The synthesis and pharmacology of two potential glutamic acid receptor ligands are described. Preparation of the bicyclic 3-hydroxy-Δ2-isoxazoline-cyclopentane derivatives (±)-7 and (±)-8 was accomplished via 1,3-dipolar cycloaddition of bromonitrile oxide to suitably protected 1-amino-cyclopent-3-enecarboxylic acids. Their structure was established using a combination of 1H NMR spectroscopy and molecular mechanics calculations carried out on the intermediate cycloadducts (±)-11 and (±)-12. Amino acid derivatives (±)-7 and (±)-8 were assayed at ionotropic and metabotropic glutamic acid receptor subtypes and their activity compared with that of trans-ACPD and cis-ACPD. The results show that the replacement of the ω-carboxylic group of the model compounds with the 3-hydroxy-Δ2-isoxazoline moiety abolishes or reduces drastically the activity at the metabotropic glutamate receptors. Conversely, on passing from cis-ACPD to derivative (±)-8, the agonist activity at NMDA receptors is almost unaffected.
Synthesis and pharmacology of 3-hydroxy-Δ2-isoxazoline-cyclopentane analogues of glutamic acid / P. Conti, M. De Amici, H. Bräuner-Osborne, U. Madsen, L. Toma, C. De Micheli. - In: IL FARMACO. - ISSN 0014-827X. - 57:11(2003), pp. 889-895.
|Titolo:||Synthesis and pharmacology of 3-hydroxy-Δ2-isoxazoline-cyclopentane analogues of glutamic acid|
CONTI, PAOLA (Primo)
DE AMICI, MARCO (Secondo)
DE MICHELI, CARLO (Ultimo)
|Parole Chiave:||1,3-Dipolar cycloaddition; Ionotropic glutamic acid receptors; Isoxazoline-cyclopentane amino acids; Metabotropic glutamic acid receptors; NMDA agonist|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
|Data di pubblicazione:||2003|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/S0014-827X(02)01307-1|
|Appare nelle tipologie:||01 - Articolo su periodico|