title: Uridine phosphorylase inhibitors: chemical modification of benzyloxybenzyl-barbituric acid and its effects on urdpase inhibition.
abstract: 5-(o-Benzyloxy)benzylbarbituric acid (6) and 5-(p-benzyloxy)benzylbarbituric acid (7) were prepared and their inhibitory activities compared to 5-(m-benzyloxy)-benzylbarbituric acid (BBB) a known, potent inhibitor of uridine phosphorylase (UrdPase). Compounds 6 and 7 were 18-fold and 51-fold less active, respectively, than BBB in inhibiting UrdPase. These data provide solid evidence that the 5-benzylbarbituric acids possessing meta substituents are the most active inhibitors. In addition, 2-thioBBB (11) was synthesized and it was shown to be as active an inhibitor as BBB.
authors.affiliation: Department of Biomedical Sciences, University of Rhode Island, Kingston 02881-0809, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Guerin
authors.forename: D
authors.initials: D
authors.lastname: Mazeas
authors.forename: M S
authors.initials: MS
authors.lastname: Musale
authors.forename: F N
authors.initials: FN
authors.lastname: Naguib
authors.forename: O N
authors.initials: ON
authors.lastname: Al Safarjalani
authors.forename: M H
authors.initials: MH
authors.lastname: el Kouni
authors.forename: R P
authors.initials: RP
authors.lastname: Panzica
mesh_terms: D006801:Humans; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D014543:Uridine Phosphorylase / Q000037:antagonists & inhibitors*
chemical_list: C084557:5-benzyloxybenzylbarbituric acid; D014498:Uracil; D014543:Uridine Phosphorylase