Journal article

Deducing the bioactive face of hydantoin anticonvulsant drugs using NMR spectroscopy

Kathryn E Tiedje, Donald F Weaver

CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES | CANADIAN J NEUROL SCI INC | Published : 2008

Abstract

BACKGROUND: The general purpose of this study was to deduce the geometry of the bioactive face (pharmacophore) for the hydantoin class of anticonvulsants. METHODS: Six hydantoin analogs, selected as probes of hydantoin structure, were synthesized. Nuclear magnetic resonance spectroscopy and molecular modelling calculations were used to determine the geometric relationship between the aromatic group and the amide group in the hydantoin pharmacophore. RESULTS: In accord with both theoretical and experimental results, the biologically inactive hydantoin analogs containing a benzyl substituent existed in a folded conformation with the benzene flopped over the hydantoin ring. Conversely the biolo..

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University of Melbourne Researchers