A novel 1 beta-methylcarbapenem antibiotic, S-4661. Synthesis and structure-activity relationships of 2-(5-substituted pyrrolidin-3-ylthio)-1 beta-methylcarbapenems

J Antibiot (Tokyo). 1996 Feb;49(2):199-209. doi: 10.7164/antibiotics.49.199.

Abstract

The synthesis and biological activity of (1R,5S,6S)-2-[(3S,5S)-5-substituted pyrrolidin-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1- methylcarbapen-2-em-3-carboxylic acids are described. These compounds exhibit potent antibacterial activity against a wide range of both Gram-positive and Gram-negative bacteria including Pseudomonas aeruginosa. Of these new carbapenems, (1R,5S,6S)-2-[(3S,5S)-5-sulfamoylaminomethyl pyrrolidin-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarb apen- 2-em-3-carboxyli c acid (S-4661) showed the most potent and well balanced activity and was selected as a candidate for further evaluation.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Carbapenems / chemical synthesis
  • Carbapenems / chemistry
  • Carbapenems / pharmacology
  • Doripenem
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Magnetic Resonance Spectroscopy
  • Spectrophotometry, Infrared
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Doripenem