Orally efficacious NR2B-selective NMDA receptor antagonists.
A novel series of benzamidines was synthesized and shown to exhibit NR2B-subtype selective NMDA antagonist activity. Compound 31 is orally active in a carrageenan-induced rat hyperalgesia model of pain and shows no motor coordination side effects.
Claiborne
Christopher F
CF
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
McCauley
John A
JA
Libby
Brian E
BE
Curtis
Neil R
NR
Diggle
Helen J
HJ
Kulagowski
Janusz J
JJ
Michelson
Stuart R
SR
Anderson
Kenneth D
KD
Claremon
David A
DA
Freidinger
Roger M
RM
Bednar
Rodney A
RA
Mosser
Scott D
SD
Gaul
Stanley L
SL
Connolly
Thomas M
TM
Condra
Cindra L
CL
Bednar
Bohumil
B
Stump
Gary L
GL
Lynch
Joseph J
JJ
Macaulay
Alison
A
Wafford
Keith A
KA
Koblan
Kenneth S
KS
Liverton
Nigel J
NJ
D000284:Administration, Oral; D000818:Animals; D001550:Benzamidines / Q000138:chemical synthesis / Q000494:pharmacology*; D002351:Carrageenan; D004353:Drug Evaluation, Preclinical; D006930:Hyperalgesia / Q000188:drug therapy; D010146:Pain / Q000188:drug therapy; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D001550:Benzamidines; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D002351:Carrageenan