McCauley John A, Theberge Cory R, Romano Joseph J, Billings Susan B, Anderson Kenneth D, Claremon David A, Freidinger Roger M, Bednar Rodney A, Mosser Scott D, Gaul Stanley L, Connolly Thomas M, Condra Cindra L, Xia Menghang, Cunningham Michael E, Bednar Bohumil, Stump Gary L, Lynch Joseph J, Macaulay Alison, Wafford Keith A, Koblan Kenneth S, Liverton Nigel J
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
J Med Chem. 2004 Apr 8;47(8):2089-96. doi: 10.1021/jm030483s.
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.
两类5-取代苯并咪唑被鉴定为N-甲基-D-天冬氨酸（NMDA）受体NR2B亚型的有效拮抗剂。所选化合物对NMDA受体的NR2A、NR2C和NR2D亚型以及对hERG通道活性和α(1)-肾上腺素能结合表现出非常好的选择性。苯并咪唑37a在大鼠角叉菜胶诱导的机械性痛觉过敏试验中表现出优异的活性，在犬类中也具有良好的药代动力学行为。
