3-(4-phenylbutyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-1-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 3-(4-phenylbutyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-1-ol
• 英文别名: 3-(4-Phenylbutyl)-1,2,4,5-tetrahydro-3-benzazepin-5-ol；3-(4-phenylbutyl)-1,2,4,5-tetrahydro-3-benzazepin-5-ol
• 化学式: C₂₀H₂₅NO
• 分子量: 295.425
• InChiKey: CQLJUEWREOSTCY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-[N-(2-phenylethyl)-N-(trifluoromethylsulfonyl)amino]aceticacid 在 sodium tetrahydroborate 、 四磷十氧化物 、 四丁基碘化铵 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 氘代乙腈 、 乙腈 为溶剂， 反应 69.0h， 生成 3-(4-phenylbutyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-1-ol
  参考文献：
  名称：

  Role of the phenolic OH moiety of GluN2B-selective NMDA antagonists with 3-benzazepine scaffold

  摘要：

  In order to analyze the role of the phenolic OH moiety of ifenprodil (1) and 3-benzazepin-1,7-diol 2 for the affinity and selectivity at GluN2B subunit containing NMDA receptors, the 3-benzazepin-1-ols 3 were designed, synthesized and pharmacologically evaluated and furthermore, the molecular interactions of the phenylbutyl derivative 3c with the GluN2B receptor were investigated. In order to avoid decarbonylation during the intramolecular Friedel-Crafts acylation of 11, the N-atom has to be protected with a trifluoromethylsulfonyl group. The second key step of the synthesis was the removal of the N-triflyl group, which was realized by K2CO3 induced elimination of trifluoromethanelsulfinate (F3CSO2-). In receptor binding studies with the radioligand [3H] ifenprodil the 3-benzazepin-1-ol 3c revealed a GluN2B affinity of 73 nM indicating that the phenolic OH moiety of 1 and 2 is not essential but favorable for high GluN2B affinity. In docking studies 3-benzazepin-1-ol 3c shows the same binding pose as ifenprodil-keto 1A in the X-ray crystal structure. H-bond interactions and lipophilic interactions of 3c and 1A are very similar. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.12.067

文献信息

• Role of the phenolic OH moiety of GluN2B-selective NMDA antagonists with 3-benzazepine scaffold
  作者：Sougata Dey、Dirk Schepmann、Bernhard Wünsch

  DOI：10.1016/j.bmcl.2015.12.067

  日期：2016.2

  In order to analyze the role of the phenolic OH moiety of ifenprodil (1) and 3-benzazepin-1,7-diol 2 for the affinity and selectivity at GluN2B subunit containing NMDA receptors, the 3-benzazepin-1-ols 3 were designed, synthesized and pharmacologically evaluated and furthermore, the molecular interactions of the phenylbutyl derivative 3c with the GluN2B receptor were investigated. In order to avoid decarbonylation during the intramolecular Friedel-Crafts acylation of 11, the N-atom has to be protected with a trifluoromethylsulfonyl group. The second key step of the synthesis was the removal of the N-triflyl group, which was realized by K2CO3 induced elimination of trifluoromethanelsulfinate (F3CSO2-). In receptor binding studies with the radioligand [3H] ifenprodil the 3-benzazepin-1-ol 3c revealed a GluN2B affinity of 73 nM indicating that the phenolic OH moiety of 1 and 2 is not essential but favorable for high GluN2B affinity. In docking studies 3-benzazepin-1-ol 3c shows the same binding pose as ifenprodil-keto 1A in the X-ray crystal structure. H-bond interactions and lipophilic interactions of 3c and 1A are very similar. (C) 2015 Elsevier Ltd. All rights reserved.