methyl 3-(benzyloxy)-4-(3-benzyloxy-4-nitrobenzamido)-benzoate | 1379520-51-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 3-(benzyloxy)-4-(3-benzyloxy-4-nitrobenzamido)-benzoate
• 英文别名: Methyl 4-[(4-nitro-3-phenylmethoxybenzoyl)amino]-3-phenylmethoxybenzoate；methyl 4-[(4-nitro-3-phenylmethoxybenzoyl)amino]-3-phenylmethoxybenzoate
• CAS: 1379520-51-0
• 化学式: C₂₉H₂₄N₂O₇
• 分子量: 512.519
• InChiKey: XZYSFMXWWNIFSW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-(benzyloxy)-4-nitrobenzoic acid 在 草酰氯 、 N,N-二甲基苯胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 2.0h， 生成 methyl 3-(benzyloxy)-4-(3-benzyloxy-4-nitrobenzamido)-benzoate
  参考文献：
  名称：

  Perturbation of the c-Myc–Max Protein–Protein Interaction via Synthetic α-Helix Mimetics

  摘要：

  The rational design of inhibitors of the bHLH-ZIP oncoprotein c-Myc is hampered by a lack of structure in its monomeric state. We describe herein the design of novel, low-molecular-weight, synthetic a-helix mimetics that recognize helical c-Myc in its transcriptionally active coiled-coil structure in association with its obligate bHLH-ZIP partner Max. These compounds perturb the heterodimers binding to its canonical E-box DNA sequence without causing protein-protein dissociation, heralding a new mechanistic class of direct c-Myc inhibitors. In addition to electrophoretic mobility shift assays, this model was corroborated by further biophysical methods, including NMR spectroscopy and surface plasmon resonance. Several compounds demonstrated a 2-fold or greater selectivity for c-Myc-Max heterodimers over Max-Max homodimers with IC50 values as low as 5.6 mu M. Finally, these compounds inhibited the proliferation of c-Myc-expressing cell lines in a concentration-dependent manner that correlated with the loss of expression of a c-Myc-dependent reporter plasmid despite the fact that c-MycMax heterodimers remained intact.

  DOI：

  10.1021/jm501440q

文献信息

• Conformational properties of O-alkylated benzamides
  作者：Panchami Prabhakaran、Valeria Azzarito、Tia Jacobs、Michaele J. Hardie、Colin A. Kilner、Thomas A. Edwards、Stuart L. Warriner、Andrew J. Wilson

  DOI：10.1016/j.tet.2011.11.078

  日期：2012.6

  conformational pre-organization and side chains can interact with each other within a molecule. In the solid-state three-dimensional arrangement, the molecules further interact with each other through non-covalent interactions. Given, the demonstrated potential of this class of scaffolds to act as helix mimetics for the inhibition of protein–protein interactions (PPIs), these results provide key insight for future

  在本文中，我们报告了基于两个支架的O-烷基化芳族苯甲酰胺的合成，固态和溶液态构象研究。分子内氢键提供构象预组织，并且侧链可以在分子内彼此相互作用。在固态三维排列中，分子还通过非共价相互作用彼此相互作用。鉴于这类脚手架具有被证明可以作为螺旋模拟物抑制蛋白质-蛋白质相互作用（PPI）的潜力，这些结果为未来抑制剂的设计提供了重要的见识。
• Perturbation of the c-Myc–Max Protein–Protein Interaction via Synthetic α-Helix Mimetics
  作者：Kwan-Young Jung、Huabo Wang、Peter Teriete、Jeremy L. Yap、Lijia Chen、Maryanna E. Lanning、Angela Hu、Lester J. Lambert、Toril Holien、Anders Sundan、Nicholas D. P. Cosford、Edward V. Prochownik、Steven Fletcher

  DOI：10.1021/jm501440q

  日期：2015.4.9

  The rational design of inhibitors of the bHLH-ZIP oncoprotein c-Myc is hampered by a lack of structure in its monomeric state. We describe herein the design of novel, low-molecular-weight, synthetic a-helix mimetics that recognize helical c-Myc in its transcriptionally active coiled-coil structure in association with its obligate bHLH-ZIP partner Max. These compounds perturb the heterodimers binding to its canonical E-box DNA sequence without causing protein-protein dissociation, heralding a new mechanistic class of direct c-Myc inhibitors. In addition to electrophoretic mobility shift assays, this model was corroborated by further biophysical methods, including NMR spectroscopy and surface plasmon resonance. Several compounds demonstrated a 2-fold or greater selectivity for c-Myc-Max heterodimers over Max-Max homodimers with IC50 values as low as 5.6 mu M. Finally, these compounds inhibited the proliferation of c-Myc-expressing cell lines in a concentration-dependent manner that correlated with the loss of expression of a c-Myc-dependent reporter plasmid despite the fact that c-MycMax heterodimers remained intact.