Patent Evaluation: Novel Quinolinecarboxylic Acids as Potent Antibacterial Agents

Summary

Novelty: Novel quinolinecarboxylic acid derivatives which have a condensed teteracycline ring (9,1-iminomethano-5H-thiazolo[3,2–1]quinoline ring) are disclosed. A process for preparing these compounds and intermediates is also described. These compositions are said to have excellent antibacterial activity.

Biology: Minimum inhibitory concentration (MIC) values were assessed for twenty-five strains of clinically isolated Staphylococcus aureus, including sixteen methicillin resistant strains, twenty-five strains of clinically isolated Staphylococcus epidermidis, twenty-five strains of clinically isolated Enterococcus faecalis and twenty-five strains of clinically isolated Enterococcus faecium. MIC₅₀ values and MIC₉₀ values are given for twenty compounds, all compounds exhibit MIC₅₀ values of less than 1μg/ml and MIC₉₀ values of less than 7 μg/ml. ED₅₀ values were also calculated for various compounds and fall in the range 10.8–1.9 mg/kg.

Chemistry: The syntheses of twenty-eight compounds are described in detail. All compounds were prepared by conventional methods. Seventeen compounds are specifically claimed including 9,1-(methylimino)methano-7-fluoro-8-(2-methylmorpholino)-5-oxo-5H-thia zolo-[3,2-a]quinoline-4-carboxylic acid.

Structure: