3-(bromomethyl)-4-phenyl-1,2,5-oxadiazole 2-oxide | 169614-78-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(bromomethyl)-4-phenyl-1,2,5-oxadiazole 2-oxide
• 英文别名: 3-Bromomethyl-4-phenyl-furazan 2-oxide；3-(bromomethyl)-2-oxido-4-phenyl-1,2,5-oxadiazol-2-ium
• CAS: 169614-78-2
• 化学式: C₉H₇BrN₂O₂
• 分子量: 255.071
• InChiKey: JFUNGPNNBPZYIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  51.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(bromomethyl)-4-phenyl-1,2,5-oxadiazole 2-oxide 在 水 、 pyridinium chlorochromate 、 calcium carbonate 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 4-phenylfuroxan-3-carboxaldehyde
  参考文献：
  名称：

  Synthesis of furoxan derivatives: DABCO-mediated cascade sulfonylation/cyclization reaction of α-nitro-ketoximes

  摘要：

  A convenient and efficient method for the synthesis of furoxan derivatives from alpha-nitro-ketoximes and sulfonyl chlorides is reported. A wide variety of furoxan derivatives were smoothly obtained in good yields via a DABCO-mediated cascade sulfonylation/cyclization process under mild conditions. The usefulness of this method was also demonstrated by the conversions of the furoxan products into other promising compounds. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2015.01.031
• 作为产物：
  描述：

  3-methyl-4-phenylfuroxan 在 N-溴代丁二酰亚胺(NBS) 、 过氧化氢苯甲酰 作用下， 以 四氯化碳 为溶剂， 反应 24.0h， 以85%的产率得到3-(bromomethyl)-4-phenyl-1,2,5-oxadiazole 2-oxide
  参考文献：
  名称：

  Gasco, Andrea Marcello; Boschi, Donatella; Gasco, Alberto, Journal of Heterocyclic Chemistry, 1995, vol. 32, # 3, p. 811 - 814

  摘要：

  DOI：

文献信息

• Design, Synthesis, and <i>in vitro</i> Evaluation of P2X7 Antagonists
  作者：Dimitra T. Pournara、Anna Durner、Eftichia Kritsi、Alexios Papakostas、Panagiotis Zoumpoulakis、Annette Nicke、Maria Koufaki

  DOI：10.1002/cmdc.202000303

  日期：2020.12.15

  is a promising target for the treatment of various diseases due to its significant role in inflammation and immune cell signaling. This work describes the design, synthesis, and in vitro evaluation of a series of novel derivatives bearing diverse scaffolds as potent P2X7 antagonists. Our approach was based on structural modifications of reported (adamantan‐1‐yl)methylbenzamides able to inhibit the receptor

  由于 P2X7 受体在炎症和免疫细胞信号传导中的重要作用，它是治疗各种疾病的有希望的靶点。这项工作描述了一系列带有多种支架的新型衍生物作为有效的 P2X7 拮抗剂的设计、合成和体外评估。我们的方法基于已报道的（金刚烷-1-基）甲基苯甲酰胺的结构修饰，能够抑制受体激活。金刚烷部分和酰胺键被替换，并通过基于配体的药效团模型评估替换。通过双电极电压钳实验评估合成类似物的拮抗效力，使用非洲爪蟾表达人 P2X7 受体的卵母细胞。SAR 研究表明，用芳基-环己基部分取代金刚烷环是对抗 P2X7 阳离子通道激活的最有效拮抗剂，类似物 2-氯-N- [1-(3-(硝基氧基甲基)苯基)环己基)甲基]苯甲酰胺 ( 56 ) 表现出最佳效力，IC 50值为 0.39 μM。
• [EN] FUROXANS AS THERAPIES FOR NEURODEGENERATIVE DISORDERS<br/>[FR] FUROXANES UTILISÉS EN TANT QUE THÉRAPIES POUR DES TROUBLES NEURODÉGÉNÉRATIFS
  申请人：UNIV TOLEDO

  公开号：WO2018093762A1

  公开（公告）日：2018-05-24

  Furoxan compounds, compositions comprising the same, and methods of making and using the same, are described.

  Furoxan化合物、包含该化合物的组合物以及制备和使用该化合物的方法被描述。
• Furoxans (Oxadiazole-4<i>N</i>-oxides) with Attenuated Reactivity are Neuroprotective, Cross the Blood Brain Barrier, and Improve Passive Avoidance Memory
  作者：Austin Horton、Kevin Nash、Ethel Tackie-Yarboi、Alexander Kostrevski、Adam Novak、Aparna Raghavan、Jatin Tulsulkar、Qasim Alhadidi、Nathan Wamer、Bryn Langenderfer、Kalee Royster、Maxwell Ducharme、Katelyn Hagood、Megan Post、Zahoor A. Shah、Isaac T. Schiefer

  DOI：10.1021/acs.jmedchem.8b00389

  日期：2018.5.24

  Nitric oxide (NO) mimetics and other agents capable of enhancing NO/cGMP signaling have demonstrated efficacy as potential therapies for Alzheimer’s disease. A group of thiol-dependent NO mimetics known as furoxans may be designed to exhibit attenuated reactivity to provide slow onset NO effects. The present study describes the design, synthesis, and evaluation of a furoxan library resulting in the

  一氧化氮（NO）模拟物和其他能够增强NO / cGMP信号传导的药物已证明可作为治疗阿尔茨海默氏病的有效方法。可以设计一组称为呋喃喃的硫醇依赖性NO模拟物，以表现出减弱的反应性，从而提供缓慢的NO效应。本研究描述了呋喃聚糖文库的设计，合成和评估，从而鉴定出了呋喃喃原型5a，该原型已被确定可用于中枢神经系统。在生理条件下，呋喃喃5a对普通细胞硫醇的反应性可忽略不计。尽管如此，仍观察到了cGMP依赖性神经保护作用，并且5a（20 mg / kg）在被动回避恐惧记忆的小鼠模型中逆转了胆碱能记忆缺陷。重要的是，可以将5a制成可药用盐的形式，并在口服12小时后在大脑中观察到，这表明每日给药的潜力和出色的代谢稳定性。继续研究呋喃喃类药物作为中枢神经系统的减毒NO模拟物是有必要的。
• Furoxans as therapies for neurodegenerative disorders
  申请人：The University of Toledo

  公开号：US10590119B2

  公开（公告）日：2020-03-17

  Furoxan compounds, compositions comprising the same, and methods of making and using the same, are described.

  描述了呋喃类化合物、包含呋喃类化合物的组合物以及制造和使用呋喃类化合物的方法。
• Novel Nitric Oxide-Releasing Derivatives of Brusatol as Anti-Inflammatory Agents: Design, Synthesis, Biological Evaluation, and Nitric Oxide Release Studies
  作者：Weibin Tang、Jianlin Xie、Song Xu、Haining Lv、Mingbao Lin、Shaopeng Yuan、Jinye Bai、Qi Hou、Shishan Yu

  DOI：10.1021/jm5007534

  日期：2014.9.25

  Brusatol, a biologically active natural product, was modified in four distinct positions through the covalent attachment of a furoxan moiety, which acts as a nitric oxide (NO) donor. Forty derivatives were synthesized and evaluated for their inhibitory effects on excess NO biosynthesis in activated macrophages. Among them, compound 75 demonstrated inhibition (IC50 = 0.067 mu M) comparable to that of brusatol but were less cytotoxic. More importantly, even at very low doses (2 mu mol/kg/day), compound 75 also showed substantial inhibitory efficacy against chronic obstructive pulmonary disease (COPD)-like inflammation in the mouse model induced by cigarette smoke (CS) and lipopolysaccharide (LPS). Particularly, this compound was over 100-fold less toxic (LD50 > 3852 mu mol/kg) than brusatol and could be a promising lead for further studies. Notably, the improved properties of this derivative are associated with its NO-releasing capability.