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Phosphonate prodrugs: an overview and recent advances

    Kenneth M Heidel

    Department of Chemistry, George Washington University, Washington, DC 20052, USA

    &
    Cynthia S Dowd

    *Author for correspondence:

    E-mail Address: cdowd@gwu.edu

    Department of Chemistry, George Washington University, Washington, DC 20052, USA

    Published Online:https://doi.org/10.4155/fmc-2018-0591

    Phosphonates, often used as isosteric replacements for phosphates, can provide important interactions with an enzyme. Due to their high charge at physiological pH, however, permeation into cells can be a challenge. Protecting phosphonates as prodrugs has shown promise in drug delivery. Thus, a variety of structures and cleavage/activation mechanisms exist, enabling release of the active compound. This review describes the structural diversity of these pro-moieties, relevant cleavage mechanisms and recent advances in the design of phosphonate prodrugs.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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