Morpholine is a heterocycle featured in numerous approved and
experimental drugs as well as bioactive molecules. It is often employed
in the field of medicinal chemistry for its advantageous
physicochemical, biological, and metabolic properties, as well as its
facile synthetic routes. The morpholine ring is a versatile and readily
accessible synthetic building block, it is easily introduced as an amine
reagent or can be built according to a variety of available synthetic
methodologies. This versatile scaffold, appropriately substituted,
possesses a wide range of biological activities. There are many examples
of molecular targets of morpholine bioactive in which the significant
contribution of the morpholine moiety has been demonstrated; it is an
integral component of the pharmacophore for certain enzyme active-site
inhibitors whereas it bestows selective affinity for a wide range of
receptors. A large body of in vivo studies has demonstrated morpholine's
potential to not only increase potency but also provide compounds with
desirable drug-like properties and improved pharamacokinetics. In this
review we describe the medicinal chemistry/pharmacological activity of
morpholine derivatives on various therapeutically related molecular
targets, attempting to highlight the importance of the morpholine ring
in drug design and development as well as to justify its classification
as a privileged structure