methyl 4-[(Z)-2-(4-nitrophenyl)ethenyl]benzoate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: methyl 4-[(Z)-2-(4-nitrophenyl)ethenyl]benzoate
• 化学式: C16H13NO4
• 分子量: 283.28
• InChiKey: PTBDNZRVAGPHKG-IHWYPQMZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-溴甲基苯甲酸甲酯 在 potassium tert-butylate 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 2.0h， 生成 (E)-甲基4-(4-硝基苯乙烯)苯甲酸 、 methyl 4-[(Z)-2-(4-nitrophenyl)ethenyl]benzoate
  参考文献：
  名称：

  What doesn't fit is made to fit: Pim‐1 kinase adapts to the configuration of stilbene‐based inhibitors

  摘要：

  Recently, we have developed novel Pim‐1 kinase inhibitors starting from a dihydrobenzofuran core structure using a computational approach. Here, we report the design and synthesis of stilbene‐based Pim‐1 kinase inhibitors obtained by formal elimination of the dihydrofuran ring. These inhibitors of the first design cycle, which were obtained as inseparable cis/trans mixtures, showed affinities in the low single‐digit micromolar range. To be able to further optimize these compounds in a structure‐based fashion, we determined the X‐ray structures of the protein‐ligand‐complexes. Surprisingly, only the cis‐isomer binds upon crystallization of the cis/trans‐mixture of the ligands with Pim‐1 kinase and the substrate PIMTIDE, the binding mode being largely consistent with that predicted by docking. After crystallization of the exclusively trans‐configured derivatives, a markedly different binding mode for the inhibitor and a concomitant rearrangement of the glycine‐rich loop is observed, resulting in the ligand being deeply buried in the binding pocket.

  DOI：

  10.1002/ardp.202400094

文献信息

• What doesn't fit is made to fit: Pim‐1 kinase adapts to the configuration of stilbene‐based inhibitors
  作者：Phil M. M. Hochban、Lukas Heyder、Andreas Heine、Wibke E. Diederich

  DOI：10.1002/ardp.202400094

  日期：——

  Recently, we have developed novel Pim‐1 kinase inhibitors starting from a dihydrobenzofuran core structure using a computational approach. Here, we report the design and synthesis of stilbene‐based Pim‐1 kinase inhibitors obtained by formal elimination of the dihydrofuran ring. These inhibitors of the first design cycle, which were obtained as inseparable cis/trans mixtures, showed affinities in the low single‐digit micromolar range. To be able to further optimize these compounds in a structure‐based fashion, we determined the X‐ray structures of the protein‐ligand‐complexes. Surprisingly, only the cis‐isomer binds upon crystallization of the cis/trans‐mixture of the ligands with Pim‐1 kinase and the substrate PIMTIDE, the binding mode being largely consistent with that predicted by docking. After crystallization of the exclusively trans‐configured derivatives, a markedly different binding mode for the inhibitor and a concomitant rearrangement of the glycine‐rich loop is observed, resulting in the ligand being deeply buried in the binding pocket.