4-phenylfuroxan-3-carboxaldehyde | 135733-34-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-phenylfuroxan-3-carboxaldehyde
• 英文别名: 3-formyl-4-phenyl-1,2,5-oxadiazole 2-oxide；3-formyl-4-phenyl-1,2,5-oxadiazole N²-oxide；4-phenyl-1,2,5-oxadiazol-3-carbaldehyde 2-oxide；3-formyl-4-phenylfuroxan；4-phenyl-1,2,5-oxadiazole-3-carbonyl-2-oxide；1,2,5-Oxadiazole-3-carboxaldehyde, 4-phenyl-, 2-oxide；2-oxido-4-phenyl-1,2,5-oxadiazol-2-ium-3-carbaldehyde
• CAS: 135733-34-5
• 化学式: C₉H₆N₂O₃
• 分子量: 190.158
• InChiKey: MNNADPGXJASGIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  68.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-phenylfuroxan-3-carboxaldehyde 在 盐酸羟胺 、 sodium acetate 作用下， 以 乙醇 为溶剂， 生成 4-phenyl-3-furoxanylcarbaldehyde oxime
  参考文献：
  名称：

  Structure Mechanism Insights and the Role of Nitric Oxide Donation Guide the Development of Oxadiazole-2-Oxides as Therapeutic Agents against Schistosomiasis

  摘要：

  Schistosomiasis is a chronic parasitic disease affecting hundreds of millions of individuals worldwide. Current treatment depends on a single agent, praziquantel, raising concerns of emergence of resistant parasites. Here, we continue our explorations of an oxadiazole-2-oxide class of compounds we recently identified as inhibitors of thioredoxin glutathione reductase (TGR), a selenocysteine-containing flavoenzyme required by the parasite to maintain proper cellular redox balance. Through systematic evaluation of the core molecular structure of this chemotype, we define the essential pharmacophore, establish a link between the nitric oxide donation and TGR inhibition, determine the selectivity for this chemotype versus related reductase enzymes, and present evidence that these agents can be modified to possess appropriate drug metabolism and pharmacokinetic properties. The mechanistic link between exogenous NO donation and parasite injury is expanded and better defined. The results of these studies verify the utility of oxadiazole-2-oxides as novel inhibitors of TGR and as efficacious antischistosomal agents.

  DOI：

  10.1021/jm901021k
• 作为产物：
  描述：

  肉桂醇 在 溶剂黄146 、 pyridinium chlorochromate 、 sodium nitrite 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 生成 4-phenylfuroxan-3-carboxaldehyde
  参考文献：
  名称：

  Synthesis and Preliminary Evaluation of N-Oxide Derivatives for the Prevention of Atherothrombotic Events

  摘要：

  血栓形成是许多心血管疾病的主要结局。目前用于预防血栓形成事件的治疗方法涉及长期使用抗血小板药物。然而，这种疗法存在若干局限性，因此有必要开发新药物。一系列 N-氧化物衍生物（呋喃并氧化物和苯并呋喃并氧化物）被合成并表征为潜在的抗血小板/抗血栓化合物。所有化合物（3a,b, 4a,b, 8a,b, 9a,b, 13a,b 和 14a,b）均抑制由二磷酸腺苷、胶原和花生四烯酸诱导的血小板聚集。所有化合物均能保护小鼠免受由胶原和肾上腺素混合物诱导的肺血栓栓塞；然而，苯并呋喃并氧化物衍生物（13a,b 和 14a,b）是活性最高的化合物，能将血栓栓塞事件减少高达 80%。N-氧化物衍生物 14a 在体内未诱导基因毒性。总之，14a 已成为一种新的抗血小板/抗血栓原型，对预防动脉粥样血栓形成事件具有重要意义。

  DOI：

  10.3390/molecules201018185

文献信息

• Leishmanicidal Activities of Novel Synthetic Furoxan and Benzofuroxan Derivatives
  作者：Luiz Antônio Dutra、Letícia de Almeida、Thais G. Passalacqua、Juliana Santana Reis、Fabio A. E. Torres、Isabel Martinez、Rosangela Gonçalves Peccinini、Chung Man Chin、Konstantin Chegaev、Stefano Guglielmo、Roberta Fruttero、Marcia A. S. Graminha、Jean Leandro dos Santos

  DOI：10.1128/aac.00052-14

  日期：2014.8

  A novel series of furoxan (1,2,5-oxadiazole 2-oxide) (compounds 3, 4a and -b, 13a and -b, and 14a to -f) and benzofuroxan (benzo[c][1,2,5]oxadiazole 1-oxide) (compounds 7 and 8a to -c) derivatives were synthesized, characterized, and evaluated for in vitro activity against promastigote and intracellular amastigote forms of Leishmania amazonensis. The furoxan derivatives exhibited the ability to generate

  一系列新型呋喃（1,2,5-恶二唑 2-氧化物）（化合物 3、4a 和 -b，13a 和 -b，以及 14a 至 -f）和苯并呋喃（苯并[c][1,2,5 ]恶二唑 1-氧化物）（化合物 7 和 8a 至 -c）衍生物被合成、表征和评估对亚马逊利什曼原虫的前鞭毛体和细胞内无鞭毛体形式的体外活性。呋喃衍生物表现出产生不同水平一氧化氮的能力（7.8% 至 27.4%）。苯并呋喃衍生物 8a 能够在 48 小时后以 0.75 mM 的浓度增加来自感染 L. amazonensis 的鼠巨噬细胞的培养基上清液中亚硝酸盐的产量。呋喃和苯并呋喃衍生物对前鞭毛体和细胞内无鞭毛体形式均表现出显着的杀利什曼原虫活性。化合物8a、14a和-b，和 14d 的选择性杀利什曼原虫活性优于两性霉素 B 和喷他脒。pH 5.4 的体外研究表明，化合物 8a 在 8 小时之前是稳定的，并且化合物 14a 作为前药，释放活性醛
• Synthesis and Herbicidal Activity of <i>N</i>-Oxide Derivatives
  作者：Hugo Cerecetto、Eduardo Dias、Rossanna Di Maio、Mercedes González、Sandra Pacce、Patricia Saenz、Gustavo Seoane、Leopoldo Suescun、Alvaro Mombrú、Grisel Fernández、Marisa Lema、Juana Villalba

  DOI：10.1021/jf9904766

  日期：2000.7.1

  As part of an ongoing program on the chemistry and biological activity of N-oxide-containing molecules, a number of novel 1,2, 5-oxadiazole N-oxide, benzo[1,2-c]1,2,5-oxadiazole N-oxide, and quinoxaline N,N'-dioxide derivatives were synthesized and evaluated for their herbicidal activity. Many of these compounds exhibited moderate to good herbicidal pre-emergence activity against Triticum aestivum

  作为正在进行的有关含氮氧化物分子化学和生物学活性的计划的一部分，许多新型的1,2,5-恶二唑N-氧化物，苯并[1,2-c] 1,2,5-恶二唑合成了N-氧化物和喹喔啉N，N'-二氧化物衍生物，并对其除草活性进行了评估。这些化合物中有许多对普通小麦表现出中等至良好的除草前出苗活性。在更具代表性的化合物（12、20和26）上进行了剂量反应研究。活性最强的丁基氨基甲酰基苯并[1,2-c] 1,2,5-恶二唑N-氧化物26在低至24 g / ha的浓度下表现出除草活性。
• An expedient synthesis of new 2-(furoxan-3-yl)thiazolidin-4-one derivatives
  作者：Singam Naveen Kumar、Chebolu Naga Sesha Sai Pavan Kumar、Sri Ranga Vanarasi Anudeep、Kirti Kumari Sharma、Vaidya Jayathirtha Rao、Nanubolu Jagadeesh Babu

  DOI：10.3998/ark.5550190.p009.669

  日期：——

  A series of new biologically interesting furoxan-3-thiazolidinones have been synthesized via onepot three-component reaction of furoxan aldehydes, anilines and mercaptoacetic acid. The multicomponent reaction involves condensation of furoxan aldehyde with aniline to give imine; the formed imine undergoes nucleophilic addition with mercaptoacetic acid, followed by cyclisation with loss of H2O to obtain

  通过呋喃醛、苯胺和巯基乙酸的一锅三组分反应合成了一系列具有生物学意义的新呋喃-3-噻唑烷酮。多组分反应包括呋喃醛与苯胺缩合得到亚胺；形成的亚胺与巯基乙酸进行亲核加成，然后环化失去水，得到所需的产物。所有合成的化合物都使用光谱技术进行了很好的表征，并通过一种化合物的 X 射线晶体结构进行了确认。
• Thermally induced rearrangement of the arylhydrazones of furoxan-3-yl carbonyl compounds
  作者：Sergey I. Molotov、Margarita A. Epishina、Alexander S. Kulikov、Yulia V. Nelyubina、Konstantin A. Lyssenko、Kirill Yu. Suponitsky、Nina N. Makhova

  DOI：10.1070/mc2006v016n05abeh002359

  日期：2006.1

  A thermally induced rearrangement of arylhydrazones 5 of furoxan-3-yl carbonyl compounds into 2-aryl-5-(hydroximino)(aryl)- methyl-2H-1,2,3-triazole 1-oxides 6 has been found for the first time; the crystal packing of compound 6a has been studied by X-ray diffraction analysis.

  首次发现将呋喃喃-3-基羰基化合物的芳基hydr5热诱导重排为2-芳基-5-（氢氧氨基）（芳基）-甲基-2H-1,2,3-三唑1-氧化物6时间; 通过X射线衍射分析研究了化合物6a的晶体堆积。
• Discovery of phenylsulfonylfuroxan derivatives as gamma globin inducers by histone acetylation
  作者：Thais Regina Ferreira de Melo、Chutima Kumkhaek、Guilherme Felipe dos Santos Fernandes、Maria Elisa Lopes Pires、Rafael Consolin Chelucci、Karina Pereira Barbieri、Fernanda Coelho、Ticiana Sidorenko de Oliveira Capote、Carolina Lanaro、Iracilda Zeppone Carlos、Sisi Marcondes、Konstantin Chegaev、Stefano Guglielmo、Roberta Fruttero、Man Chin Chung、Fernando Ferreira Costa、Griffin P. Rodgers、Jean Leandro dos Santos

  DOI：10.1016/j.ejmech.2018.05.008

  日期：2018.6

  of the compounds demonstrated the capacity to releasing nitric oxide at different levels ranging from 0.8 to 30.1%, in vivo analgesic activity and ability to reduce TNF-α levels in the supernatants of monocyte cultures. The most active compound (8b) protected 50.1% against acetic acid-induced abdominal constrictions, while dipyrone, which was used as a control only protected 35%. Compounds 8a and 8b

  N-氧化物衍生物5（ab），8（ab）和11（ac）在体外和体内被设计，合成和评估，它们是能够缓解镰状细胞病（SCD）症状的潜在药物。所有化合物均显示出释放浓度范围从0.8％至30.1％的一氧化氮的能力，体内止痛活性以及降低单核细胞培养上清液中TNF-α水平的能力。活性最高的化合物（8b）保护50.1％免受乙酸引起的腹部收缩，而用作对照的双嘧啶仅保护35％。化合物8a和8b分别抑制ADP诱导的血小板凝集84％和76.1％。两种化合物均以100μM的浓度增加K562细胞中的γ-珠蛋白。γ-珠蛋白增加的机制与这些化合物诱导的组蛋白H3和H4的乙酰化有关。在体外，最有前途的化合物（8b）没有细胞毒性，诱变性和遗传毒性。