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Synthesis and evaluation of 5'-modified thymidines and 5-hydroxymethyl-2'-deoxyuridines as Mycobacterium tuberculosis thymidylate kinase inhibitors

Authors :
Kiran S. Toti
Frederick Verbeke
Hélène Munier-Lehmann
Vladimir Frecer
Serge Van Calenbergh
Martijn D. P. Risseeuw
Laboratory for Medicinal Chemistry
Faculty of Pharmaceutical Sciences
Department of Physical Chemistry of Drugs
Faculty of Pharmacy, Comenius University
Chimie et Biocatalyse
Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]
Laboratory for Medicinal Chemistry-FWW
Universiteit Gent = Ghent University [Belgium] (UGENT)
Comenius University in Bratislava
Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Universiteit Gent = Ghent University (UGENT)
Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Source :
BIOORGANIC & MEDICINAL CHEMISTRY, Bioorganic and Medicinal Chemistry, Bioorganic and Medicinal Chemistry, Elsevier, 2013, 21 (1), pp.257-68. ⟨10.1016/j.bmc.2012.10.018⟩, Bioorganic and Medicinal Chemistry, 2013, 21 (1), pp.257-68. ⟨10.1016/j.bmc.2012.10.018⟩
Publication Year :
2013

Abstract

International audience; 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.

Details

Language :
English
ISSN :
09680896 and 14643391
Database :
OpenAIRE
Journal :
BIOORGANIC & MEDICINAL CHEMISTRY, Bioorganic and Medicinal Chemistry, Bioorganic and Medicinal Chemistry, Elsevier, 2013, 21 (1), pp.257-68. ⟨10.1016/j.bmc.2012.10.018⟩, Bioorganic and Medicinal Chemistry, 2013, 21 (1), pp.257-68. ⟨10.1016/j.bmc.2012.10.018⟩
Accession number :
edsair.doi.dedup.....c2ca6afbcc1db300c88c619cdf2e2ca2
Full Text :
https://doi.org/10.1016/j.bmc.2012.10.018⟩