Structure-activity relationship of 2,4,5-trioxoimidazolidines as inhibitors of thymidine phosphorylase

Mehdi Rajabi, David Mansell, Sally Freeman, Richard A. Bryce

    Research output: Contribution to journalArticlepeer-review


    Novel non-nucleobase-derived inhibitors of the angiogenic enzyme, thymidine phosphorylase, have been identified using molecular modelling, synthesis and biological evaluation. These inhibitors are 2,4,5-trioxoimidazolidines bearing N-(substituted)phenylalkyl groups, together with, in most cases, N′-(CH2)n-carboxylic acid, ester or amide side chains. The best compound from this series is 3-(2,4,5-trioxo-3-phenylethyl- imidazolodin-1-yl)propionamide, with an IC50 of 40 μM against Escherichia coli TP. Molecular modelling suggests that this ligand, when complexed with closed-cleft human TP, would have the phenylalkyl group in the active site region normally occupied by a thymine-containing structure. © 2011 Elsevier Masson SAS. All rights reserved.
    Original languageEnglish
    Pages (from-to)1165-1171
    Number of pages6
    JournalEuropean Journal of Medicinal Chemistry
    Issue number4
    Publication statusPublished - Apr 2011


    • Anti-angiogenic
    • Hydantoin
    • Molecular modelling
    • Parabanic acid
    • Thymidine phosphorylase
    • Trioxoimidazolidine


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