Synthesis and structure-activity relationships of new 7-[3-(fluoromethyl)piperazinyl]- and -(fluorohomopiperazinyl)quinolone antibacterials

作者：Carl B. Ziegler, Panayota Bitha, N. A. KUCK, T. J. Fenton, P. J. Petersen, Y. LIN · 发表于：Journal of Medicinal Chemistry · 年份：1990 · DOI：10.1021/jm00163a024 · 被引用次数：45 · 研究领域：Synthesis and Biological Evaluation、Cancer therapeutics and mechanisms、Antibiotics Pharmacokinetics and Efficacy

Some novel 6-fluoro-7-substituted-1,4-dihydro-4-oxoquinoline-3-carboxylic acids have been prepared. At the N-1 position "standard" substitution was employed with the ethyl, cyclopropyl, and p-fluorophenyl groups being used. At C-7 the introduction of some novel piperazines was made. Most notably, 2-(fluoromethyl)piperazine (10) and hexahydro-6-fluoro-1H-1,4-diazepine (16, fluorohomopiperazine) at the quinolone C-7 position produced products with similar in vitro antibacterial activity as the ciprofloxacin reference. The in vivo efficacy of 1-cyclopropyl-6-fluoro-7-[3-(fluoromethyl)piperazinyl]-1,4-dihydro-4- oxoquinoline-3-carboxylic acid (20) was excellent with better oral absorption than ciprofloxacin (2).