Anti-MRSA cephems. Part 1: C-3 substituted thiopyridinium derivatives.
Sixteen novel cephalosporin derivatives with activity against methicillin-resistant Staphylococcus aureus (MRSA) are described. The compounds were synthesized using substituted thiopyridones, generated either by cyclization of functionalized precursors, or by direct alkylation of the enolate of 2-methyl substituted pyrones. The most active compound in vitro against a strain of MRSA (A27223) displayed an MIC of 0.5 microg/mL. The most efficacious compound in vivo had a PD50 of 2.1 mg/kg.
Anti-infective Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492, USA. springed@bms.com
D M
DM
Springer
B Y
BY
Luh
J J
JJ
Bronson
D002511:Cephalosporins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D011725:Pyridines / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship
C429406:A 27223; D002511:Cephalosporins; D011725:Pyridines; C029347:2-thiopyridine