[4-(7-fluoropyrrolo[1,2-a]quinoxalin-4-yl)piperazin-1-yl]acetic acid | 1159633-21-2

• 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: [4-(7-fluoropyrrolo[1,2-a]quinoxalin-4-yl)piperazin-1-yl]acetic acid
• 英文别名: 2-[4-(7-fluoropyrrolo[1,2-a]quinoxalin-4-yl)piperazin-1-yl]acetic acid
• CAS: 1159633-21-2
• 化学式: C₁₇H₁₇FN₄O₂
• 分子量: 328.346
• InChiKey: SKCKAXNJSSPUAS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  61.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  甲基磺酰胺 、 [4-(7-fluoropyrrolo[1,2-a]quinoxalin-4-yl)piperazin-1-yl]acetic acid 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 四氢呋喃 为溶剂， 以67%的产率得到7-fluoro-4-[4-(methanesulfonamidoacetyl)piperazin-1-yl]pyrrolo[1,2-a]quinoxaline
  参考文献：
  名称：

  Specific Targeting of Peripheral Serotonin 5-HT₃ Receptors. Synthesis, Biological Investigation, and Structure−Activity Relationships

  摘要：

  The synthesis and the biological characterization of novel highly selective pyrroloquinoxaline 5-HT3 receptor (5-HT3R) ligands are described. In functional and in vivo biological studies the novel quinoxalines modulated cardiac parameters by direct interaction with myocardial 5-HT(3)Rs. The potent 5-HT3R ligands 4h and 4n modulate chronotropy (right atrium) but not inotropy (left atrium) at the cardiac level, being antagonist and partial agonist, respectively. Preliminary pharmacokinetic studies indicate that (S)-4n and 4a, representatives of the novel 5-HT3R ligands, possess poor blood-brain barrier permeability, being the prototypes of peripherally acting 5-HT3R modulators endowed with a clear-cut pharmacological activity at the cardiac level. The unique properties of 4h and 4n, compared to their previously described centrally active N-methyl analogue 5a, are mainly due to the hydrophilic groups at the distal piperazine nitrogen. These analogues represent novel pharmacological tools for investigating the role of peripheral 5-HT3R in the modulation of cardiac parameters.

  DOI：

  10.1021/jm900018b
• 作为产物：
  描述：

  [4-(7-fluoropyrrolo[1,2-a]quinoxalin-4-yl)piperazin-1-yl]acetic acid benzyl ester 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以89%的产率得到[4-(7-fluoropyrrolo[1,2-a]quinoxalin-4-yl)piperazin-1-yl]acetic acid
  参考文献：
  名称：

  Specific Targeting of Peripheral Serotonin 5-HT₃ Receptors. Synthesis, Biological Investigation, and Structure−Activity Relationships

  摘要：

  The synthesis and the biological characterization of novel highly selective pyrroloquinoxaline 5-HT3 receptor (5-HT3R) ligands are described. In functional and in vivo biological studies the novel quinoxalines modulated cardiac parameters by direct interaction with myocardial 5-HT(3)Rs. The potent 5-HT3R ligands 4h and 4n modulate chronotropy (right atrium) but not inotropy (left atrium) at the cardiac level, being antagonist and partial agonist, respectively. Preliminary pharmacokinetic studies indicate that (S)-4n and 4a, representatives of the novel 5-HT3R ligands, possess poor blood-brain barrier permeability, being the prototypes of peripherally acting 5-HT3R modulators endowed with a clear-cut pharmacological activity at the cardiac level. The unique properties of 4h and 4n, compared to their previously described centrally active N-methyl analogue 5a, are mainly due to the hydrophilic groups at the distal piperazine nitrogen. These analogues represent novel pharmacological tools for investigating the role of peripheral 5-HT3R in the modulation of cardiac parameters.

  DOI：

  10.1021/jm900018b

文献信息

• Specific Targeting of Peripheral Serotonin 5-HT₃ Receptors. Synthesis, Biological Investigation, and Structure−Activity Relationships
  作者：Elena Morelli、Sandra Gemma、Roberta Budriesi、Giuseppe Campiani、Ettore Novellino、Caterina Fattorusso、Bruno Catalanotti、Salvatore Sanna Coccone、Sindu Ros、Giuseppe Borrelli、Marco Persico、Isabella Fiorini、Vito Nacci、Pierfranco Ioan、Alberto Chiarini、Michel Hamon、Alfredo Cagnotto、Tiziana Mennini、Claudia Fracasso、Milena Colovic、Silvio Caccia、Stefania Butini

  DOI：10.1021/jm900018b

  日期：2009.6.11

  The synthesis and the biological characterization of novel highly selective pyrroloquinoxaline 5-HT3 receptor (5-HT3R) ligands are described. In functional and in vivo biological studies the novel quinoxalines modulated cardiac parameters by direct interaction with myocardial 5-HT(3)Rs. The potent 5-HT3R ligands 4h and 4n modulate chronotropy (right atrium) but not inotropy (left atrium) at the cardiac level, being antagonist and partial agonist, respectively. Preliminary pharmacokinetic studies indicate that (S)-4n and 4a, representatives of the novel 5-HT3R ligands, possess poor blood-brain barrier permeability, being the prototypes of peripherally acting 5-HT3R modulators endowed with a clear-cut pharmacological activity at the cardiac level. The unique properties of 4h and 4n, compared to their previously described centrally active N-methyl analogue 5a, are mainly due to the hydrophilic groups at the distal piperazine nitrogen. These analogues represent novel pharmacological tools for investigating the role of peripheral 5-HT3R in the modulation of cardiac parameters.