3-<2-(3-quinuclidinylaminocarbonyl)ethenyl>-4,6-dichloroindole-2-carboxylic acid ethyl ester | 223457-19-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3-<2-(3-quinuclidinylaminocarbonyl)ethenyl>-4,6-dichloroindole-2-carboxylic acid ethyl ester
• CAS: 223457-19-0
• 化学式: C₂₁H₂₃Cl₂N₃O₃
• 分子量: 436.338
• InChiKey: SDBKYZXUAKNSDC-ONEGZZNKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.88
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  74.43
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-<2-(3-quinuclidinylaminocarbonyl)ethenyl>-4,6-dichloroindole-2-carboxylic acid ethyl ester 在 lithium hydroxide 作用下， 以 乙醇 为溶剂， 反应 1.5h， 生成 3-[(E)-3-(1-azabicyclo[2.2.2]octan-3-ylamino)-3-oxoprop-1-enyl]-4,6-dichloro-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  Cycloalkyl Indole-2-Carboxylates as Useful Tools for Mapping the "North-Eastern" Region of the Glycine Binding Site Associated with the NMDA Receptor

  摘要：

  A novel series of indole-2-carboxylate analogues of GV 150526 (1) in-which the terminal phenyl ring belonging to the side chain present in the position C-3 has been replaced with a bridged cycloalkyl group was synthesized and evaluated for its pharmacological profile. Modelling studies on this class of novel glycine antagonist allowed us to identify an asymmetric lipophilic pocket present in the "North-Eastern" region of the pharmacophoric model of the glycine binding site associated to the NMDA receptor. Among the derivatives prepared, 3-[2-(1-adamantylaminocarbonyl)ethenyl]-4,6-dichloroindole-2-carboxylic acid 6b and 3-[2(norbornylaminocarbonyl)ethenyl]-4,6-dichloroindole-2-carboxylic acid 61 were found to be antagonists acting at the strychnine-insensitive glycine binding site, showing nanomolar affinity for the glycine binding site (K-i = 63 and 19 nM, respectively), coupled with high glutamate receptor selectivity (IC50 > 10(-5) M at the NMDA, AMPA, KA binding sites) and high in vivo potency after :systemic administration by inhibition of convulsion induced by NMDA in mice.

  DOI：

  10.1002/(sici)1521-4184(19993)332:3<73::aid-ardp73>3.0.co;2-5
• 作为产物：
  描述：

  ethyl (E)-3-(3-(tert-butoxy)-3-oxoprop-1-en-1-yl)-4,6-dichloro-1H-indole-2-carboxylate 在 甲酸 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 6.5h， 生成 3-<2-(3-quinuclidinylaminocarbonyl)ethenyl>-4,6-dichloroindole-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  Cycloalkyl Indole-2-Carboxylates as Useful Tools for Mapping the "North-Eastern" Region of the Glycine Binding Site Associated with the NMDA Receptor

  摘要：

  A novel series of indole-2-carboxylate analogues of GV 150526 (1) in-which the terminal phenyl ring belonging to the side chain present in the position C-3 has been replaced with a bridged cycloalkyl group was synthesized and evaluated for its pharmacological profile. Modelling studies on this class of novel glycine antagonist allowed us to identify an asymmetric lipophilic pocket present in the "North-Eastern" region of the pharmacophoric model of the glycine binding site associated to the NMDA receptor. Among the derivatives prepared, 3-[2-(1-adamantylaminocarbonyl)ethenyl]-4,6-dichloroindole-2-carboxylic acid 6b and 3-[2(norbornylaminocarbonyl)ethenyl]-4,6-dichloroindole-2-carboxylic acid 61 were found to be antagonists acting at the strychnine-insensitive glycine binding site, showing nanomolar affinity for the glycine binding site (K-i = 63 and 19 nM, respectively), coupled with high glutamate receptor selectivity (IC50 > 10(-5) M at the NMDA, AMPA, KA binding sites) and high in vivo potency after :systemic administration by inhibition of convulsion induced by NMDA in mice.

  DOI：

  10.1002/(sici)1521-4184(19993)332:3<73::aid-ardp73>3.0.co;2-5