Benzimidazole analogs as WTA biosynthesis inhibitors targeting methicillin resistant Staphylococcus aureus.

Abstract A series of benzimidazole analogs have been synthesized to improve the profile of the previous lead compounds tarocin B and 1 . The syntheses, structure–activity relationships, and selected biochemical data of these analogs are described. The optimization efforts allowed the identification of 21 , a fluoro-substituted benzimidazole, exhibiting potent TarO inhibitory activity and typical profile for a wall teichoic acid (WTA) biosynthesis inhibitor. Compound 21 displayed a potent synergistic and bactericidal effect in combination with imipenem against diverse methicillin-resistant Staphylococci.