Abstract
A series of 2-substituted-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzothiazine-6 -carboxylic acids has been prepared and evaluated for in vitro antibacterial activity. These derivatives were less active than corresponding desmethylated analogues. Among these derivatives, the most active compound 22a was selected for preliminary pharmacokinetics in rats. The pharmacokinetic data indicated that 22a was rapidly absorbed and induced lasting plasma and urinary levels. In comparison with rufloxacin, it was excreted in low quantity in urine; a significant amount of desmethylated piperazinyl urinary metabolite was observed.
MeSH terms
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Animals
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Anti-Infective Agents / pharmacokinetics
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Anti-Infective Agents / pharmacology*
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Benzothiadiazines / chemical synthesis
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Benzothiadiazines / pharmacokinetics
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Benzothiadiazines / pharmacology
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Carboxylic Acids / chemical synthesis
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Carboxylic Acids / pharmacokinetics
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Carboxylic Acids / pharmacology
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Enterococcus faecalis / drug effects
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Fluoroquinolones*
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Gram-Negative Bacteria / drug effects
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Hydrocarbons, Fluorinated / chemical synthesis
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Hydrocarbons, Fluorinated / pharmacokinetics
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Hydrocarbons, Fluorinated / pharmacology
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Male
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Microbial Sensitivity Tests
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Piperazines / chemical synthesis
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Piperazines / pharmacokinetics
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Piperazines / pharmacology
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Quinolines / chemical synthesis*
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Quinolines / pharmacokinetics
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Quinolines / pharmacology*
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Quinolones / pharmacokinetics
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Quinolones / pharmacology*
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Rats
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Rats, Wistar
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Staphylococcus aureus / drug effects
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Structure-Activity Relationship
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Sulfones / chemical synthesis
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Sulfones / pharmacokinetics
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Sulfones / pharmacology
Substances
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Anti-Infective Agents
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Benzothiadiazines
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Carboxylic Acids
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Fluoroquinolones
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Hydrocarbons, Fluorinated
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Piperazines
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Quinolines
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Quinolones
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Sulfones
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rufloxacin