Design and synthesis of bridged gamma-lactams as analogues of beta-lactam antibiotics.
Anti-Bredt bridged bicyclo[3.2.1] gamma-lactams were designed as inhibitors of penicillin binding proteins (PBPs). The compounds were prepared by a carbenoid insertion into a lactam N-H bond. Their weak antibacterial activity could either be explained by a poor chemical stability or by unfavorable steric interactions of the methylene bridge of the gamma-lactam with the targeted enzymes.
Aszodi
Jozsef
J
Medicinal Chemistry, Aventis pharma, 102, route de Noisy, 93235 Romainville Cedex, France.
Rowlands
David A
DA
Mauvais
Pascale
P
Collette
Pascal
P
Bonnefoy
Alain
A
Lampilas
Maxime
M
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000494:pharmacology; D015195:Drug Design; D004355:Drug Stability; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D020128:Inhibitory Concentration 50; D007769:Lactams / Q000138:chemical synthesis* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D046915:Penicillin-Binding Proteins / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D065093:beta-Lactamase Inhibitors
D000900:Anti-Bacterial Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007769:Lactams; D046915:Penicillin-Binding Proteins; D065093:beta-Lactamase Inhibitors