methyl 4-((2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)benzoate

• 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: methyl 4-((2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)benzoate
• 英文别名: methyl 4-[(2,4-dioxo-1H-quinazolin-3-yl)methyl]benzoate
• 化学式: C₁₇H₁₄N₂O₄
• 分子量: 310.309
• InChiKey: BJQFPCHYEXQYBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 4-((2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)benzoate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以88%的产率得到4-((2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)benzoic acid
  参考文献：
  名称：

  [EN] INHIBITORS OF RESPIRATORY SYNCYTIAL VIRUS
  [FR] INHIBITEURS DU VIRUS RESPIRATOIRE SYNCYTIAL

  摘要：

  本文描述了一种治疗呼吸道合胞病毒感染或抑制呼吸道合胞病毒复制的化合物、药物组合物和方法。

  公开号：

  WO2013184806A1
• 作为产物：
  描述：

  4-氨甲基苯甲酸甲酯盐酸盐 在 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 作用下， 以 二氯甲烷 为溶剂， 反应 40.17h， 生成 methyl 4-((2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)benzoate
  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

• [EN] INHIBITORS OF RESPIRATORY SYNCYTIAL VIRUS<br/>[FR] INHIBITEURS DU VIRUS RESPIRATOIRE SYNCYTIAL
  申请人：UNIV KANSAS

  公开号：WO2013184806A1

  公开（公告）日：2013-12-12

  Described herein are compounds, pharmaceutical compositions and methods for treating a respiratory syncytial virus infection in a subject, or for inhibiting replication of respiratory syncytial virus.

  本文描述了一种治疗呼吸道合胞病毒感染或抑制呼吸道合胞病毒复制的化合物、药物组合物和方法。
• INHIBITORS OF RESPIRATORY SYNCYTIAL VIRUS
  申请人：University of Kansas

  公开号：US20150119411A1

  公开（公告）日：2015-04-30

  Described herein are compounds, pharmaceutical compositions and methods for treating a respiratory syncytial virus infection in a subject, or for inhibiting replication of respiratory syncytial virus.

  本文描述了一些化合物、药物组合物和方法，用于治疗主体的呼吸道合胞病毒感染，或抑制呼吸道合胞病毒的复制。
• US6774134B2
  申请人：——

  公开号：US6774134B2

  公开（公告）日：2004-08-10
• US9499496B2
  申请人：——

  公开号：US9499496B2

  公开（公告）日：2016-11-22
• 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.