Syntheses of N3-substituted thymine acyclic nucleoside phosphonates and a comparison of their inhibitory effect towards thymidine phosphorylase.
A series of N(3)-substituted thymine acyclic nucleoside phosphonates bearing a number of (phosphonomethoxy)alkyl groups were synthesized and investigated for their ability to inhibit the human thymidine phosphorylase expressed in V79 Chinese hamster cells, as well as thymidine phosphorylase from SD-lymphoma, Escherichia coli and human placenta. In comparison to N(1)- substituted analogues which possess a considerable inhibitory activity towards thymidine phosphorylase from SD-lymphoma, the results showed a marginal inhibitory effect of these compounds. None of the presented N(3)-substituted derivatives possess a significant cytostatic activity.
Pomeisl
Karel
K
Gilead Sciences & IOCB Research Centre, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i, Centre for New Antivirals and Antineoplastics (IOCB), Prague, Czech Republic.
Holý
Antonín
A
Votruba
Ivan
I
Pohl
Radek
R
D000818:Animals; D006224:Cricetinae; D003412:Cricetulus; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D016399:Lymphoma, T-Cell / Q000201:enzymology; D063065:Organophosphonates / Q000138:chemical synthesis / Q000494:pharmacology; D010920:Placenta / Q000201:enzymology; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors*; D013941:Thymine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D004791:Enzyme Inhibitors; D063065:Organophosphonates; D011741:Pyrimidine Nucleosides; D013939:Thymidine Phosphorylase; D013941:Thymine