Open AccessPhosphonate prodrugs: an overview and recent advances
Author(s) -
Kenneth M. Heidel,
Cynthia S. Dowd
Publication year - 2019
Publication title -
future medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.708
H-Index - 69
eISSN - 1756-8927
pISSN - 1756-8919
DOI - 10.4155/fmc-2018-0591
Subject(s) - prodrug , phosphonate , combinatorial chemistry , cleavage (geology) , chemistry , drug , drug delivery , nanotechnology , biochemistry , pharmacology , materials science , organic chemistry , biology , fracture (geology) , composite material
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.