N-cyclohexyl-4-((2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)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: N-cyclohexyl-4-((2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)benzamide
• 英文别名: N-cyclohexyl-4-[(2,4-dioxo-1H-quinazolin-3-yl)methyl]benzamide
• 化学式: C₂₂H₂₃N₃O₃
• 分子量: 377.443
• InChiKey: MZCQPZQHJRMUAO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  78.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-cyclohexyl-4-((2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)benzamide 、 alkaline earth salt of/the/ methylsulfuric acid 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以33%的产率得到N-cyclohexyl-4-((1-(4-methylbenzyl)-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)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
• 作为产物：
  描述：

  4-氨甲基苯甲酸甲酯盐酸盐 在 lithium hydroxide monohydrate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 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 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 41.17h， 生成 N-cyclohexyl-4-((2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)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

文献信息

• Optimization of Potent and Selective Quinazolinediones: Inhibitors of Respiratory Syncytial Virus That Block RNA-Dependent RNA-Polymerase Complex Activity
  作者：Daljit S. Matharu、Daniel P. Flaherty、Denise S. Simpson、Chad E. Schroeder、Donghoon Chung、Dan Yan、James W. Noah、Colleen B. Jonsson、E. Lucile White、Jeffrey Aubé、Richard K. Plemper、William E. Severson、Jennifer E. Golden

  DOI：10.1021/jm500902x

  日期：2014.12.26

  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.