ethyl 3-[(E)-3-[4-[2-(carbamoylamino)ethyl]anilino]-3-oxoprop-1-enyl]-4,6-dichloro-1H-indole-2-carboxylate | 182314-74-5

• 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: ethyl 3-[(E)-3-[4-[2-(carbamoylamino)ethyl]anilino]-3-oxoprop-1-enyl]-4,6-dichloro-1H-indole-2-carboxylate
• CAS: 182314-74-5
• 化学式: C₂₃H₂₂Cl₂N₄O₄
• 分子量: 489.358
• InChiKey: KRFZCJQNJXIYMT-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-[(E)-3-[4-[2-(carbamoylamino)ethyl]anilino]-3-oxoprop-1-enyl]-4,6-dichloro-1H-indole-2-carboxylate 在 lithium hydroxide 作用下， 以 乙醇 为溶剂， 生成 (E)-4,6-dichloro-3-[2-[(4-ethylureidophenyl)carbamoyl]vinyl]-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  Substituted Analogues of GV150526 as Potent Glycine Binding Site Antagonists in Animal Models of Cerebral Ischemia

  摘要：

  A series of analogues of the indole-2-carboxylate GV150526, currently in clinical trials as a potential neuroprotective agent for the control of the cerebral damage after stroke onset, was designed based on previous studies dealing with the electronic features of the north-east region of the glycine binding site associated with the NMDA receptor. In particular, the substitution of the para position of the terminal phenyl ring of GV150526 with suitable hydrophilic groups resulted in the identification of a new class of glycine antagonists. These compounds exhibited nanomolar in vitro affinity to the glycine binding site, high receptor selectivity, and outstanding in vivo potency. In particular, 3-[(E)-2-[(4-ureidomethylphenyl)aminocarbonyl]ethenyl]-4,6-dichloroindole-2-carboxylic acid was found to be highly effective in the middle cerebral artery occlusion (MCAo) model in the rat, an animal model of focal ischemia, when given both prior to and after the occlusion of the middle cerebral artery. Notably, a significant; neuroprotective effect was seen in this model postischamia, when the administration of this compound was delayed up to 6 h from the occlusion of the middle cerebral artery, further confirming the wide therapeutic window seen for GV150526A.

  DOI：

  10.1021/jm980576n
• 作为产物：
  描述：

  2-(4-氨基苯)乙胺 在 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 3.0h， 生成 ethyl 3-[(E)-3-[4-[2-(carbamoylamino)ethyl]anilino]-3-oxoprop-1-enyl]-4,6-dichloro-1H-indole-2-carboxylate
  参考文献：
  名称：

  Substituted Analogues of GV150526 as Potent Glycine Binding Site Antagonists in Animal Models of Cerebral Ischemia

  摘要：

  A series of analogues of the indole-2-carboxylate GV150526, currently in clinical trials as a potential neuroprotective agent for the control of the cerebral damage after stroke onset, was designed based on previous studies dealing with the electronic features of the north-east region of the glycine binding site associated with the NMDA receptor. In particular, the substitution of the para position of the terminal phenyl ring of GV150526 with suitable hydrophilic groups resulted in the identification of a new class of glycine antagonists. These compounds exhibited nanomolar in vitro affinity to the glycine binding site, high receptor selectivity, and outstanding in vivo potency. In particular, 3-[(E)-2-[(4-ureidomethylphenyl)aminocarbonyl]ethenyl]-4,6-dichloroindole-2-carboxylic acid was found to be highly effective in the middle cerebral artery occlusion (MCAo) model in the rat, an animal model of focal ischemia, when given both prior to and after the occlusion of the middle cerebral artery. Notably, a significant; neuroprotective effect was seen in this model postischamia, when the administration of this compound was delayed up to 6 h from the occlusion of the middle cerebral artery, further confirming the wide therapeutic window seen for GV150526A.

  DOI：

  10.1021/jm980576n

文献信息

• Substituted Analogues of GV150526 as Potent Glycine Binding Site Antagonists in Animal Models of Cerebral Ischemia
  作者：Romano Di Fabio、Nadia Conti、Elisabetta De Magistris、Aldo Feriani、Stefano Provera、Fabio Maria Sabbatini、Angelo Reggiani、Luca Rovatti、Robert J. Barnaby

  DOI：10.1021/jm980576n

  日期：1999.9.1

  A series of analogues of the indole-2-carboxylate GV150526, currently in clinical trials as a potential neuroprotective agent for the control of the cerebral damage after stroke onset, was designed based on previous studies dealing with the electronic features of the north-east region of the glycine binding site associated with the NMDA receptor. In particular, the substitution of the para position of the terminal phenyl ring of GV150526 with suitable hydrophilic groups resulted in the identification of a new class of glycine antagonists. These compounds exhibited nanomolar in vitro affinity to the glycine binding site, high receptor selectivity, and outstanding in vivo potency. In particular, 3-[(E)-2-[(4-ureidomethylphenyl)aminocarbonyl]ethenyl]-4,6-dichloroindole-2-carboxylic acid was found to be highly effective in the middle cerebral artery occlusion (MCAo) model in the rat, an animal model of focal ischemia, when given both prior to and after the occlusion of the middle cerebral artery. Notably, a significant; neuroprotective effect was seen in this model postischamia, when the administration of this compound was delayed up to 6 h from the occlusion of the middle cerebral artery, further confirming the wide therapeutic window seen for GV150526A.