CHEMICAL MODIFICATION OF TAZOBACTAM - SYNTHESIS OF 2-BETA-[(4-SUBSTITUTED)-1,2,3-TRIAZOL-1-YL]METHYL PENICILLANIC ACID SULFONE DERIVATIVES

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