5-(phenylethenyl)benzo[1,2,5]oxadiazole 1-oxide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 5-(phenylethenyl)benzo[1,2,5]oxadiazole 1-oxide
• 英文别名: 1-Oxido-5-(2-phenylethenyl)-2,1,3-benzoxadiazol-1-ium
• 化学式: C₁₄H₁₀N₂O₂
• 分子量: 238.246
• InChiKey: CWZSPVXVZKGUJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 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：

  5-(phenylethenyl)benzo[1,2,5]oxadiazole 1-oxide 在 三苯基膦 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 5-(phenylethenyl)benzo[1,2,5]oxadiazole
  参考文献：
  名称：

  Benzo[1,2-c]1,2,5-oxadiazole N-oxide derivatives as potential antitrypanosomal drugs. Part 3: Substituents-clustering methodology in the search for new active compounds

  摘要：

  The results of a study on the use of Hansch's series design, cluster methodology, for the generation of newbenzo[1,2-c] 1,2, 5-oxadiazole N-oxide derivatives as antitrypanosomal compounds are described. In vitro activity of these compounds was tested against Tulahuen 2 strain of Trypanosoma cruzi. Clearly, the Hansch methodology allowed identifying two cluster-substituents suitable for further structural modifications. The most effective drugs, derivatives 11, 18, and 21, with 50% inhibitory concentration (IC50) of the same order as that of the reference drug, represent an excellent structural point of chemical modifications for the design of future drugs. Preliminary results from the study of the mechanism of action of these benzofuroxans point to perturbation of the mitochondrial electron chain, inhibiting parasite respiration. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.05.020

文献信息

• 2<i>H</i>-Benzimidazole 1,3-Dioxide Derivatives:  A New Family of Water-Soluble Anti-Trypanosomatid Agents
  作者：Mariana Boiani、Lucía Boiani、Ana Denicola、Susana Torres de Ortiz、Elva Serna、Ninfa Vera de Bilbao、Luis Sanabria、Gloria Yaluff、Héctor Nakayama、Antonieta Rojas de Arias、Celeste Vega、Miriam Rolan、Alicia Gómez-Barrio、Hugo Cerecetto、Mercedes González

  DOI：10.1021/jm0600343

  日期：2006.6.1

  Three series of benzimidazole N-oxide derivatives were developed and were examined for their activity against trypanosomatid parasites (Trypanosoma cruzi and Leishmania spp.). 2H-Benzimidazole 1,3-dioxides displayed remarkable in vitro activities against both parasites, with derivatives 28, 29, and 32 being the most potent (IC50 < 5 mu M) against the epimastigote form of T. cruzi and 28, 33, and 35 the most potent against the promastigote form of Leishmania spp. Unspecific cytotoxicity was evaluated using murine macrophages, and derivative 33 was not toxic at a concentration 30 times that of its IC50 against T. cruzi that was completely toxic for Leishmania spp., implying that the series of 2H-benzimidazole 1,3-dioxides is selective toward both trypanosomatid parasites. Derivatives 33 and 35 were submitted to an in vivo assay using an acute model of Chagas' disease and a short-term treatment (30 mg/kg/day orally administrated as aqueous solution, during 10 days). While in the control (untreated) and Benznidazole (50 mg/kg/day) groups survival fraction was 60.0% and 87.5%, respectively, none of the animals treated with derivatives 33 and 35 died. From the preliminary structure-activity relationship studies reduction potential and electrophilicity were found relevant to anti-T. cruzi activity. Active compounds are better electrophiles and more easily reduced than inactive ones.
• Benzo[1,2-c]1,2,5-oxadiazole N-oxide derivatives as potential antitrypanosomal drugs. Part 3: Substituents-clustering methodology in the search for new active compounds
  作者：Gabriela Aguirre、Lucía Boiani、Hugo Cerecetto、Rossanna Di Maio、Mercedes González、Williams Porcal、Ana Denicola、Matías Möller、Leonor Thomson、Verónica Tórtora

  DOI：10.1016/j.bmc.2005.05.020

  日期：2005.12

  The results of a study on the use of Hansch's series design, cluster methodology, for the generation of newbenzo[1,2-c] 1,2, 5-oxadiazole N-oxide derivatives as antitrypanosomal compounds are described. In vitro activity of these compounds was tested against Tulahuen 2 strain of Trypanosoma cruzi. Clearly, the Hansch methodology allowed identifying two cluster-substituents suitable for further structural modifications. The most effective drugs, derivatives 11, 18, and 21, with 50% inhibitory concentration (IC50) of the same order as that of the reference drug, represent an excellent structural point of chemical modifications for the design of future drugs. Preliminary results from the study of the mechanism of action of these benzofuroxans point to perturbation of the mitochondrial electron chain, inhibiting parasite respiration. (c) 2005 Elsevier Ltd. All rights reserved.