STUDIES ON β-LACTAM ANTIBIOTICS I. SYNTHESIS AND IN VITRO ANTI-PSEUDOMONAL ACTIVITY OF 3-ISOTHIAZOLE-CEPHALOSPORIN DERIVATIVES

• Published in: Journal of antibiotics Vol. 40; no. 2; pp. 173 - 181
• Main Authors: NAGANO, NORIAKI, NAKANO, Komi, SHIBANUMA, TADAO, MURAKAMI, YUKIYASU, HARA, RYUICHIRO
• Format: Journal Article
• Language: English
• Published: Tokyo JAPAN ANTIBIOTICS RESEARCH ASSOCIATION 01.02.1987; Japan Antibiotics Research Association
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Cephalosporins - chemical synthesis; Cephalosporins - pharmacology; Chemistry; Exact sciences and technology; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Organic chemistry; Preparations and properties; Pseudomonas aeruginosa - drug effects; Spectrophotometry, Infrared; Structure-Activity Relationship; Thiazoles - chemical synthesis; Thiazoles - pharmacology; Sulfur nitrogen heterocycle; Five membered ring; Carboxylic acid; Lactam; Bicyclic compound; Ketoxime; Antibacterial agent; Biological activity; Organic sulfide
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.40.173

The synthesis and in vitro activity of 7β-[(Z)-2-(2-amino-4-thiazolyl)-2-(2-carboxy-2-alkoxyimino)acetamido]cephalosporins with a (4-carboxy-3-hydroxy-5-isothiazolyl)thiomethyl group at the 3-position are described. These cephalosporins (9a-9i) showed excellent activity against Gram-negative bacteria including β-lactamase producing strains. The most interesting compound of the series was 7β-[(Z)-2-(2-amino-4-thiazolyl)-2-(2-carboxy-2-propoxyimino)acetamido]-3-cephem-4-carboxylic acid (9g, YM-13115) because of its outstanding inhibitory potency against Pseudomonas aeruginosa and highly prolonged plasma half-life in rats.