methyl benzofuroxan-5-carboxylate | 53178-59-9

• 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: methyl benzofuroxan-5-carboxylate
• 英文别名: Methyl 2,1,3-benzoxadiazole-5-carboxylate 3-oxide；methyl 3-oxido-2,1,3-benzoxadiazol-3-ium-5-carboxylate
• CAS: 53178-59-9
• 化学式: C₈H₆N₂O₄
• 分子量: 194.147
• InChiKey: TTZOWRBWQBLGAB-UHFFFAOYSA-N

物化性质

• 沸点：
  325.5±34.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  77.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl benzofuroxan-5-carboxylate 在 N-溴代丁二酰亚胺(NBS) 、 potassium tert-butylate 、 过氧化苯甲酰 作用下， 以 甲醇 、 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 methyl 5,10-dioxyphenazine-2-carboxylate
  参考文献：
  名称：

  NEW SYNTHESIS OF 5,10-DIOXYPHENAZINE-2-CARBOXYLIC ACID

  摘要：

  Phenazine di-N-oxides substituted in the 2-position by a carboxylic function were prepared in few steps from 4-amino-3-nitrobenzoic acid via the formation of methyl 5,10-dioxy-6,7,8,9-tetrahydrophenazine-2-carboxylate without purification of the intermediates.

  DOI：

  10.1081/scc-100104833
• 作为产物：
  描述：

  4-氟-3-硝基苯甲酸甲酯 在 sodium azide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 以60%的产率得到methyl benzofuroxan-5-carboxylate
  参考文献：
  名称：

  将邻卤硝基苯转化为苯并呋喃的一锅法

  摘要：

  摘要邻卤硝基苯与叠氮化钠在 DMF/H2O 回流下反应，一步得到苯并呋喃，收率中等至良好。与涉及邻硝基苯基叠氮化物的制备和随后热解的常规程序相比，这是一种更快的方法。为了比较，该反应也在相转移催化下进行。图形概要

  DOI：

  10.1080/00397911.2016.1276932

文献信息

• Synthesis and activity of benzimidazole-1,3-dioxide inhibitors of separase
  作者：Ha T. Do、Nenggang Zhang、Debananda Pati、Scott R. Gilbertson

  DOI：10.1016/j.bmcl.2016.07.080

  日期：2016.9

  other alkyl chains at the C2 moderately improves the effects on the inhibitory activity of those compounds. Modifications on 2H-benzimidazole-1,3-dioxide or the skeleton have variable effect on inhibition of separase enzymatic activity. Density-functional theory (DFT) calculations suggest there may be a correlation between the charges on the oxide moieties on these compounds and their activity in inhibiting

  由于粘蛋白蛋白酶，separase在人癌细胞中的致癌活性，对separase酶活性的调节可能构成靶向抗性，separase过表达的非整倍性肿瘤的新治疗策略。在这里，我们报告了基于铅分子2,2-二甲基-5-硝基-2H-苯并咪唑-1,3-二氧化物（称为Sepin）的修饰，分离酶抑制剂的合成，结构信息和构效关系（SAR） -1，（1）从高通量屏幕中识别。用其他官能团取代C5处的-NO2会降低Separase酶法测定中的抑制活性。两个甲基在C2处被其他烷基链取代可适度改善对这些化合物的抑制活性的影响。对2H-苯并咪唑-1的修饰 3-二氧化物或骨架对Separase酶活性的抑制作用不同。密度泛函理论（DFT）计算表明，这些化合物上的氧化物部分上的电荷与其抑制Separase酶的活性之间可能存在相关性。
• <i>In vitro</i> and <i>In Vivo</i> Evaluation of Quinoxaline 1,4-di-N-oxide Against <i>Giardia lamblia</i>
  作者：Elizabeth Barbosa-Cabrera、Rosa Moo-Puc、Antonio Monge、Alma Delia Paz-González、Virgilio Bocanegra-García、Gildardo Rivera

  DOI：10.2174/1570180816666190618115854

  日期：2020.4.25

  Giardiasis is an important public health problem. However, its pharmacological treatment is limited mainly to two drugs, metronidazole and nitazoxanide. Objectives: Screening four series of esters (methyl, ethyl, isopropyl and n-propyl) of quinoxaline-7- carboxylate 1,4-di-N-oxide in in vitro and in vivo models as antigiardiasis agents.

  Screening four series of esters (methyl, ethyl, isopropyl and n-propyl) of quinoxaline-7- carboxylate 1,4-di-N-oxide in in vitro and in vivo models as antigiardiasis agents.

  Briefly, 4 × 104 trophozoites of G. lamblia were incubated for 48 h at 37 °C with different concentrations of esters of quinoxaline-7-carboxylate 1,4-di-N-oxide, albendazole, metronidazole and nitazoxanide. Afterwards, trophozoites were counted and the half maximal inhibitory concentration (IC50) was calculated by Probit analysis. The in vivo antigiardial activity of the compounds was demonstrated using experimental infections of G. lamblia in suckling female CD-1 mice.

  Compound T-069 with a thienyl, a trifluoromethyl and an isopropyl group at R1-, R2- and R3-position, respectively, on the quinoxaline 1,4-di-N-oxide ring in an in vitro model showed an IC50 value of 0.0014 µM, and 3502 and 1108 times more giardicidal activity than nitazoxanide and metronidazole in an in vivo model.

  Isopropyl ester of quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives showed better giardicidal activity than the reference drugs; therefore, these compounds are good candidates to develop new pharmacological treatment for giardiasis.

  背景：贾第虫病是一个重要的公共卫生问题。然而，其药物治疗主要局限于两种药物，甲硝唑和硝唑酮。目标：在体外和体内模型中筛选四系列喹诺酮-7-羧酸二-N-氧化物（甲基、乙基、异丙基和正丙基）的酯类化合物作为抗贾第虫药剂。 目标：在体外和体内模型中筛选四系列喹诺酮-7-羧酸二-N-氧化物（甲基、乙基、异丙基和正丙基）的酯类化合物作为抗贾第虫药剂。 方法：简而言之，将4 × 104个贾第虫滋养体与不同浓度的喹诺酮-7-羧酸二-N-氧化物酯类、阿苯达唑、甲硝唑和硝唑酮一起在37°C下孵育48小时。然后，对滋养体进行计数，并通过Probit分析计算半最大抑制浓度（IC50）。这些化合物的体内抗贾第虫活性是通过在哺乳期雌性CD-1小鼠中进行贾第虫实验性感染来证明的。 结果：在体外模型中，具有噻吩基、三氟甲基和异丙基基团分别位于喹诺酮-7-羧酸二-N-氧化物环的R1、R2和R3位置的化合物T-069显示出IC50值为0.0014微米，在体内模型中的贾第杀灭活性比硝唑酮和甲硝唑分别高出3502倍和1108倍。 结论：喹诺酮-7-羧酸二-N-氧化物的异丙基酯衍生物显示出比参考药物更好的贾第杀灭活性；因此，这些化合物是开发新的贾第虫病药物治疗的良好候选。
• Synthesis and in vitro evaluation of new ethyl and methyl quinoxaline-7-carboxylate 1,4-di-N-oxide against Entamoeba histolytica
  作者：Blanca Estela Duque-Montaño、Lilia Citlalli Gómez-Caro、Mario Sanchez-Sanchez、Antonio Monge、Efrén Hernández-Baltazar、Gildardo Rivera、Oscar Torres-Angeles

  DOI：10.1016/j.bmc.2013.05.036

  日期：2013.8

  In our search for new antiamoebic agents, a new series of ethyl and methyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives have been synthesized using the Beirut reaction. All compounds were characterized by spectroscopic techniques and elemental analysis. Antiamoebic activity was evaluated in vitro against Entamoeba histolytica strain HM1:IMSS by the microdilution method, and the structure-activity relationship was analyzed. We found that eleven quinoxaline derivatives showed greater activity than metronidazole and nitazoxanide with IC50 values in the range 1.99-0.35 mu M. Compounds T-001 and T-016 shows IC50 values of 1.41 and 1.47 mu M, respectively, with a value of selectivity index >60. (C) 2013 Elsevier Ltd. All rights reserved.
• New trypanocidal hybrid compounds from the association of hydrazone moieties and benzofuroxan heterocycle
  作者：Williams Porcal、Paola Hernández、Lucía Boiani、Mariana Boiani、Ana Ferreira、Agustina Chidichimo、Juan J. Cazzulo、Claudio Olea-Azar、Mercedes González、Hugo Cerecetto

  DOI：10.1016/j.bmc.2008.05.038

  日期：2008.7

  Hybrid compounds containing hydrazones and benzofuroxan pharmacophores were designed as potential Trypanosoma cruzi-enzyme inhibitors. The majority of the designed compounds was successfully synthesized and biologically evaluated displaying remarkable in vitro activity against different strains of T. cruzi. Unspecific cytotoxicity was evaluated using mouse macrophages, displaying isothiosemicarbazone 10 and thiosemicarbazone 12 selectivity indexes (macrophage/parasite) of 21 and 27, respectively. In addition, the mode of anti-trypanosomal action of the derivatives was investigated. Some of these derivatives were moderate inhibitors of cysteinyl active site enzymes of T. cruzi, cruzipain and trypanothione reductase. ESR experiments using T. cruzi microsomal fraction suggest that the main mechanism of action of the trypanocidal effects is the production of oxidative stress into the parasite. (c) 2008 Elsevier Ltd. All rights reserved.
• ABUSHANAB E.; ALTERI JR. N. D., J. ORG. CHEM. <JOCE-AH>, 1975, 40, NO 2, 157-160 D=#2#-
  作者：ABUSHANAB E.、 ALTERI JR. N. D.

  DOI：——

  日期：——