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Synthesis and NMD A Antagonistic Properties of the Enantiomers of 4‐(3‐phosphonopropyl)piperazine‐2‐carboxylic acid (CPP) and of the unsaturated analogue ( E )‐4‐(3‐phosphonoprop‐2‐enyl)piperazine‐2‐carboxylic acid (CPP‐ene)
Author(s) -
Aebischer Bernard,
Frey Peter,
Haerter HansPeter,
Herrling Paul L.,
Mueller Werner,
Olverman Henry J.,
Watkins Jeffrey C.
Publication year - 1989
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19890720522
Subject(s) - chemistry , piperazine , enantiomer , nmda receptor , carboxylic acid , stereochemistry , antagonist , receptor , organic chemistry , biochemistry
The ( R )‐ and ( s )‐enantiomers of 4‐(3‐phosphonopropyl)piperazine‐2‐carboxylic acid ( D ‐ and L ‐CPP, resp.; 15 and 16 , resp.), and of its unsaturated analogue ( E )‐4‐(3‐phosphonoprop‐2‐enyl)piperazine‐2‐carboxylic acid ( D ‐ and L ‐CPP‐ene, resp.; 13 and 14 , resp.) were prepared. The absolute configuration of the enantiomers was determined by a chemical correlation of the menthyl ester 7 with D ‐asparagine. The affinity of these derivatives for the NMDA receptor was determined by displacement of [ 3 H]CPP in rat cerebral cortical membranes. In two functional tests (the frog hemisected spinal cord preparation and the sodium efflux test from rat brain slices), D ‐CPP‐ene appears to be the most potent, enantiomerically pure, competitive NMDA antagonist known to date.