Elaboration of a proprietary thymidylate kinase inhibitor motif towards anti-tuberculosis agents

Lijun Song (1) , Martijn D.P. Risseeuw (1) , Matheus Froeyen (2) , Izet Karalic (1) , Jan Goeman (1) , Davie Cappoen (3) , Johan van Der Eycken (1) , Paul Cos (3) , Hélène Munier-Lehmann (4) , Serge van Calenbergh (1) , Martijn D P Risseeuw , Mathy Froeyen (5)

1 UGENT - Universiteit Gent = Ghent University
2 Rega Institute for Medical Research [Leuven, België]
3 UA - University of Antwerp
4 Chimie et Biocatalyse
5 KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven

We report the design and synthesis of a series of non-nucleoside MtbTMPK inhibitors (1-14) based on the gram-positive bacterial TMPK inhibitor hit compound 1. A practical synthesis was developed to access these analogues. Several compounds show promising MtbTMPK inhibitory potency and allow the establishment of a structure-activity relationship, which is helpful for further optimization.

Keywords: Inhibitors; Mycobacterium tuberculosis; Thymidine monophosphate kinase; Thymine derivatives; XDR-TB; extensively drug-resistant tuberculosis

Domains: Chemical Sciences; Life Sciences [q-bio]

Lijun Song, Martijn D.P. Risseeuw, Matheus Froeyen, Izet Karalic, Jan Goeman, et al.. Elaboration of a proprietary thymidylate kinase inhibitor motif towards anti-tuberculosis agents. Bioorganic and Medicinal Chemistry, 2016, 24 (21), pp.5172 - 5182. ⟨10.1016/j.bmc.2016.08.041⟩. ⟨pasteur-01616045⟩