Abstract
Forty-five novel cephalosporin derivatives with activity against methicillin-resistant Staphylococcus aureus (MRSA) are described. The compounds contain novel cinnamic acid moieties at C-7 that were synthesized using a key Heck reaction followed by nucleophilic aromatic substitution reactions. The most active compound (41) displayed an MIC(90) against MRSA of 1.0 microg/mL, and a PD(50) of 0.8 mg/kg. Compound 14 was found to be very safe in a mouse model of acute toxicity.
MeSH terms
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Animals
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / pharmacology*
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Cephalosporins / chemistry*
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Cephalosporins / pharmacology*
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Cinnamates / chemistry*
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Cinnamates / pharmacology*
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Disease Models, Animal
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Lethal Dose 50
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Methicillin Resistance
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Mice
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Microbial Sensitivity Tests
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Staphylococcal Infections / microbiology
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Staphylococcus aureus / drug effects*
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Staphylococcus aureus / pathogenicity
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Structure-Activity Relationship
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Toxicity Tests, Acute
Substances
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Anti-Bacterial Agents
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Cephalosporins
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Cinnamates