ethyl 3-methoxy-5-methyl-2-oxo-8-oxabicyclo[3.2.1]octa-3,6-diene-6-carboxylate | 1414861-08-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: ethyl 3-methoxy-5-methyl-2-oxo-8-oxabicyclo[3.2.1]octa-3,6-diene-6-carboxylate
• 英文别名: Ethyl 3-methoxy-5-methyl-2-oxo-8-oxabicyclo[3.2.1]octa-3,6-diene-6-carboxylate
• CAS: 1414861-08-7
• 化学式: C₁₂H₁₄O₅
• 分子量: 238.24
• InChiKey: DQIFFKUAPRTTPJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 3-methoxy-5-methyl-2-oxo-8-oxabicyclo[3.2.1]octa-3,6-diene-6-carboxylate 在 三氯化硼 、 三溴化硼 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 73.0h， 生成 4,6-dihydroxy-2-methyl-5-oxocyclohepta-1,3,6-triene-1-carboxylic acid
  参考文献：
  名称：

  [EN] COMPOSITIONS AND METHODS FOR INHIBITING INFLUENZA RNA POLYMERASE PA ENDONUCLEASE
  [FR] COMPOSITIONS ET PROCÉDÉS POUR INHIBER L'ENDONUCLÉASE DE LA PA DE L'ARN POLYMÉRASE DE LA GRIPPE

  摘要：

  其中提供了金属酶抑制剂，例如流感A病毒RNA依赖性RNA聚合酶PA亚基内切酶的抑制剂，以及其合成和使用方法。

  公开号：

  WO2017156194A1
• 作为产物：
  描述：

  (2-氯甲基)-5-羟基-4H-吡喃-4-酮 在 盐酸 、 N,N-二异丙基乙胺 、 锌 作用下， 以 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 0.42h， 生成 ethyl 3-methoxy-5-methyl-2-oxo-8-oxabicyclo[3.2.1]octa-3,6-diene-6-carboxylate
  参考文献：
  名称：

  [EN] COMPOSITIONS AND METHODS FOR INHIBITING INFLUENZA RNA POLYMERASE PA ENDONUCLEASE
  [FR] COMPOSITIONS ET PROCÉDÉS POUR INHIBER L'ENDONUCLÉASE DE LA PA DE L'ARN POLYMÉRASE DE LA GRIPPE

  摘要：

  其中提供了金属酶抑制剂，例如流感A病毒RNA依赖性RNA聚合酶PA亚基内切酶的抑制剂，以及其合成和使用方法。

  公开号：

  WO2017156194A1

文献信息

• Compositions and methods for inhibiting influenza RNA polymerase PA endonuclease
  申请人：The Regents of the University of California

  公开号：US10889556B2

  公开（公告）日：2021-01-12

  There are provided inter alia metalloenzyme inhibitors, such as inhibitors of influenza A RNA dependent RNA polymerase PA subunit endonuclease, and methods of synthesis and use of the same.

  除其他外，还提供了金属酶抑制剂，例如甲型流感 RNA 依赖性 RNA 聚合酶 PA 亚基内切酶抑制剂，以及合成和使用这些抑制剂的方法。
• Structure–Activity Relationships in Metal-Binding Pharmacophores for Influenza Endonuclease
  作者：Cy V. Credille、Benjamin L. Dick、Christine N. Morrison、Ryjul W. Stokes、Rebecca N. Adamek、Nicholas C. Wu、Ian A. Wilson、Seth M. Cohen

  DOI：10.1021/acs.jmedchem.8b01363

  日期：2018.11.21

  Metalloenzymes represent an important target space for drug discovery. A limitation to the early development of metalloenzyme inhibitors has been the lack of established structure-activity relationships (SARs) for molecules that bind the metal ion cofactor(s) of a metalloenzyme. Herein, we employed a bioinorganic perspective to develop an SAR for inhibition of the metalloenzyme influenza RNA polymerase PA(N) endonuclease. The identified trends highlight the importance of the electronics of the metal-binding pharmacophore (MBP), in addition to MBP sterics, for achieving improved inhibition and selectivity. By optimization of the MBPs for PA(N) endonuclease, a class of highly active and selective fragments was developed that displays IC50 values <50 nM. This SAR led to structurally distinct molecules that also displayed IC50 values of similar to 10 nM, illustrating the utility of a metal-centric development campaign in generating highly active and selective metalloenzyme inhibitors.
• An Oxidopyrylium Cyclization/Ring-Opening Route to Polysubstituted α-Hydroxytropolones
  作者：Christine Meck、Noushad Mohd、Ryan P. Murelli

  DOI：10.1021/ol302892g

  日期：2012.12.7

  alpha-Hydroxytropolones are a class of molecules with therapeutic potential against several human diseases. However, structure-activity relationship studies on these molecules have been limited due to a scarcity of efficient synthetic methods to access them. It is demonstrated herein that alpha-hydroxytropolones can be generated through a BCl3-mediated ring-opening/aromatization/demethylation process on 8-oxabicyclo[3.2.1]octenes. Used in conjunction with an improved method based on established oxidopyrylium dipolar cycloadditions, several polysubstituted alpha-hydroxytropolones can be accessed in three steps from readily available alpha-hydroxy-gamma-pyrones.
• COMPOSITIONS AND METHODS FOR INHIBITING INFLUENZA RNA POLYMERASE PA ENDONUCLEASE
  申请人：The Regents of the University of California

  公开号：US20190106398A1

  公开（公告）日：2019-04-11

  There are provided inter alia metalloenzyme inhibitors, such as inhibitors of influenza A RNA dependent RNA polymerase PA subunit endonuclease, and methods of synthesis and use of the same.