Synthesis and enzymatic evaluation of pyridinium-substituted uracil derivatives as novel inhibitors of thymidine phosphorylase

Bioorg Med Chem. 2002 Mar;10(3):525-30. doi: 10.1016/s0968-0896(01)00309-1.

Abstract

A series of water soluble N(1)- and C(6)-substituted uracil pyridinium compounds were prepared as potential inhibitors of thymidine phosphorylase (TP). The C(6)-uracil substituted derivatives were the most active. 1-[(5-Chloro-2,4-dihydroxypyrimidin-6-yl)methyl]pyridinium chloride, was identified as the best inhibitor being 5-fold more potent than the known inhibitor, 6-amino-5-bromouracil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Escherichia coli / enzymology
  • Inhibitory Concentration 50
  • Neovascularization, Pathologic / drug therapy
  • Pyridinium Compounds / chemical synthesis*
  • Pyridinium Compounds / pharmacology
  • Solubility
  • Structure-Activity Relationship
  • Thymidine Phosphorylase / antagonists & inhibitors*
  • Uracil / analogs & derivatives
  • Uracil / chemical synthesis*
  • Uracil / pharmacology

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Pyridinium Compounds
  • Uracil
  • Thymidine Phosphorylase