benzyl 1-hydroxy-7-methoxy-1,2,4,5-tetrahydro-3H-benzo[d]azepine-3-carboxylate | 1229622-23-4

• 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: benzyl 1-hydroxy-7-methoxy-1,2,4,5-tetrahydro-3H-benzo[d]azepine-3-carboxylate
• CAS: 1229622-23-4
• 化学式: C₁₉H₂₁NO₄
• 分子量: 327.38
• InChiKey: JDAJLHGGNPRHEJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.92
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  59.0
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  7-methoxy-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-ol 、 氯甲酸苄酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 benzyl 1-hydroxy-7-methoxy-1,2,4,5-tetrahydro-3H-benzo[d]azepine-3-carboxylate
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of 3-Benzazepin-1-ols as NR2B-Selective NMDA Receptor Antagonists

  摘要：

  AbstractCleavage and reconstitution of a bond in the piperidine ring of ifenprodil (1) leads to 7‐methoxy‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepin‐1‐ols, a novel class of NR2B‐selective NMDA receptor antagonists. The secondary amine 7‐methoxy‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepin‐1‐ol (12), which was synthesized in six steps starting from 2‐phenylethylamine 3, represents the central building block for the introduction of several N‐linked residues. A distance of four methylene units between the basic nitrogen atom and the phenyl residue in the side chain results in high NR2B affinity. The 4‐phenylbutyl derivative 13 (WMS‐1405, Ki=5.4 nM) and the conformationally restricted 4‐phenylcyclohexyl derivative 31 (Ki=10 nM) represent the most potent NR2B ligands of this series. Whereas 13 shows excellent selectivity, the 4‐phenylcyclohexyl derivative 31 also interacts with σ1 (Ki=33 nM) and σ2 receptors (Ki=82 nM). In the excitotoxicity assay the phenylbutyl derivative 13 inhibits the glutamate‐induced cytotoxicity with an IC50 value of 360 nM, indicating that 13 is an NMDA antagonist.

  DOI：

  10.1002/cmdc.201000005