4-((4-methoxybenzyl)thio)-7-nitrobenzo[c][1,2,5]oxadiazole | 882289-31-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶二唑类
• 英文名称: 4-((4-methoxybenzyl)thio)-7-nitrobenzo[c][1,2,5]oxadiazole
• 英文别名: 4-[(4-methoxyphenyl)methylsulfanyl]-7-nitro-2,1,3-benzoxadiazole
• CAS: 882289-31-8
• 化学式: C₁₄H₁₁N₃O₄S
• 分子量: 317.325
• InChiKey: KIUBYIRTUBYMAX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  119
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-((4-methoxybenzyl)thio)-7-nitrobenzo[c][1,2,5]oxadiazole 在 盐酸 、 sodium 、 铁粉 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.42h， 生成 7-(4-methoxybenzylthio)-N-methylbenzo[c][1,2,5]oxadiazol-4-amine
  参考文献：
  名称：

  Discovery and synthesis of novel benzofurazan derivatives as inhibitors of influenza A virus

  摘要：

  The identification of a novel hit compound inhibitor of the protein-protein interaction between the influenza RNA-polymerase PA and PB1 subunits has been accomplished by means of high-throughput screening. A small family of structurally related molecules has been synthesized and biologically evaluated with most of the compounds showing micromolar potency of inhibition against viral replication. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.048
• 作为产物：
  描述：

  4-甲氧基苄硫醇 、 4-氯-7-硝基苯并-2-氧杂-1,3-二唑 在 吡啶 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以64%的产率得到4-((4-methoxybenzyl)thio)-7-nitrobenzo[c][1,2,5]oxadiazole
  参考文献：
  名称：

  [EN] BENZO[C][1,2,5]OXADIAZOLE FOR THE TREATMENT OF DISEASES CAUSED BY HELICOBACTER
  [FR] BENZO [C] [1,2,5] OXADIAZOLE POUR LE TRAITEMENT DE MALADIES PROVOQUÉES PAR HELICOBACTER

  摘要：

  本发明涉及一种新的化合物，即苯并[c][1,2,5]噁二唑衍生物，以及其在治疗由幽门螺杆菌引起的传染病中的应用。此外，本发明涉及一种药物组合物和一种包含该化合物的联合制剂。

  公开号：

  WO2020234424A1

文献信息

• The Fight against the Influenza A Virus H1N1: Synthesis, Molecular Modeling, and Biological Evaluation of Benzofurazan Derivatives as Viral RNA Polymerase Inhibitors
  作者：Mafalda Pagano、Daniele Castagnolo、Martina Bernardini、Anna Lucia Fallacara、Ilaria Laurenzana、Davide Deodato、Ulrich Kessler、Beatrice Pilger、Lilli Stergiou、Stephan Strunze、Cristina Tintori、Maurizio Botta

  DOI：10.1002/cmdc.201300378

  日期：2014.1

  The influenza RNA polymerase complex, which consists of the three subunits PA, PB1, and PB2, is a promising target for the development of new antiviral drugs. A large library of benzofurazan compounds was synthesized and assayed against influenza virus A/WSN/33 (H1N1). Most of the new derivatives were found to act by inhibiting the viral RNA polymerase complex through disruption of the complex formed

  由PA，PB1和PB2三个亚基组成的流感RNA聚合酶复合物是开发新抗病毒药物的有希望的目标。合成了庞大的苯并呋喃化合物文库，并针对流感病毒A / WSN / 33（H1N1）进行了分析。发现大多数新衍生物通过破坏亚基PA和PB1之间形成的复合物来抑制病毒RNA聚合酶复合物而发挥作用。还进行了对接研究，以阐明PA中PB1结合位点内苯并呋喃类的结合方式，并鉴定参与其作用机理的氨基酸。预测的结合姿势与生物学数据完全一致，为合理开发更有效的PA–PB1抑制剂奠定了基础。
• COMPOSITION FOR TREATING INFECTIOUS DISEASES CAUSED BY HELICOBACTER
  申请人：Universidad de Zaragoza

  公开号：EP2130824A1

  公开（公告）日：2009-12-09

  The invention relates to a compound of general formula (I) for use in a pharmaceutical composition for treating infectious diseases caused by Helicobacter pylori. R1 and R2 are O, S or N, and can be identical or different; R3 is O or S; R4 is H or a (C1-C6) alkyl group; n represents a value between 0 and 3; and R5 is an NO2, COOR' or So3R' radical wherein R' is a hydrogen (H) atom or a (C1-C6) alkyl group.

  本发明涉及通式（I）化合物，用于治疗幽门螺旋杆菌引起的传染性疾病的药物组合物中。R1和R2为O、S或N，可以相同或不同；R3为O或S；R4为H或（C1-C6）烷基；n代表0至3之间的值；R5为NO2、COOR'或So3R'基，其中R'为氢（H）原子或（C1-C6）烷基。
• Improved Flavodoxin Inhibitors with Potential Therapeutic Effects against <i>Helicobacter pylori</i> Infection
  作者：Juan J. Galano、Miriam Alías、Reyes Pérez、Adrian Velázquez-Campoy、Paul S. Hoffman、Javier Sancho

  DOI：10.1021/jm400786q

  日期：2013.8.8

  Helicobacter pylori (Hp) infection affects one-half of the human population and produces a variety of diseases from peptic ulcer to cancer. Current eradication therapies achieve modest success rates (around 70%), resistance to the antibiotics of choice is on the rise, and vaccination has not proved to be successful yet. Using an essential Hp protein, flavodoxin, as target, we identified three low-molecular-weight flavodoxin inhibitors with bactericidal anti-Hp properties. To improve their therapeutic indexes, we have now identified and tested 123 related compounds. We have first tested similar compounds available. Then we have designed, synthesized, and tested novel variants for affinity to flavodoxin, MIC for Hp, cytotoxicity, and bactericidal effect. Some are novel bactericidal inhibitors with therapeutic indexes of 9, 38 and 12, significantly higher than those of their corresponding leads. Developing novel Hp-specific antibiotics will help fighting Hp resistance and may have the advantage of not generally perturbing the bacterial flora.
• Design, Synthesis, and Efficacy Testing of Nitroethylene- and 7-Nitrobenzoxadiazol-Based Flavodoxin Inhibitors against <i>Helicobacter pylori</i> Drug-Resistant Clinical Strains and in <i>Helicobacter pylori</i>-Infected Mice
  作者：Sandra Salillas、Miriam Alías、Valérie Michel、Alejandro Mahía、Ainhoa Lucía、Liliana Rodrigues、Jessica Bueno、Juan José Galano-Frutos、Hilde De Reuse、Adrián Velázquez-Campoy、José Alberto Carrodeguas、Carlos Sostres、Javier Castillo、José Antonio Aínsa、María Dolores Díaz-de-Villegas、Ángel Lanas、Eliette Touati、Javier Sancho

  DOI：10.1021/acs.jmedchem.9b00355

  日期：2019.7.11

  Helicobacter pylori (Hp) infection is the main cause of peptic ulcer and gastric cancer. Hp eradication rates have fallen due to increasing bacterial resistance to currently used broad-spectrum antimicrobials. We have designed, synthesized, and tested redox variants of nitroethylene- and 7-nitrobenzoxadiazole-based inhibitors of the essential Hp protein flavodoxin. Derivatives of the 7-nitrobenzoxadiazole lead, carrying reduced forms of the nitro group and/or oxidized forms of a sulfur atom, display high therapeutic indexes against several reference Hp strains. These inhibitors are effective against metronidazole-, clarithromycin-, and rifampicin-resistant Hp clinical isolates. Their toxicity for mice after oral administration is low, and, when administered individually at single daily doses for 8 days in a mice model of Hp infection, they decrease significantly Hp gastric colonization rates and are able to eradicate the infection in up to 60% of the mice. These flavodoxin inhibitors constitute a novel family of Hp-specific antimicrobials that may help fight the constant increase of Hp antimicrobial-resistant strains.
• 2,1,3-BENZOXADIAZOL DERIVATIVES FOR THE INHIBITION OF INFLUENZA A AND B VIRUS AND RESPIRATORY SYNCYTIAL VIRUS REPLICATION
  申请人：Pike Pharma GmbH

  公开号：EP2427442A1

  公开（公告）日：2012-03-14