Semisynthetic beta-lactam antibiotics. IV. Synthesis and antibacterial activity of 7 beta-[2-(hetero aromatic methoxyimino)-2-(2-aminothiazol-4-yl)acetamido]cephalosporins.

A series of 7 beta-[2-(hetero aromatic methoxyimino)-2-(2-aminothiazol-4-yl)acetamido]- cephalosporins have been synthesized and bacteriologically evaluated. Several substances in this series showed exceptional in vitro activity, especially those with a five-membered hetero aromatic substituent moiety at the 7-position and a quaternary ammonium group as the 3-function of the cephem nucleus. The most active derivative, 7 beta-[2-(imidazol-4-ylmethoxyimino)-2-(2-aminothiazol-4-yl)a cetamido]-3-(pyridiniomethyl)ceph-3-em-4-carboxylate (13a) was the most evenly balanced with respect to activity against Gram-positive and Gram-negative bacteria. Furthermore, 13 was stable to various types of beta-lactamases and had high affinities for penicillin binding protein-3 and -1Bs of both Escherichia coli and Pseudomonas aeruginosa.