5-chloro-2-[1-(5-fluoropyrimidin-2-yl)ethoxy]-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine | 1099727-62-4

• 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: 5-chloro-2-[1-(5-fluoropyrimidin-2-yl)ethoxy]-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine
• CAS: 1099727-62-4
• 化学式: C₁₄H₁₃ClFN₇O
• 分子量: 349.755
• InChiKey: WZPILCWIFRRMQR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 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：
  102
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-chloro-2-[1-(5-fluoropyrimidin-2-yl)ethoxy]-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine 在 二甲基十二/十四烷基叔胺 作用下， 以 异丙醇 为溶剂， 以16%的产率得到(S)-5-chloro-2-[1-(5-fluoropyrimidin-2-yl)ethoxy]-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
• 作为产物：
  描述：

  2-氰基-5-氟嘧啶 在 sodium tetrahydroborate 、 sodium t-butanolate 作用下， 以 甲醇 、 乙醚 、 正丁醇 为溶剂， 生成 5-chloro-2-[1-(5-fluoropyrimidin-2-yl)ethoxy]-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

• [EN] CHEMICAL COMPOUNDS 916-1<br/>[FR] COMPOSÉS CHIMIQUES 916-1
  申请人：ASTRAZENECA AB

  公开号：WO2009007753A2

  公开（公告）日：2009-01-15

  The present invention relates to compounds of Formula (I) and to their salts, pharmaceutical compositions, methods of use, and methods for their preparation. These compounds provide a treatment for myeloproliferative disorders and cancer.
• 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.