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Discovery of MK-7655, a β-lactamase inhibitor for combination with Primaxin®
Timothy A Blizzard1, Helen Chen1, Seongkon Kim1
1Department of Medicinal Chemistry, Merck Research Labs, Rahway, NJ 07065, USA.
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.
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