Discovery of bicyclic thymidine analogues as selective and high-affinity inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase.

Veerle Vanheusden (1) , Hélène Munier-Lehmann (2) , Matheus Froeyen (3) , Roger Busson (3) , Jef Rozenski (3) , Piet Herdewijn (3) , Serge van Calenbergh (1)

1 Laboratory for Medicinal Chemistry-FWW
2 Chimie Organique
3 Laboratory of Medicinal Chemistry

Thymidine monophosphate kinase of Mycobacterium tuberculosis (TMPKmt) represents an attractive target for selectively blocking bacterial DNA synthesis. Hereby, we report on the discovery of a novel class of bicyclic nucleosides (10 and 11) and one dinucleoside (12), belonging to the most selective inhibitors of TMPKmt discovered so far.

Veerle Vanheusden, Hélène Munier-Lehmann, Matheus Froeyen, Roger Busson, Jef Rozenski, et al.. Discovery of bicyclic thymidine analogues as selective and high-affinity inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase.. Journal of Medicinal Chemistry, 2004, 47 (25), pp.6187-94. ⟨10.1021/jm040847w⟩. ⟨pasteur-00166959⟩