Prodrugs-Current and Future Drug Development Strategy

The  focus  of  traditional  prodrug  approach  was  on  altering  various  physiochemical  parameters, whereas the current modern computational approach considers designing prodrugs through attaching appropriate  linkers  with  drugs  having  poor  bioavailability  which  upon  exposure  to  physiological environments release the parent active drugs in a programmable (controlled) manner resulting in an improvement of their bioavailability. With the possibility of designing prodrugs with different linkers, the release rate of the parent active drugs can be controlled. The future of  prodrug  technology  is  exciting  and  yet  challenging. Advances must be made in understanding the chemistry of many organic reactions that can be effectively utilized to enable the development of more types of prodrugs. The understanding of organic reaction mechanisms of certain processes, particularly intramolecular reactions, will be the next major milestone in this field. It is envisioned that the future of prodrug technology holds the  ability  to  create  safe and  efficacious delivery of a wide range of active small molecules and biotherapeutics. This goal can be achieved using computational chemistry methods such as ab initio, semi-empirical and density functional theory (DFT), and molecular mechanics (MM) to calculate physicochemical and molecular  properties of current marketed drugs suffer low bioavailability or/and unpleasant taste or odor.

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