Quinolonecarboxylic acids. 2. Synthesis and antibacterial evaluation of 7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzothiazine-6-carboxylic acids.
A series of pyridobenzothiazine acid derivatives was synthesized and their in vitro antibacterial activity was evaluated. The 1,4-benzothiazine intermediates, which by Gould-Jacobs quinoline synthesis produced pyridobenzothiazine acids, were prepared by hydrolytic basic cleavage of substituted 2-aminobenzothiazoles and successive cyclocondensation with 1-bromo-2-chloroethane or alternatively with monochloroacetic acid, hence reduction by LiAlH4. The pyridobenzothiazine acids 10c, 30, and 31 show potent antibacterial activities against Gram-positive and Gram-negative pathogens. Structure-activity relationships are discussed. The compound 9-fluoro-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-d e] [1,4]benzothiazine-6-carboxylic acid (31) (MF-934) has been found to possess, together with the antibacterial activity, a weak acute toxicity and interesting pharmacokinetic characteristics in several animal species (rat, dog, monkey, man).
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D002851:Chromatography, High Pressure Liquid; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D011728:Pyridones / Q000138:chemical synthesis* / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013843:Thiazines / Q000138:chemical synthesis* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; D011728:Pyridones; D013843:Thiazines