Synthesis and beta-Lactamase Inhibition Activity of Diazabicyclooctane Derivatives in Combination with Imipenem

摘要

beta-Lactamase inhibition is an integral part of combination therapy to tackle antibiotic resistance. So far clavulanic acid is the only beta-lactamase inhibitor that exhibits oral bioavailability. We synthesized new diazabicyclooctane derivatives by replacing the SO3H with CHXCOOR moiety. The antibacterial activity of these compounds, in combination with imipenem, was determined against ten bacterial strains. All compounds showed variable profile of beta-lactamase inhibition, however, most of the compounds were potent against K. pneumoniae 700603 with two- to six-fold minimization of MIC value of imipenem.