Subtype-Selective N-Methyl-d-aspartate Receptor Antagonists: Benzimidazalone and Hydantoin as Phenol Replacements
Authors:
- Po-Wai YuenPYPo-Wai Yuen
- Kevin SerpaKSKevin Serpa
- Leonard T. MeltzerLMLeonard T. Meltzer
- Lawrence D. WiseLWLawrence D. Wise
- Edward R. WhittemoreEWEdward R. Whittemore
- Richard M. WoodwardRWRichard M. Woodward
- 24 March 2000
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 43 (9) , 1892-1897
Abstract
Previous work in our laboratories investigating compounds with structural similarity to ifenprodil (5) and 6 (CP101,606) resulted in compound 7 as a potent and selective antagonist of the NR1/2B subtype of the NMDA receptors. Replacement of the phenol group of 7 with a benzimidazalone group tethered by a three-carbon chain to 4-benzylpiperidine resulted in a slightly less active, but selective, compound. Lengthening the carbon tether resulted in a decrease in NR1/2B potency. Replacement of the phenol ring with a hydantoin resulted in weak antagonists. Compound 11a was one of the most potent NR1/2B antagonists from this study. Compound 11a also potentiated the effects of l-DOPA in a rat model of Parkinson's disease (the 6-hydroxydopamine-lesioned rat), dosed at 30 mg/kg orally.Keywords
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