Substituted benzyl-pyrimidines targeting thymidine monophosphate kinase of Mycobacterium tuberculosis: Synthesis and in vitro anti-mycobacterial activity. - Archive ouverte HAL Access content directly
Journal Articles Bioorganic and Medicinal Chemistry Year : 2008

Substituted benzyl-pyrimidines targeting thymidine monophosphate kinase of Mycobacterium tuberculosis: Synthesis and in vitro anti-mycobacterial activity.

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Cécile Gasse
  • Function : Author
Valérie Huteau
  • Function : Author
Gilles Marchal
  • Function : Author
Hélène Munier-Lehmann
Sylvie Pochet
  • Function : Correspondent author
  • PersonId : 852562

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Abstract

A series of N(1)-(4-substituted-benzyl)-pyrimidines were synthesized as potential inhibitors of thymidine monophosphate kinase of Mycobacterium tuberculosis (TMPKmt). Key SAR parameters included the chain length substitution in para position of the benzyl ring, the functional group terminating the alkyl chain, and the substituent on the C-5 pyrimidine ring. Synthesized molecules were assayed against both recombinant enzyme and mycobacteria cultures. The most potent compounds have K(i) values in the micromolar range and an MIC(50) of 50microg/mL against Mycobacterium bovis. These results will guide the design of a new generation of lead compounds.

Dates and versions

pasteur-00307723 , version 1 (29-07-2008)

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Cécile Gasse, Dominique Douguet, Valérie Huteau, Gilles Marchal, Hélène Munier-Lehmann, et al.. Substituted benzyl-pyrimidines targeting thymidine monophosphate kinase of Mycobacterium tuberculosis: Synthesis and in vitro anti-mycobacterial activity.. Bioorganic and Medicinal Chemistry, 2008, 16 (11), pp.6075-85. ⟨10.1016/j.bmc.2008.04.045⟩. ⟨pasteur-00307723⟩
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