4-((1-(4-methylbenzyl)-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)-N-(thiazol-2-yl)benzamide

• 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: 4-((1-(4-methylbenzyl)-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)-N-(thiazol-2-yl)benzamide
• 英文别名: 4-[[1-[(4-methylphenyl)methyl]-2,4-dioxoquinazolin-3-yl]methyl]-N-(1,3-thiazol-2-yl)benzamide
• 化学式: C₂₇H₂₂N₄O₃S
• 分子量: 482.563
• InChiKey: AIMOBLKFMXTZRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-((2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)benzoic acid 在 potassium carbonate 、 N,N-二异丙基乙胺 、 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， 反应 16.0h， 生成 4-((1-(4-methylbenzyl)-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)-N-(thiazol-2-yl)benzamide
  参考文献：
  名称：

  Optimization of Potent and Selective Quinazolinediones: Inhibitors of Respiratory Syncytial Virus That Block RNA-Dependent RNA-Polymerase Complex Activity

  摘要：

  A quinazolinedione-derived screening hit 2 was discovered with cellular antiviral activity against respiratory syncytial virus (CPE EC50 = 2.1 mu M), moderate efficacy in reducing viral progeny (4.2 log at 10 mu M), and marginal cytotoxic liability (selectivity index, SI similar to 24). Scaffold optimization delivered analogs with improved potency and selectivity profiles. Most notable were compounds 15 and 19 (EC50 = 300-500 nM, CC50 > 50 mu M, SI > 100), which significantly reduced viral titer (>400,000-fold), and several analogs were shown to block the activity of the RNA-dependent RNA-polymerase complex of RSV.

  DOI：

  10.1021/jm500902x