(+/-)-7-(benzyloxy)-3-(3-[2-(4-methoxyphenyl)-5,5-dimethyl-1,3-dioxan-2-yl]propyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-1-ol | 1257108-43-2

• 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: (+/-)-7-(benzyloxy)-3-(3-[2-(4-methoxyphenyl)-5,5-dimethyl-1,3-dioxan-2-yl]propyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-1-ol
• 英文别名: 3-[3-[2-(4-Methoxyphenyl)-5,5-dimethyl-1,3-dioxan-2-yl]propyl]-8-phenylmethoxy-1,2,4,5-tetrahydro-3-benzazepin-5-ol
• CAS: 1257108-43-2
• 化学式: C₃₃H₄₁NO₅
• 分子量: 531.692
• InChiKey: YACCVVUNICRPSW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  60.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (+/-)-7-(benzyloxy)-3-(3-[2-(4-methoxyphenyl)-5,5-dimethyl-1,3-dioxan-2-yl]propyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-1-ol 在 盐酸 、 碳酸氢钠 作用下， 以 乙醚 、 水 为溶剂， 反应 16.0h， 以80%的产率得到(+/-)-4-(7-benzyloxy-1-hydroxy-2,3,4,5-tetrahydro-1H-3-benzazepin-3-yl)-1-(4-methoxyphenyl)butan-1-one
  参考文献：
  名称：

  Conformationally constrained NR2B selective NMDA receptor antagonists derived from ifenprodil: Synthesis and biological evaluation of tetrahydro-3-benzazepine-1,7-diols

  摘要：

  NR2B selective NMDA receptor antagonists with tetrahydro-3-benzazepine-1,7-diol scaffold have been designed by formal cleavage and reconstitution of the piperidine ring of the lead compound ifenprodil (1). The secondary amine 10 represents the central building block for the synthesis of more than 25 tetrahydro-3-benzazepin-1-ols. Generally 7-hydroxy derivatives display higher NR2B receptor affinities than the corresponding 7-benzyloxy compounds. A distance of four atoms (five bond lengths) between the basic amino group and the terminal aryl moiety led to highest NR2B affinity. 3-(4-Phenylbutyl)-2,3,4,5- tetrahydro-1H-3-benzazepine-1,7-diol (WMS-1410, 25) represents the most promising NR2B antagonist of this series showing a K-i-value of 14 nM. Compound 25 reveals excellent selectivity over more than 100 further relevant target proteins, antagonizes glutamate induced excitotoxicity (IC50 = 18.4 nM) and is metabolically more stable than ifenprodil. Up to a dose of 100 mg/kg 25 is well tolerated by mice and it shows dose dependent analgesic activity in the late neuropathic pain phase of the formalin assay. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.09.026
• 作为产物：
  描述：

  2-(4-methoxyphenyl)-2-(3-chloropropyl)-5,5-dimethyl-1,3-dioxane 、 7-benzyloxy-2,3,4,5-tetrahydro-1H-3-benzazepine-1-ol 在 四丁基碘化铵 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 50.0h， 以76%的产率得到(+/-)-7-(benzyloxy)-3-(3-[2-(4-methoxyphenyl)-5,5-dimethyl-1,3-dioxan-2-yl]propyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-1-ol
  参考文献：
  名称：

  Conformationally constrained NR2B selective NMDA receptor antagonists derived from ifenprodil: Synthesis and biological evaluation of tetrahydro-3-benzazepine-1,7-diols

  摘要：

  NR2B selective NMDA receptor antagonists with tetrahydro-3-benzazepine-1,7-diol scaffold have been designed by formal cleavage and reconstitution of the piperidine ring of the lead compound ifenprodil (1). The secondary amine 10 represents the central building block for the synthesis of more than 25 tetrahydro-3-benzazepin-1-ols. Generally 7-hydroxy derivatives display higher NR2B receptor affinities than the corresponding 7-benzyloxy compounds. A distance of four atoms (five bond lengths) between the basic amino group and the terminal aryl moiety led to highest NR2B affinity. 3-(4-Phenylbutyl)-2,3,4,5- tetrahydro-1H-3-benzazepine-1,7-diol (WMS-1410, 25) represents the most promising NR2B antagonist of this series showing a K-i-value of 14 nM. Compound 25 reveals excellent selectivity over more than 100 further relevant target proteins, antagonizes glutamate induced excitotoxicity (IC50 = 18.4 nM) and is metabolically more stable than ifenprodil. Up to a dose of 100 mg/kg 25 is well tolerated by mice and it shows dose dependent analgesic activity in the late neuropathic pain phase of the formalin assay. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.09.026