title: Synthesis and enzymatic evaluation of pyridinium-substituted uracil derivatives as novel inhibitors of thymidine phosphorylase.
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.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Oxford Road, Manchester M13 9PL, UK.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Murray
authors.forename: Virginia A
authors.initials: VA
authors.lastname: McNally
authors.forename: Stacey D
authors.initials: SD
authors.lastname: Lockyer
authors.forename: Kaye J
authors.initials: KJ
authors.lastname: Williams
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Stratford
authors.forename: Mohammed
authors.initials: M
authors.lastname: Jaffar
authors.forename: Sally
authors.initials: S
authors.lastname: Freeman
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D020128:Inhibitory Concentration 50; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011726:Pyridinium Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D012995:Solubility; D013329:Structure-Activity Relationship; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors*; D014498:Uracil / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011726:Pyridinium Compounds; D014498:Uracil; D013939:Thymidine Phosphorylase