Synthesis and structure-activity relationship of new cephalosporins with amino heterocycles at C-7. Dependence of the antibacterial spectrum and β-lactamase stability on the pK(a) of the C-7 heterocycle

Article abstract of DOI:10.1021/jm00107a035

Cephalosporins with new aminobenzimidazole and aminoimidazoline heterocycles at C-7 have been synthesized starting with versatile C-7 isocyanide dihalide synthons. The aminobenzimidazoles have a broad spectrum of antibacterial activity, including Gram-positive and Gram-negative organisms, but possess limited β-lactamase stability. In contrast, the aminoimidazolines have a narrow spectrum of antibacterial activity, limited to Gram-negative strains only, but possess outstanding β-lactamase stability. Structure-activity relationships are discussed in terms of their dependence on the pK(a) of the C-7 amino heterocycle, basic C-7 residues giving cephalosporins with exceptional β-lactamase stability.