1-azabicyclo[2.2.2]octan-3-yl benzimidazole-2-carboxylate

• 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: 1-azabicyclo[2.2.2]octan-3-yl benzimidazole-2-carboxylate
• 英文别名: 1-azabicyclo[2.2.2]octan-3-yl 1H-benzimidazole-2-carboxylate
• 化学式: C₁₅H₁₇N₃O₂
• 分子量: 271.319
• InChiKey: FSMCRPDZVADSEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  58.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1H-苯并咪唑-2-甲酸 、 奎宁环-3-醇 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 21.0h， 以42%的产率得到1-azabicyclo[2.2.2]octan-3-yl benzimidazole-2-carboxylate
  参考文献：
  名称：

  Benzimidazole-2-carboxylic acid amides and esters: a new structural class of 5-HT3 ligands

  摘要：

  A series of novel benzimidazole-2-carboxylic acid amides and esters with a quinuclidine or a tropane moiety were synthesized and evaluated for in vitro affinity for the 5-HT(3), 5-HT(4) and D(2) receptors. Compounds 15a, 13j and 13h exhibited affinity for the 5-HT(3) receptor (K(i) = 20.2, 18.4 and 12.7 nM, respectively) and no significant affinity for both 5-HT(4) and D(2) receptors. The amide-ester replacement did not induce significant changes in the affinity profile. The enantioselectivity for the 5-HT(3) receptor was reversed with regard to the zacopride pattern and the (R)-enantiomer 13c showed higher affinity (K(i) = 56.4 nM) than the (S)-enantiomer 13d (Y = 242.3 nM). An increment of the steric hindrance around the nitrogen atom at the 1-position of the benzimidazole ring led to an improvement in the affinity. The 5-HT(3) receptor antagonist activity of compounds with higher affinity was performed by evaluating the inhibition of the 5-HT induced von Bezold-Jarisch reflex. They displayed moderate 5-HT(3) antagonist activity (ED(50) = 10.6-29.1 mu g/kg i.v.). (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(99)80091-9

文献信息

• Benzimidazole-2-carboxylic acid amides and esters: a new structural class of 5-HT3 ligands
  作者：Aurelio Orjales、Luisa Alonso-Cires、Pedro López-Tudanca、Inés Tapia、Ramón Mosquera、Luis Labeaga

  DOI：10.1016/s0223-5234(99)80091-9

  日期：1999.5

  A series of novel benzimidazole-2-carboxylic acid amides and esters with a quinuclidine or a tropane moiety were synthesized and evaluated for in vitro affinity for the 5-HT(3), 5-HT(4) and D(2) receptors. Compounds 15a, 13j and 13h exhibited affinity for the 5-HT(3) receptor (K(i) = 20.2, 18.4 and 12.7 nM, respectively) and no significant affinity for both 5-HT(4) and D(2) receptors. The amide-ester replacement did not induce significant changes in the affinity profile. The enantioselectivity for the 5-HT(3) receptor was reversed with regard to the zacopride pattern and the (R)-enantiomer 13c showed higher affinity (K(i) = 56.4 nM) than the (S)-enantiomer 13d (Y = 242.3 nM). An increment of the steric hindrance around the nitrogen atom at the 1-position of the benzimidazole ring led to an improvement in the affinity. The 5-HT(3) receptor antagonist activity of compounds with higher affinity was performed by evaluating the inhibition of the 5-HT induced von Bezold-Jarisch reflex. They displayed moderate 5-HT(3) antagonist activity (ED(50) = 10.6-29.1 mu g/kg i.v.). (C) Elsevier, Paris.