Synthesis and structure-activity relationship of new cephalosporins with amino heterocycles at C-7. Dependence of the antibacterial spectrum and .beta.-lactamase stability on the pKa of the C-7 heterocycle

Journal of Medicinal Chemistry
1991.0

Abstract

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 beta-lactamase stability. In contrast, the aminoimidazolines have a narrow spectrum of antibacterial activity, limited to Gram-negative strains only, but possess outstanding beta-lactamase stability. Structure-activity relationships are discussed in terms of their dependence on the pKa of the C-7 amino heterocycle, basic C-7 residues giving cephalosporins with exceptional beta-lactamase stability.

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