Uridine phosphorylase inhibitors: chemical modification of benzyloxybenzyl-barbituric acid and its effects on urdpase inhibition.
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.
Guerin
D J
DJ
Department of Biomedical Sciences, University of Rhode Island, Kingston 02881-0809, USA.
Mazeas
D
D
Musale
M S
MS
Naguib
F N
FN
Al Safarjalani
O N
ON
el Kouni
M H
MH
Panzica
R P
RP
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*
C084557:5-benzyloxybenzylbarbituric acid; D014498:Uracil; D014543:Uridine Phosphorylase