title: NR2B-selective N-methyl-D-aspartate antagonists: synthesis and evaluation of 5-substituted benzimidazoles.
abstract: Two classes of 5-substituted benzimidazoles were identified as potent antagonists of the NR2B subtype of the N-methyl-d-aspartate (NMDA) receptor. Selected compounds show very good selectivity versus the NR2A, NR2C, and NR2D subtypes of the NMDA receptor as well as versus hERG-channel activity and alpha(1)-adrenergic binding. Benzimidazole 37a shows excellent activity in the carrageenan-induced mechanical hyperalgesia assay in rats as well as good pharmacokinetic behavior in dogs.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. john_mccauley@merck.com
authors.forename: John A
authors.initials: JA
authors.lastname: McCauley
authors.forename: Cory R
authors.initials: CR
authors.lastname: Theberge
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Romano
authors.forename: Susan B
authors.initials: SB
authors.lastname: Billings
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Anderson
authors.forename: David A
authors.initials: DA
authors.lastname: Claremon
authors.forename: Roger M
authors.initials: RM
authors.lastname: Freidinger
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Bednar
authors.forename: Scott D
authors.initials: SD
authors.lastname: Mosser
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Gaul
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Connolly
authors.forename: Cindra L
authors.initials: CL
authors.lastname: Condra
authors.forename: Menghang
authors.initials: M
authors.lastname: Xia
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cunningham
authors.forename: Bohumil
authors.initials: B
authors.lastname: Bednar
authors.forename: Gary L
authors.initials: GL
authors.lastname: Stump
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Lynch
authors.forename: Alison
authors.initials: A
authors.lastname: Macaulay
authors.forename: Keith A
authors.initials: KA
authors.lastname: Wafford
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Koblan
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Liverton
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002351:Carrageenan; D002460:Cell Line; D004285:Dogs; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy; D066298:In Vitro Techniques; D008297:Male; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D001562:Benzimidazoles; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D002351:Carrageenan; D002118:Calcium