trans-4-Dimethylamino-1-(4-methyl benzenesulphonyl)-1,3,4,5-tetrahydrobenz[cd]indol-5-ol | 40380-88-9

• 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: trans-4-Dimethylamino-1-(4-methyl benzenesulphonyl)-1,3,4,5-tetrahydrobenz[cd]indol-5-ol
• 英文别名: (4S,5S)-4-(dimethylamino)-1-(4-methylphenyl)sulfonyl-4,5-dihydro-3H-benzo[cd]indol-5-ol
• CAS: 40380-88-9
• 化学式: C₂₀H₂₂N₂O₃S
• 分子量: 370.472
• InChiKey: OVDROBGSEQOKQB-ICSRJNTNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  70.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  聚合甲醛 、 4-amino-1-(4-methyl)benzensulfonyl-1,3,4,5-tetrahydrobenz[cd]indol-5-ole 在 10percent Pd/C 氢气 、 溶剂黄146 作用下， 以 乙醇 、 水 为溶剂， 反应 65.0h， 以86%的产率得到trans-4-Dimethylamino-1-(4-methyl benzenesulphonyl)-1,3,4,5-tetrahydrobenz[cd]indol-5-ol
  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

• COMBINATION OF A CHOLINESTERASE INHIBITOR AND A COMPOUND WITH 5-HT6 RECEPTOR AFFINITY
  申请人：Codony-Soler Xavier

  公开号：US20100120747A1

  公开（公告）日：2010-05-13

  The present invention relates to an active substance combination comprising at least one compound with 5-HT6 receptor affinity, and at least one cholinesterase inhibitor, a medicament comprising said active substance combination, and the use of said active substance combination for the manufacture of a medicament.
• US6187805B1
  申请人：——

  公开号：US6187805B1

  公开（公告）日：2001-02-13
• [EN] COMBINATION OF A CHOLINESTERASE INHIBITOR AND A COMPOUND WITH 5-HT6 RECEPTOR AFFINITY<br/>[FR] COMBINAISON D'UN INHIBITEUR DE LA CHOLINESTÉRASE ET D'UN COMPOSÉ AYANT UNE AFFINITÉ ENVERS LE RÉCEPTEUR 5-HT6
  申请人：ESTEVE LABOR DR

  公开号：WO2007147883A1

  公开（公告）日：2007-12-27

  [EN] The present invention relates to an active substance combination comprising at least one compound with 5-HT6 receptor affinity, and at least one cholinesterase inhibitor, a medicament comprising said active substance combination, and the use of said active substance combination for the manufacture of a medicament.
  [FR] La présente invention concerne une combinaison de substances actives comprenant au moins un composé ayant une affinité pour le récepteur 5-HT6 et au moins un inhibiteur de la cholinestérase. L'invention concerne également un médicament comprenant ladite combinaison de substances actives et l'utilisation de ladite combinaison lors de la fabrication d'un médicament.
• <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.