naproxen A

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: naproxen A
• 英文别名: 3-(6-Methoxynaphthalen-2-yl)pentanedioic acid；3-(6-methoxynaphthalen-2-yl)pentanedioic acid
• 化学式: C₁₆H₁₆O₅
• 分子量: 288.3
• InChiKey: IRZGDKNZOVKALS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  83.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-甲氧基-2-萘甲醛 在 哌啶 、 水 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 75.5h， 生成 naproxen A
  参考文献：
  名称：

  Structure-based design of novel naproxen derivatives targeting monomeric nucleoprotein of Influenza A virus

  摘要：

  The nucleoprotein (NP) binds the viral RNA genome as oligomers assembled with the polymerase in a ribonucleoprotein complex required for transcription and replication of influenza A virus. Novel antiviral candidates targeting the nucleoprotein either induced higher order oligomers or reduced NP oligomerization by targeting the oligomerization loop and blocking its insertion into adjacent nucleoprotein subunit. In this study, we used a different structure-based approach to stabilize monomers of the nucleoprotein by drugs binding in its RNA-binding groove. We recently identified naproxen as a drug competing with RNA binding to NP with antiinflammatory and antiviral effects against influenza A virus. Here, we designed novel derivatives of naproxen by fragment extension for improved binding to NP. Molecular dynamics simulations suggested that among these derivatives, naproxen A and C0 were most promising. Their chemical synthesis is described. Both derivatives markedly stabilized NP monomer against thermal denaturation. Naproxen C0 bound tighter to NP than naproxen at a binding site predicted by MD simulations and shown by competition experiments using wt NP or single-point mutants as determined by surface plasmon resonance. MD simulations suggested that impeded oligomerization and stabilization of monomeric NP is likely to be achieved by drugs binding in the RNA grove and inducing close to their binding site conformational changes of key residues hosting the oligomerization loop as observed for the naproxen derivatives. Naproxen C0 is a potential antiviral candidate blocking influenza nucleoprotein function.

  DOI：

  10.1080/07391102.2014.979230

文献信息

• ANTIVIRAL COMPOSITIONS DIRECTED AGAINST THE INFLUENZA VIRUS NUCLEOPROTEIN
  申请人：Slama Schwok Anny

  公开号：US20140163107A1

  公开（公告）日：2014-06-12

  A pharmaceutical composition for treating viral infections by an influenza type A virus, includes a compound capable of acting as an inhibitor of the binding of the viral RNA to the nucleoprotein of influenza type A viruses, and capable of binding to the viral-RNA-binding domain on the nucleoprotein. A pharmaceutical composition for treating viral infections by an orthomyxovirus, includes a compound capable of acting as an inhibitor of the binding of the viral RNA to the nucleoprotein of orthomyxoviruses, and capable of binding to the viral-RNA-binding domain on the nucleoprotein of the viruses. A compound acting as an inhibitor of the binding of the viral RNA to the nucleoprotein of influenza type A viruses, and binding to the viral-RNA-binding domain on the nucleoprotein of influenza type A viruses and a method for identifying such a compound having these properties are also described.

  一种治疗流感A型病毒引起的病毒感染的药物组合物，包括一种能够作为流感A型病毒的核蛋白与病毒RNA结合的抑制剂的化合物，并且能够结合到核蛋白上的病毒-RNA结合结构域。一种治疗正黏病毒引起的病毒感染的药物组合物，包括一种能够作为正黏病毒的核蛋白与病毒RNA结合的抑制剂的化合物，并且能够结合到病毒的核蛋白上的病毒-RNA结合结构域。还描述了一种作为流感A型病毒的核蛋白与病毒RNA结合的抑制剂，并且能够结合到流感A型病毒的核蛋白上的病毒-RNA结合结构域的化合物，以及识别具有这些特性的化合物的方法。
• ANTIVIRAL COMPOSITIONS DIRECTED AGAINST THE NUCLEOPROTEIN OF INFLUENZA VIRUSES
  申请人：INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE

  公开号：US20180028478A1

  公开（公告）日：2018-02-01

  Pharmaceutical compositions for the treatment of a viral infection by a type-A influenza virus are provided. The compositions include a compound having the property of acting as an inhibitor of the attachment of the viral RNA to the nucleoprotein of the type-A influenza virus, the compound having the property of binding to the binding domain of the viral RNA to the nucleoprotein. Methods of treating an infection by influenza virus by administering an effective amount of the compound to a subject are also disclosed. A process for identifying a compound having the property of binding to the binding domain of the viral RNA to the nucleoprotein of the type-A influenza viruses are further disclosed.
• US9783482B2
  申请人：——

  公开号：US9783482B2

  公开（公告）日：2017-10-10
• Structure-based design of novel naproxen derivatives targeting monomeric nucleoprotein of Influenza A virus
  作者：Bogdan Tarus、Hélène Bertrand、Gloria Zedda、Carmelo Di Primo、Stéphane Quideau、Anny Slama-Schwok

  DOI：10.1080/07391102.2014.979230

  日期：2015.9.2

  The nucleoprotein (NP) binds the viral RNA genome as oligomers assembled with the polymerase in a ribonucleoprotein complex required for transcription and replication of influenza A virus. Novel antiviral candidates targeting the nucleoprotein either induced higher order oligomers or reduced NP oligomerization by targeting the oligomerization loop and blocking its insertion into adjacent nucleoprotein subunit. In this study, we used a different structure-based approach to stabilize monomers of the nucleoprotein by drugs binding in its RNA-binding groove. We recently identified naproxen as a drug competing with RNA binding to NP with antiinflammatory and antiviral effects against influenza A virus. Here, we designed novel derivatives of naproxen by fragment extension for improved binding to NP. Molecular dynamics simulations suggested that among these derivatives, naproxen A and C0 were most promising. Their chemical synthesis is described. Both derivatives markedly stabilized NP monomer against thermal denaturation. Naproxen C0 bound tighter to NP than naproxen at a binding site predicted by MD simulations and shown by competition experiments using wt NP or single-point mutants as determined by surface plasmon resonance. MD simulations suggested that impeded oligomerization and stabilization of monomeric NP is likely to be achieved by drugs binding in the RNA grove and inducing close to their binding site conformational changes of key residues hosting the oligomerization loop as observed for the naproxen derivatives. Naproxen C0 is a potential antiviral candidate blocking influenza nucleoprotein function.