Structure-based design of beta-lactamase inhibitors. 2. Synthesis and evaluation of bridged sulfactams and oxamazins.
A series of bridged monocyclic beta-lactams activated by various groups on the beta-lactam nitrogen (X = OCH2CO2H, OSO3H) has been synthesized and evaluated. Among them, the bridged sulfactams (X = OSO3H) were found to be effective beta-lactamase inhibitors. They inhibit both class A and class C beta-lactamases.
Preclinical Research, F. Hoffmann-La Roche Ltd., CH-4070 Basle, Switzerland.
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D000085:Acetates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002443:Ceftriaxone / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology; D016971:Citrobacter freundii / Q000187:drug effects / Q000201:enzymology; D015195:Drug Design; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D007700:Kinetics; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology; D013451:Sulfonic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000085:Acetates; D002511:Cephalosporins; D004791:Enzyme Inhibitors; D013451:Sulfonic Acids; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D002443:Ceftriaxone