1-(2-fluorobenzyl)-1H-benzo[d][1,3]oxazine-2,4-dione | 57384-90-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 1-(2-fluorobenzyl)-1H-benzo[d][1,3]oxazine-2,4-dione
• 英文别名: 1-(o-Fluorbenzyl)-2H-3,1-benzoxazin-2,4(1H)-dion；1-[(2-Fluorophenyl)methyl]-3,1-benzoxazine-2,4-dione
• CAS: 57384-90-4
• 化学式: C₁₅H₁₀FNO₃
• 分子量: 271.248
• InChiKey: VBJDNHOHZGVCOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2-fluorobenzyl)-1H-benzo[d][1,3]oxazine-2,4-dione 在 N,N-二甲基乙酰胺 、 sodium hydride 作用下， 以 mineral oil 为溶剂， 反应 3.25h， 生成 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：

  2-氟溴苄 、 靛红酸酐 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 以70%的产率得到1-(2-fluorobenzyl)-1H-benzo[d][1,3]oxazine-2,4-dione
  参考文献：
  名称：

  N1-官能化喹唑啉-2,4-二酮的 (Isoxazolidin-3-yl) 膦酸酯缀合物的设计、合成、抗水痘带状疱疹和抗菌活性

  摘要：

  N-取代的C- (二乙氧基膦酰基)硝酮与N 3 -烯丙基-N 1 -苄基喹唑啉-2,4-二酮的偶极环加成产生非对映异构体3-(二乙氧基膦酰基)异恶唑烷与N 1 -苄基喹唑啉-2,4-的混合物C5 处的二酮单元。评估获得的化合物的抗病毒和抗菌活性。几种化合物对 VZV 显示出中等抑制活性，EC 50值在 12.63–58.48 µM 范围内。异恶唑烷顺式- 20c /反式- 20c (6:94) 的混合物被发现对蜡状芽孢杆菌最有效PCM 1948，MIC 值为 0.625 mg/mL，在该浓度下也没有致突变性。

  DOI：

  10.3390/molecules27196526

文献信息

• The chemistry of 2<i>H</i>-3,1-benzoxazine-2,4(1<i>H</i>)dione (isatoic anhydrides) 1. The synthesis of<i>N</i>-substituted 2<i>H</i>-3,1-benzoxazine-2,4(1<i>H</i>)diones
  作者：Goetz E. Hardtmann、Gabor Koletar、Oskar R. Pfister

  DOI：10.1002/jhet.5570120325

  日期：1975.6

  Three methods for the preparation of N-substituted 2H-3,1-benzoxazine-2,4(1H)diones (isatoic anhydrides) (1) utilizing 2-chloro-, 2-nitrobenzoic acids and N-unsubstituted isatoic anhydrides as starting materials, are described.

  三种制备N-取代的2 H -3,1-苯并恶嗪-2,4（1 H）二酮（乙酸酐）的方法（1）使用2-氯-，2-硝基苯甲酸和N-未取代的等角酸酐作为制备方法描述了起始材料。
• HARDTMANN G. E.; KOLETAR G.; PFISTER O. R.; GOGERTY J. H.; IORIO L. C., J. MED. CHEM. <JMCM-AR>, 1975, 18, NO 5, 447-453
  作者：HARDTMANN G. E.、 KOLETAR G.、 PFISTER O. R.、 GOGERTY J. H.、 IORIO L. C.

  DOI：——

  日期：——
• 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.
• Design, Synthesis, Anti-Varicella-Zoster and Antimicrobial Activity of (Isoxazolidin-3-yl)Phosphonate Conjugates of N1-Functionalised Quinazoline-2,4-Diones
  作者：Magdalena Łysakowska、Iwona E. Głowacka、Graciela Andrei、Dominique Schols、Robert Snoeck、Paweł Lisiecki、Magdalena Szemraj、Dorota G. Piotrowska

  DOI：10.3390/molecules27196526

  日期：——

  diastereoisomeric 3-(diethoxyphosphonyl)isoxazolidines with a N1-benzylquinazoline-2,4-dione unit at C5. The obtained compounds were assessed for antiviral and antibacterial activities. Several compounds showed moderate inhibitory activities against VZV with EC50 values in the range of 12.63–58.48 µM. A mixture of isoxazolidines cis-20c/trans-20c (6:94) was found to be the most active against B. cereus PCM

  N-取代的C- (二乙氧基膦酰基)硝酮与N 3 -烯丙基-N 1 -苄基喹唑啉-2,4-二酮的偶极环加成产生非对映异构体3-(二乙氧基膦酰基)异恶唑烷与N 1 -苄基喹唑啉-2,4-的混合物C5 处的二酮单元。评估获得的化合物的抗病毒和抗菌活性。几种化合物对 VZV 显示出中等抑制活性，EC 50值在 12.63–58.48 µM 范围内。异恶唑烷顺式- 20c /反式- 20c (6:94) 的混合物被发现对蜡状芽孢杆菌最有效PCM 1948，MIC 值为 0.625 mg/mL，在该浓度下也没有致突变性。