STUDIES ON FK482 (CEFDINIR) .4. 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]cephems.