6-(substituted methylene)penems, potent broad spectrum inhibitors of bacterial beta-lactamase. III. Structure-activity relationships of the 5-membered heterocyclic derivatives.
Sodium (5RS)-Z-6-(heterocyclylmethylene)penem-3-carboxylates (2) are a series of extremely potent inhibitors of bacterial beta-lactamases. A variety of 5-membered heteroaromatic derivatives have been prepared and structure-activity studies reveal a preferred substituent orientation. One of these derivatives, the 1-methyl-1,2,3-triazolyl compound (5m) is a more potent synergist of amoxycillin than clavulanic acid, sulbactam or tazobactam.
Bennett
I
I
Smith Kline Beecham Pharmaceuticals, Chemotherapeutic Research Centre, Surrey, UK.
Broom
N J
NJ
Bruton
G
G
Calvert
S
S
Clarke
B P
BP
Coleman
K
K
Edmondson
R
R
Edwards
P
P
Jones
D
D
Osborne
N F
NF
D000658:Amoxicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology; D004357:Drug Synergism; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D065093:beta-Lactamase Inhibitors
D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D000658:Amoxicillin