(4-methyl-1,1-dioxo-1,4-dihydrobenzo[1,2,4]thiadiazin-3-yl)acetic acid ethyl ester | 465520-32-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻二嗪
• 英文名称: (4-methyl-1,1-dioxo-1,4-dihydrobenzo[1,2,4]thiadiazin-3-yl)acetic acid ethyl ester
• 英文别名: Ethyl 2-(4-methyl-1,1-dioxo-1lambda6,2,4-benzothiadiazin-3-yl)acetate；ethyl 2-(4-methyl-1,1-dioxo-1λ6,2,4-benzothiadiazin-3-yl)acetate
• CAS: 465520-32-5
• 化学式: C₁₂H₁₄N₂O₄S
• 分子量: 282.32
• InChiKey: UTHJMMNEBNPEQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  84.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4-methyl-1,1-dioxo-1,4-dihydrobenzo[1,2,4]thiadiazin-3-yl)acetic acid ethyl ester 、 1-(3-methylbutyl)-1H-benzo[d][1,3]oxazine-2,4-dione 在 sodium hydride 、 溶剂黄146 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.17h， 生成 4-Hydroxy-1-(3-methylbutyl)-3-(4-methyl-1,1-dioxo-1lambda6,2,4-benzothiadiazin-3-yl)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-甲基氨基苯磺酰胺 在 吡啶 、 三氯氧磷 作用下， 以 氯仿 为溶剂， 反应 2.0h， 生成 (4-methyl-1,1-dioxo-1,4-dihydrobenzo[1,2,4]thiadiazin-3-yl)acetic acid ethyl ester
  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
• US7196194B2
  申请人：——

  公开号：US7196194B2

  公开（公告）日：2007-03-27