6-(1-hydroxyalkyl)penam sulfone derivatives as inhibitors of class a and class C β-lactamases I

Five 6-(1-hydroxyalkyl)penam sulfone derivatives and two 6-(hydroxymethyl)penams were synthesized for β-lactamase inhibitor screens. The substituent effects and stereochemical requirements of 6α- and 6β-(1-hydroxyalkyl) groups for the biological activity of penam sulfone derivatives were investigated. Of these substituents, only the 6β-hydroxymethyl group of 15 improved the activity of sulbactam against both TEM-1 and AmpC β-lactamases. The sulfone moiety is required for the enhancement of the β-lactamase inhibitory activity. 6β-Hydroxymethylsulbactam (15) was able to restore the activity of piperacillin in vitro and in vivo against various β-lactamase producing microorganisms.