STUDIES ON ORALLY ACTIVE CEPHALOSPORINS

I. SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIPS OF NEW 3-SUBSTITUTED CARBAMOYLOXYMETHYL CEPHALOSPORINS

Abstract

The synthesis and antibacterial activities of 7β-[2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetarnido]-3-N, N-dimethylcarbamoyloxymethyl-3-cephem-4-carboxylic acid (E1 100) and its analogs are described, as well as oral absorbability and in vivo activities of the l-(isopropoxycarbonyloxy)ethyl ester (E1 101) and its analogous esters. The introduction of acyclic and cyclic lower alkyl groups at the N-position of 3-carbamoyloxymethyl cephems influences antibacterial activities, especially against H. influenzae, and oral absorbability of their prodrug esters. The structure-activity relationships are also discussed.