Chemical Modification of Tazobactam Synthesis of 2β-[(4-Substituted)-l, 2, 3-triazol-l-yl]methyl Penicillanic Acid Sulfone Derivatives

EDUARDO L. SETTI; CHARLES FIAKPUI; OLUDOTUN A. PHILLIPS; DAVID P. CZAJKOWSKI; KEVIN ATCHISON; RONALD G. MICETICH; SAMARENDRA N. MAITI; CHIEKO KUNUGITA; AKIO HYODO

doi:10.7164/antibiotics.48.1320

Chemical Modification of Tazobactam

Synthesis of 2β-[(4-Substituted)-l, 2, 3-triazol-l-yl]methyl Penicillanic Acid Sulfone Derivatives

EDUARDO L. SETTI, CHARLES FIAKPUI, OLUDOTUN A. PHILLIPS, DAVID P. CZAJKOWSKI, KEVIN ATCHISON, RONALD G. MICETICH, SAMARENDRA N. MAITI, CHIEKO KUNUGITA, AKIO HYODO

Author information

EDUARDO L. SETTI
SynPhar Laboratories Inc., #2, Taiho Alberta Center
CHARLES FIAKPUI
SynPhar Laboratories Inc., #2, Taiho Alberta Center
OLUDOTUN A. PHILLIPS
SynPhar Laboratories Inc., #2, Taiho Alberta Center
DAVID P. CZAJKOWSKI
SynPhar Laboratories Inc., #2, Taiho Alberta Center
KEVIN ATCHISON
SynPhar Laboratories Inc., #2, Taiho Alberta Center
RONALD G. MICETICH
SynPhar Laboratories Inc., #2, Taiho Alberta Center
SAMARENDRA N. MAITI
SynPhar Laboratories Inc., #2, Taiho Alberta Center
CHIEKO KUNUGITA
Tokushima Research Institute, Taiho Pharm. Co. Ltd.
AKIO HYODO
Tokushima Research Institute, Taiho Pharm. Co. Ltd.

JOURNAL FREE ACCESS

1995 Volume 48 Issue 11 Pages 1320-1329

DOI https://doi.org/10.7164/antibiotics.48.1320

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Abstract

A series of 2β-[(4-substituted)-l, 2, 3-triazol-l-yl]methyl penicillanic acid sulfones was synthesized as β-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-2β-[(4-pyridiniummethyl)-l, 2, 3-triazol-lyl]methyl-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.

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