The morpholine ring is considered the most preferred and versatile
heterocylic ring in medicinal chemistry due to its distinctive mechanistic activities that
give it various biological activities. The eminence of the morpholine ring to modulate
the pharmacokinetic properties of the compound, further makes it a fundamental
pharmacophore in developing lead molecules. Multi-drug resistance in cancer leads to
discovering selective and potent chemotherapeutic agents. Researchers are designing
and synthesizing morpholine derivatives as potential anticancer drugs those act by
targeting various signaling pathways driven by various protein kinases in the cell, i.e.
Ras-Raf-MEK-ERK (ERK) and PI3K/Akt/mTOR, thereby inhibiting cell proliferation
and growth. The potency of natural and synthetic derivatives of morpholine makes it a
drug of choice for cancer treatment. Many of the morpholine containing anticancer
drugs are under clinical trials. Hence, morpholine ring synthesis also becomes a central
target for various scientists using green synthesis by straightforward one-step methods.
A substantial literature is available on synthetic techniques of morpholine and
substituted morpholine. The present chapter updates diverse new synthetic strategies of
the morpholine ring and morpholine derivatives with potent anticancer activity. The
chapter will also highlight the clinical data of morpholine derivatives with anticancer
activity and mechanism of action. The latest information on novel anticancer
morpholine derivatives with structural activity relationship (SAR) is also included. This
chapter provides information about the necessary structural modifications required in
drugs' chemical structure and contribute to the anticancer drug discovery program.