5,6-Cis-penems: broad-spectrum anti-methicillin-resistant Staphylococcus aureus beta-lactam antibiotics.
5,6-cis-Penem derivatives have been synthesized and evaluated as anti-MRSA antibiotics. The cis-penems 5 and 6 showed potent activities against not only MRSA but also a wide variety of bacteria including beta-lactamase-producing microorganisms. These compounds were designed to have high affinity to the penicillin-binding protein 2a of MRSA and to form stable acyl intermediates with beta-lactamases by blocking the deacylating water molecule.
Ishiguro
M
M
Suntory Institute for Bioorganic Research, Institute for Biomedical Research, Osaka, Japan.
Tanaka
R
R
Namikawa
K
K
Nasu
T
T
Inoue
H
H
Nakatsuka
T
T
Oyama
Y
Y
Imajo
S
S
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007202:Indicators and Reagents; D007769:Lactams; D009682:Magnetic Resonance Spectroscopy; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D047090:beta-Lactams
C106948:2-((1-phenacylpyrrolidin-3-yl)thio)-6-(1-hydroxypropyl)penem-3-carboxylic acid; C106947:2-((pyrrolidin-3-yl)thio)-6-(1-hydroxypropyl)penem-3-carboxylic acid; D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; D007769:Lactams; D047090:beta-Lactams