1‐(benzenesulfonyl)‐6‐(4‐acetylpiperazin‐1‐yl)‐1H‐indole

• 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: 1‐(benzenesulfonyl)‐6‐(4‐acetylpiperazin‐1‐yl)‐1H‐indole
• 英文别名: 1-[4-[1-(Benzenesulfonyl)indol-6-yl]piperazin-1-yl]ethanone；1-[4-[1-(benzenesulfonyl)indol-6-yl]piperazin-1-yl]ethanone
• 化学式: C₂₀H₂₁N₃O₃S
• 分子量: 383.471
• InChiKey: YCNXXIJDRSOXKB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  71
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  苯磺酰氯 在 四丁基溴化铵 、 palladium diacetate 、 caesium carbonate 、 sodium hydroxide 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 21.0h， 生成 1‐(benzenesulfonyl)‐6‐(4‐acetylpiperazin‐1‐yl)‐1H‐indole
  参考文献：
  名称：

  Rationally designed N-phenylsulfonylindoles as a tool for the analysis of the non-basic 5-HT6R ligands binding mode

  摘要：

  Among all of the monoaminergic receptors, the 5-HT₆R has the highest number of non-basic ligands (approximately 5% of compounds stored in 25th version of ChEMBL database have the strongest basic pKa below 5, calculated using the Instant JChem calculator plugin). These compounds, when devoid of a basic nitrogen, exhibit high affinity and remarkable selectivity. Despite a decade of research, no clues have been given for explanation of such an intriguing phenomenon. Here, a series of analogs of four known 5-HT₆R ligands, has been rationally designed to approach this issue. For each of the synthesized 42 compounds, a binding affinity for 5-HT₆R has been measured, together with a selectivity profile against 5-HT_1AR, 5-HT_2AR, 5-HT₇R and D₂R. Performed induced fit docking and molecular dynamics experiments revealed that no particular interaction was responsible for the activity of non-basic compounds. In fact, a plain N-phenylsulfonylindole (1e) was found to possess a moderate (5-HT₆R, K_i = 159 nM) affinity. No other monoaminergic receptor has as simple and selective ligand as this one. Thus, it is stated that it binds to the receptor solely based on its conformation and as such, possesses a minimum amount of features, required for binding. Also, any functional group able to form an additional interaction with the receptor increase the binding affinity, like in the case of two highly active non-basic compounds 3e and 5g (5-HT₆R, K_i = 65 nM and 38 nM, respectively).

  DOI：

  10.1016/j.ejmech.2020.112916

文献信息

• Rationally designed N-phenylsulfonylindoles as a tool for the analysis of the non-basic 5-HT6R ligands binding mode
  作者：Jakub Staroń、Ryszard Bugno、Wojciech Pietruś、Grzegorz Satała、Stefan Mordalski、Dawid Warszycki、Agata Hogendorf、Adam S. Hogendorf、Justyna Kalinowska-Tłuścik、Tomasz Lenda、Bogusław Pilarski、Andrzej J. Bojarski

  DOI：10.1016/j.ejmech.2020.112916

  日期：2021.1

  Among all of the monoaminergic receptors, the 5-HT₆R has the highest number of non-basic ligands (approximately 5% of compounds stored in 25th version of ChEMBL database have the strongest basic pKa below 5, calculated using the Instant JChem calculator plugin). These compounds, when devoid of a basic nitrogen, exhibit high affinity and remarkable selectivity. Despite a decade of research, no clues have been given for explanation of such an intriguing phenomenon. Here, a series of analogs of four known 5-HT₆R ligands, has been rationally designed to approach this issue. For each of the synthesized 42 compounds, a binding affinity for 5-HT₆R has been measured, together with a selectivity profile against 5-HT_1AR, 5-HT_2AR, 5-HT₇R and D₂R. Performed induced fit docking and molecular dynamics experiments revealed that no particular interaction was responsible for the activity of non-basic compounds. In fact, a plain N-phenylsulfonylindole (1e) was found to possess a moderate (5-HT₆R, K_i = 159 nM) affinity. No other monoaminergic receptor has as simple and selective ligand as this one. Thus, it is stated that it binds to the receptor solely based on its conformation and as such, possesses a minimum amount of features, required for binding. Also, any functional group able to form an additional interaction with the receptor increase the binding affinity, like in the case of two highly active non-basic compounds 3e and 5g (5-HT₆R, K_i = 65 nM and 38 nM, respectively).