4-(benzylthio)-7-nitrobenzo[c][1,2,5]oxadiazole | 16322-24-0

• 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: 4-(benzylthio)-7-nitrobenzo[c][1,2,5]oxadiazole
• 英文别名: MC2766；4-benzylsulfanyl-7-nitro-benzo[1,2,5]oxadiazole；4-nitro-7-(phenylmethylsulfanyl)-2,1,3-benzoxadiazole；7-Benzylmercapto-4-nitro-benzofurazan；4-Benzylsulfanyl-7-nitro-2,1,3-benzoxadiazole
• CAS: 16322-24-0
• 化学式: C₁₃H₉N₃O₃S
• 分子量: 287.299
• InChiKey: XEAGLFCHDKJWSY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(benzylthio)-7-nitrobenzo[c][1,2,5]oxadiazole 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以510 mg的产率得到4-(benzylsulfonyl)-7-nitrobenzo[c][1,2,5]oxadiazole
  参考文献：
  名称：

  Irreversible binding of an anticancer compound (BI-94) to plasma proteins

  摘要：

  1. We investigated the mechanisms responsible for the in vivo instability of a benzofurazan compound BI-94 (NSC228148) with potent anti-cancer activity.2. BI-94 was stable in MeOH, water, and in various buffers at pHs 2.5-5, regardless of the buffer composition. In contrast, BI-94 was unstable in NaOH and at pHs 7-9, regardless of the buffer composition. BI-94 disappeared immediately after spiking into mice, rat, monkey, and human plasma. BI-94 stability in plasma can be only partially restored by acidifying it, which indicated other mechanisms in addition to pH for BI-94 instability in plasma.3. BI-94 formed adducts with the trapping agents, glutathione (GSH) and N-acetylcysteine (NAC), in vivo and in vitro via nucleophilic aromatic substitution reaction. The kinetics of adduct formation showed that neutral or physiological pHs enhanced and accelerated GSH and NAC adduct formation with BI-94, whereas acidic pHs prevented it. Therefore, physiological pHs not only altered BI-94 chemical stability but also enhanced adduct formation with endogenous nucleophiles. In addition, adduct formation with human serum albumin-peptide 3 (HSA-T3) at the Cys34 position was demonstrated.4. In conclusion, BI-94 was unstable at physiological conditions due to chemical instability and irreversible binding to plasma proteins.

  DOI：

  10.3109/00498254.2015.1025250
• 作为产物：
  描述：

  2,6-二氯亚硝基苯 在 硫酸 、 硝酸 作用下， 以 乙醇 为溶剂， 生成 4-(benzylthio)-7-nitrobenzo[c][1,2,5]oxadiazole
  参考文献：
  名称：

  潜在的抗白血病和免疫抑制药物。一些苯并-2,1,3-恶二唑（苯并呋喃）及其N-氧化物（苯并呋喃）的制备及其体外药理活性。

  摘要：

  DOI：

  10.1021/jm00308a027

文献信息

• 4-R-7-Nitrobenzofurazans in [3+2] cycloaddition reactions with N-methylazomethine ylide
  作者：S. Yu. Pechenkin、A. M. Starosotnikov、M. A. Bastrakov、I. V. Glukhov、S. A. Shevelev

  DOI：10.1007/s11172-012-0011-z

  日期：2012.1

  A number of new tetrahydroisoindole derivatives fused with the furazan ring were synthesized based on the 1,3-dipolar cycloaddition of N-methylazomethine ylide with substituted 4-nitrobenzofurazans. Substituents in the benzene ring were found to affect the cycloaddition process.

  通过 N-甲基偶氮甲烷与取代的 4-硝基苯并呋喃的 1,3-二极环加成反应，合成了一些新的与呋喃环融合的四氢异吲哚衍生物。研究发现苯环上的取代基会影响环加成过程。
• Discovery and synthesis of novel benzofurazan derivatives as inhibitors of influenza A virus
  作者：Ulrich Kessler、Daniele Castagnolo、Mafalda Pagano、Davide Deodato、Martina Bernardini、Beatrice Pilger、Charlene Ranadheera、Maurizio Botta

  DOI：10.1016/j.bmcl.2013.08.048

  日期：2013.10

  The identification of a novel hit compound inhibitor of the protein-protein interaction between the influenza RNA-polymerase PA and PB1 subunits has been accomplished by means of high-throughput screening. A small family of structurally related molecules has been synthesized and biologically evaluated with most of the compounds showing micromolar potency of inhibition against viral replication. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis and structure–activity relationship of new cytotoxic agents targeting human glutathione-S-transferases
  作者：Dante Rotili、Anastasia De Luca、Domenico Tarantino、Silvia Pezzola、Mariantonietta Forgione、Blasco Morozzo della Rocca、Mattia Falconi、Antonello Mai、Anna Maria Caccuri

  DOI：10.1016/j.ejmech.2014.10.033

  日期：2015.1

  The 6((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)hexan-1-ol (NBDHEX, 1), a "suicide inhibitor" of the glutathione-S-transferase GSTP1-1, showed pro-apoptotic properties in tumor cells, but in vivo studies were limited by poor bioavailability and high affinity towards GSTM2-2, expressed in many non-cancerous tissues. Here we describe the synthesis and biological characterization of new 1 analogs (2-40), in which the hydroxyhexyl portion at the C4-sulfur atom has been replaced with phenyl-containing moieties as well as substituted alkyl chains. Some of the new compounds displayed 10-100 times increased water-solubility (8, 11, 17, 26-28, 34, 35), and most of them showed higher GSTP1-1 selectivity (2-20, 23-26, 31-33, 35) than 1. The presence of a phenyl ring with polar substituents is in general associated, with some exceptions (23, 24) to low cytotoxicity in osteosarcoma U-2OS cells. Differently, some alkyl derivatives possess cytotoxicity comparable (26, 34,35) or higher (30, 32) than 1. Among the novel compounds, selected ones (26, 27, 34, and 35) deserve further investigation for their anticancer potential. (C) 2014 Elsevier Masson SAS. All rights reserved.
• 2,1,3-BENZOXADIAZOL DERIVATIVES FOR THE INHIBITION OF INFLUENZA A AND B VIRUS AND RESPIRATORY SYNCYTIAL VIRUS REPLICATION
  申请人：Pike Pharma GmbH

  公开号：EP2427442A1

  公开（公告）日：2012-03-14
• GAIN-OF-FUNCTION BCL-2 INHIBITORS
  申请人：HOCKENBERY David

  公开号：US20120252839A1

  公开（公告）日：2012-10-04

  Compounds are described that are useful for treating an apoptosis-associated disease, which are specifically cytotoxic to tumor cells that are overexpressing Bcl-x L , and are much less cytotoxic in isogenic cells that are not overexpressing Bcl-x L . Also described is a method for treating an apoptosis-associated disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an active compound that is specifically cytotoxic to tumor cells that are overexpressing Bcl-x L , and are much less cytotoxic in isogenic cells that are not overexpressing Bcl-x L . Several scaffolds of active compounds are described.