ethyl 1-(2-fluorobenzyl)-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate | 1415728-90-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: ethyl 1-(2-fluorobenzyl)-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate
• 英文别名: Ethyl 1-[(2-fluorophenyl)methyl]-4-hydroxy-2-oxoquinoline-3-carboxylate；ethyl 1-[(2-fluorophenyl)methyl]-4-hydroxy-2-oxoquinoline-3-carboxylate
• CAS: 1415728-90-3
• 化学式: C₁₉H₁₆FNO₄
• 分子量: 341.339
• InChiKey: PVQLFSRKKIEVQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-amino-5-(methylsulfonamido)benzamide 、 ethyl 1-(2-fluorobenzyl)-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate 在 potassium hydroxide 、 盐酸 作用下， 以 水 为溶剂， 反应 3.25h， 以45%的产率得到N-[2-[1-[(2-fluorophenyl)methyl]-4-hydroxy-2-oxoquinolin-3-yl]-4-oxo-3H-quinazolin-6-yl]methanesulfonamide
  参考文献：
  名称：

  A highly selective structure-based virtual screening model of Palm I allosteric inhibitors of HCV Ns5b polymerase enzyme and its application in the discovery and optimization of new analogues

  摘要：

  First structure-based activity prediction model of topologically diverse inhibitors of Palm I allosteric site of HCV NS5b polymerase enzyme is reported here. The model is a workflow of structure-based pharmacophore followed by guided docking. The pharmacophore was constructed using a novel procedure which includes PLIF (protein ligand interaction fingerprint), Hypogen, contact-based pharmacophore and shape constraints. The guided docking was tweaked using both a scoring function of high correlation with activity (ChemPLP) and essential pharmacophore features. Statistically, ROC analysis for the workflow, deploying the novel technique of virtual decoys, yielded AUC of 0.947. Experimentally, the model was used to screen Asinex GOLD database yielding a new hit with a different scaffold which was further confirmed by synthesis and biological evaluation. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.04.016
• 作为产物：
  描述：

  靛红酸酐 在 N,N-二甲基乙酰胺 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 19.0h， 生成 ethyl 1-(2-fluorobenzyl)-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  A highly selective structure-based virtual screening model of Palm I allosteric inhibitors of HCV Ns5b polymerase enzyme and its application in the discovery and optimization of new analogues

  摘要：

  First structure-based activity prediction model of topologically diverse inhibitors of Palm I allosteric site of HCV NS5b polymerase enzyme is reported here. The model is a workflow of structure-based pharmacophore followed by guided docking. The pharmacophore was constructed using a novel procedure which includes PLIF (protein ligand interaction fingerprint), Hypogen, contact-based pharmacophore and shape constraints. The guided docking was tweaked using both a scoring function of high correlation with activity (ChemPLP) and essential pharmacophore features. Statistically, ROC analysis for the workflow, deploying the novel technique of virtual decoys, yielded AUC of 0.947. Experimentally, the model was used to screen Asinex GOLD database yielding a new hit with a different scaffold which was further confirmed by synthesis and biological evaluation. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.04.016

文献信息

• A highly selective structure-based virtual screening model of Palm I allosteric inhibitors of HCV Ns5b polymerase enzyme and its application in the discovery and optimization of new analogues
  作者：Amr H. Mahmoud、Dalal A. Abou El Ella、Mohamed A.H. Ismail、Khaled A.M. Abouzid

  DOI：10.1016/j.ejmech.2012.04.016

  日期：2012.11

  First structure-based activity prediction model of topologically diverse inhibitors of Palm I allosteric site of HCV NS5b polymerase enzyme is reported here. The model is a workflow of structure-based pharmacophore followed by guided docking. The pharmacophore was constructed using a novel procedure which includes PLIF (protein ligand interaction fingerprint), Hypogen, contact-based pharmacophore and shape constraints. The guided docking was tweaked using both a scoring function of high correlation with activity (ChemPLP) and essential pharmacophore features. Statistically, ROC analysis for the workflow, deploying the novel technique of virtual decoys, yielded AUC of 0.947. Experimentally, the model was used to screen Asinex GOLD database yielding a new hit with a different scaffold which was further confirmed by synthesis and biological evaluation. (C) 2012 Elsevier Masson SAS. All rights reserved.