Two non-racemic preparations of a piperidine-based NMDA antagonist with analgesic activity

(2 R,3 S,1′ R)-3-(1-Hydroxy-2-phosphonoethyl)-2-piperidinecarboxylic acid 1 has been synthesized by two different methods. The NMDA receptor binding affinities ( K i values) are 74 nM for compound 1, and 64 nM for the corresponding ketone 2. The analgesic effects were evaluated using the mouse hot-plate test and the mouse formalin model. The ED 50 values for the racemates of compounds 1 and 2, using the mouse hotplate and intrathecal injection, were 0.53 and 0.51 nmol, respectively. The non-racemic preparation of 1 is described. The analgesic effects of (±)-1 and the earlier described (±)-2 were evaluated using the mouse hot-plate test and the mouse formalin model.