1-(2,3-difluorophenyl)-1H-pyrrole-2-carbonitrile | 195711-25-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1-(2,3-difluorophenyl)-1H-pyrrole-2-carbonitrile
• 英文别名: 1H-Pyrrole-2-carbonitrile, 1-(2,3-difluorophenyl)-；1-(2,3-difluorophenyl)pyrrole-2-carbonitrile
• CAS: 195711-25-2
• 化学式: C₁₁H₆F₂N₂
• 分子量: 204.179
• InChiKey: OVVLIDLIGXNBSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 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：
  28.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2,3-difluorophenyl)-1H-pyrrole-2-carbonitrile 在 氢氧化钾 、 三氯氧磷 作用下， 以 叔丁醇 为溶剂， 反应 8.0h， 生成 6-Fluoro-4-(4-methyl-piperazin-1-yl)-pyrrolo[1,2-a]quinoxaline
  参考文献：
  名称：

  Novel and Highly Potent 5-HT₃ Receptor Agonists Based on a Pyrroloquinoxaline Structure

  摘要：

  The synthesis and the biological evaluation of a series of novel pyrroloquinoxaline derivatives are described. In binding studies several compounds proved to be potent and selective 5-HT3 receptor ligands. The most active pyrroloquinoxalines, 11d and 11e, showed a subnanomolar affinity for 5-HT3 receptor and were able to functionally discriminate the central and peripheral 5-HT3 receptors, being agonists and antagonists, respectively. In functional studies ([C-14]-guanidinium accumulation test in NG 108-15 cells, in vitro) most of the synthesized compounds showed clear-cut 5-HT3 agonist properties. In in vivo studies on the von Bezold-Jarisch reflex test (a peripheral interaction model) the behavior of the tested compounds ranged from agonist to antagonist, while clear agonist properties were obtained with 12a on cortical acetylcholine release in freely moving rats. Pharmacokinetic studies with 11e and 12c indicate that the compounds easily cross the blood-brain barrier (BBB) after systemic administration with a brain/plasma ratio of 17.5 and 37.5, respectively. Thus compounds 11e and 12c represent the most potent central 5-HT3 agonists identified to date that are able to cross the blood-brain barrier.

  DOI：

  10.1021/jm970376w
• 作为产物：
  描述：

  2,3-二氟苯胺 在 盐酸羟胺 、 sodium acetate 、 乙酸酐 、 N,N-二甲基甲酰胺 作用下， 以 溶剂黄146 为溶剂， 反应 1.0h， 生成 1-(2,3-difluorophenyl)-1H-pyrrole-2-carbonitrile
  参考文献：
  名称：

  Novel and Highly Potent 5-HT₃ Receptor Agonists Based on a Pyrroloquinoxaline Structure

  摘要：

  The synthesis and the biological evaluation of a series of novel pyrroloquinoxaline derivatives are described. In binding studies several compounds proved to be potent and selective 5-HT3 receptor ligands. The most active pyrroloquinoxalines, 11d and 11e, showed a subnanomolar affinity for 5-HT3 receptor and were able to functionally discriminate the central and peripheral 5-HT3 receptors, being agonists and antagonists, respectively. In functional studies ([C-14]-guanidinium accumulation test in NG 108-15 cells, in vitro) most of the synthesized compounds showed clear-cut 5-HT3 agonist properties. In in vivo studies on the von Bezold-Jarisch reflex test (a peripheral interaction model) the behavior of the tested compounds ranged from agonist to antagonist, while clear agonist properties were obtained with 12a on cortical acetylcholine release in freely moving rats. Pharmacokinetic studies with 11e and 12c indicate that the compounds easily cross the blood-brain barrier (BBB) after systemic administration with a brain/plasma ratio of 17.5 and 37.5, respectively. Thus compounds 11e and 12c represent the most potent central 5-HT3 agonists identified to date that are able to cross the blood-brain barrier.

  DOI：

  10.1021/jm970376w

文献信息

• Novel and Highly Potent 5-HT₃ Receptor Agonists Based on a Pyrroloquinoxaline Structure
  作者：Giuseppe Campiani、Andrea Cappelli、Vito Nacci、Maurizio Anzini、Salvatore Vomero、Michel Hamon、Alfredo Cagnotto、Claudia Fracasso、Chiara Uboldi、Silvio Caccia、Silvana Consolo、Tiziana Mennini

  DOI：10.1021/jm970376w

  日期：1997.10.1

  The synthesis and the biological evaluation of a series of novel pyrroloquinoxaline derivatives are described. In binding studies several compounds proved to be potent and selective 5-HT3 receptor ligands. The most active pyrroloquinoxalines, 11d and 11e, showed a subnanomolar affinity for 5-HT3 receptor and were able to functionally discriminate the central and peripheral 5-HT3 receptors, being agonists and antagonists, respectively. In functional studies ([C-14]-guanidinium accumulation test in NG 108-15 cells, in vitro) most of the synthesized compounds showed clear-cut 5-HT3 agonist properties. In in vivo studies on the von Bezold-Jarisch reflex test (a peripheral interaction model) the behavior of the tested compounds ranged from agonist to antagonist, while clear agonist properties were obtained with 12a on cortical acetylcholine release in freely moving rats. Pharmacokinetic studies with 11e and 12c indicate that the compounds easily cross the blood-brain barrier (BBB) after systemic administration with a brain/plasma ratio of 17.5 and 37.5, respectively. Thus compounds 11e and 12c represent the most potent central 5-HT3 agonists identified to date that are able to cross the blood-brain barrier.