Literature

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.

DOI： 10.1016/j.bmc.2011.10.021

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

Bioorganic & Medicinal Chemistry 2011.0

Rational Design of 5‘-Thiourea-Substituted α-Thymidine Analogues as Thymidine Monophosphate Kinase Inhibitors Capable of Inhibiting Mycobacterial Growth

Journal of Medicinal Chemistry 2007.0

Thymidine and thymidine-5′-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase

Bioorganic & Medicinal Chemistry Letters 2003.0

Synthesis and evaluation of thymidine-5′-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase

Bioorganic & Medicinal Chemistry Letters 2002.0

Discovery of Bicyclic Thymidine Analogues as Selective and High-Affinity Inhibitors of Mycobacterium tuberculosis Thymidine Monophosphate Kinase

Journal of Medicinal Chemistry 2004.0

Substituted benzyl-pyrimidines targeting thymidine monophosphate kinase of Mycobacterium tuberculosis: Synthesis and in vitro anti-mycobacterial activity