Quinolinecarboxylic acids. 3. Synthesis and antibacterial evaluation of 2-substituted-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de] [1,4]benzothiazine-6-carboxylic acids related to rufloxacin.
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.
Cecchetti
V
V
Istituto di Chimica Farmaceutica e Tecnica Farmaceutica, Università di Perugia, Italy.
Fravolini
A
A
Pagella
P G
PG
Savino
A
A
Tabarrini
O
O
D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001581:Benzothiadiazines / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D013293:Enterococcus faecalis / Q000187:drug effects; D024841:Fluoroquinolones; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008826:Microbial Sensitivity Tests; D010879:Piperazines / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D015363:Quinolones / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology
D000890:Anti-Infective Agents; D001581:Benzothiadiazines; D002264:Carboxylic Acids; D024841:Fluoroquinolones; D006845:Hydrocarbons, Fluorinated; D010879:Piperazines; D011804:Quinolines; D015363:Quinolones; D013450:Sulfones; C060328:rufloxacin