Ethyl (3s,4aR,6S,8aR)-6-(4-ethoxycar-bonylimidazol-1-ylmethyl) decahydroiso-quinoline-3-carboxylic ester: A prodrug of a GluR5 kainate receptor antagonist active in two animal models of acute migraine

Sandra A. Filla, Mark A. Winter, Kirk W. Johnson, David Bleakman, Michael G. Bell, Thomas J. Bleisch, Ana M. Castaño, Amy Clemens-Smith, Miriam Del Prado, Donna K. Dieckman, Esteban Dominguez, Ana Escribano, Ken H. Ho, Kevin J. Hudziak, Mary A. Katofiasc, Jose A. Martinez-Perez, Ana Mateo, Brian M. Mathes, Edward L. Mattiuz, Ann Marie L. OgdenLee A. Phebus, Douglas R. Stack, Robert E. Stratford, Paul L. Ornstein

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Amino diacid 3, a highly selective competitive GluR5 kainate receptor antagonist, exhibited high GluR5 receptor affinity and selectivity over other glutamate receptors. Its diethyl ester prodrug 4 was orally active in two models of migraine: the neurogenic dural plasma protein extravasation model and the nucleus caudalis c-fos expression model. These data suggest that a GluR5 kainate receptor antagonist might be an efficacious antimigraine therapy with a novel mechanism of action.

Original languageEnglish (US)
Pages (from-to)4383-4386
Number of pages4
JournalJournal of Medicinal Chemistry
Volume45
Issue number20
DOIs
StatePublished - Sep 26 2002

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Filla, S. A., Winter, M. A., Johnson, K. W., Bleakman, D., Bell, M. G., Bleisch, T. J., Castaño, A. M., Clemens-Smith, A., Del Prado, M., Dieckman, D. K., Dominguez, E., Escribano, A., Ho, K. H., Hudziak, K. J., Katofiasc, M. A., Martinez-Perez, J. A., Mateo, A., Mathes, B. M., Mattiuz, E. L., ... Ornstein, P. L. (2002). Ethyl (3s,4aR,6S,8aR)-6-(4-ethoxycar-bonylimidazol-1-ylmethyl) decahydroiso-quinoline-3-carboxylic ester: A prodrug of a GluR5 kainate receptor antagonist active in two animal models of acute migraine. Journal of Medicinal Chemistry, 45(20), 4383-4386. https://doi.org/10.1021/jm025548q