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Bioorg Med Chem. 2003 Jan 17;11(2):265-79.

Anti-MRSA cephems. Part 2: C-7 cinnamic acid derivatives.

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Anti-infective Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, PO Box 5100, Wallingford, CT 06492, USA.


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.

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