Morpholine as ubiquitous pharmacophore in medicinal chemistry: Deep insight into the structure-activity relationship (SAR)

Morpholine is a versatile moiety, a privileged pharmacophore and an outstanding heterocyclic motif with wide ranges of pharmacological activities due to different mechanisms of action. The ability of morpholine to enhance the potency of the molecule through molecular interactions with the target protein (kinases) or to modulate the pharmacokinetic properties propelled medicinal chemists and researchers to synthesize morpholine ring by the efficient ways and to incorporate this moiety to develop various lead compounds with diverse therapeutic activities. The present review primarily focused on discussing the most promising synthetic leads containing morpholine ring along with structure-activity relationship (SAR) to reveal the active pharmacophores accountable for anticancer, anti-inflammatory, antiviral, anticonvulsant, antihyperlipidemic, antioxidant, antimicrobial and antileishmanial activity. This review outlines some of the recent effective chemical synthesis for morpholine ring. The review also highlighted the metabolic liability of some clinical drugs containing this nucleus and various researches on modified morpholine to enhance the metabolic stability of drugs as well. Drugs bearing morpholine ring and those under clinical trials are also mentioned with the role of morpholine and their mechanism of action. This review will provide the necessary knowledge base to the medicinal chemists in making strategic structural changes in designing morpholine derivatives.