Synthesis and in vitro activity of 1 beta-methyl C-2 quaternary heterocyclic alkylthio carbapenems

J Med Chem. 1989 Mar;32(3):601-4. doi: 10.1021/jm00123a015.

Abstract

New 1 beta-methylcarbapenems having various (substituted) quaternary heterocyclic alkythio groups at the C-2 position were synthesized and tested for antibacterial activity and renal dipeptidase susceptibility. Compounds having the 1 beta-methyl substituent were found to possess an increased stability to the enzyme. In addition, combination of the 1 beta-methyl substituent and the C-2 quaternary heterocyclic alkylthio side chain generated compounds with excellent antipseudomonal activity and improved stability toward hydrolysis by renal dipeptidase.

MeSH terms

  • Chemical Phenomena
  • Chemistry
  • Dipeptidases / metabolism
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Hydrolysis
  • Microbial Sensitivity Tests
  • Structure-Activity Relationship
  • Thienamycins / chemical synthesis*
  • Thienamycins / metabolism
  • Thienamycins / pharmacology

Substances

  • Thienamycins
  • Dipeptidases