NR2B-Selective N-Methyl-<SCP>d</SCP>-aspartate Antagonists: Synthesis and Evaluation of 5-Substituted Benzimidazoles

Authors :: McCauley, J. A.
Theberge, C. R.
Romano, J. J.
Billings, S. B.
Anderson, K. D.
Claremon, D. A.
Freidinger, R. M.
Bednar, R. A.
Mosser, S. D.
Gaul, S. L.
Connolly, T. M.
Condra, C. L.
Xia, M.
Cunningham, M. E.
Bednar, B.
Stump, G. L.
Lynch, J. J.
Macaulay, A.
Wafford, K. A.
Koblan, K. S.
Liverton, N. J.
Source :: Journal of Medicinal Chemistry; April 2004, Vol. 47 Issue: 8 p2089-2096, 8p
Publication Year :: 2004
Abstract: Two classes of 5-substituted benzimidazoles were identified as potent antagonists of the NR2B subtype of the N-methyl-<SCP>d</SCP>-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 α<INF>1</INF>-adrenergic binding. Benzimidazole <BO>37a</BO> shows excellent activity in the carrageenan-induced mechanical hyperalgesia assay in rats as well as good pharmacokinetic behavior in dogs.

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