Synthesis and pharmacological characterization at glutamate receptors of the four enantiopure isomers of tricholomic acid.
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.
Pinto
Andrea
A
Istituto di Chimica Farmaceutica e Tossicologica P. Pratesi, Università degli Studi di Milano, Via Mangiagalli 25, Milan, Italy.
Conti
Paola
P
De Amici
Marco
M
Tamborini
Lucia
L
Madsen
Ulf
U
Nielsen
Birgitte
B
Christesen
Thomas
T
Bräuner-Osborne
Hans
H
De Micheli
Carlo
C
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D003500:Cyclization; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000596:Amino Acids; D007555:Isoxazoles; D017470:Receptors, Glutamate; C529451:tricholomic acid; D005998:Glycine