2-[5-chloro-2-[[(1S)-1-(5-fluoropyridin-2-yl)ethyl]amino]-6-[(5-propan-2-yloxy-1H-pyrazol-3-yl)amino]pyrimidin-4-yl]oxypropane-1,3-diol | 915720-28-4

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 2-[5-chloro-2-[[(1S)-1-(5-fluoropyridin-2-yl)ethyl]amino]-6-[(5-propan-2-yloxy-1H-pyrazol-3-yl)amino]pyrimidin-4-yl]oxypropane-1,3-diol
• 英文别名: (S)-2-(5-chloro-2-(1-(5-fluoropyridin-2-yl)ethylamino)-6-(5-isopropoxy-1H-pyrazol-3-ylamino)pyrimidin-4-yloxy)propane-1,3-diol；2-[5-chloro-2-[[(1S)-1-(5-fluoropyridin-2-yl)ethyl]amino]-6-[(3-propan-2-yloxy-1H-pyrazol-5-yl)amino]pyrimidin-4-yl]oxypropane-1,3-diol
• CAS: 915720-28-4
• 化学式: C₂₀H₂₅ClFN₇O₄
• 分子量: 481.914
• InChiKey: CZCROGVITASFKE-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  150
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  5-chloro-2-N-[(1S)-1-(5-fluoropyridin-2-yl)ethyl]-6-[(2-phenyl-1,3-dioxan-5-yl)oxy]-4-N-(3-propan-2-yloxy-1H-pyrazol-5-yl)pyrimidine-2,4-diamine 在 三氟乙酸 作用下， 生成 2-[5-chloro-2-[[(1S)-1-(5-fluoropyridin-2-yl)ethyl]amino]-6-[(5-propan-2-yloxy-1H-pyrazol-3-yl)amino]pyrimidin-4-yl]oxypropane-1,3-diol
  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

• US8114989B2
  申请人：——

  公开号：US8114989B2

  公开（公告）日：2012-02-14