(E)-4-(3-carbamoylphenylamino)-4-oxobut-2-enoic acid | 1394131-73-7

• 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: (E)-4-(3-carbamoylphenylamino)-4-oxobut-2-enoic acid
• 英文别名: (2E)-4-[(3-carbamoylphenyl)amino]-4-oxobut-2-enoic acid；(E)-4-(3-carbamoylanilino)-4-oxobut-2-enoic acid
• CAS: 1394131-73-7
• 化学式: C₁₁H₁₀N₂O₄
• mdl: MFCD00977880
• 分子量: 234.211
• InChiKey: GNFSYBNDPOBXLJ-SNAWJCMRSA-N

物化性质

• 沸点：
  561.7±50.0 °C(Predicted)
• 密度：
  1.441±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-4-(3-carbamoylphenylamino)-4-oxobut-2-enoic acid 、 盐酸甲胺 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 68.0h， 以38%的产率得到N¹-(3-carbamoylphenyl)-N⁴-methylfumaramide
  参考文献：
  名称：

  Towards small molecule inhibitors of mono-ADP-ribosyltransferases

  摘要：

  Protein ADP-ribosylation is a post-translational modification involved in DNA repair, protein degradation, transcription regulation, and epigenetic events. Intracellular ADP-ribosylation is catalyzed predominantly by ADP-ribosyltransferases with diphtheria toxin homology (ARTDs). The most prominent member of the ARTD family, poly(ADP-ribose) polymerase-1 (ARTD1/PARP1) has been a target for cancer drug development for decades. Current PARP inhibitors are generally non-selective, and inhibit the mono-ADP-ribosyltransferases with low potency. Here we describe the synthesis of acylated amino benzamides and screening against the mono-ADP-ribosyltransferases ARTD7/PARP15, ARTD8/PARP14, ARTD10/PARP10, and the poly-ADP-ribosyltransferase ARTD1/PARP1. The most potent compound inhibits ARTD10 with sub-micromolar IC50. (C) 2015 The Authors. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.03.067
• 作为产物：
  描述：

  3-氨基苯甲酰胺 、 富马酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 1,4-二氧六环 为溶剂， 反应 23.0h， 以41%的产率得到(E)-4-(3-carbamoylphenylamino)-4-oxobut-2-enoic acid
  参考文献：
  名称：

  Discovery of Ligands for ADP-Ribosyltransferases via Docking-Based Virtual Screening

  摘要：

  The diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are an enzyme family that catalyzes the transfer of ADP-ribose units onto substrate proteins by using nicotinamide adenine dinucleotide (NAD(+)) as a cosubstrate. They have a documented role in chromatin remodelling and DNA repair, and inhibitors of ARTD1 and 2 (PARP1 and 2) are currently in clinical trials for the treatment of cancer. The detailed function of most other ARTDs is still unknown. By using virtual screening, we identified small ligands of ARTD7 (PARP15/BAL3) and ARTD8 (PARP14/BAL2). Thermal-shift assays confirmed that 16 compounds, belonging to eight structural classes, bound to ARTD7/ARTD8. Affinity measurements with isothermal titration calorimetry for two isomers of the most promising hit compound confirmed binding in the low micromolar range to ARTD8. Crystal structures showed anchoring of the hits in the nicotinamide pocket. These results form a starting point in the development of chemical tools for the study of the role and function of ARTD7 and ARTD8.

  DOI：

  10.1021/jm300746d

文献信息

• Towards small molecule inhibitors of mono-ADP-ribosyltransferases
  作者：Torun Ekblad、Anders E.G. Lindgren、C. David Andersson、Rémi Caraballo、Ann-Gerd Thorsell、Tobias Karlberg、Sara Spjut、Anna Linusson、Herwig Schüler、Mikael Elofsson

  DOI：10.1016/j.ejmech.2015.03.067

  日期：2015.5

  Protein ADP-ribosylation is a post-translational modification involved in DNA repair, protein degradation, transcription regulation, and epigenetic events. Intracellular ADP-ribosylation is catalyzed predominantly by ADP-ribosyltransferases with diphtheria toxin homology (ARTDs). The most prominent member of the ARTD family, poly(ADP-ribose) polymerase-1 (ARTD1/PARP1) has been a target for cancer drug development for decades. Current PARP inhibitors are generally non-selective, and inhibit the mono-ADP-ribosyltransferases with low potency. Here we describe the synthesis of acylated amino benzamides and screening against the mono-ADP-ribosyltransferases ARTD7/PARP15, ARTD8/PARP14, ARTD10/PARP10, and the poly-ADP-ribosyltransferase ARTD1/PARP1. The most potent compound inhibits ARTD10 with sub-micromolar IC50. (C) 2015 The Authors. Published by Elsevier Masson SAS.
• Discovery of Ligands for ADP-Ribosyltransferases via Docking-Based Virtual Screening
  作者：C. David Andersson、Tobias Karlberg、Torun Ekblad、Anders E. G. Lindgren、Ann-Gerd Thorsell、Sara Spjut、Urszula Uciechowska、Moritz S. Niemiec、Pernilla Wittung-Stafshede、Johan Weigelt、Mikael Elofsson、Herwig Schüler、Anna Linusson

  DOI：10.1021/jm300746d

  日期：2012.9.13

  The diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are an enzyme family that catalyzes the transfer of ADP-ribose units onto substrate proteins by using nicotinamide adenine dinucleotide (NAD(+)) as a cosubstrate. They have a documented role in chromatin remodelling and DNA repair, and inhibitors of ARTD1 and 2 (PARP1 and 2) are currently in clinical trials for the treatment of cancer. The detailed function of most other ARTDs is still unknown. By using virtual screening, we identified small ligands of ARTD7 (PARP15/BAL3) and ARTD8 (PARP14/BAL2). Thermal-shift assays confirmed that 16 compounds, belonging to eight structural classes, bound to ARTD7/ARTD8. Affinity measurements with isothermal titration calorimetry for two isomers of the most promising hit compound confirmed binding in the low micromolar range to ARTD8. Crystal structures showed anchoring of the hits in the nicotinamide pocket. These results form a starting point in the development of chemical tools for the study of the role and function of ARTD7 and ARTD8.