[Studies on FK482. II. Synthesis and structure-activity relationships of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-substituted acetamido]-3-vinyl-3-cephem-4-carboxylic acid derivatives].
Various 7 beta-[2-(2-aminothiazol-4-yl)-2-substituted acetamido]-3-vinyl-3-cephem-4-carboxylic acid derivatives (Ia--e, IIa--g) were synthesized in order to find a new orally active cephalosporin improving the antibacterial activity of cefixime (CFIX) against Staphylococcus aureus. These derivatives include three types of alpha-substituted 2-(2-aminothiazol-4-yl)acetyl side chain; i) mono or non substituted acetyl moiety, ii) carboxyalkoxyimino acetyl moiety, iii) phosphonomethoxyimino and hydroxyimino acetyl moiety. Their structure-activity relationships and urinary recoveries in rats were studied. As a result, the compound with a hydroxyimino acetyl side chain (IIg, FK482) showed good oral absorption and excellent antibacterial activity against both gram-positive and gram-negative bacteria and was selected as a candidate for clinical trial.
Inamoto
Y
Y
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Chiba
T
T
Sakane
K
K
Kamimura
T
T
Takaya
T
T
D000818:Animals; D001419:Bacteria / Q000187:drug effects*; D000077525:Cefdinir; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D007408:Intestinal Absorption; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D002511:Cephalosporins; D000077525:Cefdinir