1‐(benzenesulfonyl)‐4‐(4‐methylpiperazin‐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)‐4‐(4‐methylpiperazin‐1‐yl)‐1H‐indole
• 英文别名: 4-(4-Methyl-1-piperazinyl)-1-(phenylsulfonyl)-1H-indole；1-(benzenesulfonyl)-4-(4-methylpiperazin-1-yl)indole
• 化学式: C₁₉H₂₁N₃O₂S
• 分子量: 355.461
• InChiKey: BJISURBWZYFXNY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  53.9
• 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)‐4‐(4‐methylpiperazin‐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

• 2,4-Substituted indoles and methods of use
  申请人：Roche Palo Alto LLC

  公开号：US20040072844A1

  公开（公告）日：2004-04-15

  The present invention provides a compound of the formula: 1 a pharmaceutically acceptable salt or a prodrug thereof, where R 1 , R 2 , R 3 , R 4 , p and n are those defined herein. The present invention also provides compositions comprising, methods for using, and methods for preparing Compound of Formula I.

  本发明提供了一种化合物，其化学式为：1a药用盐或其前药，其中R1、R2、R3、R4、p和n如本文所定义。本发明还提供了包含该化合物的组合物、使用方法和制备化合物I的方法。
• 2,4-SUBSTITUTED INDOLES AND THEIR USE AS 5-HT6 MODULATORS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP1542973A1

  公开（公告）日：2005-06-22
• US7381739B2
  申请人：——

  公开号：US7381739B2

  公开（公告）日：2008-06-03
• US7524839B2
  申请人：——

  公开号：US7524839B2

  公开（公告）日：2009-04-28
• [EN] 2,4-SUBSTITUTED INDOLES AND THEIR USE AS 5-HT6 MODULATORS<br/>[FR] INDOLES 2,4-SUBSTITUES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2004026831A1

  公开（公告）日：2004-04-01

  The present invention provides a compound of the formula (I): a pharmaceutically acceptable salt or a prodrug thereof, where R1, R2, R3, R4, p and n are those defined here. The present invention also provides compositions comprising, methods for using, and methods for preparing Compound of Formula (I).