Synthesis and biological activity of benzothiazolo[3,2-a]quinolone antibacterial agents.
A new class of heterocyclic compounds with potent antibacterial activity, namely, 2-substituted amino-3-fluoro-5,12-dihydro-5-oxobenzothiazolo[3, 2-a]quinoline-6-carboxylic acids, is described. The compounds are conformationally restricted analogues of 7-substituted amino-6-fluoro-1-aryl-1, 4-dihydro-4-oxoquinoline-3-carboxylic acids. Compounds 7 and 10, having a 4-methylpiperazinyl and a piperazinyl substitution at the 2-position, respectively, possess in vitro antibacterial activities comparable to norfloxacin (15). Compound 8, which has a 4-acetylpiperazinyl substitution at the 2-position, is active against Gram-positive organisms and nearly inactive against Gram-negative organisms. An efficient and short synthesis of this novel heterocyclic system via an intramolecular nucleophilic displacement cyclization reaction is reported.
D000150:Acinetobacter / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004754:Enterobacter / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects; D013297:Streptococcus pyogenes / Q000187:drug effects; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D011804:Quinolines; D013844:Thiazoles