3-(1,1-二氧代-1,4-二氢苯并[1,2,4]噻二嗪-3-基)-4-羟基-1-(3-甲基丁基)-1H-喹啉-2-酮 | 303776-89-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻二嗪
• 中文名称: 3-(1,1-二氧代-1,4-二氢苯并[1,2,4]噻二嗪-3-基)-4-羟基-1-(3-甲基丁基)-1H-喹啉-2-酮
• 英文名称: 3-(1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1-(3-methylbutyl)-2(1H)-quinolinone
• 英文别名: 3-(1,1-Dioxido-4h-1,2,4-Benzothiadiazin-3-Yl)-4-Hydroxy-1-(3-Methylbutyl)quinolin-2(1h)-One；3-(1,1-dioxo-4H-1λ6,2,4-benzothiadiazin-3-yl)-4-hydroxy-1-(3-methylbutyl)quinolin-2-one
• CAS: 303776-89-8
• 化学式: C₂₁H₂₁N₃O₄S
• 分子量: 411.481
• InChiKey: MQFPIRFODWNQIO-UHFFFAOYSA-N

物化性质

• 沸点：
  585.0±60.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(1,1-二氧代-1,4-二氢苯并[1,2,4]噻二嗪-3-基)-4-羟基-1-(3-甲基丁基)-1H-喹啉-2-酮 在 ammonium hydroxide 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 172.0h， 生成 4-amino-3-(1,1-dioxo-4H-1lambda6,2,4-benzothiadiazin-3-yl)-1-(3-methylbutyl)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：

  异戊基碘 在 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基乙酰胺 为溶剂， 反应 22.5h， 生成 3-(1,1-二氧代-1,4-二氢苯并[1,2,4]噻二嗪-3-基)-4-羟基-1-(3-甲基丁基)-1H-喹啉-2-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

• Synthesis and biological activity of heteroaryl 3-(1,1-dioxo-2H-(1,2,4)-benzothiadizin-3-yl)-4-hydroxy-2(1H)-quinolinone derivatives as hepatitis C virus NS5B polymerase inhibitors
  作者：Rosanna Tedesco、Deping Chai、Michael G. Darcy、Dashyant Dhanak、Duke M. Fitch、Adam Gates、Victor K. Johnston、Richard M. Keenan、Juili Lin-Goerke、Robert T. Sarisky、Antony N. Shaw、Klara L. Valko、Kenneth J. Wiggall、Michael N. Zimmerman、Kevin J. Duffy

  DOI：10.1016/j.bmcl.2009.05.080

  日期：2009.8

  2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones into heteroaromatic systems was investigated to enhance physicochemical properties and potency profile of this class of inhibitors. The synthesis and biological activity of the derived compounds is discussed.

  研究了将 3-(1,1-dioxo-2 H -(1,2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1 H )-quinolinones的苯并环修饰为杂芳族体系增强这类抑制剂的物理化学性质和效力特征。讨论了衍生化合物的合成和生物活性。
• Novel anti-infectives
  申请人：——

  公开号：US20040034041A1

  公开（公告）日：2004-02-19

  Novel anti-infectives and methods of using them are provided.

  提供了新型抗感染药物及其使用方法。
• 4-hydroxy-2-quinolones. 42. Synthesis and biological activity of 1-R-2-oxo-3-(2H-1,2,4-benzothiadiazine-1,1-dioxid-3-yl)-4-hydroxyquinolines
  作者：I. V. Ukrainets、E. A. Taran、O. V. Gorokhova、N. A. Jaradat、L. N. Voronina、I. V. Porokhnyak

  DOI：10.1007/bf02256875

  日期：2000.3
• NOVEL ANTI-INFECTIVES
  申请人：SmithKline Beecham Corporation

  公开号：EP1292310A1

  公开（公告）日：2003-03-19
• Quantitative assay for detection of newly synthesized rna in a cell-free system and indentification of rna synthesis inhibitors
  申请人：Huang Mingjun

  公开号：US20070141558A1

  公开（公告）日：2007-06-21

  Methods for detecting populations of newly synthesized and newly initiated RNAs in a cell-free system are described. Suitable templates for the populations of newly synthesized and newly initiated RNAs are viral replicon RNAs, particularly HCV viral replicon RNA. The newly synthesized and newly initiated RNAs may be formed in the presence of a labeled nucleotide analog suitable for detection and/or quantitation of the RNAs. The assay may be employed to identify small molecule inhibitors of RNA synthesis of positive strand RNA viruses such as Hepatitis C Virus.