title: 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.
abstract: 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.
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-ENSCM-Université Montpellier 1-Université Montpellier 2, Bâtiment de Recherche Max Mousseron, École Nationale Supérieure de Chimie de Montpellier, 8 rue de l'École Normale, 34296 Montpellier Cedex, France; Centre d'Études d'Agents Pathogènes et Biotechnologies pour la Santé (CPBS), UMR 5236, CNRS-Université Montpellier 1-Université Montpellier 2, 1919 route de Mende, F-34293 Montpellier Cedex 5, France.
authors.forename: François
authors.initials: F
authors.lastname: Turtaut
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-ENSCM-Université Montpellier 1-Université Montpellier 2, Bâtiment de Recherche Max Mousseron, École Nationale Supérieure de Chimie de Montpellier, 8 rue de l'École Normale, 34296 Montpellier Cedex, France; Centre d'Études d'Agents Pathogènes et Biotechnologies pour la Santé (CPBS), UMR 5236, CNRS-Université Montpellier 1-Université Montpellier 2, 1919 route de Mende, F-34293 Montpellier Cedex 5, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Lopez
authors.affiliation: Centre d'Études d'Agents Pathogènes et Biotechnologies pour la Santé (CPBS), UMR 5236, CNRS-Université Montpellier 1-Université Montpellier 2, 1919 route de Mende, F-34293 Montpellier Cedex 5, France.
authors.forename: Safia
authors.initials: S
authors.lastname: Ouahrani-Bettache
authors.affiliation: Centre d'Études d'Agents Pathogènes et Biotechnologies pour la Santé (CPBS), UMR 5236, CNRS-Université Montpellier 1-Université Montpellier 2, 1919 route de Mende, F-34293 Montpellier Cedex 5, France.
authors.forename: Stephan
authors.initials: S
authors.lastname: Köhler
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-ENSCM-Université Montpellier 1-Université Montpellier 2, Bâtiment de Recherche Max Mousseron, École Nationale Supérieure de Chimie de Montpellier, 8 rue de l'École Normale, 34296 Montpellier Cedex, France. Electronic address: jean-yves.winum@univ-montp2.fr.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Winum
mesh_terms: D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D041021:Brucella suis / Q000187:drug effects / Q000201:enzymology*; D002006:Brucellosis / Q000382:microbiology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006639:Histidine / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D015394:Molecular Structure; D011743:Pyrimidines / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D037521:Virulence Factors / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011743:Pyrimidines; D054852:Small Molecule Libraries; D037521:Virulence Factors; D006639:Histidine; D000429:Alcohol Oxidoreductases; C021358:histidinol dehydrogenase; C030986:pyrimidine
keywords: Anti-infectious agents; Brucella suis; Enzyme inhibitors; Histidinol dehydrogenase; Oxo-imidazopyrimidines