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 β-LACTAMASE STABILITY

Abstract

Cephalosporins with new aminoimidazole heterocycles at C-7 have been synthesized by reaction of anti-α-aminooximes with C-7 dihaloisocyanocephalosporins esters or by direct condensation of 2-fluoroimidazoles with C-7 aminocephalosporins esters. These compounds combine a broad spectrum of antibacterial activity, including Gram-negative and Gram-positive organisms with a good β-lactamase stability. Activity is discussed in terms of its relationship to the pKa. of the C-7 aminoimidazole heterocycle, basic C-7 aminoimidazole residues gave cephalosporins with the best β-lactamase stability but the poorest activity against Gram-positive organisms. An additional interesting property of the C-7 imidazolylaminocephalosporins is the oral activity present in some compounds of this series.