title: Synthesis and evaluation of 5'-modified thymidines and 5-hydroxymethyl-2'-deoxyuridines as Mycobacterium tuberculosis thymidylate kinase inhibitors.
abstract: We report the synthesis of 5'-modified thymidines (16, 18, 21, 23) and 5,5'-bis-substituted 2'-deoxyuridine analogues (30, 47) as inhibitors of thymidine monophosphate kinase of Mycobacterium tuberculosis (TMPKmt). These analogues were evaluated for their capacity to inhibit TMPKmt and solely two 5'-modified thymidines were found to possess moderate inhibitory activity. In addition, a feasibility study of protecting groups for the 5-CH(2)OH moiety of 2'-deoxyuridines is described that enables to introduce the desired 5'-modification.
authors.affiliation: Laboratory for Medicinal Chemistry, Faculty of Pharmaceutical Sciences (FFW), Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium.
authors.forename: Kiran S
authors.initials: KS
authors.lastname: Toti
authors.forename: Frederick
authors.initials: F
authors.lastname: Verbeke
authors.forename: Martijn D P
authors.initials: MD
authors.lastname: Risseeuw
authors.forename: Vladimir
authors.initials: V
authors.lastname: Frecer
authors.forename: Hélène
authors.initials: H
authors.lastname: Munier-Lehmann
authors.forename: Serge
authors.initials: S
authors.lastname: Van Calenbergh
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology*; D009703:Nucleoside-Phosphate Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013936:Thymidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; C018080:5-hydroxymethyl-2'-deoxyuridine; D009703:Nucleoside-Phosphate Kinase; C020093:dTMP kinase; D013936:Thymidine