Document Report Card

Basic Information

ID: ALA1759944

Journal: Eur J Med Chem

Title: Structure-activity relationship of 2,4,5-trioxoimidazolidines as inhibitors of thymidine phosphorylase.

Authors: Rajabi M, Mansell D, Freeman S, Bryce RA.

Abstract: Novel non-nucleobase-derived inhibitors of the angiogenic enzyme, thymidine phosphorylase, have been identified using molecular modelling, synthesis and biological evaluation. These inhibitors are 2,4,5-trioxoimidazolidines bearing N-(substituted)phenylalkyl groups, together with, in most cases, N'-(CH(2))(n)-carboxylic acid, ester or amide side chains. The best compound from this series is 3-(2,4,5-trioxo-3-phenylethyl-imidazolodin-1-yl)propionamide, with an IC(50) of 40 μM against Escherichia coli TP. Molecular modelling suggests that this ligand, when complexed with closed-cleft human TP, would have the phenylalkyl group in the active site region normally occupied by a thymine-containing structure.

CiteXplore: 21324566

DOI: 10.1016/j.ejmech.2011.01.035