Document Report Card

ID: ALA1121746

Journal: J Med Chem

Title: Anticoccidial derivatives of 6-azauracil. 4. A 1000-fold enhancement of potency by phenyl sulfide and phenyl sulfone side chains.

Authors: Miller MW, Mylari BL, Howes HL, Figdor SK, Lynch MJ, Lynch JE, Gupta SK, Chappel LR, Koch RC.

Abstract: We report further progress in exploiting our earlier discovery that the anticoccidial activity of 6-azauracil increases markedly when appropriately substituted benzyl or phenyl groups are attached at N-1. With guidance from previous structure-activity relationships and a multiple linear regression analysis, 6-azauracils containing phenyl sulfone or phenyl sulfide side chains were prepared. These prevented a broad spectrum of coccidial infections in chickens at minimum inhibitory concentrations by weight in feed as low as 0.25 ppm, a 4000-fold increase in potency over 6-azauracil, and had shorter plasma half-lives than earlier potent analogues. Sulfides were more potent than sulfones, although they were oxidized rapidly to sulfones in vivo.

CiteXplore: 6895527

DOI: 10.1021/jm00143a015