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Bioorg Med Chem. 2011 Dec 15;19(24):7603-11. doi: 10.1016/j.bmc.2011.10.021. Epub 2011 Oct 18.

Synthesis and inhibitory activity of thymidine analogues targeting Mycobacterium tuberculosis thymidine monophosphate kinase.

Author information

1
Laboratory for Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.

Abstract

We report on Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) inhibitory activities of a series of new 3'- and 5'-modified thymidine analogues including α- and β-derivatives. In addition, several analogues were synthesized in which the 4-oxygen was replaced by a more lipophilic sulfur atom to probe the influence of this modification on TMPKmt inhibitory activity. Several compounds showed an inhibitory potency in the low micromolar range, with the 5'-arylthiourea 4-thio-α-thymidine analogue being the most active one (K(i)=0.17 μM). This compound was capable of inhibiting mycobacteria growth at a concentration of 25 μg/mL.

PMID:
22061826
DOI:
10.1016/j.bmc.2011.10.021
[Indexed for MEDLINE]

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