(S)-5,6-dichloro-N2-[1-(5-fluoropyrimidin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine | 1260222-59-0

• 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: (S)-5,6-dichloro-N2-[1-(5-fluoropyrimidin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine
• 英文别名: 5,6-dichloro-2-N-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-4-N-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine
• CAS: 1260222-59-0
• 化学式: C₁₄H₁₃Cl₂FN₈
• 分子量: 383.215
• InChiKey: VQYTWUGYKDRCHP-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (S)-5,6-dichloro-N2-[1-(5-fluoropyrimidin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine 在 N,N-二异丙基乙胺 作用下， 以 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：

  (S)-1-(5-氟嘧啶-2-基)乙胺盐酸盐 、 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 为溶剂， 生成 (S)-5,6-dichloro-N2-[1-(5-fluoropyrimidin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine
  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

• Discovery of 5-Chloro-<i>N</i>²-[(1<i>S</i>)-1-(5-fluoropyrimidin-2-yl)ethyl]-<i>N</i>⁴-(5-methyl-1<i>H</i>-pyrazol-3-yl)pyrimidine-2,4-diamine (AZD1480) as a Novel Inhibitor of the Jak/Stat Pathway
  作者：Stephanos Ioannidis、Michelle L. Lamb、Tao Wang、Lynsie Almeida、Michael H. Block、Audrey M. Davies、Bo Peng、Mei Su、Hai-Jun Zhang、Ethan Hoffmann、Caroline Rivard、Isabelle Green、Tina Howard、Hannah Pollard、Jon Read、Marat Alimzhanov、Geraldine Bebernitz、Kirsten Bell、Minwei Ye、Dennis Huszar、Michael Zinda

  DOI：10.1021/jm1011319

  日期：2011.1.13

  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.