5-(benzyloxy)-3-{2-[4-(biphenyl-4-yl)piperazin-1-yl]ethyl}-1H-indole | 1610998-31-6

• 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: 5-(benzyloxy)-3-{2-[4-(biphenyl-4-yl)piperazin-1-yl]ethyl}-1H-indole
• CAS: 1610998-31-6
• 化学式: C₃₃H₃₃N₃O
• 分子量: 487.645
• InChiKey: JQJJBICGUHPHKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.78
• 重原子数：
  37.0
• 可旋转键数：
  8.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  31.5
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  5-(benzyloxy)-3-{2-[4-(biphenyl-4-yl)piperazin-1-yl]ethyl}-1H-indole 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、405.33 kPa 条件下， 反应 6.0h， 以42%的产率得到3-{2-[4-(biphenyl-4-yl)piperazin-1-yl]ethyl}-1H-indol-5-ol
  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
• 作为产物：
  描述：

  5-苄氧基吲哚 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 5-(benzyloxy)-3-{2-[4-(biphenyl-4-yl)piperazin-1-yl]ethyl}-1H-indole
  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