Elaboration of a proprietary thymidylate kinase inhibitor motif towards anti-tuberculosis agents.
Song L, Risseeuw MDP, Froeyen M, Karalic I, Goeman J, Cappoen D, Van der Eycken J, Cos P, Munier-Lehmann H, Van Calenbergh S.
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.