Synthesis and structure-activity relationships of a new series of cephalosporins, E1040 and related compounds.

Abstract

The synthesis and in vitro antibacterial activity of a series of 7-[(Z)-2-aminoaryl-2-oxyiminoacetamido]-3-ammoniomethyl++ +-3-cephems are described. Variation of an oxyimino moiety with aminoaryl at the C-7 side chain and a quaternary ammonium moiety at the C-3 side chain were examined and structure-activity relationships were studied. E1040, the 3-(4-carbamoylquinuclidinio)methyl derivative of the 7-alpha-methoxyimino series of aminothiadiazolyl cephalosporins, exhibited excellent activity against both Gram-positive and Gram-negative bacteria, particularly against Pseudomonas aeruginosa, and possessed high stability to beta-lactamases.