Prodrugs of Phosphonates and Phosphates: Crossing the Membrane Barrier

  • Andrew J. Wiemer
  • David F. WiemerEmail author
Part of the Topics in Current Chemistry book series (TOPCURRCHEM, volume 360)


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 











1-Deoxy-d-xylulose 5-phosphate


Epstein–Barr virus


G protein coupled receptor




Hepatitis B virus


Hepatitis C virus




Human immunodeficiency virus




Herpes-simplex virus


Nucleoside analogue










S-Acylthioalkyl ester



Financial support from the University of Connecticut, Department of Pharmaceutical Sciences (AJW) and from the Roy J. Carver Charitable Trust as a Research Program of Excellence (DFW) and the NIH (R01CA-172070, DFW) is gratefully acknowledged.


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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Department of Pharmaceutical SciencesUniversity of ConnecticutStorrsUSA
  2. 2.Departments of Chemistry and PharmacologyUniversity of IowaIowa CityUSA

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