1-(3-methylbutyl)-1H-benzo[d][1,3]oxazine-2,4-dione | 57384-50-6

• 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-(3-methylbutyl)-1H-benzo[d][1,3]oxazine-2,4-dione
• 英文别名: 1-(3-methylbutyl)-2H-3,1-benzoxazine-2,4(1H)-dione；1-(3-methyl-butyl)-1H-benzo[d][1,3]oxazine-2,4-dione；1-isoamyl isatoic anhydride；1-(3-Methylbutyl)-2H-3,1-benzoxazin-2,4(1H)-dion；1-(3-methylbutyl)-2,4-dihydro-1H-3,1-benzoxazine-2,4-dione；1-(3-methylbutyl)-3,1-benzoxazine-2,4-dione
• CAS: 57384-50-6
• 化学式: C₁₃H₁₅NO₃
• mdl: MFCD06490510
• 分子量: 233.267
• InChiKey: OWSDIKSPNCPMCL-UHFFFAOYSA-N

物化性质

• 熔点：
  74-77 °C
• 沸点：
  344.4±25.0 °C(Predicted)
• 密度：
  1.173±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.384
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3-methylbutyl)-1H-benzo[d][1,3]oxazine-2,4-dione 在 ammonium hydroxide 、 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 174.5h， 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：

  靛红酸酐 、 异戊醇 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， 以69%的产率得到1-(3-methylbutyl)-1H-benzo[d][1,3]oxazine-2,4-dione
  参考文献：
  名称：

  Substituted benzothiadizine inhibitors of Hepatitis C virus polymerase

  摘要：

  The synthesis and optimisation of HCV NS5B polymerase inhibitors with improved potency versus the existing compound 1 is described. Substitution in the benzothiadiazine portion of the molecule, furnishing improvement in potency in the high protein Replicon assay, is highlighted, culminating in the discovery of 12h, a highly potent oxyacetamide derivative. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.05.091

文献信息

• Heterocyclic antiviral compounds
  申请人：Blake F. James

  公开号：US20060040927A1

  公开（公告）日：2006-02-23

  Compounds having the formula I wherein A, m and R 1 are herein defined are Hepatitis C virus polymerase inhibitors. Also disclosed are compositions and methods for treating diseases mediated by HCV and for inhibiting hepatitis replication. Also disclosed are processes for making the compounds and synthetic intermediates used in the process

  具有公式I的化合物，其中A、m和R1如本文所定义，是丙型肝炎病毒聚合酶抑制剂。还公开了用于治疗HCV介导的疾病和抑制肝炎复制的组合物和方法。还公开了制备这些化合物和用于该过程的合成中间体的方法。
• 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。
• The chemistry of 2<i>H</i>-3,1-benzoxazine-2,4(1<i>H</i>)dione (isatoic anhydrides) 1. The synthesis of<i>N</i>-substituted 2<i>H</i>-3,1-benzoxazine-2,4(1<i>H</i>)diones
  作者：Goetz E. Hardtmann、Gabor Koletar、Oskar R. Pfister

  DOI：10.1002/jhet.5570120325

  日期：1975.6

  Three methods for the preparation of N-substituted 2H-3,1-benzoxazine-2,4(1H)diones (isatoic anhydrides) (1) utilizing 2-chloro-, 2-nitrobenzoic acids and N-unsubstituted isatoic anhydrides as starting materials, are described.

  三种制备N-取代的2 H -3,1-苯并恶嗪-2,4（1 H）二酮（乙酸酐）的方法（1）使用2-氯-，2-硝基苯甲酸和N-未取代的等角酸酐作为制备方法描述了起始材料。
• [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。