2-(1-methylpropyldisulfanyl)-5-nitro-1H-benzo[d]imidazole | 141400-52-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-(1-methylpropyldisulfanyl)-5-nitro-1H-benzo[d]imidazole
• 英文别名: 2-[(Butan-2-yl)disulfanyl]-6-nitro-1H-benzimidazole；2-(butan-2-yldisulfanyl)-6-nitro-1H-benzimidazole
• CAS: 141400-52-4
• 化学式: C₁₁H₁₃N₃O₂S₂
• 分子量: 283.375
• InChiKey: GKOFVQMAKBQPDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  125
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-巯基-5-硝基苯并咪唑 、 2-丁硫醇 在 碳酸氢钠 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 生成 2-(1-methylpropyldisulfanyl)-5-nitro-1H-benzo[d]imidazole
  参考文献：
  名称：

  二硫化物作为具有硫氧还蛋白抑制作用的抗癌剂的合成和生物学评价

  摘要：

  改变氧化还原稳态作为癌细胞的标志被癌细胞用于生长和存活。硫氧还蛋白 (Trx) 是维持细胞内氧化还原稳态的重要调节剂，被广泛认为是开发抗癌药物的有希望的靶点。在此，我们合成了 72 种二硫化物并评估了它们 对 Trx 和抗肿瘤活性的抑制作用。首先，我们建立了一种高效快速的筛选Trx抑制剂的方法，利用我们团队开发的探针NBL-SS来检测活细胞中的Trx功能。在对这些化合物的 Trx 抑制活性进行初步筛选后，8 种化合物对 Trx 显示出显着的抑制活性。然后我们评估了这 8 种二硫化物、化合物68和69的细胞毒性对 HeLa 细胞显示出高细胞毒性，但对正常细胞系不太敏感。接下来，我们对两种二硫化物进行了动力学研究，68比69对 Trx 的抑制更快。进一步的研究表明，68导致活性氧的积累，并最终通过抑制 Trx诱导 Hela 细胞凋亡。筛选Trx抑制剂的方法的建立和具有显着Trx抑制作用的68的

  DOI：

  10.1016/j.bioorg.2021.104814

文献信息

• Methods and compositions to prevent or treat bacterial infections
  申请人：Ketter Patrick

  公开号：US10398682B2

  公开（公告）日：2019-09-03

  Certain embodiments are directed to methods and compositions for preventing or treating bacterial infections. In certain embodiments the compositions comprise thioredoxin inhibitors, and/or thioredoxin-like inhibitors.

  某些实施方案涉及预防或治疗细菌感染的方法和组合物。在某些实施方案中，组合物包括硫氧还蛋白抑制剂和/或硫氧还蛋白样抑制剂。
• Selective Inhibition of Extracellular Thioredoxin by Asymmetric Disulfides
  作者：Thomas R. DiRaimondo、Nicholas M. Plugis、Xi Jin、Chaitan Khosla

  DOI：10.1021/jm301775s

  日期：2013.2.14

  Whereas the role of mammalian thioredoxin (Trx) as an intracellular protein cofactor is widely appreciated, its function in the extracellular environment is not well-understood. Only few extracellular targets of Trx-mediated thiol disulfide exchange are known. For example, Trx activates extracellular transglutaminase 2 (TG2) via reduction of an intramolecular disulfide bond. Because hyperactive TG2 is thought to play a role in various diseases, understanding the biological role of utracellular Trx may provide critical insight into the pathogenesis of these disorders. Starting from a clinical-stage asymmetric disulfide lead, we have identified analogs with >100-fold specificity for Trx. Structure-activity relationship and computational docking model analyses have provided insights into the features important for enhancing potency and specificity. The most active compound identified had an IC50 below 0.1 mu M in cell culture and may be appropriate for in vivo use to interrogate the role of extracellular Trx in health and disease.
• Synthesis and evaluation of imidazolyl disulfides for selective cytotoxicity to hypoxic EMT6 tumor cells in vitro
  作者：D Lynn Kirkpatrick、ML Jimale、KM King、T Chen

  DOI：10.1016/0223-5234(92)90057-8

  日期：1992.1

  Two series of disulfides were synthesized and evaluated in vitro for selective hypoxic tumor cell cytotoxicity using EMT6 cells. While the series of alkyl 5-nitrobenzimidazolyl disulfides displayed no selectivity, two alkyl imidazolyl disulfides, devoid of a nitro function, showed preferential toxicity to EMT6 cells treated under hypoxic conditions. Select agents of the alkyl imidazolyl series were found to deplete cellular glutathione (GSH) while the corresponding alkyl nitrobenzimidazolyl derivatives did not. One disulfide displaying selective hypoxic cell toxicity, n-butyl 2-imidazolyl disulfide, 10, caused significantly greater depletion of GSH under aerobic conditions. Removal of cellular GSH with buthionine sulfoximine (BSO) prior to exposure to 10 caused an increase in its toxicity and a loss of any differential between aerobic and hypoxic conditions. It is speculated that the diminished aerobic vs hypoxic toxicity of the agent toward EMT6 cells is due to a greater ability of 10 to interact with GSH under aerobic conditions as reflected by the greater GSH depletion.
• MODULATION OF TISSUE TRANSGLUTAMINASE ACTIVATION IN DISEASE
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：EP2721169A2

  公开（公告）日：2014-04-23
• Modulation of Tissue Transglutaminase Activation in Disease
  申请人：DiRaimondo Thomas

  公开号：US20140322278A1

  公开（公告）日：2014-10-30

  Compositions and methods are provided for modulating the physiological activation of tissue transglutaminase (TG2); which methods can include inhibiting the activation of TG2 associated with enteric inflammatory disorders, which disorders may include celiac disease, irritable bowel syndrome, Crohn's Disease, dermatitis herpetiformis, and the like. In other embodiments of the invention, methods are provided for reducing undesirable paracellular transport in enteric tissues, in particular the paracellular transport of molecules greater than about 500 mw, e.g. peptides, including without limitation immunogenic gluten peptides.