Comparative laboratory studies on alpha-methoxyimino furyl- and phenylacetamido cephalosporins: structure-activity...

Eleven new cephalosporins (three phenylacetamido and eight furylacetamido) containing a methoxyimino group on the 7 beta-acyl side chain and having various substituents at their 3-positions, exhibited similar qualitative, but differing quantitative in vitro antibacterial spectra compared to that of cefuroxime, the first therapeutically used alpha-methoxyimino cephalosporin. The syn-isomers and the alpha-acyl substituted compounds are more active than either the anti-isomer or the beta-acyl substituted compounds. Compounds containing substituted tetrazole rings at the 3-position are likewise more active than those containing other types of substituents in this position. In vivo (mouse) the heterocyclic furylacetamido compounds are more efficacious (protective) than the aromatic phenylacetamido compounds. The furylacetamido alpha-methoxyimino cephalosporins containing at the 3-position the tetrazole group carrying an acidic function possess favorable pharmacokinetic properties, i.e., higher serum levels and prolonged biological half-lives in mouse and squirrel monkey and extensive binding to serum proteins.