7,8-dimethoxy-N-(2-(piperidin-yl)ethyl)-2,3,4,4a,5,9b-hexahydro-1H-indeno[1,2-b]pyridine-1-carbothioamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 7,8-dimethoxy-N-(2-(piperidin-yl)ethyl)-2,3,4,4a,5,9b-hexahydro-1H-indeno[1,2-b]pyridine-1-carbothioamide
• 英文别名: 7,8-dimethoxy-N-(2-piperidin-1-ylethyl)-2,3,4,4a,5,9b-hexahydroindeno[1,2-b]pyridine-1-carbothioamide
• 化学式: C₂₂H₃₃N₃O₂S
• 分子量: 403.589
• InChiKey: BGYBSOCHWMXEFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  69.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(5,6-dimethoxy-1H-inden-3-yl)piperidine 在 sodium tetrahydroborate 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 7,8-dimethoxy-N-(2-(piperidin-yl)ethyl)-2,3,4,4a,5,9b-hexahydro-1H-indeno[1,2-b]pyridine-1-carbothioamide
  参考文献：
  名称：

  Efficient synthesis of hexahydroindenopyridines and their potential as melatoninergic ligands

  摘要：

  Hexahydroindenopyridine (HHIP) is an interesting tricyclic piperidine nucleus that is structurally related to melatonin, a serotonin-derived neurohormone. Melatonin receptor ligands have applications in several cellular, neuroendocrine and neurophysiological disorders, including depression and/or insomnia. We report herein an efficient two-step method to prepare new HHIP via enamine C-alkylation-cyclization. The influence of substituents on the benzene ring and the nitrogen atom on melatoninergic receptors has been studied. Among the 25 synthesized HHIPs, some of them containing methylenedioxy (series 2) and 8-chloro-7-methoxy substituents (series 4) on the benzene ring revealed affinity for the MT1 and/or the MT2 receptors within the nanomolar range or low micromolar. Similar activities were also encountered for those presenting urea (4g), N-aryl (2e) and N-alkyl (2f) acetamide functions. Therefore, new synthesized compounds with a HHIP nucleus have emerged as new promising leads towards the discovery of melatoninergic ligands which could provide new therapeutic agents.

  DOI：

  10.1016/j.ejmech.2014.09.038

文献信息

• Efficient synthesis of hexahydroindenopyridines and their potential as melatoninergic ligands
  作者：Javier Párraga、Laura Moreno、Amelia Diaz、Noureddine El Aouad、Abraham Galán、María Jesús Sanz、Daniel-Henri Caignard、Bruno Figadère、Nuria Cabedo、Diego Cortes

  DOI：10.1016/j.ejmech.2014.09.038

  日期：2014.10

  Hexahydroindenopyridine (HHIP) is an interesting tricyclic piperidine nucleus that is structurally related to melatonin, a serotonin-derived neurohormone. Melatonin receptor ligands have applications in several cellular, neuroendocrine and neurophysiological disorders, including depression and/or insomnia. We report herein an efficient two-step method to prepare new HHIP via enamine C-alkylation-cyclization. The influence of substituents on the benzene ring and the nitrogen atom on melatoninergic receptors has been studied. Among the 25 synthesized HHIPs, some of them containing methylenedioxy (series 2) and 8-chloro-7-methoxy substituents (series 4) on the benzene ring revealed affinity for the MT1 and/or the MT2 receptors within the nanomolar range or low micromolar. Similar activities were also encountered for those presenting urea (4g), N-aryl (2e) and N-alkyl (2f) acetamide functions. Therefore, new synthesized compounds with a HHIP nucleus have emerged as new promising leads towards the discovery of melatoninergic ligands which could provide new therapeutic agents.