To investigate the preferred spatial relationship of the distal phosphonic acid to the a-amino acid group of the established competitive N-methyl-D-aspartic acid (NMDA) antagonists APH (1) and APV (2), we have prepared a series of ortho-, meta-, and para-substituted (phosphonoalky1) phenylglycine and-phenylalanine derivatives. With use of a [3H] CPP receptor binding assay, significant binding activity was observed to be critically dependent ...