Abstract: MATH/CHEM/COMP 2002, Dubrovnik, June 24-29, 2002

 

 

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 -lactamase enzymes in pathogenic bacteria is the most common form of resistance to -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 -lactamases no inhibitor of Class C -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.