Inhibition of Uridine Phosphorylase. Synthesis and Structure−ActivityRelationships of Aryl-Substituted1-((2-Hydroxyethoxy)methyl)-5-(3-phenoxybenzyl)uracil
Structure−activity relationship studies on a series of1-((2-hydroxyethoxy)methyl)-5-(3-(substituted-phenoxy)benzyl)uracils as inhibitors of murineliver uridine phosphorylase haveled to compounds with IC50s as low as 1.4 nM. The twomost potent compounds, 10j(3-cyanophenoxy) and 11f (3-chlorophenoxy) were testedin vivo for effects on steady-stateconcentrations of circulating uridine in mice and rats. Bothcompounds were substantiallymore efficacious than BAU (5-benzylacyclouridine) both invitro and in vivo.