6-(substituted methylene)penems, potent broad spectrum inhibitors of bacterial beta-lactamase. V. Chiral 1,2,3-triazolyl derivatives.
Structure-activity relationships in a series of (5R)-6-triazolylmethylene penems with potent beta-lactamase inhibitory activity are described. In most cases, their in vitro synergistic activity with amoxycillin is superior to that of clavulanic acid, sulbactam and tazobactam (YTR 830). Against an Escherichia coli TEM-1 infection in mice, the compounds showed a broad range of potencies; an optimum polarity was found, however, which gave maximum potency.
SmithKline Beecham Pharmaceuticals, Chemotherapeutic Research Centre, Betchworth, Surrey, UK.
I S
IS
Bennett
G
G
Brooks
N J
NJ
Broom
S H
SH
Calvert
K
K
Coleman
I
I
François
D000658:Amoxicillin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004357:Drug Synergism; D004927:Escherichia coli Infections / Q000188:drug therapy; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D065093:beta-Lactamase Inhibitors
D000900:Anti-Bacterial Agents; D014230:Triazoles; D065093:beta-Lactamase Inhibitors; D000658:Amoxicillin