1-(2-Cyclopropyl-ethyl)-6-nitro-1H-benzo[d][1,3]oxazine-2,4-dione | 477932-66-4

• 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-(2-Cyclopropyl-ethyl)-6-nitro-1H-benzo[d][1,3]oxazine-2,4-dione
• 英文别名: 1-(2-Cyclopropylethyl)-6-nitro-3,1-benzoxazine-2,4-dione；1-(2-cyclopropylethyl)-6-nitro-3,1-benzoxazine-2,4-dione
• CAS: 477932-66-4
• 化学式: C₁₃H₁₂N₂O₅
• 分子量: 276.249
• InChiKey: QJGQYHDUHYGBHJ-UHFFFAOYSA-N

物化性质

• 沸点：
  447.6±47.0 °C(Predicted)
• 密度：
  1.453±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  92.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2-Cyclopropyl-ethyl)-6-nitro-1H-benzo[d][1,3]oxazine-2,4-dione 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 3.0h， 生成 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：

  2-环丙基乙醇 、 5-硝基靛红酸酐 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 生成 1-(2-Cyclopropyl-ethyl)-6-nitro-1H-benzo[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

• 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。
• 3-(1,1-Dioxo-2<i>H</i>-(1,2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1<i>H</i>)-quinolinones, Potent Inhibitors of Hepatitis C Virus RNA-Dependent RNA Polymerase
  作者：Rosanna Tedesco、Antony N. Shaw、Ramesh Bambal、Deping Chai、Nestor O. Concha、Michael G. Darcy、Dashyant Dhanak、Duke M. Fitch、Adam Gates、Warren G. Gerhardt、Dina L. Halegoua、Chao Han、Glenn A. Hofmann、Victor K. Johnston、Arun C. Kaura、Nannan Liu、Richard M. Keenan、Juili Lin-Goerke、Robert T. Sarisky、Kenneth J. Wiggall、Michael N. Zimmerman、Kevin J. Duffy

  DOI：10.1021/jm050855s

  日期：2006.2.1

  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.