disoproxil

Disoproxil is a prodrug moiety used in medicinal chemistry to improve the oral bioavailability of nucleotide analogs bearing phosphonate or phosphate groups. The disoproxil group consists of two isopropyl-containing carbonate esters attached to a phosphonate, masking its charged, hydrophilic character and increasing lipophilicity. This design facilitates absorption from the gastrointestinal tract and enables delivery of the active drug to systemic circulation, where esterases cleave the ester bonds to release the active nucleotide monophosphate.

The most widely known application is in tenofovir disoproxil fumarate, an oral prodrug of tenofovir used in the treatment of HIV-1 infection and chronic hepatitis B. In this formulation, the disoproxil moiety enhances oral bioavailability; after absorption, enzymatic hydrolysis removes the disoproxil groups, releasing tenofovir, which is subsequently phosphorylated intracellularly to the active diphosphate form that inhibits viral polymerases.

As a prodrug element, disoproxil has no antiviral activity on its own; its value lies in improving pharmacokinetic properties to enable effective delivery of the active drug. The disoproxil strategy has been applied to other phosphonate nucleoside analogs in various developmental and approved antiviral agents, illustrating a broader approach in nucleotide pharmacology and prodrug design.

Chemistry and metabolism: Disoproxil denotes a class of diester prodrugs in which two isopropyl carbonate groups are cleaved in vivo by esterases. The resulting byproducts are typically nonactive metabolites derived from the carbonate and isopropanol fragments.