Logo image
Prodrugs of Phosphonates and Phosphates: Crossing the Membrane Barrier
Book chapter

Prodrugs of Phosphonates and Phosphates: Crossing the Membrane Barrier

Andrew J Wiemer and David F Wiemer
Phosphorus Chemistry I, pp.115-160
Topics in Current Chemistry, Springer International Publishing
11/13/2014
DOI: 10.1007/128_2014_561
PMCID: PMC4774048
PMID: 25391982

View Online

Abstract

A substantial portion of metabolism involves transformation of phosphate esters, including pathways leading to nucleotides and oligonucleotides, carbohydrates, isoprenoids and steroids, and phosphorylated proteins. Because the natural substrates bear one or more negative charges, drugs that target these enzymes generally must be charged as well, but small charged molecules can have difficulty traversing the cell membrane by means other than endocytosis. The resulting dichotomy has stimulated a great deal of effort to develop effective prodrugs, compounds that carry little or no charge to enable them to transit biological membranes, but able to release the parent drug once inside the target cell. This chapter presents recent studies on advances in prodrug forms, along with representative examples of their application to marketed and developmental drugs.
Bisphosphonate Isoprenoid Nucleotide Phosphate Phosphonate Prodrugs

Details

Logo image