n-(3-Cyanopropyl)isatoic anhydride | 372962-29-3

• 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: n-(3-Cyanopropyl)isatoic anhydride
• 英文别名: 4-(2,4-dioxo-3,1-benzoxazin-1-yl)butanenitrile
• CAS: 372962-29-3
• 化学式: C₁₂H₁₀N₂O₃
• 分子量: 230.223
• InChiKey: FDHQUINGGKJTRK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  70.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  n-(3-Cyanopropyl)isatoic anhydride 在 硫酸 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 6.5h， 生成 4-[3-(1,1-Dioxo-1,4-dihydro-1λ⁶-benzo[1,2,4]thiadiazin-3-yl)-4-hydroxy-2-oxo-2H-quinolin-1-yl]-butyramide
  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：

  靛红酸酐 、 4-溴丁腈 在 sodium hydride 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 20.0h， 生成 n-(3-Cyanopropyl)isatoic anhydride
  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：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。
• NOVEL ANTI-INFECTIVES
  申请人：SmithKline Beecham Corporation

  公开号：EP1292310A1

  公开（公告）日：2003-03-19
• [EN] NOVEL ANTI-INFECTIVES<br/>[FR] NOUVEAUX ANTI-INFECTIEUX
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2001085172A1

  公开（公告）日：2001-11-15

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