(S)-N-methoxy-N-methyl-2-(3-(4-oxo-3,4-dihydroquinazolin-2-yl)propanamido)-3-phenylpropanamide | 1498333-56-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-N-methoxy-N-methyl-2-(3-(4-oxo-3,4-dihydroquinazolin-2-yl)propanamido)-3-phenylpropanamide
• 英文别名: (2S)-N-methoxy-N-methyl-2-[3-(4-oxo-3H-quinazolin-2-yl)propanoylamino]-3-phenylpropanamide
• CAS: 1498333-56-4
• 化学式: C₂₂H₂₄N₄O₄
• 分子量: 408.457
• InChiKey: DNZTZAXJZHRVHZ-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  30.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  104.39
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  BOC-L-苯丙氨酸 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.08h， 生成 (S)-N-methoxy-N-methyl-2-(3-(4-oxo-3,4-dihydroquinazolin-2-yl)propanamido)-3-phenylpropanamide
  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