N¹-(3-carbamoylphenyl)-N⁴-methylfumaramide

• 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: N¹-(3-carbamoylphenyl)-N⁴-methylfumaramide
• 英文别名: (E)-N'-(3-carbamoylphenyl)-N-methylbut-2-enediamide
• 化学式: C₁₂H₁₃N₃O₃
• 分子量: 247.254
• InChiKey: FYQRBLGGKLIYRQ-AATRIKPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  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

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.