(E)-8-chloro-1-(4-methoxybenzyl)-2-oxo-5-phenylcarbamoylmethylene-2,3,4,5-tetrahydro-1H-benzo[b]azepine-3-carboxylic acid tert-butyl ester | 274926-28-2

• 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: (E)-8-chloro-1-(4-methoxybenzyl)-2-oxo-5-phenylcarbamoylmethylene-2,3,4,5-tetrahydro-1H-benzo[b]azepine-3-carboxylic acid tert-butyl ester
• CAS: 274926-28-2
• 化学式: C₃₁H₃₁ClN₂O₅
• 分子量: 547.051
• InChiKey: SBAUOUMTPOEGGA-HEHNFIMWSA-N

物化性质

• 熔点：
  188-191 °C
• 沸点：
  771.7±60.0 °C(Predicted)
• 密度：
  1.298±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.27
• 重原子数：
  39.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  84.94
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (E)-8-chloro-1-(4-methoxybenzyl)-2-oxo-5-phenylcarbamoylmethylene-2,3,4,5-tetrahydro-1H-benzo[b]azepine-3-carboxylic acid tert-butyl ester 在 硫酸 、 苯甲醚 、 三氟乙酸 作用下， 反应 1.0h， 以74%的产率得到(E)-8-chloro-2-oxo-5-phenylcarbamoylmethylene-1,2,3,4-tetrahydro-1H-benzo[b]azepine-3-carboxylic acid
  参考文献：
  名称：

  Benzoazepine derivative as potent antagonists of the glycine binding site associated to the NMDA receptor

  摘要：

  A series of benzoazepine derivatives, bearing suitable substituents at the C-3 position, was designed and evaluated by superimposition with the pharmacophore model of the glycine binding site. To fully explore the SAR of this class of compounds and to allow the preparation of new different compounds at the C-3 position, appropriate synthetic routes were set up. The benzoazepines were evaluated in terms of in vitro affinity using [3H]glycine binding assay and in vivo potency by inhibition of convulsions induced by N-methyl-D-aspartate (NMDA) in mice. This further analysis confirmed the preliminary results previously reported and that compound 27 is the most promising compound (Ki=32 nM, ED(50)=0.09 mg/kg, i.v.) in this series. Significant neuroprotective effect was observed after both pre- and post-ischaemia administration in the MCAo model. In particular, after post-ischaemia administration, it was found to be still effective when the administration was delayed up to 6 h after occlusion of the middle cerebral artery.

  DOI：

  10.1016/s0014-827x(03)00166-6
• 作为产物：
  描述：

  4-氯-1-碘-2-硝基苯 在 四(三苯基膦)钯 lithium hydroxide 、 sodium hexamethyldisilazane 、 铁粉 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium iodide 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 (E)-8-chloro-1-(4-methoxybenzyl)-2-oxo-5-phenylcarbamoylmethylene-2,3,4,5-tetrahydro-1H-benzo[b]azepine-3-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and pharmacological properties of novel glycine antagonists

  摘要：

  The NMDA receptor is an ionotropic receptor complex widely distributed in the central nervous system and its activation, particularly in hypoxic conditions such as stroke, traumatic head injury and hypoglycemia, results in a massive influx of calcium ions into the post-synaptic neurones, leading to cell death through the activation of several neurotoxic cascades. The NMDA receptor is a unique ionotropic receptor complex because its activation requires the simultaneous binding of glutamate and glycine and selective antagonists at the glycine binding site are endowed with a better side-effect profile than competitive NMDA antagonists. Then, considerable efforts have been devoted to find potent and selective ligands, resulting in the identification of several classes of glycine antagonists. The research at Glaxo Wellcome has been aimed at the identification of novel in vivo active glycine antagonists, and led to the synthesis and pharmacological characterization of a number of novel, potent and systemically active compounds belonging to different chemical classes.

  DOI：

  10.1016/s0031-6865(99)00059-x