6-Fluoro-1-[(4-fluoro-3-methylphenyl)methyl]-3,1-benzoxazine-2,4-dione | 877142-72-8

• 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: 6-Fluoro-1-[(4-fluoro-3-methylphenyl)methyl]-3,1-benzoxazine-2,4-dione
• 英文别名: 6-fluoro-1-[(4-fluoro-3-methylphenyl)methyl]-3,1-benzoxazine-2,4-dione
• CAS: 877142-72-8
• 化学式: C₁₆H₁₁F₂NO₃
• 分子量: 303.265
• InChiKey: PHZYUKMBPVWYIM-UHFFFAOYSA-N

物化性质

• 沸点：
  444.5±55.0 °C(Predicted)
• 密度：
  1.414±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-Fluoro-1-[(4-fluoro-3-methylphenyl)methyl]-3,1-benzoxazine-2,4-dione 、 (7-nitro-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,4]thiazin-3-yl)-acetic acid ethyl ester 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  Non-nucleoside inhibitors of HCV polymerase NS5B. Part 2: Synthesis and structure–activity relationships of benzothiazine-substituted quinolinediones

  摘要：

  A new series of benzothiazine-substituted quinolinediones were evaluated as inhibitors of HCV polymerase NS5B. SAR studies on this series revealed a methyl sulfonamide group as a high affinity feature. Analogues with this group showed submicromolar potencies in the HCV cell based replicon assay. Pharmacokinetic and toxicology studies were also performed on a selected compound (34) to evaluate in vivo properties of this new class of inhibitors of HCV NS5B polymerase.

  DOI：

  10.1016/j.bmcl.2009.05.004
• 作为产物：
  描述：

  4-氟-3-甲基溴苄 在 sodium hydride 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 2.17h， 以90%的产率得到6-Fluoro-1-[(4-fluoro-3-methylphenyl)methyl]-3,1-benzoxazine-2,4-dione
  参考文献：
  名称：

  Heterocyclic antiviral compounds

  摘要：

  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。

  公开号：

  US20060040927A1

文献信息

• HETEROCYCLIC ANTIVIRAL COMPOUNDS
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1786807B1

  公开（公告）日：2009-07-29
• US7479489B2
  申请人：——

  公开号：US7479489B2

  公开（公告）日：2009-01-20
• 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。
• Non-nucleoside inhibitors of HCV polymerase NS5B. Part 2: Synthesis and structure–activity relationships of benzothiazine-substituted quinolinediones
  作者：Javier de Vicente、Robert T. Hendricks、David B. Smith、Jay B. Fell、John Fischer、Stacey R. Spencer、Peter J. Stengel、Peter Mohr、John E. Robinson、James F. Blake、Ramona K. Hilgenkamp、Calvin Yee、George Adjabeng、Todd R. Elworthy、Jahari Tracy、Elbert Chin、Jim Li、Beihan Wang、Joe T. Bamberg、Rebecca Stephenson、Connie Oshiro、Seth F. Harris、Manjiri Ghate、Vincent Leveque、Isabel Najera、Sophie Le Pogam、Sonal Rajyaguru、Gloria Ao-Ieong、Ludmila Alexandrova、Susan Larrabee、Michael Brandl、Andrew Briggs、Sunil Sukhtankar、Robert Farrell、Brian Xu

  DOI：10.1016/j.bmcl.2009.05.004

  日期：2009.7

  A new series of benzothiazine-substituted quinolinediones were evaluated as inhibitors of HCV polymerase NS5B. SAR studies on this series revealed a methyl sulfonamide group as a high affinity feature. Analogues with this group showed submicromolar potencies in the HCV cell based replicon assay. Pharmacokinetic and toxicology studies were also performed on a selected compound (34) to evaluate in vivo properties of this new class of inhibitors of HCV NS5B polymerase.