Department of Chemistry, George Washington University, Washington, DC 20052, USA.
Future Med Chem. 2019 Jul;11(13):1625-1643. doi: 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.
膦酸酯通常被用作磷酸盐的等排体替换物，可以与酶提供重要的相互作用。然而，由于其在生理 pH 下带高电荷，因此渗透进入细胞可能是一个挑战。将膦酸酯保护为前药已显示出在药物传递方面的应用前景。因此，存在各种结构和裂解/激活机制，能够释放活性化合物。本综述描述了这些前药基团的结构多样性、相关的裂解机制以及膦酸酯前药设计的最新进展。
