N-(1-isobutyl-4-piperidyl)-6-chlorobenzimidazole-4-carboxamide | 258345-17-4

• 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: N-(1-isobutyl-4-piperidyl)-6-chlorobenzimidazole-4-carboxamide
• 英文别名: N-[(1-iso-butyl-4-piperidyl)methyl]-6-chlorobenzimidazole-4-carboxamide；UCM-91776；6-Chloro-1H-benzoimidazole-4-carboxylic acid (1-isobutyl-piperidin-4-ylmethyl)-amide；6-chloro-N-[[1-(2-methylpropyl)piperidin-4-yl]methyl]-1H-benzimidazole-4-carboxamide
• CAS: 258345-17-4
• 化学式: C₁₈H₂₅ClN₄O
• 分子量: 348.876
• InChiKey: GJOQATQYBJWPMX-UHFFFAOYSA-N

物化性质

• 沸点：
  581.2±35.0 °C(Predicted)
• 密度：
  1.195±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  61
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [11C]methyl iodide 、 N-(1-isobutyl-4-piperidyl)-6-chlorobenzimidazole-4-carboxamide 生成
  参考文献：
  名称：

  Wilson, Alan A.; Garcia, A.; Bell, T., Journal of labelled compounds and radiopharmaceuticals, 2001, vol. 44, p. S999 - S1001

  摘要：

  DOI：
• 作为产物：
  描述：

  5-氯-7-甲基-1H-苯并咪唑 在 sodium hydroxide 、 potassium permanganate 、 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 N-(1-isobutyl-4-piperidyl)-6-chlorobenzimidazole-4-carboxamide
  参考文献：
  名称：

  Benzimidazole derivatives. Part 1: Synthesis and structure–activity relationships of new benzimidazole-4-carboxamides and carboxylates as potent and selective 5-HT4 receptor antagonists

  摘要：

  New benzimidazole-4-carboxamides 1-16 and -carboxylates 17-26 were synthesized and evaluated for binding affinity at serotonergic 5-HT4 and 5-HT3 receptors in the CNS. Most of the synthesized compounds exhibited moderate to-very high affinity tin many cases subnanomolar) for the 5-HT4 binding site and no significant affinity for the 5-HT3 receptor. SAR observations and structural analyses (molecular modeling, INSIGHT II) indicated that the presence of a voluminous substituent in the basic nitrogen atom of the amino moiety and a distance of ca. 8.0 Angstrom from this nitrogen to the aromatic ring are of great importance for high affinity and selectivity for 5-HT4 receptors. These results confirm our recently proposed model for recognition by the 5-HT4 binding site. Amides 12-15 and esters 24 and 25 bound at central 5-HT4 sites with very high affinity (K-j = 0.11-2.9 nM) and excellent selectivity over serotonin 5-HT3, 5-HT2A, and S-HT1A receptors (K-i > 1000-10,000 nM). Analogues 12 (k(i)(5-HT4) = 0.32 nM), 13 (K-i(5-HT4)= 0.11 nM), 14 (K-i(5-HT4) = 0.29 nM) and 15 (K-i(5-HT4) = 0.54 nM) were pharmacologically characterized as selective 5-HT4 antagonists in the isolated guinea pig ileum (pA(2) = 7.6, 7.9, 8.2 and 7.9, respectively), with a potency comparable to the 5-HT4 receptor antagonist RS 39604 (pA(2) = 8.2). The benzimidazoe-4-carboxylic acid derivatives described in this paper represent a novel class of potent and selective 5-HT4 receptor antagonists. In particular, compounds 12-15 could be interesting pharmacological tools for the understanding of the role of 5-HT4 receptors. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00172-8

文献信息

• Study of the bioactive conformation of novel 5-HT4 receptor ligands: influence of an intramolecular hydrogen bond
  作者：Marı́a L López-Rodrı́guez、Bellinda Benhamú、Alma Viso、Marta Murcia、Leonardo Pardo

  DOI：10.1016/s0040-4020(01)00621-4

  日期：2001.7

  methods, we have studied the prototropic equilibrium present in the benzimidazole ring of a series of derivatives acting at serotonin 5-HT4 receptors. The structural study has allowed us to get insight into the bioactive conformation of the novel 5-HT4 receptor ligands which has been supported by biological data. This will help the docking of the ligands into a 3-D model of the receptor binding site

  通过使用NMR和IR技术以及理论方法，我们研究了一系列作用于5-羟色胺5-HT 4受体的衍生物在苯并咪唑环中的质子平衡。结构研究使我们能够深入了解新型5-HT 4受体配体的生物活性构象，该构象已得到生物学数据的支持。这将有助于将配体对接到受体结合位点的3-D模型中，从而指导具有预定药理活性的新化合物的设计和合成。
• 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.