Studies on FK482 (Cefdinir). IV. Synthesis and structure-activity relationships of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]- 3-substituted cephalosporin derivatives

The synthesis of 7 beta-(Z)-2-(aminothiazol-4-yl)-2-hydroxyiminoacetamido] cephalosporins (Ia-i) modified at the C-3 position of a cephem nucleus and the effect of the C-3 substituents on the antibacterial activity and oral absorbability are discussed. The cephems (Ie, h and i) having a C-3 substituent such as 1-propenyl, ethylthio and vinylthio group as well as FK482 (cefdinir) exhibited excellent antibacterial activities against both gram-positive and gram-negative bacteria. However, those compounds showed poor absorption rate after oral administration in rats. It is concluded that the vinyl moiety at the 3-position is necessary to display fairly oral absorptivity in a series of 7 beta-(Z)-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]c eph ems.