Application of Nitrile in Drug Design

Nitrile-containing compounds comprise a substantial proportion in the therapeutic drugs.It is an important strategy to introduce nitrile substitute in the small molecule for structure-based medicinal chemistry.The application of nitrile in drug design is reviewed.The nitrile can modulate the physicochemical and pharmacokinetic properties to improve bioavailability, enhance the selectivities and binding affinity to target proteins by hydrogen bond interactions, covalent interactions, polar interactions, and π-π interactions.Meanwhile, the nitrile acts as bioisostere of various functional groups such as carbonyl and halogen groups.In addition, introducing the nitrile to drug molecules can block metabolically labile sites to increase the metabolic stability of drugs.