N-(3-{methyl[3-(4-phenylpiperazin-1-yl)propyl]amino}pheny)acetamide | 1610999-17-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-(3-{methyl[3-(4-phenylpiperazin-1-yl)propyl]amino}pheny)acetamide
• 英文别名: N-[3-[methyl-[3-(4-phenylpiperazin-1-yl)propyl]amino]phenyl]acetamide
• CAS: 1610999-17-1
• 化学式: C₂₂H₃₀N₄O
• 分子量: 366.506
• InChiKey: CJYNYHWPJXZSIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  38.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-硝基-N-甲基苯胺 在 palladium 10% on activated carbon 、 氢气 、 碳酸氢钠 、 三乙胺 、 diborane(6) 作用下， 以 四氢呋喃 、 乙醇 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 22.33h， 生成 N-(3-{methyl[3-(4-phenylpiperazin-1-yl)propyl]amino}pheny)acetamide
  参考文献：
  名称：

  Towards the development of 5-HT7 ligands combining serotonin-like and arylpiperazine moieties

  摘要：

  Many known 5-HT7 ligands contain either a serotonin-like or an arylpiperazine structure that, in published SAR studies, are generally supposed to bind the same receptor pocket. Conversely, we explored the hypothesis that two such moieties can co-exist in the same ligand, binding to different pockets. We thus designed and synthesized a set of compounds including both a 5-hydroxyindol-3-ylethyl and a 1-arylpiperazine moieties connected by a short linker. The compounds were tested for their affinity for human 5-HT7 serotonin receptor. We further prepared a novel series of 5-HT7 ligands, where the 5-hydroxyindol-3-ylethyl moiety was bioisosterically replaced by a 3-hydroxyanilinoalkyl one. Among the newly synthesized compounds, potent ligands at the 5-HT7 receptor, behaving as antagonists in functional tests, were identified, even if they showed limited subtype selectivity. Docking studies within a model of the 5-HT7 receptor showed that the binding site can actually accommodate both moieties, with the serotonin-like one in the putative orthosteric site and the arylpiperazine one occupying an accessory pocket. The present results demonstrate that it is possible to devise and develop new 5-HT7 ligands merging two privileged structures in the same molecule.

  DOI：

  10.1016/j.ejmech.2014.04.034

文献信息

• Towards the development of 5-HT7 ligands combining serotonin-like and arylpiperazine moieties
  作者：Gilberto Spadoni、Annalida Bedini、Silvia Bartolucci、Daniele Pala、Marco Mor、Teresa Riccioni、Franco Borsini、Walter Cabri、Diana Celona、Mauro Marzi、Giorgio Tarzia、Silvia Rivara、Patrizia Minetti

  DOI：10.1016/j.ejmech.2014.04.034

  日期：2014.6

  Many known 5-HT7 ligands contain either a serotonin-like or an arylpiperazine structure that, in published SAR studies, are generally supposed to bind the same receptor pocket. Conversely, we explored the hypothesis that two such moieties can co-exist in the same ligand, binding to different pockets. We thus designed and synthesized a set of compounds including both a 5-hydroxyindol-3-ylethyl and a 1-arylpiperazine moieties connected by a short linker. The compounds were tested for their affinity for human 5-HT7 serotonin receptor. We further prepared a novel series of 5-HT7 ligands, where the 5-hydroxyindol-3-ylethyl moiety was bioisosterically replaced by a 3-hydroxyanilinoalkyl one. Among the newly synthesized compounds, potent ligands at the 5-HT7 receptor, behaving as antagonists in functional tests, were identified, even if they showed limited subtype selectivity. Docking studies within a model of the 5-HT7 receptor showed that the binding site can actually accommodate both moieties, with the serotonin-like one in the putative orthosteric site and the arylpiperazine one occupying an accessory pocket. The present results demonstrate that it is possible to devise and develop new 5-HT7 ligands merging two privileged structures in the same molecule.