4-(1-(5-(3-methoxy-2-thioxopyridin-1(2H)-yl)pentyl)-1H-1,2,3-triazol-4-yl)-2-(trifluoromethyl)benzonitrile | 1416915-60-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(1-(5-(3-methoxy-2-thioxopyridin-1(2H)-yl)pentyl)-1H-1,2,3-triazol-4-yl)-2-(trifluoromethyl)benzonitrile
• CAS: 1416915-60-0
• 化学式: C₂₁H₂₀F₃N₅OS
• 分子量: 447.484
• InChiKey: SVNVQDOEGJHRDE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.25
• 重原子数：
  31.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  68.66
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  4-(1-(5-(3-methoxy-2-thioxopyridin-1(2H)-yl)pentyl)-1H-1,2,3-triazol-4-yl)-2-(trifluoromethyl)benzonitrile 在 三溴化硼 、 甲醇 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 以66%的产率得到4-(1-(5-(3-hydroxy-2-thioxopyridin-1(2H)-yl)pentyl)-1H-1,2,3-triazol-4-yl)-2-(trifluoromethyl)benzonitrile
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationship of 3-Hydroxypyridine-2-thione-Based Histone Deacetylase Inhibitors

  摘要：

  We previously identified 3-hydroxypyridine-2-thione (3HPT) as a novel zinc binding group for histone deacetylase (HDAC) inhibition. Early structure activity relationship (SAR) studies led to various small molecules possessing selective inhibitory activity against HDAC6 or HDAC8 but devoid of HDAC1 inhibition. To delineate further the depth of the SAR of 3HPT-derived HDAC inhibitors (HDACi), we have extended the SAR studies to include the linker region and the surface recognition group to optimize the HDAC inhibition. The current efforts resulted in the identification of two lead compounds, 10d and 14e, with potent HDAC6 and HDAC8 activities that are inactive against HDAC1. These new HDACi possess anticancer activities against various cancer cell lines including Jurkat J.gamma 1 for which SAHA and the previously disclosed 3HPT-derived HDACi were inactive.

  DOI：

  10.1021/jm401225q
• 作为产物：
  描述：

  1-(1-(5-azidopentyl))-3-methoxypyridin-2-one 在 劳森试剂 、 copper(l) iodide 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二甲基亚砜 、 甲苯 为溶剂， 反应 16.0h， 生成 4-(1-(5-(3-methoxy-2-thioxopyridin-1(2H)-yl)pentyl)-1H-1,2,3-triazol-4-yl)-2-(trifluoromethyl)benzonitrile
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationship of 3-Hydroxypyridine-2-thione-Based Histone Deacetylase Inhibitors

  摘要：

  We previously identified 3-hydroxypyridine-2-thione (3HPT) as a novel zinc binding group for histone deacetylase (HDAC) inhibition. Early structure activity relationship (SAR) studies led to various small molecules possessing selective inhibitory activity against HDAC6 or HDAC8 but devoid of HDAC1 inhibition. To delineate further the depth of the SAR of 3HPT-derived HDAC inhibitors (HDACi), we have extended the SAR studies to include the linker region and the surface recognition group to optimize the HDAC inhibition. The current efforts resulted in the identification of two lead compounds, 10d and 14e, with potent HDAC6 and HDAC8 activities that are inactive against HDAC1. These new HDACi possess anticancer activities against various cancer cell lines including Jurkat J.gamma 1 for which SAHA and the previously disclosed 3HPT-derived HDACi were inactive.

  DOI：

  10.1021/jm401225q