Oxo- and thiooxo-imidazo[1,5-c]pyrimidine molecule library: Beyond their interest in inhibition of Brucella suis histidinol dehydrogenase, a powerful protection tool in the synthesis of histidine analogues

François Turtaut (1, 2) , Marie Lopez (1, 2) , Safia Ouahrani-Bettache (2) , Stephan Köhler (2) , Jean-Yves Winum (1)

1 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
2 CPBS - Centre d’études d’Agents Pathogènes et Biotechologies pour la Santé

Histidinol dehydrogenase (HDH) has been established as a virulence factor for the human pathogen bacterium Brucella suis. Targeting such a virulence factor is a relevant anti-infectious approach as it could decrease the frequency of antibiotic resistance appearance. In this paper, we describe the synthesis of a family of oxo- and thioxo-imidazo[1,5-c]pyrimidines, potential enzyme inhibitors. Beyond their anti-HDH activity, the synthesis approach of these molecules, never described before, is highly original and these oxo- and thioxo- derivatives can improve dramatically the efficiency of the histidine protection pathway for the synthesis of histidine analogues.

Mots clés: Anti-infectious agents; Brucella suis; Oxo-imidazopyrimidines; Histidinol dehydrogenase; Enzyme inhibitors

Domaines: Chimie organique; Chimie thérapeutique; Chimie

François Turtaut, Marie Lopez, Safia Ouahrani-Bettache, Stephan Köhler, Jean-Yves Winum. Oxo- and thiooxo-imidazo[1,5-c]pyrimidine molecule library: Beyond their interest in inhibition of Brucella suis histidinol dehydrogenase, a powerful protection tool in the synthesis of histidine analogues. Bioorganic and Medicinal Chemistry Letters, 2014, 24 (21), pp.5008-5010. ⟨10.1016/j.bmcl.2014.09.020⟩. ⟨hal-02425098⟩