1-(2-环丙基乙基) -6-氟-2H-3,1-苯并噁嗪-2,4-二酮 | 477933-12-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 中文名称: 1-(2-环丙基乙基) -6-氟-2H-3,1-苯并噁嗪-2,4-二酮
• 中文别名: 1-(2-环丙基乙基)-6-氟-2H-3,1-苯并噁嗪-2,4-二酮；1-(2-环丙基乙基)-6-氟-1H-苯并[d][1,3]噁嗪-2,4-二酮
• 英文名称: 1-(2-cyclopropylethyl)-6-fluoro-1H-benzo[d][1,3]oxazine-2,4-dione
• 英文别名: 1-(2-cyclopropylethyl)-6-fluorobenzo[d][1,3]oxazine-2,4-dione；1-(2-cyclopropylethyl)-6-fluoro-benzoxazine-2,4(1H)-dione；1-(2-cyclopropylethyl)-6-fluoro-2H-3,1-benzoxazine-2,4(1H)-dione；1-(2-cyclopropylethyl)-6-fluoro-3,1-benzoxazine-2,4-dione
• CAS: 477933-12-3
• 化学式: C₁₃H₁₂FNO₃
• 分子量: 249.242
• InChiKey: GHLUJHVVLMJROO-UHFFFAOYSA-N

物化性质

• 熔点：
  73-75°C
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 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-环丙基乙基) -6-氟-2H-3,1-苯并噁嗪-2,4-二酮 、 丙二酸二乙酯 在 sodium hydride 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 20.5h， 以83%的产率得到1-(2-环丙基乙基)-6-氟-1,2-二氢-4-羟基-2-氧代-3-喹啉羧酸乙酯
  参考文献：
  名称：

  WO2007/38571

  摘要：

  公开号：
• 作为产物：
  描述：

  2-氨基-5-氟苯甲酸 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 氯仿 、 甲苯 为溶剂， 生成 1-(2-环丙基乙基) -6-氟-2H-3,1-苯并噁嗪-2,4-二酮
  参考文献：
  名称：

  3-(1,1-Dioxo-2H-(1,2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones, Potent Inhibitors of Hepatitis C Virus RNA-Dependent RNA Polymerase

  摘要：

  Recently, we disclosed a new class of HCV polymerase inhibitors discovered through high-throughput screening (HTS) of the GlaxoSmithKline proprietary compound collection. This interesting class of 3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones potently inhibits HCV polymerase enzymatic activity and inhibits the ability of the subgenomic HCV replicon to replicate in Huh-7 cells. This report will focus on the structure-activity relationships (SAR) of substituents on the quinolinone ring, culminating in the discovery of 1-(2-cyclopropylethyl)-3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-6-fluoro-4-hydroxy-2(1H)-quinolinone (130), an inhibitor with excellent potency in biochemical and cellular assays possessing attractive molecular properties for advancement as a clinical candidate. The potential for development and safety assessment profile of compound 130 will also be discussed.

  DOI：

  10.1021/jm050855s

文献信息

• Heterocyclic antiviral compounds
  申请人：Blake F. James

  公开号：US20060040927A1

  公开（公告）日：2006-02-23

  Compounds having the formula I wherein A, m and R 1 are herein defined are Hepatitis C virus polymerase inhibitors. Also disclosed are compositions and methods for treating diseases mediated by HCV and for inhibiting hepatitis replication. Also disclosed are processes for making the compounds and synthetic intermediates used in the process

  具有公式I的化合物，其中A、m和R1如本文所定义，是丙型肝炎病毒聚合酶抑制剂。还公开了用于治疗HCV介导的疾病和抑制肝炎复制的组合物和方法。还公开了制备这些化合物和用于该过程的合成中间体的方法。
• PHOSPHADIAZINE HCV POLYMERASE INHIBITORS I AND II
  申请人：Dousson Cyril

  公开号：US20090060866A1

  公开（公告）日：2009-03-05

  Provided herein are phosphadiazine polymerase inhibitor, for example, of any of Formula I, II, III, I′, II′, I″, II″, Ia, IIa, or IIIa, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof.

  本发明提供了磷二嗪聚合酶抑制剂，例如任何式I、II、III、I′、II′、I″、II″、Ia、IIa或IIIa的化合物，包含这些化合物的药物组合物，以及它们的制备方法。还提供了用于治疗宿主中HCV感染的方法。
• [EN] NOVEL ANTI-INFECTIVES<br/>[FR] NOUVEAUX ANTI-INFECTIEUX
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2002098424A1

  公开（公告）日：2002-12-12

  Compounds useful as HCV anti-infectives having the formula: wherein the formula variables are as defined herein, are disclosed. Also disclosed are methods of making and using the same.

  本发明揭示了具有以下式的HCV抗感染剂有用的化合物：其中，公式变量如本文所定义。同时还揭示了制备和使用该化合物的方法。
• Novel anti-infectives
  申请人：——

  公开号：US20040147739A1

  公开（公告）日：2004-07-29

  Compounds useful as HCV anti-infectives having the formula: wherein the formula variables are as defined herein, are disclosed. Also disclosed are methods of making and using the same.

  本文披露了具有以下公式的HCV抗感染剂有用的化合物：其中公式变量如本文所定义。同时，还披露了制备和使用这些化合物的方法。
• Substituted benzothiadizine inhibitors of Hepatitis C virus polymerase
  作者：Antony N. Shaw、Rosanna Tedesco、Ramesh Bambal、Deping Chai、Nestor O. Concha、Michael G. Darcy、Dashyant Dhanak、Kevin J. Duffy、Duke M. Fitch、Adam Gates、Victor K. Johnston、Richard M. Keenan、Juili Lin-Goerke、Nannan Liu、Robert T. Sarisky、Kenneth J. Wiggall、Michael N. Zimmerman

  DOI：10.1016/j.bmcl.2009.05.091

  日期：2009.8

  The synthesis and optimisation of HCV NS5B polymerase inhibitors with improved potency versus the existing compound 1 is described. Substitution in the benzothiadiazine portion of the molecule, furnishing improvement in potency in the high protein Replicon assay, is highlighted, culminating in the discovery of 12h, a highly potent oxyacetamide derivative. (C) 2009 Elsevier Ltd. All rights reserved.