Organic Pharmaceutical Chemistry: Prodrugs

Bioprecursor prodrugs do not contain a carrier or promoiety but rather contain a latent functionality that is metabolically or chemically transformed to the active drug molecule. The types of activation often involve:
1.Oxidative activation,
2.Reductive activation,
3.Phosphorylation,
4.Chemical activation (in some cases ) Oxidation is commonly seen, since a number of endogenous enzymes can carry out these transformations. Phosphorylation has been widely exploited in the development of antiviral agents and many currently available agents depend on this type of activation.
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Bioprecursor Prodrugs

NSAIDs produce stomach irritation. This irritation is associated in part with the presence of an acidic functionality in these agents.
The carboxylic acid functionality commonly found in these agents is un-ionized
in the highly acidic environment of the stomach.
As a result, these agents are more lipophilic in nature and may pass into the cells of the gastric mucosa.
The intracellular pH of these cells is more basic than that of the stomach lumen, and the NSAID becomes ionized.
This results in backflow of H+ from the lumen into these cells, with concomitant cellular damage.
This type of damage could be prevented if the carboxylic acid function could be eliminated from these agents.
However this functional group is required for activity