1-(4-fluorophenyl)-3-hydroxy-5,6,7,8-tetrahydroisoquinoline-4-carbonitrile | 1268073-36-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-(4-fluorophenyl)-3-hydroxy-5,6,7,8-tetrahydroisoquinoline-4-carbonitrile
• 英文别名: 1-(4-fluorophenyl)-3-oxo-5,6,7,8-tetrahydro-2H-isoquinoline-4-carbonitrile
• CAS: 1268073-36-4
• 化学式: C₁₆H₁₃FN₂O
• 分子量: 268.29
• InChiKey: HVISFFNHYMOKAI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-fluorophenyl)-3-hydroxy-5,6,7,8-tetrahydroisoquinoline-4-carbonitrile 在 三氯氧磷 作用下， 反应 0.67h， 以27%的产率得到3-chloro-1-(4-fluorophenyl)-5,6,7,8-tetrahydroisoquinoline-4-carbonitrile
  参考文献：
  名称：

  Fragment based lead discovery of small molecule inhibitors for the EPHA4 receptor tyrosine kinase

  摘要：

  The in silico identification, optimization and crystallographic characterization of a 6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-1-amine scaffold as an inhibitor for the EPHA4 receptor tyrosine kinase is described. A database containing commercially available compounds was subjected to an in silico screening procedure which was focused on finding novel, EPHA4 hinge binding fragments. This resulted in the identification of 6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-1-amine derivatives as EPHA4 inhibitors. Hit exploration yielded a compound with 2 μM (IC(50)) affinity for the EPHA4 receptor tyrosine kinase domain. Soaking experiments into a crystal of the EPHA4 kinase domain gave a 2.11Å X-ray structure of the EPHA4 - inhibitor complex, which confirmed the binding mode of the scaffold as proposed by the initial in silico work. The results underscore the strength of fragment based in silico screening as a tool for the discovery of novel lead compounds as small molecule kinase inhibitors.

  DOI：

  10.1016/j.ejmech.2011.11.020
• 作为产物：
  描述：

  环己酮 在 哌啶 、 三乙胺 作用下， 以 乙醇 、 苯 为溶剂， 反应 50.0h， 生成 1-(4-fluorophenyl)-3-hydroxy-5,6,7,8-tetrahydroisoquinoline-4-carbonitrile
  参考文献：
  名称：

  Fragment based lead discovery of small molecule inhibitors for the EPHA4 receptor tyrosine kinase

  摘要：

  The in silico identification, optimization and crystallographic characterization of a 6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-1-amine scaffold as an inhibitor for the EPHA4 receptor tyrosine kinase is described. A database containing commercially available compounds was subjected to an in silico screening procedure which was focused on finding novel, EPHA4 hinge binding fragments. This resulted in the identification of 6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-1-amine derivatives as EPHA4 inhibitors. Hit exploration yielded a compound with 2 μM (IC(50)) affinity for the EPHA4 receptor tyrosine kinase domain. Soaking experiments into a crystal of the EPHA4 kinase domain gave a 2.11Å X-ray structure of the EPHA4 - inhibitor complex, which confirmed the binding mode of the scaffold as proposed by the initial in silico work. The results underscore the strength of fragment based in silico screening as a tool for the discovery of novel lead compounds as small molecule kinase inhibitors.

  DOI：

  10.1016/j.ejmech.2011.11.020

文献信息

• Fragment based lead discovery of small molecule inhibitors for the EPHA4 receptor tyrosine kinase
  作者：Oscar P.J. van Linden、Carine Farenc、Willem H. Zoutman、Liesbeth Hameetman、Maikel Wijtmans、Rob Leurs、Cornelis P. Tensen、Gregg Siegal、Iwan J.P. de Esch

  DOI：10.1016/j.ejmech.2011.11.020

  日期：2012.1

  The in silico identification, optimization and crystallographic characterization of a 6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-1-amine scaffold as an inhibitor for the EPHA4 receptor tyrosine kinase is described. A database containing commercially available compounds was subjected to an in silico screening procedure which was focused on finding novel, EPHA4 hinge binding fragments. This resulted in the identification of 6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-1-amine derivatives as EPHA4 inhibitors. Hit exploration yielded a compound with 2 μM (IC(50)) affinity for the EPHA4 receptor tyrosine kinase domain. Soaking experiments into a crystal of the EPHA4 kinase domain gave a 2.11Å X-ray structure of the EPHA4 - inhibitor complex, which confirmed the binding mode of the scaffold as proposed by the initial in silico work. The results underscore the strength of fragment based in silico screening as a tool for the discovery of novel lead compounds as small molecule kinase inhibitors.