N,N-dimethyl 2-[1-(benzenesulphonyl)-1H-indol-4-yl]ethylamine | 297751-25-8

• 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: N,N-dimethyl 2-[1-(benzenesulphonyl)-1H-indol-4-yl]ethylamine
• 英文别名: [2-(1-Benzenesulfonyl-1H-indol-4-yl)-ethyl]-dimethyl-amine；2-[1-(benzenesulfonyl)indol-4-yl]-N,N-dimethylethanamine
• CAS: 297751-25-8
• 化学式: C₁₈H₂₀N₂O₂S
• 分子量: 328.435
• InChiKey: GIHFRARKMBMXPG-UHFFFAOYSA-N

物化性质

• 熔点：
  192-195 °C
• 沸点：
  506.5±52.0 °C(predicted)
• 密度：
  1.18±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

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

• 作为反应物：
  描述：

  N,N-dimethyl 2-[1-(benzenesulphonyl)-1H-indol-4-yl]ethylamine 在 manganese(IV) oxide 、 叔丁基锂 作用下， 以 四氢呋喃 、 二氯甲烷 、 正戊烷 为溶剂， 反应 4.5h， 生成 N,N-dimethyl 2-[1-(benzenesulphonyl)-2-benzoyl-1H-indol-4-yl]ethylamine
  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
• 作为产物：
  描述：

  聚合甲醛 、 2-[1-(benzenesulphonyl)-1H-indol-4-yl]ethylamine 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 以67%的产率得到N,N-dimethyl 2-[1-(benzenesulphonyl)-1H-indol-4-yl]ethylamine
  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。
• US6187805B1
  申请人：——

  公开号：US6187805B1

  公开（公告）日：2001-02-13