Chemical modification of tazobactam. Synthesis of 2 beta-[(4-substituted)-1,2,3-triazol-1-yl]methyl penicillanic acid sulfone derivatives

Abstract

A series of 2 beta-[(4-substituted)-1,2,3-triazol-1-yl] methyl penicillanic acid sulfones was synthesized as beta-lactamase inhibitors. Many of these compounds showed good in vitro inhibitory activity against penicillinase, cefotaximase and plasmid-mediated class III TEM enzymes, but exhibited weaker cephalosporinase inhibition. One member in this series--2 beta-[(4-pyridiniummethyl)-1,2,3-triazol- 1-yl]-6,6-dihydropenicillanate 1,1-dioxide (12a), when tested in combination with piperacillin, showed excellent synergistic activity against microorganisms producing plasmid-mediated enzymes, but had insufficient activity against microorganisms producing chromosomally mediated class I enzymes.