[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]

Yakugaku Zasshi. 1990 Apr;110(4):246-57. doi: 10.1248/yakushi1947.110.4_246.
[Article in Japanese]

Abstract

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.

MeSH terms

  • Animals
  • Bacteria / drug effects*
  • Cefdinir
  • Cephalosporins / chemical synthesis*
  • Cephalosporins / pharmacokinetics
  • Cephalosporins / pharmacology
  • Drug Resistance, Microbial
  • Intestinal Absorption
  • Male
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship

Substances

  • Cephalosporins
  • Cefdinir