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

Author

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., and Liverton, N. J.

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 α1-adrenergic binding. Benzimidazole 37a shows excellent activity in the carrageenan-induced mechanical hyperalgesia assay in rats as well as good pharmacokinetic behavior in dogs.

Published
2004

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