3-(7-chloro-4-oxo-3H-quinazolin-2-yl)propanoic acid | 1498333-57-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 3-(7-chloro-4-oxo-3H-quinazolin-2-yl)propanoic acid
• CAS: 1498333-57-5
• 化学式: C₁₁H₉ClN₂O₃
• 分子量: 252.657
• InChiKey: LOZIJWVVQRCYIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  78.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(7-chloro-4-oxo-3H-quinazolin-2-yl)propanoic acid 、 L-苯甘氨醇 在 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以39%的产率得到(S)-3-(7-chloro-4-oxo-3H-quinazolin-2-yl)-N-(2-hydroxy-1-phenylethyl)propanamide
  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：

  4-(5-chloro-2-cyanophenylamino)-4-oxobutanoic acid 在 过氧化脲素 、 potassium carbonate 作用下， 以 水 、 丙酮 为溶剂， 反应 89.0h， 以75%的产率得到3-(7-chloro-4-oxo-3H-quinazolin-2-yl)propanoic acid
  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

• Convergent micro-wave assisted synthesis of quinazolinone and its precursor using the bio-sourced solvent pinane
  作者：Antoine Richieu、Philippe Bertrand

  DOI：10.1039/d3ra03702a

  日期：——

  A general microwave synthesis of 4-oxo-3,4-dihydroquinazolin-2-yl propanoic acids and their diamide precursors from the corresponding substituted benzamide and succinic anhydride is described, using pinane as a sustainable solvent that favors the cyclization step. The conditions are some of the most simple and cost effective reported.

  描述了使用蒎烷作为有利于环化步骤的可持续溶剂，从相应的取代苯甲酰胺和琥珀酸酐出发，一般微波合成 4-氧代-3,4-二氢喹唑啉-2-基丙酸及其二酰胺前体。这些条件是报道中最简单且最具成本效益的。
• 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.