Discovery of MK-7655, a β-lactamase inhibitor for combination with Primaxin®
- PMID: 24433862
- DOI: 10.1016/j.bmcl.2013.12.101
Discovery of MK-7655, a β-lactamase inhibitor for combination with Primaxin®
Abstract
β-Lactamase inhibitors with a bicyclic urea core and a variety of heterocyclic side chains were prepared and evaluated as potential partners for combination with imipenem to overcome class A and C β-lactamase mediated antibiotic resistance. The piperidine analog 3 (MK-7655) inhibited both class A and C β-lactamases in vitro. It effectively restored imipenem's activity against imipenem-resistant Pseudomonas and Klebsiella strains at clinically achievable concentrations. A combination of MK-7655 and Primaxin® is currently in phase II clinical trials for the treatment of Gram-negative bacterial infections.
Keywords: Antibacterial; Antibiotic; Imipenem; MK-7655; β-Lactamase inhibitor.
Copyright © 2014 Elsevier Ltd. All rights reserved.
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