4,5,6,7-tetrabromo-1H,3H-benzimidazol-2-thione | 642076-36-6

• 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: 4,5,6,7-tetrabromo-1H,3H-benzimidazol-2-thione
• 英文别名: 4,5,6,7-tetrabromo-1,3-dihydrobenzimidazole-2-thione
• CAS: 642076-36-6
• 化学式: C₇H₂Br₄N₂S
• 分子量: 465.788
• InChiKey: GYVCACUYQFXPLN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  56.2
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4,5,6,7-tetrabromo-1H,3H-benzimidazol-2-thione 在 potassium carbonate 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 丙酮 为溶剂， 反应 48.0h， 生成 4-(4,5,6,7-tetrabromo-1H-benzimidazol-2-ylsulfanyl)butyric acid
  参考文献：
  名称：

  CK2α and CK2α′ subunits differ in their sensitivity to 4,5,6,7-tetrabromo- and 4,5,6,7-tetraiodo-1H-benzimidazole derivatives

  摘要：

  The goal of this study was to test the inhibitory activity of a series of tetrahalogenobenzimidazoles, including a number of novel derivatives, on individual catalytic subunits of human CK2. 4,5,6,7-tetrabromo- and 4,5,6,7-tetraiodo-1H-benzimidazoles and their newly obtained N-1- and 2-S-carboxyalkyl derivatives showed potent inhibitory activity against both these subunits. CK2 alpha' was up to 6 times more sensitive to the studied compounds than CK2 alpha. The investigated iododerivatives showed, in most cases, stronger inhibitory properties than the respective brominated congeners, but the differences showed considerable dependence on the protein substrate used. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.11.002
• 作为产物：
  描述：

  2-溴苯并咪唑 在 溴 作用下， 以 乙醇 、 水 为溶剂， 反应 35.0h， 生成 4,5,6,7-tetrabromo-1H,3H-benzimidazol-2-thione
  参考文献：
  名称：

  Polyhalogenobenzimidazoles: synthesis and Their inhibitory activity against casein kinases

  摘要：

  A series of novel polyhalogenated benzimidazoles have been prepared by exhaustive bromination of a variety of 2-substituted benzimidazoles. The efficacy of both new compounds and a number of their previously described cognates as inhibitors of casein kinases CK1, CK2 and G-CK was investigated. The type of N-1 alkyl substituent as well as introduction of a polyfluoroalkyl moiety at position 2 did not markedly influence the inhibitory efficacy toward CK2 of the respective 4,5,6,7-tetra-bromobenzimidazole derivatives which conversely were almost ineffective toward CK1 and G-CK. However, 4,5,6,7-tetra-bromobenzimidazoles substituted at position 2 with either chlorine, bromine or sulfur atom, while manifesting a still considerable inhibitory activity against CK2 (IC50 in the 0.49-0.93 muM range) proved to be potentially powerful inhibitors also against CK1 (IC50 in the 18.4-2.2 muM range). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00403-6

文献信息

• From a MMP2/CK2 multitarget approach to the identification of potent and selective MMP13 inhibitors
  作者：Miryam Pastor、José María Zapico、Claire Coderch、Maciej Maslyk、Rostyslav Panchuk、Beatriz de Pascual-Teresa、Ana Ramos

  DOI：10.1039/c8ob02990c

  日期：——

  MMP2/CK2 dual targeting inhibitors. We have followed a rational drug design approach based on our experience in the selective inhibition of these two enzymes. We have successfully obtained highly active MMP2 (10, IC50 = 70 nM; 11, IC50 = 100 nM) and CK2 (16a, IC50 = 500 nM) inhibitors. However, structural fine tuning of these small molecules to simultaneously target both enzymes turned out to be an unattainable

  在本文中，我们描述了我们在寻找MMP2 / CK2双重靶向抑制剂方面的努力。我们根据选择性抑制这两种酶的经验，采用了合理的药物设计方法。我们已经成功获得了高活性的MMP2（10，IC 50 = 70 nM; 11，IC 50 = 100 nM）和CK2（16a，IC 50 = 500 nM）抑制剂。然而，对这些小分子进行结构微调以同时靶向两种酶被证明是无法实现的目标。出乎意料的是，我们很幸运地发现了新的选择性MMP13抑制剂（10，IC 50 = 3.7 nM和11，IC 50= 5.6 nM）的TBB衍生支架。这些化合物构成了进一步优化的有趣起点。
• Structural studies of 4,5,6,7-tetrabromobenzimidazole derivatives by means of solid-state 13C, 15N NMR spectroscopy and DFT calculations
  作者：K. Zawada、M. Wolniak、Z. Kazimierczuk、I. Wawer

  DOI：10.1016/j.molstruc.2008.08.001

  日期：2009.1

  Tetrabromobenzimidazole derivatives containing sulfur or nitrogen atom in a five- or six-membered saturated ring were synthesized as potential ligands of casein kinase (CK2). Structural data of these compounds are crucial for understanding their inhibitory activity as inhibitors. Solution and solid-state 13 C NMR spectra were recorded for six compounds, and 15 N MAS spectra – for two of them. 13 C CPMAS spectra were

  摘要 合成了在五元或六元饱和环中含有硫或氮原子的四溴苯并咪唑衍生物作为酪蛋白激酶（CK2）的潜在配体。这些化合物的结构数据对于理解它们作为抑制剂的抑制活性至关重要。记录了六种化合物的溶液和固态 13 C NMR 谱，以及其中两种化合物的 15 N MAS 谱。13 C CPMAS 光谱是通过与溶液数据进行比较并借助偶极去相和可变接触时间实验来指定的。通过屏蔽常数的 GIAO DFT 计算验证了 13 C 和 15 N 化学位移分配的正确性。溶液和固态化学位移值之间的差异是根据分子间相互作用来解释的。在 N 1 , N 2 -丙烯-2-氨基-4,5,6,7-四溴苯并咪唑的固态 13 C 和 15 N NMR 光谱中出现的双峰共振表明晶体学晶胞中存在两个分子。为具有两个 N1' H…N3 氢键的二聚体计算的屏蔽常数表明缔合类型不影响碳屏蔽。两个互变异构体与 N1' H 和 N3 H 共存的可能性较小。
• Synthesis and antimycobacterial activity of 2-substituted halogenobenzimidazoles
  作者：Z. Kazimierczuk、M. Andrzejewska、J. Kaustova、V. Klimešova

  DOI：10.1016/j.ejmech.2004.10.004

  日期：2005.2

  A series of substituted 2-polyfluoroalkyl and 2-nitrobenzylsulphanyl benzimidazoles was synthesized. The compounds were evaluated for their activity against four Mycobacterium strains; the activities were expressed as the minimum inhibitory concentration (MIC). The substances tested showed appreciable antimycobacterial activity, particularly 5,6-dichloro-2-nonafluorobutylbenzimidazole (2h), and 5-halogeno-(5a-c) and 4,6-dihalogeno- (5d and 5g) 2-(3,5-dinitrobenzylsulphanyl)benzimidazoles, whose MIC values for Mycobacterium kansasii and Mycobacterium avium exceeded that of isoniazide that was used as a reference compound. Relationships between structure and biological activity of the tested benzimidazole derivatives are discussed. (C) 2004 Elsevier SAS. All rights reserved.
• Optimization of Protein Kinase CK2 Inhibitors Derived from 4,5,6,7-Tetrabromobenzimidazole
  作者：Mario A. Pagano、Mariola Andrzejewska、Maria Ruzzene、Stefania Sarno、Luca Cesaro、Jenny Bain、Matthew Elliott、Flavio Meggio、Zygmunt Kazimierczuk、Lorenzo A. Pinna

  DOI：10.1021/jm049854a

  日期：2004.12.1

  Casein kinase 2 (CK2) is a ubiquitous, essential, and highly pleiotropic protein kinase whose abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and infective diseases. Thus, CK2 inhibitors designed to dissect the signaling pathways affected by this kinase, in perspective, may give rise to pharmacological tools. One of the most successful CK2 inhibitors is TBB (4,5,6,7-tetrabromobenzotriazole). Here we show that its inhibitory properties can be markedly improved by generating adducts in which N-2 is replaced by a carbon atom bound to a variety of polar functions. The most efficient inhibitor is 4,5,6,7-tetrabromo-2-(dimethylamino)benzimidazole (2c) followed by the methylsulfanyl (8), isopropylamino (2e), and amino (2a) congeners. All these compounds display K-i values < 100 nM (40 nM in the case of 2c). 2c induces apoptosis of Jurkat cells more readily than TBB (DC50 value 2.7 vs 17 muM) and, unlike TBB, it does not display any side effect on mitochondria polarization up to 10 muM concentration. Molecular modeling of the CK2-2c complex, based on the crystal structure of the CK2-TBB complex suggests that a number of additional apolar contacts between its two methyl groups and hydrophobic residues nearby could account for its superior inhibitory properties. Consequently, 2c is even more susceptible than TBB to mutations of the unique hydrophobic residues V66 and/or I174 to alanine. We propose to adopt 2c as first choice CK2 inhibitor instead of TBB, especially for in cell studies.