[2-(1-Benzenesulfonyl-1H-indol-3-yl)-ethyl]-dimethyl-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: [2-(1-Benzenesulfonyl-1H-indol-3-yl)-ethyl]-dimethyl-amine
• 英文别名: 2-{[1-(phenylsulfonyl)-1H-indol-3-yl]ethyl}-N,N-dimethylamine；N,N-dimethyl 2-(1-benzenesulphonyl-1H-indol-3-yl)ethylamine；N,N-dimethyl-2-(1-(phenylsulfonyl)-1H-indol-3-yl)ethanamine；2-[1-(benzenesulfonyl)indol-3-yl]-N,N-dimethylethanamine
• 化学式: C₁₈H₂₀N₂O₂S
• 分子量: 328.435
• InChiKey: NKLZWGMWROXIDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  50.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N,N-二甲基色胺 、 苯磺酰氯 在 四丁基硫酸氢铵 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 生成 [2-(1-Benzenesulfonyl-1H-indol-3-yl)-ethyl]-dimethyl-amine
  参考文献：
  名称：

  N-Arylsulfonylindole Derivatives as Serotonin 5-HT₆ Receptor Ligands

  摘要：

  A series of N-1-arylsulfonyltryptamines were found to be potent ligands of the human serotonin 5-HT6 receptor with the 5-methoxy-1-benzenesulfonyl analogue (19) having the highest affinity. Additionally, it was discovered that a group such as 3-(3-methoxybenzyl)-1,2,4-oxadiazol-5-yI in the 2-position of the indole ring (43) can replace the arylsulfonyl substituent in the 1-position with no loss of affinity. This suggested that the binding conformation of the aminoethyl side chain at this receptor was toward the 4-position of the indole ring and was supported by the fact that the 4-(aminoethyl)indoles (45) also displayed high affinity, as did the conformationally rigid 1,3,4,5-tetrahydrobenz[c,d]indole (49). Molecular modeling showed that 19, 43, and 45 all had low-energy conformers that overlaid well onto 49. Both 19 and 49 had good selectivity over other serotonin receptors tested, with 49 also showing excellent selectivity over all dopamine receptors. In a functional adenylate cyclase stimulation assay, 19 and 49 had no agonist activity, whereas 45 behaved as a partial agonist. Finally, it was shown that 19 had good activity in the 5-HT2A centrally mediated mescaline-induced head twitch assay, which implies that it is brain-penetrant.

  DOI：

  10.1021/jm010943m

文献信息

• Use
  申请人：——

  公开号：US20030139424A1

  公开（公告）日：2003-07-24

  The invention provides a method of treatment or prophylaxis of obesity or for the reduction of food intake, comprising administering to a patient in need of such treatment a therapeutically effective amount of an indole or indoline derivative of Formula I, II or III: 1 wherein the substituents are as described in the specification.

  本发明提供了一种治疗或预防肥胖或减少食物摄入的方法，包括向需要此类治疗的患者给予公式I、II或III的吲哚或吲哚啉衍生物的治疗有效量：1其中取代基如说明书所述。
• <i>N</i>-Arylsulfonylindole Derivatives as Serotonin 5-HT₆ Receptor Ligands
  作者：Michael G. N. Russell、Robert J. Baker、Laura Barden、Margaret S. Beer、Linda Bristow、Howard B. Broughton、Michael Knowles、George McAllister、Smita Patel、José L. Castro

  DOI：10.1021/jm010943m

  日期：2001.11.1

  A series of N-1-arylsulfonyltryptamines were found to be potent ligands of the human serotonin 5-HT6 receptor with the 5-methoxy-1-benzenesulfonyl analogue (19) having the highest affinity. Additionally, it was discovered that a group such as 3-(3-methoxybenzyl)-1,2,4-oxadiazol-5-yI in the 2-position of the indole ring (43) can replace the arylsulfonyl substituent in the 1-position with no loss of affinity. This suggested that the binding conformation of the aminoethyl side chain at this receptor was toward the 4-position of the indole ring and was supported by the fact that the 4-(aminoethyl)indoles (45) also displayed high affinity, as did the conformationally rigid 1,3,4,5-tetrahydrobenz[c,d]indole (49). Molecular modeling showed that 19, 43, and 45 all had low-energy conformers that overlaid well onto 49. Both 19 and 49 had good selectivity over other serotonin receptors tested, with 49 also showing excellent selectivity over all dopamine receptors. In a functional adenylate cyclase stimulation assay, 19 and 49 had no agonist activity, whereas 45 behaved as a partial agonist. Finally, it was shown that 19 had good activity in the 5-HT2A centrally mediated mescaline-induced head twitch assay, which implies that it is brain-penetrant.
• USE OF INDOLE AND INDOLINE DERIVATIVES IN THE TREATMENT OF OBESITY OR FOR THE REDUCTION OF FOOD INTAKE
  申请人：BIOVITRUM AB

  公开号：EP1438045A1

  公开（公告）日：2004-07-21
• COMBINATION OF A CHOLINESTERASE INHIBITOR AND A COMPOUND WITH 5-HT6 RECEPTOR AFFINITY
  申请人：Laboratorios Del. Dr. Esteve, S.A.

  公开号：EP2040755A1

  公开（公告）日：2009-04-01
• US6187805B1
  申请人：——

  公开号：US6187805B1

  公开（公告）日：2001-02-13