title: 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.
authors.affiliation: SynPhar Laboratories Inc. Edmonton, Alberta, Canada.
authors.forename: E L
authors.initials: EL
authors.lastname: Setti
authors.forename: C
authors.initials: C
authors.lastname: Fiakpui
authors.forename: O A
authors.initials: OA
authors.lastname: Phillips
authors.forename: D P
authors.initials: DP
authors.lastname: Czajkowski
authors.forename: K
authors.initials: K
authors.lastname: Atchison
authors.forename: R G
authors.initials: RG
authors.lastname: Micetich
authors.forename: S N
authors.initials: SN
authors.lastname: Maiti
authors.forename: C
authors.initials: C
authors.lastname: Kunugita
authors.forename: A
authors.initials: A
authors.lastname: Hyodo
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004357:Drug Synergism; D004563:Electrochemistry; D004791:Enzyme Inhibitors / Q000737:chemistry*; D004926:Escherichia coli / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D007711:Klebsiella pneumoniae / Q000187:drug effects; D015394:Molecular Structure; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D010957:Plasmids; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013329:Structure-Activity Relationship; D000078142:Tazobactam; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology; D065093:beta-Lactamase Inhibitors
chemical_list: C097842:2-((4-pyridiniummethyl)-1,2,3-triazol-1-yl)methyl-6,6-dihydropenicillanate 1,1-dioxide; D004791:Enzyme Inhibitors; D014230:Triazoles; D065093:beta-Lactamase Inhibitors; D000667:Ampicillin; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin