2-(4-methyl-1,4-diazepan-1-yl)quinoxaline | 1355481-39-8

• 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: 2-(4-methyl-1,4-diazepan-1-yl)quinoxaline
• CAS: 1355481-39-8
• 化学式: C₁₄H₁₈N₄
• 分子量: 242.324
• InChiKey: DUIRLPKRNHXEJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  32.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-甲基高哌嗪 、 2-氯喹恶啉 在 三乙胺 作用下， 以 甲苯 为溶剂， 以71%的产率得到2-(4-methyl-1,4-diazepan-1-yl)quinoxaline
  参考文献：
  名称：

  Structure-Activity Relationships of Quinoxaline-Based 5-HT₃A and 5-HT₃AB Receptor-Selective Ligands

  摘要：

  AbstractUntil recently, discriminating between homomeric 5‐HT3A and heteromeric 5‐HT3AB receptors was only possible with ligands that bind in the receptor pore. This study describes the first series of ligands that can discriminate between these receptor types at the level of the orthosteric binding site. During a recent fragment screen, 2‐chloro‐3‐(4‐methylpiperazin‐1‐yl)quinoxaline (VUF10166) was identified as a ligand that displays an 83‐fold difference in [3H]granisetron binding affinity between 5‐HT3A and 5‐HT3AB receptors. Fragment hit exploration, initiated from VUF10166 and 3‐(4‐methylpiperazin‐1‐yl)quinoxalin‐2‐ol, resulted in a series of compounds with higher affinity at either 5‐HT3A or 5‐HT3AB receptors. These ligands reveal that a single atom is sufficient to change the selectivity profile of a compound. At the extremes of the new compounds were 2‐amino‐3‐(4‐methylpiperazin‐1‐yl)quinoxaline, which showed 11‐fold selectivity for the 5‐HT3A receptor, and 2‐(4‐methylpiperazin‐1‐yl)quinoxaline, which showed an 8.3‐fold selectivity for the 5‐HT3AB receptor. These compounds represent novel molecular tools for studying 5‐HT3 receptor subtypes and could help elucidate their physiological roles.

  DOI：

  10.1002/cmdc.201300032

文献信息

• Structure-Activity Relationships of Quinoxaline-Based 5-HT₃A and 5-HT₃AB Receptor-Selective Ligands
  作者：Andrew J. Thompson、Mark H. P. Verheij、Jacqueline E. van Muijlwijk-Koezen、Sarah C. R. Lummis、Rob Leurs、Iwan J. P. de Esch

  DOI：10.1002/cmdc.201300032

  日期：2013.6

  AbstractUntil recently, discriminating between homomeric 5‐HT3A and heteromeric 5‐HT3AB receptors was only possible with ligands that bind in the receptor pore. This study describes the first series of ligands that can discriminate between these receptor types at the level of the orthosteric binding site. During a recent fragment screen, 2‐chloro‐3‐(4‐methylpiperazin‐1‐yl)quinoxaline (VUF10166) was identified as a ligand that displays an 83‐fold difference in [3H]granisetron binding affinity between 5‐HT3A and 5‐HT3AB receptors. Fragment hit exploration, initiated from VUF10166 and 3‐(4‐methylpiperazin‐1‐yl)quinoxalin‐2‐ol, resulted in a series of compounds with higher affinity at either 5‐HT3A or 5‐HT3AB receptors. These ligands reveal that a single atom is sufficient to change the selectivity profile of a compound. At the extremes of the new compounds were 2‐amino‐3‐(4‐methylpiperazin‐1‐yl)quinoxaline, which showed 11‐fold selectivity for the 5‐HT3A receptor, and 2‐(4‐methylpiperazin‐1‐yl)quinoxaline, which showed an 8.3‐fold selectivity for the 5‐HT3AB receptor. These compounds represent novel molecular tools for studying 5‐HT3 receptor subtypes and could help elucidate their physiological roles.