title: Synthesis and evaluation of thymidine-5'-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase.
abstract: 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.
authors.affiliation: Laboratory for Medicinal Chemistry (FFW), Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Vanheusden
authors.forename: Hélène
authors.initials: H
authors.lastname: Munier-Lehmann
authors.forename: Sylvie
authors.initials: S
authors.lastname: Pochet
authors.forename: Piet
authors.initials: P
authors.lastname: Herdewijn
authors.forename: Serge
authors.initials: S
authors.lastname: Van Calenbergh
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007700:Kinetics; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology*; D009703:Nucleoside-Phosphate Kinase / Q000037:antagonists & inhibitors*; D013938:Thymidine Monophosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000995:Antitubercular Agents; D004791:Enzyme Inhibitors; D013938:Thymidine Monophosphate; D009703:Nucleoside-Phosphate Kinase; C020093:dTMP kinase