The erythro- and threo-amino-(3'-hydroxy-4',5'-dihydro-isoxazol-5'-yl)-acetic acids, stereoisomers of tricholomic acid, were synthesized along with the corresponding higher homologues erythro- and threo-amino-(3'-carboxy-4',5'-dihydro-isoxazol-5'-yl)-acetic acids. The target compounds were prepared via the 1,3-dipolar cycloaddition of a suitable nitrile oxide to (+/-)-2-tert-butoxycarbonyl-amino-3-buten-1-ol. Such a strategy allowed the synthesis of the two stereoisomeric amino acids in comparable amounts. The pharmacological activity of these compounds was investigated at ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs) by means of receptor binding assays to rat cortical membranes, electrophysiological tests and second messenger assays at cloned receptors expressed in CHO cells. Their pharmacological profiles were compared to those Of L-glutamate and of the previously described selective NMDA receptor antagonists 5-(2-amino-2-carboxyethyl)-4,5-dihydroisoxazole-3-carboxylic acids in order to highlight the effect of increasing/reducing the distance between the amino acid moiety and the distal acid group, which represent the two pharmacophoric entities.
Synthesis and pharmacological characterization at glutamate receptors of erythro- and threo-tricholomic acid and homologues thereof / P. Conti, M. De Amici, G. Roda, A. Pinto, L. Tamborini, U. Madsen, B. Nielsen, H. Brauner-Osborne, C. De Micheli. - In: TETRAHEDRON. - ISSN 0040-4020. - 63:10(2007), pp. 2249-2256.
|Titolo:||Synthesis and pharmacological characterization at glutamate receptors of erythro- and threo-tricholomic acid and homologues thereof|
CONTI, PAOLA (Primo)
DE AMICI, MARCO (Secondo)
DE MICHELI, CARLO (Corresponding)
|Parole Chiave:||tricholomic acid; ionotropic glutamate receptors; metabotropic glutamate receptors; 1,3-dipolar cycloaddition|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
|Data di pubblicazione:||2007|
|Data ahead of print / Data di stampa:||27-dic-2006|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.tet.2006.12.066|
|Appare nelle tipologie:||01 - Articolo su periodico|