Uridine phosphorylase inhibitors: chemical modification of benzyloxybenzyl-barbituric acid and its effects on urdpase inhibition

Bioorg Med Chem Lett. 1999 Jun 7;9(11):1477-80. doi: 10.1016/s0960-894x(99)00238-3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Kinetics
  • Liver / enzymology
  • Magnetic Resonance Spectroscopy
  • Uracil / analogs & derivatives*
  • Uracil / chemical synthesis
  • Uracil / chemistry
  • Uridine Phosphorylase / antagonists & inhibitors*

Substances

  • 5-benzyloxybenzylbarbituric acid
  • Uracil
  • Uridine Phosphorylase