Thymidylate kinase (TMPK) phosphorylates thymidine 5’-monophosphate (dTMP) and has been proposed as an attractive target for Mycobacterium tuberculosis (Mt).1 By mimicking the structure of the substrate (dTMP), we have previously discovered different series of nucleoside analogues with MtTMPK inhibitory activities in a micromole range.2 Based on recently reported potent piperidin-3-yl-thymine inhibitors of Gram-positive bacterial TMPK,3 we report a series of isomeric N-benzyl-substituted piperidin-4-yl-thymine analogues, some of which demonstrate potent Mt TMPK inhibitory activity. Towards this end a convenient and high-yield synthesis was developed to access 1-substitued thymine derivatives
