Synthesis of combinatorial libraries of 3,4,5-trisubstituted 2(5H)-furanones. Part Two: Construction of a library of 4-amino-5-alkoxy-2(5H)-furanones.
A three dimensional combinatorial library of 3-halogen-4-amino-5-alkoxy-2(5H)-furanones has been prepared by applying solution phase combinatorial chemistry techniques. The substituents in the 3-4-5-positions of a butenolide scaffold were varied independently to generate with 3 butenolides, 4 alcohols and 24 amines a library of 288 compounds using a 2 stage synthetic protocol. Typical representives of the library were purified and fully characterized. Biological evaluation resulted in the discovery of a lead structure for a new class of antibiotic agents. The 4-benzylamino-2(5H)-furanone, Dr, of this library has shown a promising antibiotic activity against the multiresistant Staphillococcus aureus (MRSA 96-7778).
Lattmann
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Pharmaceutical Sciences Research Institute, Aston University, Birmingham, England. e.lattmann@aston.ac.uk
Billington
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DC
Langley
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CA
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D005663:Furans