4-((2-氰基苯基)氨基)-4-氧代丁酸 | 348152-61-4

• 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: 4-((2-氰基苯基)氨基)-4-氧代丁酸
• 英文名称: 4-[(2-cyanophenyl)amino]-4-oxobutanoic acid
• 英文别名: 4-(2-Cyanoanilino)-4-oxobutanoic acid
• CAS: 348152-61-4
• 化学式: C₁₁H₁₀N₂O₃
• mdl: MFCD00449643
• 分子量: 218.212
• InChiKey: WERGBWJJKMEKED-UHFFFAOYSA-N

物化性质

• 沸点：
  537.1±35.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.181
• 拓扑面积：
  90.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-((2-氰基苯基)氨基)-4-氧代丁酸 在 过氧化脲素 、 potassium carbonate 作用下， 以 水 、 丙酮 为溶剂， 以68%的产率得到3-(4-氧代-3,4-二氢-2-喹唑啉)-丙酸
  参考文献：
  名称：

  Chemical Probes to Study ADP-Ribosylation: Synthesis and Biochemical Evaluation of Inhibitors of the Human ADP-Ribosyltransferase ARTD3/PARP3

  摘要：

  The racemic 3-(4-oxo-3,4-dihydroquinazolin-2-yl)-N-[1-(pyridin-2-yl)ethyl]propanamide, 1, has previously been identified as a potent but unselective inhibitor of diphtheria toxin-like ADP-ribosyltransferase 3 (ARTD3). Herein we describe synthesis and evaluation of SS compounds in this class. It was found that the stereochemistry is of great importance for both selectivity and potency and that substituents on the phenyl ring resulted in poor solubility. Certain variations at the meso position were tolerated and caused a large shift in the binding pose. Changes to the ethylene linker that connects the quinazolinone to the amide were also investigated but proved detrimental to binding. By combination of synthetic organic chemistry and structure-based design, two selective inhibitors of ARTD3 were discovered.

  DOI：

  10.1021/jm401394u
• 作为产物：
  描述：

  丁二酸酐 、 2-氨基苯甲腈 以 甲苯 为溶剂， 以96%的产率得到4-((2-氰基苯基)氨基)-4-氧代丁酸
  参考文献：
  名称：

  Chemical Probes to Study ADP-Ribosylation: Synthesis and Biochemical Evaluation of Inhibitors of the Human ADP-Ribosyltransferase ARTD3/PARP3

  摘要：

  The racemic 3-(4-oxo-3,4-dihydroquinazolin-2-yl)-N-[1-(pyridin-2-yl)ethyl]propanamide, 1, has previously been identified as a potent but unselective inhibitor of diphtheria toxin-like ADP-ribosyltransferase 3 (ARTD3). Herein we describe synthesis and evaluation of SS compounds in this class. It was found that the stereochemistry is of great importance for both selectivity and potency and that substituents on the phenyl ring resulted in poor solubility. Certain variations at the meso position were tolerated and caused a large shift in the binding pose. Changes to the ethylene linker that connects the quinazolinone to the amide were also investigated but proved detrimental to binding. By combination of synthetic organic chemistry and structure-based design, two selective inhibitors of ARTD3 were discovered.

  DOI：

  10.1021/jm401394u

文献信息

• Chemical Probes to Study ADP-Ribosylation: Synthesis and Biochemical Evaluation of Inhibitors of the Human ADP-Ribosyltransferase ARTD3/PARP3
  作者：Anders E. G. Lindgren、Tobias Karlberg、Torun Ekblad、Sara Spjut、Ann-Gerd Thorsell、C. David Andersson、Ton Tong Nhan、Victor Hellsten、Johan Weigelt、Anna Linusson、Herwig Schüler、Mikael Elofsson

  DOI：10.1021/jm401394u

  日期：2013.12.12

  The racemic 3-(4-oxo-3,4-dihydroquinazolin-2-yl)-N-[1-(pyridin-2-yl)ethyl]propanamide, 1, has previously been identified as a potent but unselective inhibitor of diphtheria toxin-like ADP-ribosyltransferase 3 (ARTD3). Herein we describe synthesis and evaluation of SS compounds in this class. It was found that the stereochemistry is of great importance for both selectivity and potency and that substituents on the phenyl ring resulted in poor solubility. Certain variations at the meso position were tolerated and caused a large shift in the binding pose. Changes to the ethylene linker that connects the quinazolinone to the amide were also investigated but proved detrimental to binding. By combination of synthetic organic chemistry and structure-based design, two selective inhibitors of ARTD3 were discovered.