1. Fluorophosphonylated nucleoside derivatives as new series of thymidine phosphorylase multisubstrate inhibitors.
- Author
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Diab SA, De Schutter C, Muzard M, Plantier-Royon R, Pfund E, and Lequeux T
- Subjects
- Angiogenesis Inhibitors chemistry, Crystallography, X-Ray, Escherichia coli enzymology, Models, Molecular, Molecular Conformation, Molecular Structure, Nucleosides chemistry, Organophosphonates chemistry, Structure-Activity Relationship, Substrate Specificity, Thymidine Phosphorylase chemistry, Angiogenesis Inhibitors chemical synthesis, Nucleosides chemical synthesis, Organophosphonates chemical synthesis, Thymidine Phosphorylase antagonists & inhibitors
- Abstract
The synthesis of new class of potential TPase inhibitors containing a difluoromethylphosphonate function as phosphate mimic is reported. This new series was prepared from a readily available fluorinated building block in few steps. Two series were evaluated as potential inhibitors: a linear series and a conformational constrained series. The activity of these multisubstrate inhibitors depends on the size of the spacer introduced between the pyrimidine ring and the phosphonate function. Best results were observed from triazolyl derivatives, easily obtained from propargylthymine and corresponding azides.
- Published
- 2012
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