[2-(4-Methoxyphenyl)-2-oxoethyl]azanium

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [2-(4-Methoxyphenyl)-2-oxoethyl]azanium
• 化学式: C₉H₁₁NO₂*H
• 分子量: 166.2
• InChiKey: CNYAWQABGNEMFC-UHFFFAOYSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  53.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  [2-(4-Methoxyphenyl)-2-oxoethyl]azanium 、 苯甲酰甲酸 在 N,N'-羰基二咪唑 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 1.0h， 生成 N-(2-(4-methoxyphenyl)-2-oxoethyl)-2-phenyl-2-oxoacetamide
  参考文献：
  名称：

  Effective synthesis of 3,5-diaryl-(1H)-pyrazin-2-ones via microwave mediated ring closure

  摘要：

  In this study we report on a flexible straight forward synthesis toward novel 3,5-diaryl-(1H)-pyrazin-2-ones. Our synthetic strategy involved an acyclic di-keto derivative as key intermediate. The final pyrazin-2-one ring closure reaction was yield-optimized by using a microwave mediated procedure and ammoniumacetate as nitrogen source. Our method is a suitable alternative to palladium-catalyzed coupling reactions for the 3,5-diaryl decoration of the (1H)-pyrazin-2-one scaffold. Since the (1H)-pyrazin-2-ones is present as scaffold in a number of biologically active compounds the reported synthetic platform is a useful approach to generate a set of highly diverse 3,5-diaryl-(1H)-pyrazin-2-one compounds. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2013.05.095

文献信息

• Optimization of Potent <i>DFG-in</i> Inhibitors of Platelet Derived Growth Factor Receptorβ (PDGF-Rβ) Guided by Water Thermodynamics
  作者：Rebecca Horbert、Boris Pinchuk、Eugen Johannes、Joachim Schlosser、Dorian Schmidt、Daniel Cappel、Frank Totzke、Christoph Schächtele、Christian Peifer

  DOI：10.1021/jm500373x

  日期：2015.1.8

  In this study we report on the hit optimization of substituted 3,5-diaryl-pyrazin-2(1H)-ones toward potent and effective platelet-derived growth factor receptor (PDGF-R) beta-inhibitors. Originally, the 3,5-diaryl-pyrazin-2-one core was derived from the marine sponge alkaloid family of hamacanthins. In our first series compound 2 was discovered as a promising hit showing strong activity against PDGF-R beta in the kinase assay (IC50 = 0.5 mu M). Furthermore, 2 was shown to be selective for PDGF-R beta in a panel of 24 therapeutically relevant protein kinases. Molecular modeling studies on a PDGF-R beta homology model using prediction of water thermodynamics suggested an optimization strategy for the 3,5-diaryl-pyrazin-2-ones as DFG-in binders by using a phenolic OH function to replace a structural water molecule in the ATP binding site. Indeed, we identified compound 38 as a highly potent inhibitor with an IC50 value of 0.02 mu M in a PDGF-R beta enzymatic assay also showing activity against PDGF-R dependent cancer cells.