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. o-, m- and p-Benzyloxybenzyl barbituric acids were prepared and evaluated as uridine phosphorylase inhibitors.