Renal excretory transport of organic acids: inhibition by oxypyrimidines

¹ Department of Pharmacology, University of Louisville School of Medicine, Louisville, Kentucky

Oxypyrimidines related to barbituric acid depress active accumulation of p-aminohippurate by surviving slices of rabbit kidney cortex without depressing oxygen utilization. Selectivity of inhibition is suggested by absence of effect on transport of tetraethylammonium ion. No correlation between potency and acidic strength is indicated. Correlations between molecular structure and inhibitory potency are similar to those demonstrated for oxypurines: a three-point interaction between three oxygen atoms of the inhibitor and appropriate reactive loci on a cellular receptor molecule is postulated; sulfur may replace one of the oxygen atoms and enhances potency; absence of any one oxygen atom eliminates potency; N-methylation enhances potency, possibly by enhancing hydrogen bonding.