Quinolone antimicrobial agents substituted with morpholines at the 7-position. Syntheses and structure-activity relationships
| Autor: | Yoshito Yokoyama, Kazuhiko Araki, Eiji Iwao, Fumihiro Hirayama, Takashi Yakushiji, Satoru Uemori, Yoshifumi Ikeda, Tsuyoshi Kuroda, Akihiko Moriguchi |
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| Rok vydání: | 1993 |
| Předmět: |
Male
Staphylococcus aureus medicine.drug_class Metabolite Morpholines Microbial Sensitivity Tests Pharmacology Quinolones chemistry.chemical_compound Mice Structure-Activity Relationship Anti-Infective Agents Drug Discovery medicine Escherichia coli Animals Norfloxacin Antibacterial agent Mice Inbred ICR Fenbufen 4-Quinolones Chemistry Quinolone Antimicrobial Molecular Medicine Ofloxacin Antibacterial activity medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 36(10) |
| ISSN: | 0022-2623 |
| Popis: | A series of novel 7-substituted 1-cyclopropyl-6,8-difluoro-1, 4-dihydro-4-oxo-3-quinolinecarboxylic acids have been prepared and tested for antibacterial activities and for convulsive activities in combination with nonsteroidal antiinflammatory drug. Structure-activity relationships revealed that 7-(2-(aminomethyl)morpholino) derivative 28 had a better Gram-positive activity than the reference quinolones, such as ciprofloxacin, norfloxacin, and ofloxacin. Its Gram-negative activity was equipotent with those of norfloxacin and ofloxacin but was inferior to that of ciprofloxacin. In mouse systemic infection models, 28 showed an excellent therapeutic efficacy which might result from the potent antibacterial activity and suitable physicochemical properties. Convulsive activities of 7-morpholino derivatives in combination with nonsteroidal antiinflammatory drug fenbufen or its metabolite biphenylacetic acid markedly diminished as compared to those of 7-piperazino derivatives in the electrophysiological, biochemical, and behavioral experiments. These results suggest that 28 (Y-26611) is a novel quinolone with reduced neurotoxic excitatory adverse reaction. |
| Databáze: | OpenAIRE |
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