Design and synthesis of novel 5,6-disubstituted uracil derivatives as potent inhibitors of thymidine phosphorylase.
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.
Nencka
Radim
R
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic. nencka@uochb.cas.cz
Votruba
Ivan
I
Hrebabecký
Hubert
H
Tloust'ová
Eva
E
Horská
Kveta
K
Masojídková
Milena
M
Holý
Antonín
A
D000588:Amines / Q000737:chemistry; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000588:Amines; D004791:Enzyme Inhibitors; D014498:Uracil; D013939:Thymidine Phosphorylase