(6R,8S)-(2-benzimidazolyl)hydroxymethylpenicillanic acids as potent antibacterial agents and beta-lactamase inhibitors.
(6R,8S)-(2-Benzimidazolyl)hydroxymethylpenicillanic acids (1a-1x) are potent antibacterial agents and beta-lactamase inhibitors against Gram-positive bacteria and Haemophilus influenzae. The corresponding (6R,8R)-isomers (2a-2x), the 6,6-spiro benzimidazole-penam alcohol (3), (7R,9S)-(2-benzimidazolyl)hydroxymethylcephalosporanic acid (4), and 6 beta-(2-benzimidazolyl)aminopenicillanic acid (5) are much less active as antibacterials or beta-lactamase inhibitors. The syntheses and structure-activity relationships of these compounds are discussed. Antibacterial activity and beta-lactamase inhibition data are presented.
Chen
Y L
YL
Medicinal Chemistry Department, Central Research Division, Pfizer Inc., Groton, CT 06340.
Hedberg
K
K
Guarino
K
K
Retsema
J A
JA
Anderson
M
M
Manousos
M
M
Barrett
J
J
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006193:Haemophilus influenzae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D065093:beta-Lactamase Inhibitors
D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D010397:Penicillanic Acid