5-(1,3-Dioxolan-2-yl)benzofurazan-1-oxid | 836628-05-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶二唑类
• 英文名称: 5-(1,3-Dioxolan-2-yl)benzofurazan-1-oxid
• 英文别名: 5-(1,3-Dioxolan-2-yl)-1-oxo-2,1lambda~5~,3-benzoxadiazole；5-(1,3-dioxolan-2-yl)-1-oxido-2,1,3-benzoxadiazol-1-ium
• CAS: 836628-05-8
• 化学式: C₉H₈N₂O₄
• 分子量: 208.174
• InChiKey: JDBJOOALEHZHMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  70
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-硝基丙烷 、 5-(1,3-Dioxolan-2-yl)benzofurazan-1-oxid 在 哌啶 作用下， 以 四氢呋喃 为溶剂， 以84%的产率得到5-(1,3-Dioxolan-2-yl)-2,2-dimethyl-3-oxidobenzimidazol-1-ium 1-oxide
  参考文献：
  名称：

  2H-Benzimidazole 1,3-Dioxide Derivatives:  A New Family of Water-Soluble Anti-Trypanosomatid Agents

  摘要：

  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.

  DOI：

  10.1021/jm0600343

文献信息

• Study of benzo[a]phenazine 7,12-dioxide as selective hypoxic cytotoxin-scaffold. Identification of aerobic-antitumoral activity through DNA fragmentation
  作者：María Laura Lavaggi、Mauricio Cabrera、María de los Ángeles Aravena、Claudio Olea-Azar、Adela López de Ceráin、Antonio Monge、Gisela Pachón、Marta Cascante、Ana María Bruno、Lía I. Pietrasanta

  DOI：10.1016/j.bmc.2010.04.074

  日期：2010.6.15

  Phenazine 5,10-dioxides are prodrugs for antitumor therapy that undergo hypoxic-selective bioreduction to form cytotoxic species. Here we investigate the expanded system benzo[a]phenazine 7,12-dioxides as selective hypoxic cytotoxin-scaffold. The clonogenic survival of V79 cells on aerobic and anaerobic conditions, conduct us to study antiproliferative activity on Caco-2 tumoral cells in normoxia. Electrochemical, DNA-interaction and DNA-damage studies were performed to establish the mode of action. The results demonstrated the potential biological properties of the studied scaffold being derivatives 6-10 structural hits for further chemical-modifications to become into therapeutics for solid tumors. Compounds 6 and 8 with cytotoxicity against V79 cells in both conditions (aerobia and anaerobia) were also cytotoxic against Caco-2 tumoral cells in aerobiosis. (C) 2010 Elsevier Ltd. All rights reserved.