Prodrugs of Phosphonates, Phosphinates, and Phosphates

摘要: The aim of this chapter is to review the recent progress in design and development prodrugs phosphonate, phosphinate, phosphate functional groups improve their physicochemical properties, membrane permeability, oral bioavailability, drug targeting. Phosphonates, phosphinates, phosphates are prominently represented as pharmacophores various classes biological agents. These include antiviral anticancer nucleotides, inhibitors biosynthesis cholesterol, angiotensin-converting enzyme inhibitors, bisphosphonates for treatment osteoporosis. It generally well recognized that therapeutic potential drugs containing a or group limited by inadequate permeation absorption. Phosphonate, carry one two negative charges at physiological pH values making them very polar (Figure 1). This high polarity basis many deficiencies terms delivery. Specifically, ionized species do not readily undergo passive diffusion across cellular membranes. Because polarity, these agents often exhibit low volume distribution and, therefore, tend be subject efficient renal clearance possibly biliary excretion.