Synthesis and pharmacological characterization at glutamate receptors of the four enantiopure isomers of tricholomic acid

Andrea Pinto; Paola Conti; Marco De Amici; Lucia Tamborini; Ulf Madsen; Birgitte Nielsen; Thomas Christesen; Hans Bräuner-Osborne; Carlo De Micheli

doi:10.1021/jm701394a

Synthesis and pharmacological characterization at glutamate receptors of the four enantiopure isomers of tricholomic acid

Andrea Pinto, Paola Conti, Marco De Amici, Lucia Tamborini, Ulf Madsen, Birgitte Nielsen, Thomas Christesen, Hans Bräuner-Osborne, Carlo De Micheli

27 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Journal of Medicinal Chemistry
Vol/bind	51
Udgave nummer	7
Sider (fra-til)	2311-2315
ISSN	0022-2623
DOI	https://doi.org/10.1021/jm701394a
Status	Udgivet - 2008

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10.1021/jm701394a

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@article{29c52ab011f511ddbee902004c4f4f50,

title = "Synthesis and pharmacological characterization at glutamate receptors of the four enantiopure isomers of tricholomic acid",

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.",

keywords = "Amino Acids, Animals, CHO Cells, Cell Line, Cloning, Molecular, Cricetinae, Cricetulus, Cyclization, Glycine, Humans, Isoxazoles, Molecular Structure, Rats, Receptors, Glutamate, Stereoisomerism, Structure-Activity Relationship",

author = "Andrea Pinto and Paola Conti and {De Amici}, Marco and Lucia Tamborini and Ulf Madsen and Birgitte Nielsen and Thomas Christesen and Hans Br{\"a}uner-Osborne and {De Micheli}, Carlo",

year = "2008",

doi = "10.1021/jm701394a",

language = "English",

volume = "51",

pages = "2311--2315",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "7",

}

TY - JOUR

T1 - Synthesis and pharmacological characterization at glutamate receptors of the four enantiopure isomers of tricholomic acid

AU - Pinto, Andrea

AU - Conti, Paola

AU - De Amici, Marco

AU - Tamborini, Lucia

AU - Madsen, Ulf

AU - Nielsen, Birgitte

AU - Christesen, Thomas

AU - Bräuner-Osborne, Hans

AU - De Micheli, Carlo

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

KW - Amino Acids

KW - Animals

KW - CHO Cells

KW - Cell Line

KW - Cloning, Molecular

KW - Cricetinae

KW - Cricetulus

KW - Cyclization

KW - Glycine

KW - Humans

KW - Isoxazoles

KW - Molecular Structure

KW - Rats

KW - Receptors, Glutamate

KW - Stereoisomerism

KW - Structure-Activity Relationship

U2 - 10.1021/jm701394a

DO - 10.1021/jm701394a

M3 - Journal article

C2 - 18338843

SN - 0022-2623

VL - 51

SP - 2311

EP - 2315

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 7

ER -

Synthesis and pharmacological characterization at glutamate receptors of the four enantiopure isomers of tricholomic acid

Abstract

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