title: Fluorophosphonylated nucleoside derivatives as new series of thymidine phosphorylase multisubstrate 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.
authors.affiliation: Laboratoire de Chimie Moléculaire et Thioorganique, UMR CNRS 6507 and FR3038, ENSICAEN, Université de Caen Basse-Normandie, 6 Boulevard du Maréchal Juin, 14050 Caen Cedex, France.
authors.forename: Sonia Amel
authors.initials: SA
authors.lastname: Diab
authors.forename: Coralie
authors.initials: C
authors.lastname: De Schutter
authors.forename: Murielle
authors.initials: M
authors.lastname: Muzard
authors.forename: Richard
authors.initials: R
authors.lastname: Plantier-Royon
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Pfund
authors.forename: Thierry
authors.initials: T
authors.lastname: Lequeux
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D020533:Angiogenesis Inhibitors; D009705:Nucleosides; D063065:Organophosphonates; D013939:Thymidine Phosphorylase