3-[(2-bromopyrazolo[1,5-α]pyrimidin-7-yl)amino]phenol | 1203705-59-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 3-[(2-bromopyrazolo[1,5-α]pyrimidin-7-yl)amino]phenol
• 英文别名: 3-[(2-Bromopyrazolo[1,5-a]pyrimidin-7-yl)amino]phenol
• CAS: 1203705-59-2
• 化学式: C₁₂H₉BrN₄O
• 分子量: 305.134
• InChiKey: WJMXWDRNLASRDO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  62.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[(2-bromopyrazolo[1,5-α]pyrimidin-7-yl)amino]phenol 、 3-甲氧基羰基苯硼酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.5h， 以83%的产率得到3-{[2-(3-methylcarboxyphenyl)pyrazolo[1,5-α]pyrimidin-7-yl]amino}phenol
  参考文献：
  名称：

  Novel Synthesis and Structural Characterization of a High-Affinity Paramagnetic Kinase Probe for the Identification of Non-ATP Site Binders by Nuclear Magnetic Resonance

  摘要：

  To aid in the pursuit of selective kinase inhibitors, we have developed a unique ATP site binder tool for the detection of binders outside the ATP site by nuclear magnetic resonance (NMR). We report here the novel synthesis that led to this paramagnetic spin-labeled pyrazolopyrimidine probe (1), which exhibits nanomolar inhibitory activity against multiple kinases. We demonstrate the application of this probe by performing NMR binding experiments with Lck and Src kinases and utilize it to detect the binding of two compounds proximal to the ATP site. The complex structure of the probe with Lck is also presented, revealing how the probe fits in the ATP site and the specific interactions it has with the protein. We believe that this spin-labeled probe is a valuable tool that holds broad applicability in a screen for non-ATP site binders.

  DOI：

  10.1021/jm901525b
• 作为产物：
  描述：

  2-溴-7-氯吡唑并[1,5-a]嘧啶 、 3-氨基苯酚 以 1,4-二氧六环 、 溶剂黄146 为溶剂， 反应 0.17h， 以92%的产率得到3-[(2-bromopyrazolo[1,5-α]pyrimidin-7-yl)amino]phenol
  参考文献：
  名称：

  Novel Synthesis and Structural Characterization of a High-Affinity Paramagnetic Kinase Probe for the Identification of Non-ATP Site Binders by Nuclear Magnetic Resonance

  摘要：

  To aid in the pursuit of selective kinase inhibitors, we have developed a unique ATP site binder tool for the detection of binders outside the ATP site by nuclear magnetic resonance (NMR). We report here the novel synthesis that led to this paramagnetic spin-labeled pyrazolopyrimidine probe (1), which exhibits nanomolar inhibitory activity against multiple kinases. We demonstrate the application of this probe by performing NMR binding experiments with Lck and Src kinases and utilize it to detect the binding of two compounds proximal to the ATP site. The complex structure of the probe with Lck is also presented, revealing how the probe fits in the ATP site and the specific interactions it has with the protein. We believe that this spin-labeled probe is a valuable tool that holds broad applicability in a screen for non-ATP site binders.

  DOI：

  10.1021/jm901525b

文献信息

• Novel Synthesis and Structural Characterization of a High-Affinity Paramagnetic Kinase Probe for the Identification of Non-ATP Site Binders by Nuclear Magnetic Resonance
  作者：Franklin J. Moy、Arthur Lee、Lori Krim Gavrin、Zhang Bao Xu、Annette Sievers、Elizabeth Kieras、Wayne Stochaj、Lidia Mosyak、John McKew、Désirée H. H. Tsao

  DOI：10.1021/jm901525b

  日期：2010.2.11

  To aid in the pursuit of selective kinase inhibitors, we have developed a unique ATP site binder tool for the detection of binders outside the ATP site by nuclear magnetic resonance (NMR). We report here the novel synthesis that led to this paramagnetic spin-labeled pyrazolopyrimidine probe (1), which exhibits nanomolar inhibitory activity against multiple kinases. We demonstrate the application of this probe by performing NMR binding experiments with Lck and Src kinases and utilize it to detect the binding of two compounds proximal to the ATP site. The complex structure of the probe with Lck is also presented, revealing how the probe fits in the ATP site and the specific interactions it has with the protein. We believe that this spin-labeled probe is a valuable tool that holds broad applicability in a screen for non-ATP site binders.