2-methoxy-1,1,3,3-tetramethylisoindoline-5-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-methoxy-1,1,3,3-tetramethylisoindoline-5-carboxylic acid
• 英文别名: 2-Methoxy-1,1,3,3-tetramethylisoindole-5-carboxylic acid；2-methoxy-1,1,3,3-tetramethylisoindole-5-carboxylic acid
• 化学式: C₁₄H₁₉NO₃
• 分子量: 249.31
• InChiKey: FAJMOZIUFUFLIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-methoxy-1,1,3,3-tetramethylisoindoline-5-carboxylic acid 在 吡啶 、 氯化亚砜 作用下， 以 甲苯 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Ciprofloxacin-nitroxide hybrids with potential for biofilm control

  摘要：

  As bacterial biofilms display extreme tolerance to conventional antibiotic treatments, it has become imperative to develop new antibacterial strategies with alternative mechanisms of action. Herein, we report the synthesis of a series of ciprofloxacin-nitroxide conjugates and their corresponding methoxyamine derivatives in high yield. This was achieved by linking various nitroxides or methoxy-amines to the secondary amine of the piperazine ring of ciprofloxacin using amide bond coupling. Biological evaluation of the prepared compounds on preformed P. aeruginosa biofilms in flow cells revealed substantial dispersal with ciprofloxacin-nitroxide hybrid 25, and virtually complete killing and removal (94%) of established biofilms in the presence of ciprofloxacin-nitroxide hybrid 27. Compounds 25-28 were shown to be non-toxic in both human embryonic kidney 293 (HEK 293) cells and human muscle rhabdomyosarcoma (RD) cells at concentrations up to 40 mu M. Significantly, these hybrids demonstrate the potential of antimicrobial-nitroxide agents to overcome the resistance of biofilms to antimicrobials via stimulation of biofilm dispersal or through direct cell killing. Crown Copyright (C) 2017 Published by Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.06.058
• 作为产物：
  描述：

  二甲基亚砜 、 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl 在 ferrous(II) sulfate heptahydrate 、 双氧水 作用下， 以 水 为溶剂， 反应 0.17h， 以93%的产率得到2-methoxy-1,1,3,3-tetramethylisoindoline-5-carboxylic acid
  参考文献：
  名称：

  Ciprofloxacin-nitroxide hybrids with potential for biofilm control

  摘要：

  As bacterial biofilms display extreme tolerance to conventional antibiotic treatments, it has become imperative to develop new antibacterial strategies with alternative mechanisms of action. Herein, we report the synthesis of a series of ciprofloxacin-nitroxide conjugates and their corresponding methoxyamine derivatives in high yield. This was achieved by linking various nitroxides or methoxy-amines to the secondary amine of the piperazine ring of ciprofloxacin using amide bond coupling. Biological evaluation of the prepared compounds on preformed P. aeruginosa biofilms in flow cells revealed substantial dispersal with ciprofloxacin-nitroxide hybrid 25, and virtually complete killing and removal (94%) of established biofilms in the presence of ciprofloxacin-nitroxide hybrid 27. Compounds 25-28 were shown to be non-toxic in both human embryonic kidney 293 (HEK 293) cells and human muscle rhabdomyosarcoma (RD) cells at concentrations up to 40 mu M. Significantly, these hybrids demonstrate the potential of antimicrobial-nitroxide agents to overcome the resistance of biofilms to antimicrobials via stimulation of biofilm dispersal or through direct cell killing. Crown Copyright (C) 2017 Published by Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.06.058

文献信息

• Synergistic or antagonistic antioxidant combinations – a case study exploring flavonoid-nitroxide hybrids
  作者：Astrid C. R. Larin、Michael C. Pfrunder、Kathleen M. Mullen、Sandra Wiedbrauk、Nathan R. Boase、Kathryn E. Fairfull-Smith

  DOI：10.1039/d2ob02101c

  日期：——

  treatment option to slow down neurodegeneration, although adequate potency of treatments has not yet been achieved. Using a hybrid pharmacology approach, free radical nitroxide antioxidants were hybridised with a class of natural antioxidants, flavonoids, to form a potential multitargeted antioxidant. Modification of the Baker–Venkataraman reaction achieved the flavonoid-nitroxide hybrids (6–9) in modest yields

  神经退行性疾病给全世界人口带来了相当大的医疗和公共卫生负担。氧化应激是导致活性氧 (ROS) 生成的促氧化剂/抗氧化剂稳态失衡，与许多神经退行性疾病的进展有关。ROS 水平的操纵可能代表一种有前途的治疗选择，可以减缓神经变性，尽管尚未达到足够的治疗效力。使用混合药理学方法，将氮氧自由基抗氧化剂与一类天然抗氧化剂类黄酮杂交，形成潜在的多靶点抗氧化剂。Baker-Venkataraman 反应的改进实现了类黄酮-硝基氧化物杂化物（6-9) 适度的收益率。通过循环伏安法对杂化物的抗氧化评估表明，两种氧化还原功能仍然活跃，对氧化电位的影响很小。通过 ORAC 测定对过氧自由基清除能力的评估表明，与它们的单个成分相比，杂化物的抗氧化活性降低。假设杂化物中苯酚的存在产生更酸性的介质，其不利于氮氧化合物从相应的氧铵阳离子再生，扰乱了氮氧化合物清除过氧自由基的典型催化循环。这项工作突出了药物杂交作为新治疗开发策略所涉及的潜在复杂性。
• RADICAL ORBITAL SWITCHING
  申请人：THE AUSTRALIAN NATIONAL UNIVERSITY

  公开号：US20160075732A1

  公开（公告）日：2016-03-17

  Described herein are distonic radical anion species of formula (I): RAD-L-NEG; wherein RAD is a group comprising a radical; NEG is a group comprising an anion, which is capable of bonding to a proton or other cation; L is a linker that links NEG to RAD; and the radical of RAD is not π-conjugated to the anion of NEG.
• Ciprofloxacin-nitroxide hybrids with potential for biofilm control
  作者：Anthony D. Verderosa、César de la Fuente-Núñez、Sarah C. Mansour、Jicong Cao、Timothy K. Lu、Robert E.W. Hancock、Kathryn E. Fairfull-Smith

  DOI：10.1016/j.ejmech.2017.06.058

  日期：2017.9

  As bacterial biofilms display extreme tolerance to conventional antibiotic treatments, it has become imperative to develop new antibacterial strategies with alternative mechanisms of action. Herein, we report the synthesis of a series of ciprofloxacin-nitroxide conjugates and their corresponding methoxyamine derivatives in high yield. This was achieved by linking various nitroxides or methoxy-amines to the secondary amine of the piperazine ring of ciprofloxacin using amide bond coupling. Biological evaluation of the prepared compounds on preformed P. aeruginosa biofilms in flow cells revealed substantial dispersal with ciprofloxacin-nitroxide hybrid 25, and virtually complete killing and removal (94%) of established biofilms in the presence of ciprofloxacin-nitroxide hybrid 27. Compounds 25-28 were shown to be non-toxic in both human embryonic kidney 293 (HEK 293) cells and human muscle rhabdomyosarcoma (RD) cells at concentrations up to 40 mu M. Significantly, these hybrids demonstrate the potential of antimicrobial-nitroxide agents to overcome the resistance of biofilms to antimicrobials via stimulation of biofilm dispersal or through direct cell killing. Crown Copyright (C) 2017 Published by Elsevier Masson SAS. All rights reserved.