Bioorganic & Medicinal Chemistry 2002-03-01

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

Paul E Murray, Virginia A McNally, Stacey D Lockyer, Kaye J Williams, Ian J Stratford, Mohammed Jaffar, Sally Freeman

Index: Bioorg. Med. Chem. 10(3) , 525-30, (2002)

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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.