6-(SUBSTITUTED METHYLENE)PENEMS, POTENT BROAD-SPECTRUM INHIBITORS OF BACTERIAL BETA-LACTAMASE .3. 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.