Abstract: MATH/CHEM/COMP 2002, Dubrovnik, June 24-29, 2002
STRUCTURE-BASED DEVELOPMENT OF
CLASS C β-LACTAMASE INHIBITORS
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.