Cephalosporins. VII. Synthesis and antibacterial activity of new cephalosporins bearing a 2-imino-3-hydroxythiazoline (2-aminothiazole N-oxide) in the C-7 acylamino side chain.

ABSTRACT

Introduction of a hydroxyl group into the thiazole ring nitrogen of cephalosporins belonging to the cefotiam and cefotaxime families gave rise to products, better described by the tautomeric N-oxide form, which proved particularly active against Gram-negative bacteria. Cephems bearing a (Z)-alkoxyimino functionality are of special interest for broadness of spectrum; among them, 7 beta-[(Z)-2-(2-amino-4-thiazolyl-N-oxide)-2 -methoxyiminoacetamido]-3-(tetrazolo-[1,5-b] pyridazin-6-yl)thiomethyl-3-cephem-4-carboxylic acid (5c-7, FCE 20635), in other ways similar to cefotaxime, showed useful levels of activity against cephalosporinase-producing strains resistant to the reference drug. Preliminary in vivo studies demonstrated the therapeutic efficacy of the new compound in the treatment of experimental systemic, subcutaneous and urinary tract infections in mice.