3-(aminomethyl)-4-phenyl-1,2,5-oxadiazole 2-oxide | 169614-87-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-(aminomethyl)-4-phenyl-1,2,5-oxadiazole 2-oxide
• 英文别名: (2-Oxido-4-phenyl-1,2,5-oxadiazol-2-ium-3-yl)methanamine
• CAS: 169614-87-3
• 化学式: C₉H₉N₃O₂
• 分子量: 191.189
• InChiKey: SEBRVABDLIUINQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 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：
  77.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(aminomethyl)-4-phenyl-1,2,5-oxadiazole 2-oxide 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 锌 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 8.5h， 生成 (R)-4-methyl-N-((4-phenyl-1,2,5-oxadiazol-3-yl)methyl)-2-(phenylsulfonamido)pentanamide
  参考文献：
  名称：

  Furoxans (1,2,5-Oxadiazole-N-Oxides) as Novel NO Mimetic Neuroprotective and Procognitive Agents

  摘要：

  Furoxans (1,2,5-oxadiazole-N-oxides) are thiol-bioactivated NO-mimetics that have not hitherto been studied in the CNS. Incorporation of varied substituents adjacent to the furoxan ring system led to modulation of reactivity toward bioactivation, studied by HPLC-MS/MS analysis of reaction products. Attenuated reactivity unmasked the cytoprotective actions of NO in contrast to the cytotoxic actions of higher NO fluxes reported previously for furoxans. Neuroprotection was observed in primary neuronal cell cultures following oxygen glucose deprivation (OGD). Neuroprotective activity was observed to correlate with thiol-dependent bioactivation to produce NO2-, but not with depletion of free thiol itself. Neuroprotection was abrogated upon cotreatment with a sGC inhibitor, ODQ, thus supporting activation of the NO/sGC/CREB signaling cascade by furoxans. Long-term potentiation (LTP), essential for learning and memory, has been shown to be potentiated by NO signaling, therefore, a peptidomimetic furoxan was tested in hippocampal slices treated with oligomeric amyloid-beta peptide (A beta) and was shown to restore synaptic function. The novel observation of furoxan activity of potential therapeutic use in the CNS warrants further studies.

  DOI：

  10.1021/jm201504s
• 作为产物：
  描述：

  3-(氯甲基)-4-苯基-1,2,5-噁二唑 2-氧化物 在 一水合肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 3-(aminomethyl)-4-phenyl-1,2,5-oxadiazole 2-oxide
  参考文献：
  名称：

  Monge; Lopez de Cerain; Ezpeleta, Pharmazie, 1998, vol. 53, # 11, p. 758 - 764

  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。
• Synthesis and Biological Evaluation of 1,2,5-OxadiazoleN-Oxide Derivatives as Potential Hypoxic Cytotoxins and DNA-Binders
  作者：Hugo Cerecetto、Mercedes González、Mariela Risso、Gustavo Seoane、Adela López de Ceráin、Olga Ezpeleta、Antonio Monge、Leopoldo Suescun、Alvaro Mombrú、Ana M. Bruno

  DOI：10.1002/1521-4184(200011)333:11<387::aid-ardp387>3.0.co;2-n

  日期：2000.11

  Several new 1,2,5-oxadiazole N-oxide derivatives were synthesized to be tested both as potential selective hypoxic cell cytotoxins and as DNA-binding agents. The compounds prepared included bis(1,2,5-oxadiazole N-oxide) derivatives and oxadiazole rings linked to naphthyl residues. The compounds were tested for their cytotoxicity in oxia and hypoxia and they proved to be non-selective and less active than the parent compounds 3-formyl-4-phenyl-1,2,5-oxadiazole N2-oxide (3) and 3-chloromethyl-4-phenyl-1,2,5-oxadiazole N2-oxide (4). The DNA-affinity assays showed that the compounds tested have poor affinity for this biomolecule.
• Gasco, Andrea Marcello; Boschi, Donatella; Gasco, Alberto, Journal of Heterocyclic Chemistry, 1995, vol. 32, # 3, p. 811 - 814
  作者：Gasco, Andrea Marcello、Boschi, Donatella、Gasco, Alberto

  DOI：——

  日期：——
• Monge; Lopez de Cerain; Ezpeleta, Pharmazie, 1998, vol. 53, # 11, p. 758 - 764
  作者：Monge、Lopez de Cerain、Ezpeleta、Cerecetto、Dias、Di Maio、Gonzalez、Onetto、Seoane、Suescun、Mariezcurrena

  DOI：——

  日期：——
• Furoxans (1,2,5-Oxadiazole-<i>N</i>-Oxides) as Novel NO Mimetic Neuroprotective and Procognitive Agents
  作者：Isaac T. Schiefer、Lawren VandeVrede、Mauro Fa’、Ottavio Arancio、Gregory R. J. Thatcher

  DOI：10.1021/jm201504s

  日期：2012.4.12

  Furoxans (1,2,5-oxadiazole-N-oxides) are thiol-bioactivated NO-mimetics that have not hitherto been studied in the CNS. Incorporation of varied substituents adjacent to the furoxan ring system led to modulation of reactivity toward bioactivation, studied by HPLC-MS/MS analysis of reaction products. Attenuated reactivity unmasked the cytoprotective actions of NO in contrast to the cytotoxic actions of higher NO fluxes reported previously for furoxans. Neuroprotection was observed in primary neuronal cell cultures following oxygen glucose deprivation (OGD). Neuroprotective activity was observed to correlate with thiol-dependent bioactivation to produce NO2-, but not with depletion of free thiol itself. Neuroprotection was abrogated upon cotreatment with a sGC inhibitor, ODQ, thus supporting activation of the NO/sGC/CREB signaling cascade by furoxans. Long-term potentiation (LTP), essential for learning and memory, has been shown to be potentiated by NO signaling, therefore, a peptidomimetic furoxan was tested in hippocampal slices treated with oligomeric amyloid-beta peptide (A beta) and was shown to restore synaptic function. The novel observation of furoxan activity of potential therapeutic use in the CNS warrants further studies.