Anticoccidial derivatives of 6-azauracil. 4. A 1000-fold enhancement of potency by phenyl sulfide and phenyl sulfone side chains.
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.
D000818:Animals; D002645:Chickens; D003048:Coccidiosis / Q000188:drug therapy / Q000662:veterinary; D003049:Coccidiostats / Q000138:chemical synthesis*; D011201:Poultry Diseases / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D003049:Coccidiostats; D014498:Uracil; C100248:azauracil