Linking bisphosphonates to the free amino groups in fluoroquinolones: preparation of osteotropic prodrugs for the prevention of osteomyelitis.

摘要: Osteomyelitis is an infection located in bone and a notoriously difficult disease to manage, requiring frequent heavy doses of systemically administered antibiotics. Targeting antibiotics the after systemic administration may provide both greater efficacy treatment less administration. By taking advantage affinity bisphosphonate group for mineral, we have prepared set 13 bisphosphonated antibacterial prodrugs based on eight different linkers tethered free amino functionality fluoroquinolone While all but one were shown vitro be effective rapid binders (over 90% 1 h), only them demonstrated capacity significantly regenerate parent drug. In rat model disease, selected agents their ability prevent osteomyelitis when used circumstances under which drug had already been cleared thus inactive.