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

Abstract— β-Lactamase inhibition is an integral part of combination therapy to tackle antibiotic resistance. So far clavulanic acid is the only β-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 β-lactamase inhibition, however, most of the compounds were potent against K. pneumoniae 700603 with two- to six-fold minimization of MIC value of imipenem.