α-Substituted hydroxamic acids as novel bacterial deformylase inhibitor-based antibacterial agents

Abstract We report the synthesis and biological activity of analogues of VRC3375 ( N -hydroxy-3- R -butyl-3-[(2- S -( tert -butoxycarbonyl)-pyrrolidin-1-ylcarbonyl]propionamide), an orally active peptide deformylase inhibitor. This study explores the structure–activity relationship of various chelator groups, alpha substituents, P 2 ′ and P 3 ′ substituents in order to achieve optimal antibacterial activity with minimal toxicity liability.