O
• 分子量: 312.734
• InChiKey: DGKUUEIXZKEJIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  79
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-chloro-5-fluoro-N-(5-methyl-1H-pyrazol-3-yl)-6-(morpholin-4-yl)pyrimidin-4-amine 在 N,N-二异丙基乙胺 作用下， 以 水 、 乙腈 、 正丁醇 为溶剂， 反应 9.0h， 生成 5-fluoro-N2-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)-6-(morpholin-4-yl)pyrimidine-2,4-diamine trifluroacetate
  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：

  吗啉 、 2,6-dichloro-5-fluoro-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 为溶剂， 反应 5.0h， 生成 2-chloro-5-fluoro-N-(5-methyl-1H-pyrazol-3-yl)-6-(morpholin-4-yl)pyrimidin-4-amine
  参考文献：
  名称：

  WO2007/49041

  摘要：

  公开号：

文献信息

• 4-(3-Aminopyrazole) Pyrimidine Derivatives for Use as Tyrosine Kinase Inhibitors in the Treatment of Cancer
  申请人：Feng Xiaomei

  公开号：US20080287475A1

  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.

  本发明涉及具有公式（I）的新化合物，以及它们的药物组成物和使用方法。这些新化合物提供了一种治疗癌症的方法。
• 4-(3-AMINOPYRAZOLE) PYRIMIDINE DERIVATIVES FOR USE AS TYROSINE KINASE INHIBITORS IN THE TREATMENT OF CANCER
  申请人：Feng Xiaomei

  公开号：US20120071480A1

  公开（公告）日：2012-03-22

  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.

  本发明涉及具有公式（I）的新化合物，以及它们的制药组合物和使用方法。这些新化合物提供了一种治疗癌症的方法。
• 4-(3-aminopyrazole) pyrimidine derivatives for use as tyrosine kinase inhibitors in the treatment of cancer
  申请人：AstraZeneca AB

  公开号：US08088784B2

  公开（公告）日：2012-01-03

  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.

  本发明涉及具有公式（I）的新化合物，以及它们的制药组合物和使用方法。这些新化合物提供了一种治疗癌症的方法。
• 4- (3-aminopyrazole) pyrimidine derivatives for use as tyrosine kinase inhibitors in the treatment of cancer
  申请人：AstraZeneca AB

  公开号：EP2388259A1

  公开（公告）日：2011-11-23

  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.

  本发明涉及具有式 (I) 的新型化合物： 及其药物组合物和使用方法。这些新型化合物可用于治疗癌症。
• WO2007/49041
  申请人：——

  公开号：——

  公开（公告）日：——