Quaternary heterocyclylamino beta-lactams: a generic alternative to the classical acylamino side chain.

6 beta-[(1-Substituted-4-pyridinio)amino]penam-3-carboxylates and 7 beta-[(1-substituted-4-pyridinio)amino]ceph-3-em-4-carboxylates have been found to be interesting new classes of antibacterial beta-lactams, readily available by SN2 Ar coupling of fluoro-substituted quaternized pyridines and appropriate amino lactam carboxylic acids. Compared to penicillin G, the penam 12c exhibited a spectrum extended to Gram-negative species, such as Escherichia, Shigella, Klebsiella and Enterobacter, offset by a loss of potency against Gram-positive species. Excluding Pseudomonas, many examples of the cephems showed excellent activity against the above Gram-negative organisms, and in some cases, such as 15i, the spectrum included good performance against the staphylococci and streptococci. With Serratia and many Proteus species, there was an adverse inoculum and medium effect which was not observed in the good Gram-positive reach of the cephem series.