title: Novel anti-bacterials against MRSA: synthesis of focussed combinatorial libraries of tri-substituted 2(5H)-furanones.
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).
authors.affiliation: School of Life and Health Sciences, Pharmacy, Aston University, Birmingham B4 7ET, England. e.lattmann@aston.ac.uk
authors.forename: Eric
authors.initials: E
authors.lastname: Lattmann
authors.forename: Nison
authors.initials: N
authors.lastname: Sattayasai
authors.forename: Carl S
authors.initials: CS
authors.lastname: Schwalbe
authors.forename: Suwanna
authors.initials: S
authors.lastname: Niamsanit
authors.forename: David C
authors.initials: DC
authors.lastname: Billington
authors.forename: Pornthip
authors.initials: P
authors.lastname: Lattmann
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Langley
authors.forename: Harjit
authors.initials: H
authors.lastname: Singh
authors.forename: Simon
authors.initials: S
authors.lastname: Dunn
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017605:Bromine Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D017606:Chlorine Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D018360:Crystallography, X-Ray / Q000379:methods; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008826:Microbial Sensitivity Tests / Q000379:methods; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D013329:Structure-Activity Relationship; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000900:Anti-Bacterial Agents; D017605:Bromine Compounds; D017606:Chlorine Compounds; D005663:Furans; C014117:mucochloric acid