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

PE Murray, VA McNally, SD Lockyer, KJ Williams…

Index: Murray, Paul E; McNally, Virginia A; Lockyer, Stacey D; Williams, Kaye J; Stratford, Ian J; Jaffar, Mohammed; Freeman, Sally Bioorganic and medicinal chemistry, 2002 , vol. 10, # 3 p. 525 - 530

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Citation Number: 28

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.