TY - JOUR
T1 - Novel anti-bacterials against MRSA
T2 - Synthesis of focussed combinatorial libraries of tri-substituted 2(5H)-furanones
AU - Lattmann, Eric
AU - Sattayasai, Nison
AU - Schwalbe, Carl S.
AU - Niamsanit, Suwanna
AU - Billington, David C.
AU - Lattmann, Pornthip
AU - Langley, Christopher A.
AU - Singh, Harjit
AU - Dunn, Simon
PY - 2006
Y1 - 2006
N2 - 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 benzimidazolyl 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 μg/ml against the multiresistant Staphylococcus aureus ( MRSA). © 2006 Bentham Science Publishers Ltd.
AB - 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 benzimidazolyl 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 μg/ml against the multiresistant Staphylococcus aureus ( MRSA). © 2006 Bentham Science Publishers Ltd.
KW - 4-amino-5-alkoxy-2(5H)- furanones
KW - antibacterials
KW - benzimidazolyl-lead structure
KW - butenolides
KW - focussed combinatorial library
KW - MRSA
UR - http://www.scopus.com/inward/record.url?scp=33747870835&partnerID=8YFLogxK
UR - http://benthamscience.com/journal/abstracts.php?journalID=cddt&articleID=89729
U2 - 10.2174/157016306778108857
DO - 10.2174/157016306778108857
M3 - Article
C2 - 16925520
SN - 1570-1638
VL - 3
SP - 125
EP - 134
JO - Current Drug Discovery Technologies
JF - Current Drug Discovery Technologies
IS - 2
ER -