Two non-racemic preparations of a piperidine-based NMDA antagonist with analgesic activity.
(2R,3S,1'R)-3-(1-Hydroxy-2-phosphonoethyl)-2-piperidinecarboxyl ic acid 1 has been synthesized by two different methods. The NMDA receptor binding affinities (Ki 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 ED50 values for the racemates of compounds 1 and 2, using the mouse hotplate and intrathecal injection, were 0.53 and 0.51 nmol, respectively.
Swahn
B M
BM
Preclinical Research, Astra Pain Control AB, Södertälje, Sweden.
Edvinsson
K M
KM
Kallin
E
E
Larsson
U
U
Berge
O G
OG
Molin
H
H
Pelcman
B
B
Claesson
A
A
D000700:Analgesics / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D010875:Pipecolic Acids / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D013237:Stereoisomerism
C108653:3-(1-hydroxy-2-phosphonoethyl)-2-piperidinecarboxylic acid; D000700:Analgesics; D018691:Excitatory Amino Acid Antagonists; D063065:Organophosphonates; D010875:Pipecolic Acids; D016194:Receptors, N-Methyl-D-Aspartate; C108652:3-(1-oxo-2-phosphonoethyl)-2-piperidinecarboxylic acid; C053672:selfotel; D016202:N-Methylaspartate