6-Fluoropyrrolo[1,2-a]quinoxalin-4(5H)-one | 195711-31-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-Fluoropyrrolo[1,2-a]quinoxalin-4(5H)-one
• 英文别名: 6-fluoro-5H-pyrrolo[1,2-a]quinoxalin-4-one
• CAS: 195711-31-0
• 化学式: C₁₁H₇FN₂O
• 分子量: 202.188
• InChiKey: GTFZRHZHYIXEEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  34
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-Fluoropyrrolo[1,2-a]quinoxalin-4(5H)-one 在 三氯氧磷 作用下， 反应 4.0h， 以95%的产率得到4-Chloro-6-fluoropyrrolo[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 氢氧化钾 、 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 、 叔丁醇 为溶剂， 反应 3.0h， 生成 6-Fluoropyrrolo[1,2-a]quinoxalin-4(5H)-one
  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

• 10.1039/d4ob00741g
  作者：Panday, Surabhi、Hazra, Amitava、Gupta, Pankaj、Manna, Srimanta、Laha, Joydev K.

  DOI：10.1039/d4ob00741g

  日期：——

  for the direct synthesis of diverse pyrrole-fused heterocycles. The process involves two-component reactions of alkyl (NH)-pyrrole-2-carboxylates and 2-fluoronitroarenes, yielding pyrrolo[1,2-a]quinoxalin-4(5H)-ones, as well as three-component reactions utilizing (NH)-pyrroles, nitroarenes, and DMSO as carbon sources, resulting in various pyrrolo[1,2-a]quinoxaline derivatives. High yields were achieved

  提出了一种新型生物质衍生的葡萄糖介导的一锅多组分硝基还原环化方法，用于直接合成多种吡咯稠合杂环。该过程涉及烷基 (NH)-吡咯-2-羧酸酯和 2-氟硝基芳烃的双组分反应，生成吡咯并[1,2 -a ]喹喔啉-4(5 H )-酮，以及利用(NH)-吡咯、硝基芳烃和DMSO作为碳源，产生各种吡咯并[1,2- a ]喹喔啉衍生物。通过广泛的底物范围和克级合成能力实现了高产率，包括具有吡咯并喹喔啉支架的药物。该方法的关键创新在于能够在单锅装置中进行三到四个反应，这在吡咯化学中以前是未曾探索过的。通过生物质衍生的葡萄糖还原硝基的简单性确保了放大过程中的实际安全性，而对照实验的机理见解揭示了吡咯化学的新范例。串联工艺表现出低 PMI 值和高步骤和原子经济性，与绿色化学原理很好地吻合。
• 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.