4-(3-((2,3-dihydro-1H-inden-2-yl)oxy)-4-nitrobenzamido)-3-isobutoxybenzoic acid

• 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: 4-(3-((2,3-dihydro-1H-inden-2-yl)oxy)-4-nitrobenzamido)-3-isobutoxybenzoic acid
• 英文别名: 4-[[3-(2,3-dihydro-1H-inden-2-yloxy)-4-nitrobenzoyl]amino]-3-(2-methylpropoxy)benzoic acid
• 化学式: C₂₇H₂₆N₂O₇
• 分子量: 490.513
• InChiKey: RNRHZOZLQOPAMT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  131
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(3-((2,3-dihydro-1H-inden-2-yl)oxy)-4-nitrobenzamido)-3-isobutoxybenzoic acid 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 5.0h， 以55 mg的产率得到4-(4-amino-3-((2,3-dihydro-1H-inden-2-yl)oxy)benzamido)-3-isobutoxybenzoic acid
  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
• 作为产物：
  描述：

  2-茚醇 在 草酰氯 、 sodium hydride 、 N,N-二甲基苯胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 为溶剂， 反应 4.5h， 生成 4-(3-((2,3-dihydro-1H-inden-2-yl)oxy)-4-nitrobenzamido)-3-isobutoxybenzoic acid
  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