4,5,6,7-Tetrabromo-1,3-dihydro-benzoimidazol-2-one | 56534-23-7

• 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-1,3-dihydro-benzoimidazol-2-one
• 英文别名: 4,5,6,7-tetrabromo-1H,3H-benzimidazol-2-one；4,5,6,7-tetrabromo-1,3-dihydrobenzimidazol-2-one
• CAS: 56534-23-7
• 化学式: C₇H₂Br₄N₂O
• 分子量: 449.722
• InChiKey: BMVNFJCUHHTZQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 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：
  41.1
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  4,5,6,7-tetrabromo-1H,3H-benzimidazol-2-thione 在 盐酸 、 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 25.0h， 生成 4,5,6,7-Tetrabromo-1,3-dihydro-benzoimidazol-2-one
  参考文献：
  名称：

  Optimization of Protein Kinase CK2 Inhibitors Derived from 4,5,6,7-Tetrabromobenzimidazole

  摘要：

  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.

  DOI：

  10.1021/jm049854a

文献信息

• [EN] NEW DERIVATIVES OF 4, 5, 6, 7-TETRABROMOBENZIMIDAZOLE AND METHOD OF THEIR PREPARATION<br/>[FR] NOUVEAUX DERIVES DE 4, 5, 6, 7-TETRABROMOBENZIMIDAZOLE ET PROCEDE POUR LES PREPARER
  申请人：FUNDACJA ROZWOJU DIAGNOSTYKI I

  公开号：WO2005092866A1

  公开（公告）日：2005-10-06

  New derivatives of 4, 5, 6, 7-tetrabromobenzimidazole of formula (I); wherein R1 is hydrogen or aliphatic group, R2 is aliphatic group optionally substituted with hydrogen or substituent such as hydroxyl group or substituted amino group and method of their preparation.

  4, 5, 6, 7-四溴苯并咪唑的新衍生物的公式(I)；其中R1是氢或脂肪基团，R2是脂肪基团，可选地取代为氢或诸如羟基或取代氨基等取代基，以及其制备方法。
• Therapeutic molecules and methods-1
  申请人：Morand Francis Eric

  公开号：US20060154977A1

  公开（公告）日：2006-07-13

  Methods of inhibiting the cytokine or biological activity of Macrophage Migration Inhibitory Factor (MIF) comprising contacting MIF with a compound of formula (I) as defined herein, is provided. The invention also relates to methods of treating diseases or conditions where MIF cytokine or biological activity is implicated comprising administration of compounds of formula (I), either alone or as part of a combination therapy. Novel heterocyclic compounds are also provided for.

  本发明提供了抑制细胞因子或巨噬细胞迁移抑制因子（MIF）生物活性的方法，包括将MIF与公式（I）所定义的化合物接触。本发明还涉及治疗MIF细胞因子或生物活性参与的疾病或病况的方法，包括单独或作为联合治疗的一部分，给予公式（I）化合物。此外，还提供了新的杂环化合物。
• METHODS FOR TREATING NEOPLASMS WITH DERIVATIVES OF 4,5,6,7-TETRABROMOBENZIMIDAZOLE
  申请人：KAZIMIERCZUK Zygmunt

  公开号：US20090239921A1

  公开（公告）日：2009-09-24

  A pharmaceutical composition exhibiting an anti-neoplastic activity, comprising: a pharmaceutically-effective amount of a compound of Formula 1 and at least one inert, pharmaceutically acceptable carrier or diluent; wherein R 1 is a hydrogen or an aliphatic group; and R 2 is an aliphatic group, optionally substituted with a substituent selected from a hydroxyl and a substituted amino group; and methods of treating human neoplasms and for inhibiting caseine kinase 2 activity with said pharmaceutical composition.

  一种具有抗肿瘤活性的药物组合物，包括：公式1的化合物的药效学有效量和至少一种惰性的、药学上可接受的载体或稀释剂；其中，R1是氢或脂肪基；R2是脂肪基，可选地被羟基和取代氨基基团的取代物所取代；以及使用该药物组合物治疗人类肿瘤和抑制酪氨酸激酶2活性的方法。
• Therapeutic Molecules and Methods-1
  申请人：Morand Eric Francis

  公开号：US20100323999A1

  公开（公告）日：2010-12-23

  Methods of inhibiting the cytokine or biological activity of Macrophage Migration Inhibitory Factor (MIF) comprising contacting MIF with a compound of formula (I) as defined herein, is provided. The invention also relates to methods of treating diseases or conditions where MIF cytokine or biological activity is implicated comprising administration of compounds of formula (I), either alone or as part of a combination therapy. Novel heterocyclic compounds are also provided for.

  提供一种抑制巨噬细胞迁移抑制因子（MIF）细胞因子或生物活性的方法，包括将MIF与公式（I）所定义的化合物接触。本发明还涉及治疗与MIF细胞因子或生物活性有关的疾病或病况的方法，包括单独或作为联合治疗的一部分给予公式（I）化合物。还提供了新型杂环化合物。
• THERAPEUTIC MOLECULES AND METHODS-1
  申请人：Cortical Pty Ltd

  公开号：EP1511736A1

  公开（公告）日：2005-03-09