Synthesis and beta-lactamase inhibitory properties of 2 beta-[(1,2,3-triazol-1-yl)methyl]-2 alpha-methylpenam-3 alpha-carboxylic acid 1,1-dioxide and related triazolyl derivatives

J Med Chem. 1987 Aug;30(8):1469-74. doi: 10.1021/jm00391a032.

Abstract

Benzhydryl 2 beta-[(1,2,3-triazol-1-yl)methyl]-2 alpha-methylpenam- 3 alpha-carboxylate 1,1-dioxide was prepared by heating benzhydryl 2 beta-(azidomethyl)-2 alpha-methylpenam-3 alpha-carboxylate 1,1-dioxide with (trimethylsilyl)acetylene. The ester group was removed by hydrogenolysis to give sodium 2 beta-[(1,2,3-triazol-1-yl)methyl]-2 alpha-methylpenam-3 alpha-carboxylate 1,1-dioxide (3i, YTR-830), which was found to be a potent inhibitor of various bacterial beta-lactamases. A series of related compounds was prepared in a similar way, and all of these compounds show excellent beta-lactamase inhibitory properties.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ampicillin / pharmacology
  • Bacteria / drug effects
  • Bacteria / enzymology
  • Chemical Phenomena
  • Chemistry
  • Clavulanic Acid
  • Clavulanic Acids / pharmacology
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology
  • Penicillanic Acid / chemical synthesis
  • Penicillanic Acid / pharmacology*
  • Sulbactam
  • Tazobactam
  • Triazoles / chemical synthesis
  • Triazoles / pharmacology*
  • beta-Lactamase Inhibitors*

Substances

  • Clavulanic Acids
  • Triazoles
  • beta-Lactamase Inhibitors
  • Clavulanic Acid
  • Ampicillin
  • Penicillanic Acid
  • Sulbactam
  • Tazobactam