Bisphosphonated Benzoxazinorifamycin Prodrugs for the Prevention and Treatment of Osteomyelitis

Abstract

Benzoxazinorifamycins are potent antibacterial agents currently in development. Tethering these antibiotics to a bisphosphonate functional group by a cleavable linker allows the delivery of these agents to osseous tissues, where they can be released over time to treat bone infections. Various linker strategies are presented herein to develop osteotropic prodrugs, the activities of which are examined in vitro and in vivo.