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• W1990305593 abstract "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 postischaemia, 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." @default.
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• W1990305593 date "1999-08-21" @default.
• W1990305593 modified "2023-10-03" @default.
• W1990305593 title "Substituted Analogues of GV150526 as Potent Glycine Binding Site Antagonists in Animal Models of Cerebral Ischemia" @default.
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• W1990305593 doi "https://doi.org/10.1021/jm980576n" @default.
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