STUDIES ON β-LACTAM ANTIBIOTICS IV. AN IMPROVED SYNTHESIS OF 3-(ISOTHIAZOLYLTHIOMETHYL)CEPHALOSPORINS AND ITS APPLICATION TO NEW DERIVATIVES

• Published in: Journal of antibiotics Vol. 47; no. 4; pp. 477 - 486
• Main Authors: HARA, RYUICHIRO, NAKAI, EI-ICHI, HISAMICHI, HIROYUKI, NAGANO, NORIAKI
• Format: Journal Article
• Language: English
• Published: Tokyo JAPAN ANTIBIOTICS RESEARCH ASSOCIATION 1994; Japan Antibiotics Research Association
• Subjects: Animals; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Cephalosporins - chemical synthesis; Cephalosporins - chemistry; Cephalosporins - pharmacokinetics; Cephalosporins - pharmacology; Chromatography, High Pressure Liquid; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Humans; Magnetic Resonance Spectroscopy; Medical sciences; Mice; Microbial Sensitivity Tests; Pharmacology. Drug treatments; Protein Binding; Pseudomonas aeruginosa; Rats; Regression Analysis; Spectrophotometry, Infrared; Pseudomonadales; Antibiotic; Cephalosporin derivatives; Sensitivity resistance; Structure activity relation; Gram positive bacteria; Bacteria; Pseudomonadaceae; Pseudomonas aeruginosa; Antibacterial agent; Chemical synthesis
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.47.477

An improved synthesis and in vitro activity of cephalosporins with a (4-carboxy-3-hydroxy-5-isothiazolyl)thiomethyl group at the 3-position and its application to the preparation of new derivatives are described. These compounds showed excellent activity against Gram-negative bacteria including β-lactamase producing strains. Among them, 2f was the most interesting because of its broad spectrum of antibacterial activity, including Gram-positive bacteria, and its outstanding inhibitory potency against Pseudomonas aeruginosa.