5H4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 5H4
• 英文别名: AG 490, m-CF3；(E)-2-cyano-3-(3,4-dihydroxyphenyl)-N-[[3-(trifluoromethyl)phenyl]methyl]prop-2-enamide
• 化学式: C₁₈H₁₃F₃N₂O₃
• 分子量: 362.308
• InChiKey: CBZPIGMULPRVPO-AWNIVKPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  93.4
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-(三氟甲基)苯甲胺 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 7.0h， 生成 5H4
  参考文献：
  名称：

  Combinatorial approach to identification of tyrphostin inhibitors of cytokine signaling

  摘要：

  Aberrant or deregulated activity of certain cellular kinases has been shown to cause certain malignancies and other disorders. The tyrphostin molecule AG490 inhibits the action of the janus kinases JAK2 and JAK3. JAK2 is an indispensable molecule for transducing the signals conveyed by a large number of cytokines including IL-3 while JAK3 is essential for signaling by a smaller number of cytokines including IL-7. A synthetic combinatorial chemical library containing 599 compounds was created and screened for the ability to inhibit proliferation of IL3- and IL7-dependent cell lines to focus on molecules that interrupt those signaling pathways. This screen identified a meta-trilluoromethyl derivative of AG490, 5H4, that is approximately twice as potent as AG490 in cell-based assays. 5H4 blocked the factor-dependent proliferation of both of these cell lines, actively promoted cell death, and diminished the JAK kinase activity. Administration of 5H4 to lymphoma-prone IL-7 transgenic mice reduced their spontaneous lymphadenopathy. The improved characteristics of this novel compound bring this class of molecules closer to therapeutic utility. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.04.022

文献信息

• Combinatorial approach to identification of tyrphostin inhibitors of cytokine signaling
  作者：Ling Gu、Hui Zhuang、Brian Safina、Xiao-yi Xiao、Wallace W. Bradford、Benjamin E. Rich

  DOI：10.1016/j.bmc.2005.04.022

  日期：2005.7

  Aberrant or deregulated activity of certain cellular kinases has been shown to cause certain malignancies and other disorders. The tyrphostin molecule AG490 inhibits the action of the janus kinases JAK2 and JAK3. JAK2 is an indispensable molecule for transducing the signals conveyed by a large number of cytokines including IL-3 while JAK3 is essential for signaling by a smaller number of cytokines including IL-7. A synthetic combinatorial chemical library containing 599 compounds was created and screened for the ability to inhibit proliferation of IL3- and IL7-dependent cell lines to focus on molecules that interrupt those signaling pathways. This screen identified a meta-trilluoromethyl derivative of AG490, 5H4, that is approximately twice as potent as AG490 in cell-based assays. 5H4 blocked the factor-dependent proliferation of both of these cell lines, actively promoted cell death, and diminished the JAK kinase activity. Administration of 5H4 to lymphoma-prone IL-7 transgenic mice reduced their spontaneous lymphadenopathy. The improved characteristics of this novel compound bring this class of molecules closer to therapeutic utility. (c) 2005 Elsevier Ltd. All rights reserved.