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

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)-alkoxyimi...

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Bibliographic Details
Published in:Journal of antibiotics 1984, Vol.37(11), pp.1423-1440
Main Authors: PERRONE, ETTORE, ALPEGIANI, MARCO, GIUDICI, FRANCO, BUZZETTI, FRANCO, NANNINI, GIULIANO, MEINARDI, GIUSEPPE, GRASSO, SILVIO, BIANCHI, ALBERTA, CARNERI, IVO DE
Format: Article
Language:English
Subjects:
Animals
Bacteria - drug effects
Bacterial Infections - prevention & control
beta-Lactamases - pharmacology
Biological and medical sciences
Cephalosporins - chemical synthesis
Cephalosporins - pharmacology
Cephalosporins - therapeutic use
General pharmacology
Humans
Male
Medical sciences
Mice
Microbial Sensitivity Tests
Pharmacology. Drug treatments
Physicochemical properties. Structure-activity relationships
Structure-Activity Relationship
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Summary: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, 7β-[(Z)2-(2-amino-4-thiazolyl-N-oxide)-2-methoxyiminoacetanlido]-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.
ISSN:0021-8820
1881-1469
DOI:10.7164/antibiotics.37.1423