Molecular Pharmacology, Vol 11, 470-477, Copyright © 1975 by the American Society for Pharmacology and Experimental Therapeutics

Solution Conformations of Ethyl-1'-Methylbutylbarbituric Acids: Implications for Drug-Receptor Site Interactions

¹ Department of Chemistry, Oregon Graduate Center, Beaverton, Oregon 97005
² Department of Pharmacology, University of Oregon Medical School, Portland, Oregon 97201

Solution conformations of 5-ethyl-5-(1'-methylbutyl)-, 5-ethyl-5-(1',3'-dimethylbutyl)-, and 5-ethyl-5-(1',3',3'-trimethylbutyl)barbituric acids in a variety of solvents have been studied by nuclear magnetic resonance techniques. Implications of the results obtained in this study for discrimination between the enantiomers of 5-ethyl-5-(1',3'-dimethylbutyl)barbituric acid [R-(+), excitatory, and S-(-), depressant] at the excitatory receptor site are discussed. It is suggested that discrimination between the enantiomers is based primarily on a required binding orientation of the pyrimidinetrione ring and differing aliphatic side chain geometries resulting from a strong conformational preference of the isopropyl termini.