N-(4-溴-3-甲基苯基)-3-硝基苯甲酰胺 | 62129-28-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-(4-溴-3-甲基苯基)-3-硝基苯甲酰胺
• 英文名称: N-(4-bromo-3-methylphenyl)-3-nitrobenzamide
• 英文别名: 3-nitro-benzoic acid-(4-bromo-3-methyl-anilide)；3-Nitro-benzoesaeure-(4-brom-3-methyl-anilid)
• CAS: 62129-28-6
• 化学式: C₁₄H₁₁BrN₂O₃
• 分子量: 335.157
• InChiKey: CMGASBTUUYNEPI-UHFFFAOYSA-N

物化性质

• 沸点：
  379.4±42.0 °C(Predicted)
• 密度：
  1.576±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-溴-3-甲基苯基)-3-硝基苯甲酰胺 在 tin(II) chloride dihdyrate 、 chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′,4′,6′-tri-1-propyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II) 、 caesium carbonate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 乙醇 、 叔丁醇 为溶剂， 反应 9.5h， 生成 3-acrylamido-N-(4-((4-(4-(4-fluorophenyl)-1-methyl-2-(methylthio)-1H-imidazol-5-yl)pyridin-2-yl)amino)-3-methylphenyl)benzamide
  参考文献：
  名称：

  Tri- and Tetrasubstituted Pyridinylimidazoles as Covalent Inhibitors of c-Jun N-Terminal Kinase 3

  摘要：

  The concept of covalent inhibition of c-Jun N-terminal kinase 3 (JNK3) was successfully transferred to our well validated pyridinylimidazole scaffold varying several structural features in order to deduce crucial structure-activity relationships. Joint targeting of the hydrophobic region I and methylation of imidazole-N1 position increased the activity and reduced the number of off-targets. The most promising covalent inhibitor, the tetrasubstituted imidazole 3-acrylamido-N-(4-((4-(4-(4-fluoropheny1)-1-methyl-2-(methylthio)-1H-imidazol-S-yl)pyridin-2-yl)amino)phenyl)benzamide (7) inhibits the JNK3 in the subnanomolar range (IC50 = 0.3 nM), shows high metabolic stability in human liver microsomes, and displays excellent selectivity in a screening against a panel of 410 kinases. Covalent bond formation to Cys-154 was confirmed by incubation of the inhibitors with wild-type JNK3 and JNK3-C154A mutant followed by mass spectrometry.

  DOI：

  10.1021/acs.jmedchem.6b01180
• 作为产物：
  描述：

  4-溴-3-甲基苯胺 、 间硝基苯甲酸 在 4-acetamidophenyl triflimide 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 以86 %的产率得到N-(4-溴-3-甲基苯基)-3-硝基苯甲酰胺
  参考文献：
  名称：

  AITF（4-乙酰氨基苯基三氟甲酰亚胺）介导的酰胺、肽和酯的合成

  摘要：

  描述了一种简单、广泛适用的酰胺化和酯化反应方案。因此，结晶稳定试剂 4-乙酰氨基苯基三氟甲酰亚胺 (AITF) 可用于活化羧酸。 AITF 作为偶联剂的使用在温和条件下的肽、酰胺和酯的合成中得到了证明，产率良好至优异。值得注意的是，还完成了肽片段缩合。完成了多种合成方案，展示了广泛的底物范围和良好的官能团兼容性。在此，我们系统地总结了AITF在肽合成策略中的应用。

  DOI：

  10.1039/d3ob01351k

文献信息

• Tri- and Tetrasubstituted Pyridinylimidazoles as Covalent Inhibitors of c-Jun N-Terminal Kinase 3
  作者：Felix Muth、Ahmed El-Gokha、Francesco Ansideri、Michael Eitel、Eva Döring、Adrian Sievers-Engler、Andreas Lange、Frank M. Boeckler、Michael Lämmerhofer、Pierre Koch、Stefan A. Laufer

  DOI：10.1021/acs.jmedchem.6b01180

  日期：2017.1.26

  The concept of covalent inhibition of c-Jun N-terminal kinase 3 (JNK3) was successfully transferred to our well validated pyridinylimidazole scaffold varying several structural features in order to deduce crucial structure-activity relationships. Joint targeting of the hydrophobic region I and methylation of imidazole-N1 position increased the activity and reduced the number of off-targets. The most promising covalent inhibitor, the tetrasubstituted imidazole 3-acrylamido-N-(4-((4-(4-(4-fluoropheny1)-1-methyl-2-(methylthio)-1H-imidazol-S-yl)pyridin-2-yl)amino)phenyl)benzamide (7) inhibits the JNK3 in the subnanomolar range (IC50 = 0.3 nM), shows high metabolic stability in human liver microsomes, and displays excellent selectivity in a screening against a panel of 410 kinases. Covalent bond formation to Cys-154 was confirmed by incubation of the inhibitors with wild-type JNK3 and JNK3-C154A mutant followed by mass spectrometry.