(E)-8-chloro-2-oxo-5-phenylcarbamoylmethylene-1,2,3,4-tetrahydro-1H-benzo[b]azepine-3-carboxylic acid | 671207-67-3

• 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-2-oxo-5-phenylcarbamoylmethylene-1,2,3,4-tetrahydro-1H-benzo[b]azepine-3-carboxylic acid
• 英文别名: GV-224029 free acid；(5E)-5-(2-anilino-2-oxoethylidene)-8-chloro-2-oxo-3,4-dihydro-1H-1-benzazepine-3-carboxylic acid
• CAS: 671207-67-3
• 化学式: C₁₉H₁₅ClN₂O₄
• 分子量: 370.792
• InChiKey: NOUWUUUDUNANMH-PKNBQFBNSA-N

物化性质

• 沸点：
  701.6±60.0 °C(Predicted)
• 密度：
  1.489±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  95.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-8-chloro-2-oxo-5-phenylcarbamoylmethylene-1,2,3,4-tetrahydro-1H-benzo[b]azepine-3-carboxylic acid 在 吡啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 4.0h， 生成 (E)-2-(8-chloro-3-cyano-2-oxo-1,2,3,4-tetrahydro-1H-benzo[b]azepin-5-ylidene)-N-phenyl-acetamide
  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：

  5-氯-2-碘苯胺 在 四(三苯基膦)钯 吡啶 、 4-二甲氨基吡啶 、 lithium hydroxide 、 硫酸 、 sodium hexamethyldisilazane 、 苯甲醚 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 、 sodium iodide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 27.0h， 生成 (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

文献信息

• Benzoazepine derivative as potent antagonists of the glycine binding site associated to the NMDA receptor
  作者：Romano Di Fabio、Fabrizio Micheli、Davide Baraldi、Barbara Bertani、Nadia Conti、Giovanna Dal Forno、Aldo Feriani、Daniele Donati、Carla Marchioro、Tommaso Messeri、Andrea Missio、Alessandra Pasquarello、Giorgio Pentassuglia、Domenica A. Pizzi、Stefano Provera、Anna M. Quaglia、Fabio M. Sabbatini

  DOI：10.1016/s0014-827x(03)00166-6

  日期：2003.9

  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.