Phosphonate prodrugs: an overview and recent advances
Kenneth M Heidel1, Cynthia S Dowd1
1Department of Chemistry, George Washington University, Washington, DC 20052, USA.
Abstract:
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.
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