Abstract
The bridged monobactam β-lactamase inhibitor MK-8712 (1) effectively inhibits class C β-lactamases. Side chain N-alkylated and ring-opened analogs of 1 were prepared and evaluated for combination with imipenem to overcome class C β-lactamase mediated resistance. Although some analogs were more potent inhibitors of AmpC, none exhibited better synergy with imipenem than 1.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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Anti-Bacterial Agents / chemical synthesis
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / pharmacology
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Binding Sites
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Computer Simulation
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology
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Imipenem / pharmacology
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Microbial Sensitivity Tests
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Monobactams / chemical synthesis*
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Monobactams / pharmacology
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Protein Structure, Tertiary
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Structure-Activity Relationship
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beta-Lactamase Inhibitors*
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beta-Lactamases / metabolism
Substances
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Anti-Bacterial Agents
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Enzyme Inhibitors
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MK 8712
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Monobactams
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beta-Lactamase Inhibitors
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Imipenem
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beta-Lactamases