6-Bromo-7-nitro-1H-benzimidazole-4-carboxylic acid | 255064-09-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-Bromo-7-nitro-1H-benzimidazole-4-carboxylic acid
• 英文别名: 6-bromo-7-nitro-3H-benzimidazole-4-carboxylic acid
• CAS: 255064-09-6
• 化学式: C₈H₄BrN₃O₄
• 分子量: 286.041
• InChiKey: YRXJFWMHNISIJR-UHFFFAOYSA-N

物化性质

• 沸点：
  614.4±55.0 °C(Predicted)
• 密度：
  2.108±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-Bromo-7-nitro-1H-benzimidazole-4-carboxylic acid 在 镍 一水合肼 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.25h， 生成 7-amino-N-(1-azabicyclo[2.2.2]octan-3-yl)-6-bromo-1H-benzimidazole-4-carboxamide
  参考文献：
  名称：

  Benzimidazole Derivatives. 2. Synthesis and Structure−Activity Relationships of New Azabicyclic Benzimidazole-4-carboxylic Acid Derivatives with Affinity for Serotoninergic 5-HT₃ Receptors

  摘要：

  A new series of azabicyclic benzimidazole-4-carboxamides 2-21 and -carboxylates 22-30 were synthesized and evaluated for binding affinity at serotoninergic 5-HT3 and 5-HT4 receptors in the CNS. Most of the synthesized compounds exhibited high or very high affinity for the 5-HT3 binding site and low to no significant affinity for the 5-HT4 receptor. SAR observations indicated that a halogen atom at the Ii-position and a nitro group at the 7-position of the benzimidazole ring is the best substitution pattern for 5-HT3 affinity and 5-HT3/5-HT4 selectivity, as well as no substitution in this ring. (S)-(-)-N-(Quinuclidin-3-yl)benzimidazo-4-carboxamides 2, 8, and 14 bound at central 5-HT3 sites with high affinity (K-i = 2.6, 0.13, and 1.7 nM, respectively) and excellent selectivity over serotonin 5-HT4 and 5-HT1A receptors (K-i > 1000-10000 dM). Furthermore, these new 5-HT3 receptor ligands were pharmacologically characterized as potent and selective 5-HT3 antagonists in the isolated guinea pig ileum (pA(2) = 9.6, 9.9, and 9.1, respectively).

  DOI：

  10.1021/jm991076c
• 作为产物：
  描述：

  5-溴-3-甲基苯-1,2-二胺 在 sodium hydroxide 、 potassium permanganate 、 硫酸 、 硝酸 作用下， 以 水 为溶剂， 反应 12.0h， 生成 6-Bromo-7-nitro-1H-benzimidazole-4-carboxylic acid
  参考文献：
  名称：

  Benzimidazole Derivatives. 2. Synthesis and Structure−Activity Relationships of New Azabicyclic Benzimidazole-4-carboxylic Acid Derivatives with Affinity for Serotoninergic 5-HT₃ Receptors

  摘要：

  A new series of azabicyclic benzimidazole-4-carboxamides 2-21 and -carboxylates 22-30 were synthesized and evaluated for binding affinity at serotoninergic 5-HT3 and 5-HT4 receptors in the CNS. Most of the synthesized compounds exhibited high or very high affinity for the 5-HT3 binding site and low to no significant affinity for the 5-HT4 receptor. SAR observations indicated that a halogen atom at the Ii-position and a nitro group at the 7-position of the benzimidazole ring is the best substitution pattern for 5-HT3 affinity and 5-HT3/5-HT4 selectivity, as well as no substitution in this ring. (S)-(-)-N-(Quinuclidin-3-yl)benzimidazo-4-carboxamides 2, 8, and 14 bound at central 5-HT3 sites with high affinity (K-i = 2.6, 0.13, and 1.7 nM, respectively) and excellent selectivity over serotonin 5-HT4 and 5-HT1A receptors (K-i > 1000-10000 dM). Furthermore, these new 5-HT3 receptor ligands were pharmacologically characterized as potent and selective 5-HT3 antagonists in the isolated guinea pig ileum (pA(2) = 9.6, 9.9, and 9.1, respectively).

  DOI：

  10.1021/jm991076c

文献信息

• Benzimidazole Derivatives. 3. 3D-QSAR/CoMFA Model and Computational Simulation for the Recognition of 5-HT₄ Receptor Antagonists
  作者：María L. López-Rodríguez、Marta Murcia、Bellinda Benhamú、Alma Viso、Mercedes Campillo、Leonardo Pardo

  DOI：10.1021/jm020807x

  日期：2002.10.1

  the hydrogen bond between the carbonyl oxygen of the ligand and the hydroxyl group of Ser(5.43), (iii) the hydrogen bond between the NH group of Asn(6.55) and the aromatic ring of carboxamides or the ether oxygen of carboxylates, (iv) the interaction of the electron-rich clouds of the aromatic ring of Phe(6.51) and the electron-poor hydrogens of the carbon atoms adjacent to the protonated piperidine

  使用比较分子场分析（CoMFA）方法进行的三维定量结构亲和关系研究（3D-QSAR）和配体识别的后续计算模拟已成功地用于解释5-HT（4 ）一系列苯并咪唑-4-羧酰胺和羧酸盐衍生物1-24的受体（5-HT（4）R）。这些化合物的K（i）值在0.11至10000 nM的范围内。派生的3D-QSAR模型显示出较高的预测能力（q（2）= 0.789和r（2）= 0.997）。这种新型的5-HT（4）R拮抗剂的立体（贡献43.5％）和静电场（50.3％）和溶剂化能（6.1％）是结构活性关系的相关描述子。51）和与配体的质子化哌啶氮相邻的碳原子的贫电子氢，以及（v）配体的苯并咪唑体系与Tyr的苯环之间的pi-sigma堆积相互作用（5.38）。此外，通过在芳环的6位引入氯或溴原子，5-HT（4）R位点的效能显着提高，这归因于其额外的静电和范德华相互作用位于跨膜结构域5和6之间的小腔体中的卤素原子。
• 3-D-QSAR/CoMFA and recognition models of benzimidazole derivatives at the 5-HT4 receptor
  作者：Marı́a L López-Rodrı́guez、Marta Murcia、Bellinda Benhamú、Alma Viso、Mercedes Campillo、Leonardo Pardo

  DOI：10.1016/s0960-894x(01)00517-0

  日期：2001.11

  3-D-QSAR/CoMFA methodology and computational simulation of ligand recognition have been successfully applied to explain the binding affinities of a series of benzimidazole derivatives 1-24 acting at serotonin 5-HT(4)Rs. Both derived computational models have facilitated the identification of the structural elements of the ligands that are key to high 5-HT4R affinity. The results provide the tools for predicting the affinity of related compounds, and for guiding the design and synthesis of new ligands with predetermined affinities and selectivity. (C) 2001 Elsevier Science Ltd. All rights reserved.