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© Institut Pasteur
Cristaux de cellulase, enzyme purifiée de Clostridium thermocellum permettant la digestion de la cellulose. Image colorisée.
Publication : Bioorganic & medicinal chemistry

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Bioorganic & medicinal chemistry - 25 Apr 2008

Gasse C, Douguet D, Huteau V, Marchal G, Munier-Lehmann H, Pochet S

Link to Pubmed [PMID] – 18467107

Bioorg. Med. Chem. 2008 Jun;16(11):6075-85

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.

http://www.ncbi.nlm.nih.gov/pubmed/18467107