Synthesis and Biological Evaluation of Cyclopropyl Analogues of 2-Amino-5-phosphonopentanoic Acid

Article abstract of DOI:10.1021/jm00105a024

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 <3H>-L-glutamate as the radioligand provided affinity data, while modulation of <3H>MK-801 binding was used as a functional assay.The analogues were also evaluated in <3H>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).