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)benzylbarbituri c acid (7) were prepared and their inhibitory activities compared to 5-(m-b enzyloxy)-benzylbarbituric acid (BBB) a known, potent inhibitor of uridine phosphorylase (UrdPase). Compounds 6 and 7 were 18-fold and 51-fold less ac tive, respectively, than BBB in inhibiting UrdPase. These data provide soli d evidence that the 5-benzylbarbituric acids possessing meta substituents a re the most active inhibitors. In addition, 2-thioBBB (11) was synthesized and it was shown to be as active an inhibitor as BBB. (C) 1999 Elsevier Sci ence Ltd. All rights reserved.