Novel anti-bacterials against MRSA: synthesis of focussed combinatorial libraries of tri-substituted 2(5H)-furanones

Curr Drug Discov Technol. 2006 Jun;3(2):125-34. doi: 10.2174/157016306778108857.

Abstract

Mucobromic and mucochloric acid were used as building blocks for the construction of a chemical combinatorial library of 3,4,5-trisubstituted 2(5H)-furanones. With these 2 butenolide building blocks, and eight alcohols a sublibrary of 16 dihalogenated 5-alkoxy-2(5H)-furanones was prepared. This sublibrary of 5-alkoxylated furanones was reacted with 16 amines generating a full size focussed combinatorial library of 256 individual compounds. This three dimensional combinatorial library of 3-halogen-4-amino-5-alkoxy-2(5H)-furanones was prepared around the benzimida-zolyl furanone lead structure by applying a solution phase combinatorial chemistry concept. Typical representatives of the library were purified and fully characterized and one x-ray structures was recorded, additionally. The 3-bromo-4-benzimizazolyl-5-methoxy-2(5H)furanone, Br-A-l, showed an MIC of 8 microg/ml against the multiresistant Staphylococcus aureus (MRSA).

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology*
  • Bromine Compounds / chemical synthesis
  • Bromine Compounds / pharmacology
  • Chlorine Compounds / chemical synthesis
  • Chlorine Compounds / pharmacology
  • Combinatorial Chemistry Techniques / methods
  • Crystallography, X-Ray / methods
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Escherichia coli / drug effects
  • Escherichia coli / growth & development
  • Furans / chemical synthesis*
  • Furans / pharmacology
  • Magnetic Resonance Spectroscopy / methods
  • Microbial Sensitivity Tests / methods
  • Molecular Structure
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / growth & development
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / growth & development
  • Structure-Activity Relationship
  • Technology, Pharmaceutical / methods

Substances

  • Anti-Bacterial Agents
  • Bromine Compounds
  • Chlorine Compounds
  • Furans
  • mucochloric acid