Back to Search Start Over

Design, synthesis and enzymatic evaluation of 6-bridged imidazolyluracil derivatives as inhibitors of human thymidine phosphorylase

Authors :
Abdul M Gbaj
Philip Neil Edwards
V McNally
Sally Freeman
Richard A. Bryce
Kenneth T. Douglas
Mehdi Rajabi
Ian J. Stratford
Mohammed Jaffar
Source :
The Journal of pharmacy and pharmacology. 59(4)
Publication Year :
2007

Abstract

A series of novel imidazolyluracil conjugates were rationally designed and synthesised to probe the active site constraints of the angiogenic enzyme, thymidine phosphorylase (TP, E.C. 2.4.2.4). The lead compound in the series, 15d, showed good binding in the active site of human TP with an inhibition in the low μM range. The absence of a methylene bridge between the uracil and the imidazolyl sub-units (series 16) decreased potency (up to 3-fold). Modelling suggested that active site residues Arg202, Ser217 and His116 are important for inhibitor binding.

Details

ISSN :
00223573
Volume :
59
Issue :
4
Database :
OpenAIRE
Journal :
The Journal of pharmacy and pharmacology
Accession number :
edsair.doi.dedup.....4e041fc8b8b61bb9d03f56a10c958cac