1-(3-methylbutyl)-6-methylbenzo[d][1,3]oxazine-2,4-dione | 477932-91-5

• 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-(3-methylbutyl)-6-methylbenzo[d][1,3]oxazine-2,4-dione
• 英文别名: 6-Methyl-1-(3-methylbutyl)-3,1-benzoxazine-2,4-dione
• CAS: 477932-91-5
• 化学式: C₁₄H₁₇NO₃
• 分子量: 247.294
• InChiKey: SBUKDGSHJCDKAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3-methylbutyl)-6-methylbenzo[d][1,3]oxazine-2,4-dione 、 3-( 1,1-二氧代-4H-苯并[1,2,4]噻二嗪)基乙酸乙酯 在 sodium hydride 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以45%的产率得到3-(1,1-dioxo-1,2-dihydrobenzo[1,2,4]thiadiazin-3-yl)-4-hydroxy-6-methyl-1-(3-methylbutyl)-1H-quinolin-2-one
  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
• 作为产物：
  描述：

  2-氨基-5-甲基苯甲酸 、 alkaline earth salt of/the/ methylsulfuric acid 在 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 16.5h， 生成 1-(3-methylbutyl)-6-methylbenzo[d][1,3]oxazine-2,4-dione
  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

• [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。
• EP1401443A4
  申请人：——

  公开号：EP1401443A4

  公开（公告）日：2005-10-26
• NOVEL ANTI-INFECTIVES
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP1401443A1

  公开（公告）日：2004-03-31
• [EN] ANTI-INFECTIVES<br/>[FR] AGENTS ANTI-INFECTIEUX
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004052312A2

  公开（公告）日：2004-06-24

  Compounds useful as HCV anti-infectives are disclosed. Also disclosed are methods of making and using the same.