The intensive use of antibiotics has exerted a selective evolutionary pressure on micro-organisms to produce genetically based resistance mechanisms. Modern medicine and socio-economic behaviour exacerbates the problem of resistance development by creating slow growth situations for pathogenic microbes, e.g. in artificial joints, and by supporting long-term host reservoirs, e.g. in immuno-compromised patients.
In hospital settings, an increasing number of strains of Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus spp., and Pseudomonas aeruginosa, major sources of infections, are becoming multi-drug resistant and therefore difficult if not impossible to treat:                S. aureus is resistant to β-lactams, quinolones and now even to vancomycin;        S. pneumoniae is becoming resistant to penicillin or quinolone antibiotics and even to new macrolides;        Enteroccocci are quinolone and vancomycin resistant and β-lactam antibiotics are inefficacious against these strains;        Enterobacteriacea are cephalosporin and quinolone resistant;        P. aeruginosa are β-lactam and quinolone resistant.        
Further new emerging organisms like Acinetobacter spp. or C. difficile, which have been selected during therapy with the currently used antibiotics, are becoming a real problem in hospital settings.
In addition, microorganisms that are causing persistent infections are increasingly being recognized as causative agents or cofactors of severe chronic diseases like peptic ulcers or heart diseases.
WO 2006/010831 describes inter alia substituted 4-quinoline derivatives which do however notably not possess the oxazolidinone motif of the invention compounds.
WO 02/50040 discloses inter alia substituted 4-quinoline derivatives compounds which could have the oxazolidinone motif but always include a piperazine ring in their middle chain.
Besides, WO 2006/032466 discloses antibacterial compounds that possess certain motifs of the instant invention, i.e. the alkoxy-substituted quinoline, naphthyridine, quinoxaline or quinazoline and the benzofused bicyclic system at both ends of the molecule, but not the oxazolidinone motif attached to said benzofused bicyclic system.
USPTO Backgrounds
USPTO Backgrounds