1-{[4-(1,1-dimethylethvl)phenyl]methyl}-2H-3,1-benzoxazine-2,4(1H)-dione | 931398-98-0

• 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-{[4-(1,1-dimethylethvl)phenyl]methyl}-2H-3,1-benzoxazine-2,4(1H)-dione
• 英文别名: 1-[(4-Tert-butylphenyl)methyl]-3,1-benzoxazine-2,4-dione
• CAS: 931398-98-0
• 化学式: C₁₉H₁₉NO₃
• 分子量: 309.365
• InChiKey: HODJWMWFFQMNOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 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-{[4-(1,1-dimethylethvl)phenyl]methyl}-2H-3,1-benzoxazine-2,4(1H)-dione 、 3-( 1,1-二氧代-4H-苯并[1,2,4]噻二嗪)基乙酸乙酯 在 sodium hydride 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 生成 1-(4-tert-Butyl-benzyl)-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：

  靛红酸酐 、 4-叔丁基苄溴 在 sodium hydride 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 20.0h， 生成 1-{[4-(1,1-dimethylethvl)phenyl]methyl}-2H-3,1-benzoxazine-2,4(1H)-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

• Palladium-Catalyzed Cyclization Reaction of <i>o</i>-Iodoanilines, CO₂, and CO: Access to Isatoic Anhydrides
  作者：Wen-Zhen Zhang、Ning Zhang、Yu-Qian Sun、Yu-Wei Ding、Xiao-Bing Lu

  DOI：10.1021/acscatal.7b03000

  日期：2017.12.1

  oxidants. Herein we report a highly selective palladium-catalyzed cyclization reaction for the efficient synthesis of isatoic anhydrides from readily available o-iodoanilines, CO2, and CO. The reaction proceeds under mild conditions and is redox-neutral. Both CO2 and CO are indispensable C1 building blocks for this catalytic reaction.

  通常使用高毒性的光气或化学计量的氧化剂来制备一类酸酐，一类有价值的合成中间体和RNA结构探测试剂。本文中，我们报道了一种高度选择性的钯催化环化反应，用于从容易获得的邻碘代苯胺，CO 2和CO有效合成isatoic酸酐。该反应在温和的条件下进行，并且是氧化还原中性的。对于该催化反应，CO 2和CO都是不可或缺的C1结构单元。
• WO2007/38571
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] PROLYL HYDROXYLASE ANTAGONISTS<br/>[FR] ANTAGONISTES DE LA PROLYL-HYDROXYLASE
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2007038571A2

  公开（公告）日：2007-04-05

  [EN] This invention relates to certain 2-[(quinolin-3-yl)carbonyl]aminoacetic acid derivatives of formula (I), where the various groups are defined herein, and which are useful in treating anemia.
  [FR] Cette invention concerne certains dérivés d'acide 2-[(quinolin-3-yl)carbonyl]amino-acétique de formule (I) dans laquelle les divers groupes sont tels que définis dans le mémorandum descriptif. Ces dérivés sont utiles pour le traitement de l'anémie.
• 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.