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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
1992-6-23
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pubmed:abstractText |
A series of substituted 3-(2-carboxyindol-3-yl)propionic acids was synthesized and tested as antagonists for the strychnine-insensitive glycine binding site of the NMDA receptor. Chlorine, and other small electron-withdrawing substituents in the 4- and 6-positions of the indole ring, greatly enhanced binding and selectivity for the glycine site over the glutamate site of the NMDA receptor; one of the most potent compounds is 3-(4,6-dichloro-2-carboxyindol-3-yl)propionic acid (IC50 = 170 nM; greater than 2100-fold selective for glycine). The importance of a heteroatom NH and the enhancing effect of the propionic acid side chain were demonstrated and are consistent with previous results which suggest the presence of a pocket on the receptor which can accept an acidic side chain. Substitution of a sulfur at C3 led to the most potent compound 3-[(carboxymethyl)thio]-2-carboxy-4,6-dichloroindole (IC50 = 100 nM).
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-2623
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
35
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1791-9
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pubmed:dateRevised |
2003-11-14
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pubmed:meshHeading |
pubmed-meshheading:1534125-Animals,
pubmed-meshheading:1534125-Binding Sites,
pubmed-meshheading:1534125-Cerebral Cortex,
pubmed-meshheading:1534125-Glycine,
pubmed-meshheading:1534125-Hippocampus,
pubmed-meshheading:1534125-Indoles,
pubmed-meshheading:1534125-Mice,
pubmed-meshheading:1534125-Mice, Inbred DBA,
pubmed-meshheading:1534125-Propionic Acids,
pubmed-meshheading:1534125-Rats,
pubmed-meshheading:1534125-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:1534125-Seizures,
pubmed-meshheading:1534125-Structure-Activity Relationship,
pubmed-meshheading:1534125-Strychnine,
pubmed-meshheading:1534125-Substrate Specificity
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pubmed:year |
1992
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pubmed:articleTitle |
3-(2-Carboxyindol-3-yl)propionic acid-based antagonists of the N-methyl-D-aspartic acid receptor associated glycine binding site.
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pubmed:affiliation |
Marion Merrell Dow Research Institute, Cincinnati, Ohio 45215.
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pubmed:publicationType |
Journal Article
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