UCM-17197 | 255063-98-0

• 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: UCM-17197
• 英文别名: N-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-6-chloro-1H-benzimidazole-4-carboxamide
• CAS: 255063-98-0
• 化学式: C₁₅H₁₇ClN₄O
• 分子量: 304.779
• InChiKey: ZSVQUSFCJUITKQ-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.47
• 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：

  6-氯苯并咪唑-4-羧酸 在 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， 生成 UCM-17197
  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. 2. Synthesis and Structure−Activity Relationships of New Azabicyclic Benzimidazole-4-carboxylic Acid Derivatives with Affinity for Serotoninergic 5-HT₃ Receptors
  作者：María L. López-Rodríguez、Bellinda Benhamú、M. José Morcillo、Ignacio D. Tejada、Luis Orensanz、M. José Alfaro、M. Isabel Martín

  DOI：10.1021/jm991076c

  日期：1999.12.2

  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).