Design and synthesis of novel 5,6-disubstituted uracil derivatives as potent inhibitors of thymidine phosphorylase

Radim Nencka; Ivan Votruba; Hubert Hrebabecký; Eva Tloust'ová; Kveta Horská; Milena Masojídková; Antonín Holý

doi:10.1016/j.bmcl.2005.11.050

Design and synthesis of novel 5,6-disubstituted uracil derivatives as potent inhibitors of thymidine phosphorylase

Bioorg Med Chem Lett. 2006 Mar 1;16(5):1335-7. doi: 10.1016/j.bmcl.2005.11.050. Epub 2005 Dec 5.

Authors

Radim Nencka¹, Ivan Votruba, Hubert Hrebabecký, Eva Tloust'ová, Kveta Horská, Milena Masojídková, Antonín Holý

Affiliation

¹ Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic. nencka@uochb.cas.cz

PMID: 16337119
DOI: 10.1016/j.bmcl.2005.11.050

Abstract

We report on a series of novel 5,6-disubstituted uracils with significant inhibitory activity against human and Escherichia coli thymidine phosphorylases. Bis-uracil conjugates were identified as the most potent inhibitors of TPs in this study.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amines / chemistry
Drug Design*
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Escherichia coli / drug effects
Escherichia coli / enzymology
Humans
Inhibitory Concentration 50
Molecular Structure
Structure-Activity Relationship
Thymidine Phosphorylase / antagonists & inhibitors*
Thymidine Phosphorylase / metabolism
Uracil / analogs & derivatives*
Uracil / chemical synthesis
Uracil / chemistry
Uracil / pharmacology*

Substances

Amines
Enzyme Inhibitors
Uracil
Thymidine Phosphorylase