title: (6R,8S)-(2-benzimidazolyl)hydroxymethylpenicillanic acids as potent antibacterial agents and beta-lactamase inhibitors.
abstract: (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.
authors.affiliation: Medicinal Chemistry Department, Central Research Division, Pfizer Inc., Groton, CT 06340.
authors.forename: Y L
authors.initials: YL
authors.lastname: Chen
authors.forename: K
authors.initials: K
authors.lastname: Hedberg
authors.forename: K
authors.initials: K
authors.lastname: Guarino
authors.forename: J A
authors.initials: JA
authors.lastname: Retsema
authors.forename: M
authors.initials: M
authors.lastname: Anderson
authors.forename: M
authors.initials: M
authors.lastname: Manousos
authors.forename: J
authors.initials: J
authors.lastname: Barrett
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D010397:Penicillanic Acid