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

Veerle Vanheusden (1) , Hélène Munier-Lehmann (2) , Sylvie Pochet (3) , Piet Herdewijn (1, 4) , Serge van Calenbergh (1)

1 UGENT - Universiteit Gent = Ghent University
2 CSM - Chimie Structurale des Macromolécules
3 Chimie Organique
4 KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven

A number of 2'- and 3'-modified thymidine 5'-O-monophosphate analogues were synthesized as potential leads for new anti-mycobacterial drugs. Evaluation of their affinity for Mycobacterium tuberculosis thymidine monophosphate kinase showed that a 2'-halogeno substituent and a 3'-azido function are the most favorable leads for further development of potent inhibitors of this enzyme.

Domains: Life Sciences [q-bio]

Veerle Vanheusden, Hélène Munier-Lehmann, Sylvie Pochet, Piet Herdewijn, Serge van Calenbergh. Synthesis and evaluation of thymidine-5'-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase.. Bioorganic and Medicinal Chemistry Letters, 2002, 12 (19), pp.2695-8. ⟨10.1016/S0960-894X(02)00551-6⟩. ⟨pasteur-00166198⟩