1-(2-cyclopropylethyl)-3-(1,1-dioxo-1,4-dihydrobenzo[1,2,4]thiadiazin-3-yl)-4-hydroxy-6-nitro-1H-quinolin-2-one | 477931-07-0

• 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: 1-(2-cyclopropylethyl)-3-(1,1-dioxo-1,4-dihydrobenzo[1,2,4]thiadiazin-3-yl)-4-hydroxy-6-nitro-1H-quinolin-2-one
• 英文别名: 1-(2-cyclopropylethyl)-3-(1,1-dioxo-4H-1lambda6,2,4-benzothiadiazin-3-yl)-4-hydroxy-6-nitroquinolin-2-one；1-(2-cyclopropylethyl)-3-(1,1-dioxo-4H-1λ6,2,4-benzothiadiazin-3-yl)-4-hydroxy-6-nitroquinolin-2-one
• CAS: 477931-07-0
• 化学式: C₂₁H₁₈N₄O₆S
• 分子量: 454.463
• InChiKey: SZYLUKGMVAINQS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  153
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(2-cyclopropylethyl)-3-(1,1-dioxo-1,4-dihydrobenzo[1,2,4]thiadiazin-3-yl)-4-hydroxy-6-nitro-1H-quinolin-2-one 在 palladium on activated charcoal sodium hydroxide 、 氢气 作用下， 以 乙醇 为溶剂， 反应 0.5h， 以71%的产率得到6-Amino-1-(2-cyclopropyl-ethyl)-3-(1,1-dioxo-1,4-dihydro-1λ⁶-benzo[1,2,4]thiadiazin-3-yl)-4-hydroxy-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：

  邻氨基苯磺酰胺 在 吡啶 、 sodium hydride 、 sodium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.17h， 生成 1-(2-cyclopropylethyl)-3-(1,1-dioxo-1,4-dihydrobenzo[1,2,4]thiadiazin-3-yl)-4-hydroxy-6-nitro-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

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