Cyclic benzamidines as orally efficacious NR2B-selective NMDA receptor antagonists.
A novel series of cyclic benzamidines was synthesized and shown to exhibit NR2B-subtype selective NMDA antagonist activity. Compound 29 is orally active in a carrageenan-induced rat hyperalgesia model of pain.
Nguyen
Kevin T
KT
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. kevin_nguyen@merck.com
Claiborne
Christopher F
CF
McCauley
John A
JA
Libby
Brian E
BE
Claremon
David A
DA
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
Koblan
Kenneth S
KS
Liverton
Nigel J
NJ
D000284:Administration, Oral; D000818:Animals; D001550:Benzamidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D008954:Models, Biological; D010146:Pain / Q000188:drug therapy; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D001550:Benzamidines; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate