Syntheses of pyrimidine acyclic nucleoside phosphonates as potent inhibitors of thymidine phosphorylase (PD-ECGF) from SD-lymphoma.
In the present study, we synthesized a series of pyrimidine acyclic nucleoside phosphonates bearing a number of substituents in C-5 position of uracil moiety and in the N-1-side chain. In addition, we have investigated in particular the novel syntheses of fluorinated derivatives substituted in the N-1-side chain and uracil C-5 position because fluorine-containing substituents are often powerful modifiers of chemical and biological properties. The obtained compounds exhibit a considerable inhibitory potency of thymidine phosphorylase from SD-lymphoma. In contrast, the synthesized phosphonates are not efficient inhibitors of E. coli and human thymidine phosphorylase.
Pomeisl
Karel
K
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic. pomeisl@uochb.cas.cz
Votruba
Ivan
I
Holý
Antonín
A
Pohl
Radek
R
D000818:Animals; D002460:Cell Line; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D006801:Humans; D066298:In Vitro Techniques; D008223:Lymphoma / Q000201:enzymology; D051379:Mice; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification
D004791:Enzyme Inhibitors; D063065:Organophosphonates; D011741:Pyrimidine Nucleosides; D013939:Thymidine Phosphorylase