QUINOLONE ANTIBACTERIAL AGENTS LINKED TO OSTEOTROPIC BISPHOSPHONATE MOIETIES

Abstract Bisphosphonates are widely used in diagnosis and therapy of different bone diseases. Due to their potential to accumulate in the inorganic bone matrix hydroxylapatite they are useful agents in osteotic vectorization of different types of drugs. We linked bisphosphonate moieties to antibacterial quinolones like norfloxacin to enable a selective targeting of these agents to bone tissue. The quinolones (1,4-dihydro-4-oxo-quinoline-3-carboxylic acids) were modified at position 1 and 7 using alkylbisphosphonates with ethene-, amino- and carboxylic-groups. After coupling with the quinolones, the alkylbisphosphonic esters could smoothly be hydrolyzed via the corresponding silyl esters to obtain the free bisphosphonic acids.