Current Drug Discovery Technologies 2006-06-01

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

Eric Lattmann, Nison Sattayasai, Carl S Schwalbe, Suwanna Niamsanit, David C Billington, Pornthip Lattmann, Christopher A Langley, Harjit Singh, Simon Dunn

Index: Curr. Drug Discov. Technol. 3(2) , 125-34, (2006)

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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).