4-(dimethylamino)-5-methoxy-1-(4-methylbenzenesulfonyl)-1,3,4,5-tetrahydrobenz[cd]indole

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(dimethylamino)-5-methoxy-1-(4-methylbenzenesulfonyl)-1,3,4,5-tetrahydrobenz[cd]indole
• 英文别名: [5-Methoxy-1-(toluene-4-sulfonyl)-1,3,4,5-tetrahydro-benzo[cd]indol-4-yl]-dimethyl-amine；(4S,5S)-5-methoxy-N,N-dimethyl-1-(4-methylphenyl)sulfonyl-4,5-dihydro-3H-benzo[cd]indol-4-amine
• 化学式: C₂₁H₂₄N₂O₃S
• 分子量: 384.499
• InChiKey: IMWREOXJWBKCPU-FPOVZHCZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  59.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-溴丙酸甲酯 、 trans-4-Dimethylamino-1-(4-methyl benzenesulphonyl)-1,3,4,5-tetrahydrobenz[cd]indol-5-ol 在 sodium hydride 、 苄基三甲基氯化铵 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.17h， 以4%的产率得到4-(dimethylamino)-5-methoxy-1-(4-methylbenzenesulfonyl)-1,3,4,5-tetrahydrobenz[cd]indole
  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.