Inhibition of uridine phosphorylase. Synthesis and structure-activity relationships of aryl-substituted 1-((2-hydroxyethoxy) methyl)-5-(3-phenoxybenzyl) uracil

GF Orr, DL Musso, JL Kelley, SS Joyner…

Index: Orr, G. Faye; Musso, David L.; Kelley, James L.; Joyner, Suzanne S.; Davis, Stephen T.; Baccanari, David P. Journal of Medicinal Chemistry, 1997 , vol. 40, # 8 p. 1179 - 1185

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Citation Number: 11

Abstract

Structure-activity relationship studies on a series of 1-((2-hydroxyethoxy) methyl)-5-(3- (substituted-phenoxy) benzyl) uracils as inhibitors of murine liver uridine phosphorylase have led to compounds with IC50s as low as 1.4 nM. The two most potent compounds, 10j (3- cyanophenoxy) and 11f (3-chlorophenoxy) were tested in vivo for effects on steady-state concentrations of circulating uridine in mice and rats. Both compounds were substantially ...