INHIBITION OF URIDINE PHOSPHORYLASE - SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF ARYL-SUBSTITUTED (2-HYDROXYETHOXY)METHYL)-5-(3-PHENOXYBENZYL)URACIL

Structure-activity relationship studies on a series of xy)methyl)-5-(3 (substituted-phenoxy)benzyl)uracils as inhibitors of murine liver urid ine phosphorylase have led to compounds with IC(50)s as low as 1.4 nM. The two most potent compounds, 10j (3-cyanophenoxy) and 11f (3-chloro phenoxy) were tested in vivo for effects on steady-state concentration s of circulating uridine in mice and rats. Both compounds were substan tially more efficacious than BAU (5-benzylacyclouridine) both in vitro and in vivo.