New anti-MRSA and anti-VRE carbapenems; synthesis and structure-activity relationships of 1beta-methyl-2-(thiazol-2-ylthio)carbapenems

J Antibiot (Tokyo). 2002 Aug;55(8):722-57. doi: 10.7164/antibiotics.55.722.

Abstract

Discovery of novel antimicrobial agents effective against infections caused by drug-resistant pathogens is an important objective. In order to find a new parenteral carbapenem antibiotic, which has potent antibacterial activity especially against methicillin-resistant staphylococci, vancomycin-resistant enterococci and penicillin-resistant Streptococcus pneumoniae, a series of 1beta-methylcarbapenems with thiazol-2-ylthio groups at the C-2 position have been synthesized. Structure-activity relationships were investigated which led to SM-197436 (27), SM-232721 (44) and SM-232724 (41), being selected 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
  • Enterococcus / drug effects*
  • Humans
  • Methicillin Resistance*
  • Microbial Sensitivity Tests / methods
  • Penicillin Resistance
  • Staphylococcus aureus / drug effects*
  • Streptococcus pneumoniae / drug effects
  • Structure-Activity Relationship
  • Vancomycin Resistance*

Substances

  • 3-((4-(2,5-dihydro-1H-pyrrol-3-yl)-1,3-thiazol-2-yl)thio)-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo(3.2.0)hept-2-ene-2-carboxylic acid
  • 6-(1-hydroxyethyl)-3-((4-(2-(hydroxymethyl)-1,2,3,6-tetrahydropyridin-4-yl)-1,3-thiazol-2-yl)thio)-4-methyl-7-oxo-1-azabicyclo(3.2.0)hept-2-ene-2-carboxylic acid
  • 6-(1-hydroxyethyl)-4-methyl-3-((4-(2-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1,3-thiazol-2-yl)thio)-7-oxo-1-azabicyclo(3.2.0)hept-2-ene-2-carboxylic acid
  • Anti-Bacterial Agents
  • Carbapenems