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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
17
|
| pubmed:dateCreated |
1992-9-22
|
| pubmed:abstractText |
The tetrazole-substituted amino acid (+/-)-(2SR,4RS)-4-(1H-tetrazol-5-ylmethyl)pip eri dine-2-carboxylic acid (LY233053, (+/-)-1) was resolved into its constituent enantiomers by treatment of a key intermediate in the synthesis of the racemic amino acid, ethyl (+/-)-cis-4-(cyanomethyl)-N-allylpiperidine-2-carboxylate, with either 2S,3S- or 2R,3R-di-p-toluoyltartaric acid. These resolved amines were then converted as for the racemate to the amino acids (-)-1 and (+)-1. The activity of this potent and selective NMDA antagonist was found to reside with the (-)-isomer of 1 (LY235723). X-ray crystallographic analysis of the 2S,3S-di-p-toluoyltartaric acid salt of ethyl cis-4-(cyanomethyl)-N-allylpiperidine-2-carboxylate showed that the resolved amine, and thus (-)-1, possessed the 2R,4S absolute stereochemistry. Affinity for the NMDA receptor was determined using the specific radioligand [3H]-(2SR,4RS)-4-(phosphonomethyl)piperidine-2-carboxylic acid ([3H]CGS 19755; IC50 = 67 +/- 6 nM), and selective NMDA antagonist activity was determined using a cortical slice preparation (IC50 versus 40 microM NMDA = 1.9 +/- 0.24 microM). This compound also demonstrated potent NMDA antagonist activity in vivo following systemic administration through its ability to block NMDA-induced convulsions in neonatal rats, NMDA-induced lethality in mice, and NMDA-induced striatal neuronal degeneration in rats.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/LY 233053,
http://linkedlifedata.com/resource/pubmed/chemical/N-Methylaspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Pipecolic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrazoles,
http://linkedlifedata.com/resource/pubmed/chemical/selfotel
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
0022-2623
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
21
|
| pubmed:volume |
35
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3111-5
|
| pubmed:dateRevised |
2004-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:1387167-Animals,
pubmed-meshheading:1387167-Animals, Newborn,
pubmed-meshheading:1387167-Corpus Striatum,
pubmed-meshheading:1387167-Mice,
pubmed-meshheading:1387167-Molecular Structure,
pubmed-meshheading:1387167-N-Methylaspartate,
pubmed-meshheading:1387167-Nerve Degeneration,
pubmed-meshheading:1387167-Pipecolic Acids,
pubmed-meshheading:1387167-Rats,
pubmed-meshheading:1387167-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:1387167-Seizures,
pubmed-meshheading:1387167-Stereoisomerism,
pubmed-meshheading:1387167-Structure-Activity Relationship,
pubmed-meshheading:1387167-Tetrazoles,
pubmed-meshheading:1387167-X-Ray Diffraction
|
| pubmed:year |
1992
|
| pubmed:articleTitle |
NMDA antagonist activity of (+/-)-(2SR,4RS)-4-(1H-tetrazol-5-ylmethyl)piperidine-2-carboxylic acid resides with the (-)-2R,4S-isomer.
|
| pubmed:affiliation |
Lilly Research Laboratories, Division of Eli Lilly and Company, Indianapolis, Indiana 46285.
|
| pubmed:publicationType |
Journal Article
|