7-(benzyloxy)-4-(piperazin-1-yl)pyrrolo[1,2-a]quinoxaline | 1159633-12-1

• 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: 7-(benzyloxy)-4-(piperazin-1-yl)pyrrolo[1,2-a]quinoxaline
• CAS: 1159633-12-1
• 化学式: C₂₂H₂₂N₄O
• 分子量: 358.443
• InChiKey: ZSVBQMGQFWNAKQ-UHFFFAOYSA-N

物化性质

• 沸点：
  556.2±50.0 °C(predicted)
• 密度：
  1.27±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.48
• 重原子数：
  27.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  41.8
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  7-(benzyloxy)-4-(piperazin-1-yl)pyrrolo[1,2-a]quinoxaline 、 4-咪唑甲醛 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 、 溶剂黄146 为溶剂， 以78%的产率得到7-benzyloxy-4-[4-(1H-imidazol-4-ylmethyl)piperazin-1-yl]pyrrolo[1,2-a]quinoxaline
  参考文献：
  名称：

  新型，有力和选择性的基于喹喔啉的5-HT 3受体配体。1.进一步的结构-活性关系和药理学表征

  摘要：

  我们研究了新的基于喹喔啉的5-HT 3受体配体系列的药理学特征，该配体在哌嗪N-4上具有一个额外的碱性部分。高亲和力和选择性取决于取代基的电子性质，并且在心脏水平3a和3c上具有调制变时性，但不具有变质性。在von Bezold-Jarisch反射测试中，3a - c是部分激动剂，而3i是完全激动剂。初步的药代动力学研究表明3a是一种脑渗透剂。

  DOI：

  10.1021/jm901126m

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.