A novel series of parenteral cephalosporins exhibiting potent activities against Pseudomonas aeruginosa and other Gram-negative pathogens: Synthesis and structure–activity relationships
- 1 November 2007
- journal article
- Published by Elsevier BV in Bioorganic & Medicinal Chemistry
- Vol. 15 (21), 6716-6732
- https://doi.org/10.1016/j.bmc.2007.08.001
Abstract
A series of 7β-[2-(2-aminothiazol-4-yl)-2-(Z)-(carboxymethoxyimino)acetamido]cephalosporins bearing a 1-(substituted)-1H-pyrrolo[3,2-b]pyridinium group at C-3′ position was synthesized and their in vitro antibacterial activities against Pseudomonas aeruginosa and other Gram-negative pathogens were evaluated. Among the cephalosporins prepared, 7β-[2-(2-amino-5-chlorothiazol-4yl)-2(Z)-((S)-1-carboxyethoxyimino)acetamido]cephalosporins (42d) showed potent antibacterial activities against P. aeruginosa and other Gram-negative pathogens including the strains which produce class C β-lactamase and extended spectrum β-lactamase (ESBL). These results imply that both the Cl atom on the C-7 aminothiazole moiety and the α-substituent at the iminoether moiety are essential for the stability against β-lactamase and the potent activity against Gram-negative bacteria including P. aeruginosa.Keywords
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