title: Syntheses of N3-substituted thymine acyclic nucleoside phosphonates and a comparison of their inhibitory effect towards thymidine phosphorylase.
abstract: 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.
authors.affiliation: 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.
authors.forename: Karel
authors.initials: K
authors.lastname: Pomeisl
authors.forename: Antonín
authors.initials: A
authors.lastname: Holý
authors.forename: Ivan
authors.initials: I
authors.lastname: Votruba
authors.forename: Radek
authors.initials: R
authors.lastname: Pohl
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D063065:Organophosphonates; D011741:Pyrimidine Nucleosides; D013939:Thymidine Phosphorylase; D013941:Thymine