[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.
Inamoto
Y
Y
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Sakane
K
K
Kamimura
T
T
Takaya
T
T
D000818:Animals; D001419:Bacteria / Q000187:drug effects*; D000077525:Cefdinir; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D051381:Rats; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
D002511:Cephalosporins; D000077525:Cefdinir