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STRUCTURE-BASED
DEVELOPMENT OF
CLASS C β-LACTAMASE INHIBITORS
Tom solmajer
National Institute of Chemistry, and Lek,
d.d., Drug Discovery, POB 660, Hajdrihova 19
SI-1001 Ljubljana, Slovenia
Beta-lactam antibiotics are
estimated to have about 60% of the world antibiotic market. However, their
wide spread and over-liberal use is causing the pronounced antibiotic
resistance, both human and animal. The expression of ß-lactamase enzymes in
pathogenic bacteria is the most common form of resistance to ß-lactam
antibiotics. There is a pressing need to develop novel inhibitors which would
substitute effectively for currently used inhibitors. While inhibitors on the
market block the action of Class A ß-lactamases no inhibitor of Class C
ß-lactamase is available at present.
Our structure-based design approach has enabled us to synthesize a series of
tricyclic carbapenem inhibitors which show promising inhibitory activities in
Class C enzymes.
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