Abstract
The two enantiomeric pairs of erythro- and threo-amino-(3'-hydroxy-4',5'-dihydro-isoxazol-5'-yl)-acetic acids were synthesized via the 1,3-dipolar cycloaddition of bromonitrile oxide to ( R)- or ( S)-3-( tert-butoxycarbonyl)-2,2-dimethyl-4-vinyloxazolidine. The pharmacological profiles of the studied amino acids reflect the relationship between the activity/selectivity and the stereochemistry of the two stereogenic centers: while the (2 S,5' S) stereoisomer is an agonist at the AMPA and KA receptors, its (2 R,5' R) enantiomer interacts selectively with the NMDA receptors; the (2 S,5' R) stereoisomer is the only one capable to activate the mGluRs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acids / chemical synthesis*
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Amino Acids / chemistry
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Amino Acids / pharmacology*
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Animals
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CHO Cells
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Cell Line
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Cloning, Molecular
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Cricetinae
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Cricetulus
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Cyclization
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Glycine / analogs & derivatives*
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Glycine / chemical synthesis
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Glycine / chemistry
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Glycine / pharmacology
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Humans
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Isoxazoles / chemical synthesis*
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Isoxazoles / chemistry
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Isoxazoles / pharmacology*
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Molecular Structure
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Rats
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Receptors, Glutamate / drug effects*
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Receptors, Glutamate / metabolism
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Amino Acids
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Isoxazoles
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Receptors, Glutamate
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tricholomic acid
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Glycine