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rdf:type |
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lifeskim:mentions |
umls-concept:C0001128,
umls-concept:C0079883,
umls-concept:C0205250,
umls-concept:C0205460,
umls-concept:C0220781,
umls-concept:C0220825,
umls-concept:C0243076,
umls-concept:C0268563,
umls-concept:C0332307,
umls-concept:C0679932,
umls-concept:C1707689,
umls-concept:C1883254
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pubmed:issue |
10
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|
pubmed:dateCreated |
2001-5-3
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pubmed:abstractText |
A series of 2-amino-(phosphonoalkyl)-1H-benzimidazole-2-alkanoic acids was synthesized and evaluated for NMDA receptor affinity using a [3H]CPP binding assay. Functional antagonism of the NMDA receptor complex was evaluated in vitro using a stimulated [3H]TCP binding assay and in vivo by employing an NMDA-induced seizure model. Several compounds of the AP-6 type demonstrated potent and selective NMDA antagonistic activity both in vitro and in vivo. In particular, [R(-)]-2-amino-3-(5-chloro-1-phosphonomethyl-1H-benzoimidazol-2-yl)-propionic acid (1) displayed an IC(50) value of 7.1 nM in the [3H]CPP binding assay and an ED(50) value of 0.13 mg/kg (ip) in the NMDA lethality model. Compound 1, when administered intravenously as a single bolus dose of 3 mg/kg following permanent occlusion of the middle cerebral artery in the rat, reduced the volume of infarcted brain tissue by 45%. These results support a promising therapeutic potential for compound 1 as a neuroprotective agent.
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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 |
10
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pubmed:volume |
44
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1516-29
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11334562-Animals,
pubmed-meshheading:11334562-Arterial Occlusive Diseases,
pubmed-meshheading:11334562-Benzimidazoles,
pubmed-meshheading:11334562-Binding, Competitive,
pubmed-meshheading:11334562-Brain,
pubmed-meshheading:11334562-Carotid Artery Diseases,
pubmed-meshheading:11334562-Drug Evaluation, Preclinical,
pubmed-meshheading:11334562-Excitatory Amino Acid Antagonists,
pubmed-meshheading:11334562-Infarction, Middle Cerebral Artery,
pubmed-meshheading:11334562-Male,
pubmed-meshheading:11334562-Mice,
pubmed-meshheading:11334562-Models, Molecular,
pubmed-meshheading:11334562-Neuroprotective Agents,
pubmed-meshheading:11334562-Propionic Acids,
pubmed-meshheading:11334562-Radioligand Assay,
pubmed-meshheading:11334562-Rats,
pubmed-meshheading:11334562-Rats, Inbred F344,
pubmed-meshheading:11334562-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:11334562-Stereoisomerism
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pubmed:year |
2001
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pubmed:articleTitle |
Design, synthesis, SAR, and biological evaluation of highly potent benzimidazole-spaced phosphono-alpha-amino acid competitive NMDA antagonists of the AP-6 type.
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pubmed:affiliation |
Chemical Sciences and Division of Neuroscience, Wyeth-Ayerst Research, CN-8000, Princeton, New Jersey 08543-8000, USA. Baudyr@war.wyeth.com
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pubmed:publicationType |
Journal Article,
In Vitro
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