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: Karel Pomeisl, Antonín Holý, Ivan Votruba, Radek Pohl
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 18 Issue 4 Pg. 1364-7 (Feb 15 2008) ISSN: 1464-3405 [Electronic] England
• PMID: 18221873 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Organophosphonates
• Pyrimidine Nucleosides
• Thymidine Phosphorylase
• Thymine

Topics

• Animals
• Cricetinae
• Cricetulus
• Enzyme Inhibitors (chemical synthesis, pharmacology)
• Humans
• Lymphoma, T-Cell (enzymology)
• Organophosphonates (chemical synthesis, pharmacology)
• Placenta (enzymology)
• Pyrimidine Nucleosides (chemical synthesis, pharmacology)
• Rats
• Structure-Activity Relationship
• Thymidine Phosphorylase (antagonists & inhibitors)
• Thymine (analogs & derivatives, chemical synthesis, pharmacology)