(E)-2-Cyano-3-(4-nitro-phenyl)-acrylic acid tert-butyl ester

• 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: (E)-2-Cyano-3-(4-nitro-phenyl)-acrylic acid tert-butyl ester
• 英文别名: tert-butyl (E)-2-cyano-3-(4-nitrophenyl)prop-2-enoate
• 化学式: C₁₄H₁₄N₂O₄
• 分子量: 274.276
• InChiKey: QBFGYJOTPAHYLE-DHZHZOJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  95.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (E)-2-Cyano-3-(4-nitro-phenyl)-acrylic acid tert-butyl ester 在 三氟乙酸 作用下， 反应 0.5h， 以90%的产率得到trans-<4-Nitro-benzyliden>-malonsaeure-mononitril
  参考文献：
  名称：

  Tyrphostins I: synthesis and biological activity of protein tyrosine kinase inhibitors

  摘要：

  A novel class of low molecular weight protein tyrosine kinase inhibitors is described. These compounds constitute a systematic series of molecules with a progressive increase in affinity toward the substrate site of the EGF receptor kinase domain. These competitive inhibitors also effectively block the EGF-dependent autophosphorylation of the receptor. The potent EGF receptor kinase blockers examined were found to competitively inhibit the homologous insulin receptor kinase at 10(2)-10(3) higher inhibitor concentrations in spite of the significant homology between these protein tyrosine kinases. These results demonstrate the ability to synthesize selective tyrosine kinase inhibitors. The most potent EGF receptor kinase inhibitors also inhibit the EGF-dependent proliferation of A431/clone 15 cells with little or no effect on EGF independent cell growth. These results demonstrate the potential use of protein tyrosine kinase inhibitors as selective antiproliferative agents for proliferative diseases caused by the hyperactivity of protein tyrosine kinases. We have suggested the name "tyrphostins" for this class of antiproliferative compounds which act as protein tyrosine kinase blockers.

  DOI：

  10.1021/jm00130a020
• 作为产物：
  描述：

  对硝基苯甲醛 、 氰乙酸叔丁酯 在 magnesium 作用下， 以 水 为溶剂， 以94 %的产率得到(E)-2-Cyano-3-(4-nitro-phenyl)-acrylic acid tert-butyl ester
  参考文献：
  名称：

  水相条件下使用镁催化剂绿色合成亲电烯烃以及密度泛函理论的机理见解

  摘要：

  通过在含水条件下使用镁粉在活性亚甲基化合物和羰基化合物之间进行克诺文格尔缩合，开发了一种合成亲电子烯烃的绿色方法。在该策略中，Mg(OH) 2充当催化剂，它是通过金属镁（20 mol%）和水之间的反应原位生成的。人们发现镁是一种高效、无毒且廉价的金属催化剂体系，可以以优异的产率（≤98%）生产一系列亲电子烯烃。已经开发出克级亲电烯烃的合成方法，并且金属镁被回收并循环使用多达三次，而催化活性没有明显损失。提出了催化循环，并利用密度泛函理论研究了反应机理。关键步骤是氰基乙酸乙酯的烯醇化、C-C键形成，然后通过H 2 O复分解使催化剂再生。整个反应很容易发生，最大ΔG ° ⧧值为7.9 kcal/mol，速率为确定C-C键形成步骤。我们的方案具有多个优点，可以进一步扩展到一锅顺序 Knoevenagel 缩合和 Michael 加成，并且一锅顺序 Knoevenagel 缩合和化学选择性还原可用

  DOI：

  10.1021/acs.joc.3c01540

文献信息

• GAZIT, AVIV;YAISH, PNINA;GILON, CHAIM;LEVITZKI, ALEXANDER, J. MED. CHEM., 32,(1989) N0, C. 2344-2352
  作者：GAZIT, AVIV、YAISH, PNINA、GILON, CHAIM、LEVITZKI, ALEXANDER

  DOI：——

  日期：——
• Tyrphostins I: synthesis and biological activity of protein tyrosine kinase inhibitors
  作者：Aviv Gazit、Pnina Yaish、Chaim Gilon、Alexander Levitzki

  DOI：10.1021/jm00130a020

  日期：1989.10

  A novel class of low molecular weight protein tyrosine kinase inhibitors is described. These compounds constitute a systematic series of molecules with a progressive increase in affinity toward the substrate site of the EGF receptor kinase domain. These competitive inhibitors also effectively block the EGF-dependent autophosphorylation of the receptor. The potent EGF receptor kinase blockers examined were found to competitively inhibit the homologous insulin receptor kinase at 10(2)-10(3) higher inhibitor concentrations in spite of the significant homology between these protein tyrosine kinases. These results demonstrate the ability to synthesize selective tyrosine kinase inhibitors. The most potent EGF receptor kinase inhibitors also inhibit the EGF-dependent proliferation of A431/clone 15 cells with little or no effect on EGF independent cell growth. These results demonstrate the potential use of protein tyrosine kinase inhibitors as selective antiproliferative agents for proliferative diseases caused by the hyperactivity of protein tyrosine kinases. We have suggested the name "tyrphostins" for this class of antiproliferative compounds which act as protein tyrosine kinase blockers.