N-(1-methyl-4-piperidyl)benzimidazole-4-carboxamide | 180569-28-2

• 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: N-(1-methyl-4-piperidyl)benzimidazole-4-carboxamide
• 英文别名: N-(1-Methylpiperidin-4-yl)-1H-benzimidazole-4-carboxamide
• CAS: 180569-28-2
• 化学式: C₁₄H₁₈N₄O
• 分子量: 258.323
• InChiKey: UOPVVMIAMOXBRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  61
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-氨基-1-甲基哌啶 、 苯并咪唑-4-羧酸 在 N,N'-羰基二咪唑 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 以32%的产率得到N-(1-methyl-4-piperidyl)benzimidazole-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

• Novel benzimidazole-4-carboxylic acid derivatives as potent and selective 5-HT3 receptor ligands
  作者：María L. López-Rodríguez、Ma José Morcillo、Bellinda Benhamú、Ma Dolores Riaguas

  DOI：10.1016/0960-894x(96)00200-4

  日期：1996.6

  A series of benzimidazole-4-carboxylic acid derivatives was synthesized and evaluated for affinity at 5-HT3 and 5-HT4 serotoninergic receptors. Compounds 1b, c and j exhibited high affinity for the 5-HT3 receptors (K-i=6.1, 3.7 and 4.9 nM, respectively) and no significant affinity for 5-HT4 (K-i>1000 nM) and 5-HT1A (K-i>10 000 nM) sites. Preliminary studies showed that 1c displayed activity in the two-compartment behavioural model. Copyright (C) 1996 Elsevier Science Ltd