Recent Updates on Morpholino Pyrimidine Derivatives as Promising PI3K/Akt/mTOR Inhibitors

Phosphatidylinositol 3-kinase/Protein kinase B/Mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway is critical in cell proliferation, growth, survival, protein synthesis, and glucose metabolism. It plays an important role as drug targets in oncology ascribed to the deregulation of this signaling pathway in various human cancers. Substantial efforts have been made in drug discovery to develop therapeutic interventions, and few pharmacologically well-characterized advance leads have been discovered. The presence of a morpholine ring with a critical hydrogen bond with its oxygen is the most common feature of the inhibitors of this pathway and has served as a valuable chemical tool for developing many PI3K/Akt/mTOR inhibitors. Several research groups have reported Morpholino pyrimidine derivatives as small molecule PI3K/Akt/mTOR inhibitors. In this review, we have focused on the recent developments (from 2010 onwards) in the synthesis and biological activity studies on these morpholino pyrimidine derivatives which will be of immense use to the synthetic organic and medicinal chemists.