A series of cyclopropyl analogues related to 2-amino-5-phosphonopentanoic acid (AP5) were synthesized and their biological activity was assessed as competitive antagonists for the N-methyl-D-aspartate (NMDA) receptor. In vitro receptor binding using [H-3]-L-glutamate as the radioligand provided affinity data, while modulation of [H-3]MK-801 binding was used as a functional assay. The analogues were also evaluated in [H-3]kainate binding to assess selectivity over non-NMDA glutamate receptors. Of the compounds tested, 4,5-methano-AP5 analogue 26 was the most potent selective NMDA antagonist; however, potency was lower than that for [[(+/-)-2-carboxypiperidin-4-yl]methyl]phosphonic acid (CGS 19755, 5).
SYNTHESIS AND BIOLOGICAL EVALUATION OF CYCLOPROPYL ANALOGS OF 2-AMINO-5-PHOSPHONOPENTANOIC ACID
PELLICCIARI, Roberto;NATALINI, Benedetto;
1991
Abstract
A series of cyclopropyl analogues related to 2-amino-5-phosphonopentanoic acid (AP5) were synthesized and their biological activity was assessed as competitive antagonists for the N-methyl-D-aspartate (NMDA) receptor. In vitro receptor binding using [H-3]-L-glutamate as the radioligand provided affinity data, while modulation of [H-3]MK-801 binding was used as a functional assay. The analogues were also evaluated in [H-3]kainate binding to assess selectivity over non-NMDA glutamate receptors. Of the compounds tested, 4,5-methano-AP5 analogue 26 was the most potent selective NMDA antagonist; however, potency was lower than that for [[(+/-)-2-carboxypiperidin-4-yl]methyl]phosphonic acid (CGS 19755, 5).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
