Kazuhiko Sugita

In vitro and in vivo Antibacterial Activity and Pharmacokinetics of SC-002 and Its Derivative, SC-004: New Oral Cephalosporins

SC-002 is a novel oral cephalosporin possessing a unique thiadiazolylethenyl moiety at the 3 position. In the present study, it was the most active against gram-positive bacteria among oral cephalosporins such as cefdinir (CFDN), cefpodoxime, cefditoren and cefaclor (CCL). It was equal to or 16 times more active than CFDN against standard and clinical strains. In particular, against clinical isolates of Morganella morganii and Haemophilus influenzae, SC-002 was 8–64 times more active than CFDN. The antibacterial activity of SC-002 against some β-lactam-resistant strains was superior to that of CFDN. The in vivo antibacterial activity of SC-004, a pivaloyloxymethyl ester of SC-002, was 1.2–8 times more protective against systemic infections due to Streptococcus pneumoniae, Escherichia coli and Klebsiella pneumoniae than that of CFDN. The therapeutic effects of SC-004 on experimental respiratory tract infections caused by S. pneumoniae or H. influenzae were superior to those of CFDN and CCL. SC-004 showed higher and longer-lasting blood levels and higher urinary excretion in pharmacokinetics in mice.

Synthesis and biological properties of 3-[(Z)-2-(1,2,3-Thiadiazolyl)ethenyl]-substituted cephalosporins and related compounds: new oral cephalosporins

A series of cephalosporins possessing a [(Z-2-(1,2,3-thiadiazolyl)ethenl] moiety at C-3 were synthesized and their biological properties were examined. SC-002 (1a) exhibited excellent activity against both Gram-positive and Gram-negative bacteria. The ester SC-004 (1b) showed good bioavailability after oral administration in mice and rats.