N,N-dimethyl-2-[1-(benzenesulphonyl)-5-methoxy-1H-indol-3-yl]ethylamine | 263384-65-2

• 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: N,N-dimethyl-2-[1-(benzenesulphonyl)-5-methoxy-1H-indol-3-yl]ethylamine
• 英文别名: MS-245；2-[1-(benzenesulfonyl)-5-methoxyindol-3-yl]-N,N-dimethylethanamine
• CAS: 263384-65-2
• 化学式: C₁₉H₂₂N₂O₃S
• 分子量: 358.461
• InChiKey: AIJIQCBYMBZLJD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  59.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N,N-dimethyl-2-[1-(benzenesulphonyl)-5-methoxy-1H-indol-3-yl]ethylamine 在 甲醇 、 正丁基锂 、 氯化铵 、 magnesium 作用下， 以 乙二醇二甲醚 为溶剂， 反应 2.17h， 生成 [2-(5-Methoxy-2-propyl-1H-indol-3-yl)-ethyl]-dimethyl-amine
  参考文献：
  名称：

  2-取代的色胺：对5-HT（6）血清素受体具有选择性的试剂。

  摘要：

  几种2-烷基-5-甲氧基色胺类似物被设计和制备为潜在的5-HT（6）5-羟色胺激动剂。发现5-HT（6）受体在吲哚2位上容纳小的烷基取代基，并且所产生的化合物可以结合具有与血清素相当的亲和力。特别是，相对于5-HT（K（i），2-乙基-5-甲氧基-N，N-二甲基色胺（8）以高亲和力结合人5-HT（6）受体（K（i）= 16 nM） ）= 75 nM），并且在激活腺苷酸环化酶方面至少是与血清素（K（act）= 5.0 nM）一样有效的激动剂（8：K（act）= 3.6 nM）。化合物8对其他几个5-HT受体群体表现出适度的亲和力，尤其是h5-HT（1A）（K（i）= 170 nM），h5-HT（1D）（K（i）= 290 nM）和h5 -HT（7）（K（i）= 300 nM）受体，但否则具有选择性。化合物8代表迄今为止报道的第一个也是最具选择性的5-HT（6）激动剂。用苯基取代2-乙基取代基

  DOI：

  10.1021/jm990550b
• 作为产物：
  描述：

  5-甲氧基-N,N-二甲基色胺 、 苯磺酰氯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以61%的产率得到N,N-dimethyl-2-[1-(benzenesulphonyl)-5-methoxy-1H-indol-3-yl]ethylamine
  参考文献：
  名称：

  2-取代的色胺：对5-HT（6）血清素受体具有选择性的试剂。

  摘要：

  几种2-烷基-5-甲氧基色胺类似物被设计和制备为潜在的5-HT（6）5-羟色胺激动剂。发现5-HT（6）受体在吲哚2位上容纳小的烷基取代基，并且所产生的化合物可以结合具有与血清素相当的亲和力。特别是，相对于5-HT（K（i），2-乙基-5-甲氧基-N，N-二甲基色胺（8）以高亲和力结合人5-HT（6）受体（K（i）= 16 nM） ）= 75 nM），并且在激活腺苷酸环化酶方面至少是与血清素（K（act）= 5.0 nM）一样有效的激动剂（8：K（act）= 3.6 nM）。化合物8对其他几个5-HT受体群体表现出适度的亲和力，尤其是h5-HT（1A）（K（i）= 170 nM），h5-HT（1D）（K（i）= 290 nM）和h5 -HT（7）（K（i）= 300 nM）受体，但否则具有选择性。化合物8代表迄今为止报道的第一个也是最具选择性的5-HT（6）激动剂。用苯基取代2-乙基取代基

  DOI：

  10.1021/jm990550b

文献信息

• [EN] PYRROLOQUINOLINE DERIVATIVES AS 5-HT6 ANTAGONISTS, PREPARATION METHOD AND USE THEREOF<br/>[FR] DÉRIVÉS DE PYRROLOQUINOLINE UTILISÉS COMME ANTAGONISTES DE 5-HT6, LEUR PROCÉDÉ DE PRÉPARATION ET LEUR UTILISATION
  申请人：UNIV JAGIELLOŃSKI

  公开号：WO2015012704A1

  公开（公告）日：2015-01-29

  This invention concerns pyrroloquinoline derivatives as antagonists of 5-HT6 receptors, to methods for the preparation of these compounds and to novel intermediates useful for their synthesis. The invention also relates to the uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in schizophrenia, anxiety, depression, maniac depression, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, panic attacks, attention deficit hyperactivity disorder, attention deficit disorder, Parkinson's disease, Huntington's disease, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, obesity and type-2 diabetes, functional bowel disorder, Irritable Bowel Syndrome. The compounds have the general formula (XIV), wherein the symbols have the meanings given in the description.

  这项发明涉及吡咯喹啉衍生物作为5-HT6受体拮抗剂，以及制备这些化合物的方法和用于它们合成的新型中间体。该发明还涉及这些化合物和组合物的用途，特别是它们在向患者施用以达到治疗精神分裂症、焦虑、抑郁症、躁狂抑郁症、癫痫、强迫性障碍、情绪障碍、偏头痛、阿尔茨海默病、年龄相关认知衰退、轻度认知功能障碍、睡眠障碍、进食障碍、厌食症、贪食症、惊恐发作、注意力缺陷多动障碍、注意力缺陷障碍、帕金森病、亨廷顿病、戒除可卡因、乙醇、尼古丁或苯二氮卓类药物滥用、疼痛、肥胖和2型糖尿病、功能性肠道紊乱、肠易激综合征等方面的用途。这些化合物具有一般式（XIV），其中符号的含义如描述中所述。
• 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.
• N1-(Benzenesulfonyl)tryptamines as novel 5-HT6 antagonists
  作者：Yuching Tsai、Malgorzata Dukat、Abdelmalik Slassi、Neil MacLean、Lidia Demchyshyn、Jason E. Savage、Bryan L. Roth、Sandy Hufesein、Mase Lee、Richard A. Glennon

  DOI：10.1016/s0960-894x(00)00453-4

  日期：2000.10

  N-1-Benzenesulfonyl-5-methoxy-N,N-dimethyltryptamine (BS/5-OMe DMT; 5) was shown to bind at human 5-HT6 serotonin receptors with high affinity (K-i = 2.3 nM) relative to serotonin (K-i = 78 nM). Structural variation failed to result in significantly enhanced affinity. BS/5-OMe DMT acts as an antagonist of 5-HT-stimulated adenylate cyclase (pA(2) = 8.88 nM) and may represent the first member of a novel class of 5-HT6 antagonists. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Lee; Rangisetty; Dukat, Medicinal Chemistry Research, 2000, vol. 10, # 4, p. 230 - 242
  作者：Lee、Rangisetty、Dukat、Slassi、Maclean、Lee、Glennon

  DOI：——

  日期：——