SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF NEW CEPHALOSPORINS WITH AMINOIMIDAZOLES AT C-7 - EFFECT OF THE PKA OF THE C-7 AMINOIMIDAZOLE ON ANTIBACTERIAL SPECTRUM AND BETA-LACTAMASE STABILITY

Cephalosporins with new aminoimidazole heterocycles at C-7 have been s ynthesized by reaction of anti-alpha-aminooximes with C-7 dihaloisocya nocephalosporins esters or by direct condensation of 2-fluoroimidazole s with C-7 aminocephalosporins esters. These compounds combine a broad spectrum of antibacterial activity, including Gram-negative and Gram- positive organisms with a good beta-lactamase stability. Activity is d iscussed in terms of its relationship to the pKa of the C-7 aminoimida zole heterocycle, basic C-7 aminoimidazole residues gave cephalosporin s with the best beta-lactamase stability but the poorest activity agai nst Gram-positive organisms. An additional interesting property of the C-7 imidazolylaminocephalosporins is the oral activity present in som e compounds of this series.