Tetrabrom-2-aminobenzimidazol | 787630-06-2

• 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: Tetrabrom-2-aminobenzimidazol
• 英文别名: 4,5,6,7-tetrabromo-1H-benzoimidazol-2-ylamine；2-amino-4,5,6,7-tetrabromo-1H-benzimidazole；4,5,6,7-tetrabromo-1H-benzimidazol-2-amine
• CAS: 787630-06-2
• 化学式: C₇H₃Br₄N₃
• 分子量: 448.737
• InChiKey: WPQXWZSBYPCXKC-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：
  54.7
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2,4,5,6,7-五溴-1H-苯并咪唑 在 氨 作用下， 以 甲醇 为溶剂， 以36%的产率得到Tetrabrom-2-aminobenzimidazol
  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。
• A compound, a process for its preparation, a pharmaceutical composition, use of a compound, a method for modulating or regulating serine/threonine kinases and a serine/threonine kinases modulating agent
  申请人：SELVITA S.A.

  公开号：EP2366695A1

  公开（公告）日：2011-09-21

  The subject of the inventions are a compound, a process for its preparation, a pharmaceutical composition, use of a compound, a method for modulating or regulating serine/threonine kinases and a serine/threonine kinases modulating agent. The present invention relates to novel small-molecule compounds with kinase inhibitory activity, having superior properties as pharmaceutical agents, production method thereof and uses thereof. In particular, this invention relates to new derivatives of tetrabromobenzimidazole with serine/threonine kinases inhibitory properties, preferably selected from the group of Pim, HIPK, DYRK and CLK kinases, which exhibits superior pharmacological actions, and can be useful for the treatment of disease conditions, especially cancers depending on serine/threonine kinases, such as leukemias and prostate cancer.

  这些发明的主题是一种化合物，其制备方法，一种药物组合物，一种化合物的用途，一种调节丝氨酸/苏氨酸激酶的方法和丝氨酸/苏氨酸激酶调节剂。本发明涉及具有激酶抑制活性的新型小分子化合物，具有作为药物剂的优越性能，其生产方法及用途。具体而言，本发明涉及新型四溴苯并咪唑衍生物，具有丝氨酸/苏氨酸激酶抑制性质，优选来自Pim、HIPK、DYRK和CLK激酶组的，表现出优越的药理作用，并可用于治疗疾病状况，尤其是依赖于丝氨酸/苏氨酸激酶的癌症，如白血病和前列腺癌。
• DERIVATIVES OF TETRABROMOBENZIMIDAZOLE, A PROCESS FOR THE PREPARATION THEREOF, A PHARMACEUTICAL COMPOSITION COMPRISING THE SAME, A METHOF OF USING THE SAME, A METHOD FOR MODULATING OR REGULATING SERINE/THREONINE KINASES, AND SERINE/THREONINE KINASES MODULATING AGENT
  申请人：Brzozka Krzysztof

  公开号：US20110112091A1

  公开（公告）日：2011-05-12

  A derivative of tetrabromobenzimidazole, a process for the preparation thereof, a pharmaceutical composition, a method for using the same, a method for modulating or regulating serine/threonine kinases, and a serine/threonine kinases modulating agent. The invention relates to novel small-molecule compounds with kinase inhibitory activity, having superior properties as pharmaceutical agents, production method thereof and uses thereof. In particular, this invention relates to new derivatives of tetrabromobenzimidazole with Pim kinases inhibitory properties, which exhibits superior pharmacological actions, and can be useful for the treatment of disease conditions, especially cancers depending on Pim kinases, such as leukemias and prostate cancer.

  一种四溴苯并咪唑的衍生物，其制备方法，一种药物组合物，一种使用该衍生物的方法，一种调节丝氨酸/苏氨酸激酶的方法，以及一种丝氨酸/苏氨酸激酶调节剂。该发明涉及具有激酶抑制活性的新型小分子化合物，具有作为药物剂的优越性能，其生产方法和用途。具体而言，本发明涉及具有Pim激酶抑制性能的四溴苯并咪唑的新衍生物，表现出卓越的药理作用，并可用于治疗疾病，特别是依赖于Pim激酶的白血病和前列腺癌等癌症。
• NEW DERIVATIVES OF 4,5,6,7-TETRABROMOBENZIMIDAZOLE AND METHOD OF THEIR PREPARATION
  申请人：Kazimierczuk Zygmunt

  公开号：US20070213385A1

  公开（公告）日：2007-09-13

  Taught herein are new derivatives of 4,5,6,7-tetrabromobenzimidazole of Formula 1 wherein R 1 is a hydrogen or an aliphatic group, and R 2 is an aliphatic group, optionally substituted with a hydrogen or a substituent such as a hydroxyl group or substituted amino group, and a method of their preparation.

  本文介绍了4,5,6,7-四溴苯并咪唑的新衍生物，其化学式为1，其中R1是氢或脂肪基，R2是脂肪基，可选地带有氢或取代基，例如羟基或取代氨基，以及它们的制备方法。
• 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。