BIOMAT Database Logo BIOMAT Database Logo

Synthesis and evaluation of thymidine-5'-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase. 2002

Veerle Vanheusden, and Hélène Munier-Lehmann, and Sylvie Pochet, and Piet Herdewijn, and Serge Van Calenbergh
Laboratory for Medicinal Chemistry (FFW), Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium.

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.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D009169 Mycobacterium tuberculosis A species of gram-positive, aerobic bacteria that produces TUBERCULOSIS in humans, other primates, CATTLE; DOGS; and some other animals which have contact with humans. Growth tends to be in serpentine, cordlike masses in which the bacilli show a parallel orientation. Mycobacterium tuberculosis H37Rv
D009703 Nucleoside-Phosphate Kinase An enzyme that catalyzes reversible reactions of a nucleoside triphosphate, e.g., ATP, with a nucleoside monophosphate, e.g., UMP, to form ADP and UDP. Many nucleoside monophosphates can act as acceptor while many ribo- and deoxyribonucleoside triphosphates can act as donor. EC 2.7.4.4. Nucleoside Monophosphate Kinases,Kinase, Nucleoside-Phosphate,Kinases, Nucleoside Monophosphate,Monophosphate Kinases, Nucleoside,Nucleoside Phosphate Kinase
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D000995 Antitubercular Agents Drugs used in the treatment of tuberculosis. They are divided into two main classes: "first-line" agents, those with the greatest efficacy and acceptable degrees of toxicity used successfully in the great majority of cases; and "second-line" drugs used in drug-resistant cases or those in which some other patient-related condition has compromised the effectiveness of primary therapy. Anti-Tuberculosis Agent,Anti-Tuberculosis Agents,Anti-Tuberculosis Drug,Anti-Tuberculosis Drugs,Antitubercular Agent,Antitubercular Drug,Tuberculostatic Agent,Tuberculostatic Agents,Antitubercular Drugs,Agent, Anti-Tuberculosis,Agent, Antitubercular,Agent, Tuberculostatic,Anti Tuberculosis Agent,Anti Tuberculosis Agents,Anti Tuberculosis Drug,Anti Tuberculosis Drugs,Drug, Anti-Tuberculosis,Drug, Antitubercular
D013938 Thymidine Monophosphate 5-Thymidylic acid. A thymine nucleotide containing one phosphate group esterified to the deoxyribose moiety. DTMP,TMP,Thymidylic Acid,Deoxythymidylate,Thymidylic Acids,Acid, Thymidylic,Acids, Thymidylic,Monophosphate, Thymidine
D018360 Crystallography, X-Ray The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) X-Ray Crystallography,Crystallography, X Ray,Crystallography, Xray,X Ray Crystallography,Xray Crystallography,Crystallographies, X Ray,X Ray Crystallographies

Related Publications

Veerle Vanheusden, and Hélène Munier-Lehmann, and Sylvie Pochet, and Piet Herdewijn, and Serge Van Calenbergh
Synthesis and inhibitory activity of thymidine analogues targeting Mycobacterium tuberculosis thymidine monophosphate kinase.
December 2011, Bioorganic & medicinal chemistry,
Veerle Vanheusden, and Hélène Munier-Lehmann, and Sylvie Pochet, and Piet Herdewijn, and Serge Van Calenbergh
Synthesis and evaluation of 6-aza-2'-deoxyuridine monophosphate analogs as inhibitors of thymidylate synthases, and as substrates or inhibitors of thymidine monophosphate kinase in Mycobacterium tuberculosis.
March 2012, Chemistry & biodiversity,
Veerle Vanheusden, and Hélène Munier-Lehmann, and Sylvie Pochet, and Piet Herdewijn, and Serge Van Calenbergh
Synthesis and evaluation of 5-substituted 2'-deoxyuridine monophosphate analogues as inhibitors of flavin-dependent thymidylate synthase in Mycobacterium tuberculosis.
July 2011, Journal of medicinal chemistry,
Veerle Vanheusden, and Hélène Munier-Lehmann, and Sylvie Pochet, and Piet Herdewijn, and Serge Van Calenbergh
Design of Mycobacterium tuberculosis thymidine monophosphate kinase inhibitors.
January 2003, Nucleosides, nucleotides & nucleic acids,
Veerle Vanheusden, and Hélène Munier-Lehmann, and Sylvie Pochet, and Piet Herdewijn, and Serge Van Calenbergh
Exploring acyclic nucleoside analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase.
July 2008, ChemMedChem,
Veerle Vanheusden, and Hélène Munier-Lehmann, and Sylvie Pochet, and Piet Herdewijn, and Serge Van Calenbergh
Synthesis and evaluation of 5'-modified thymidines and 5-hydroxymethyl-2'-deoxyuridines as Mycobacterium tuberculosis thymidylate kinase inhibitors.
January 2013, Bioorganic & medicinal chemistry,
Veerle Vanheusden, and Hélène Munier-Lehmann, and Sylvie Pochet, and Piet Herdewijn, and Serge Van Calenbergh
Thymidine 5' variants as inhibitors of thymidylate kinase.
July 1974, Journal of medicinal chemistry,
Veerle Vanheusden, and Hélène Munier-Lehmann, and Sylvie Pochet, and Piet Herdewijn, and Serge Van Calenbergh
Dinucleotide analogues as inhibitors of thymidine kinase, thymidylate kinase, and ribonucleotide reductase.
July 1988, Journal of medicinal chemistry,
Veerle Vanheusden, and Hélène Munier-Lehmann, and Sylvie Pochet, and Piet Herdewijn, and Serge Van Calenbergh
Computer-assisted combinatorial design of bicyclic thymidine analogs as inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase.
January 2011, Journal of computer-aided molecular design,
Veerle Vanheusden, and Hélène Munier-Lehmann, and Sylvie Pochet, and Piet Herdewijn, and Serge Van Calenbergh
A new family of inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase.
January 2007, Nucleosides, nucleotides & nucleic acids,
Copied contents to your clipboard!