Discovery of 3-Oxabicyclo[4.1.0]heptane, a Non-nitrogen Containing Morpholine Isostere, and Its Application in Novel Inhibitors of the PI3K-AKT-mTOR Pathway was written by Hobbs, Heather;Bravi, Gianpaolo;Campbell, Ian;Convery, Maire;Davies, Hannah;Inglis, Graham;Pal, Sandeep;Peace, Simon;Redmond, Joanna;Summers, Declan. And the article was included in Journal of Medicinal Chemistry in 2019.Reference of 62968-37-0 This article mentions the following:
4-(Pyrimidin-4-yl)morpholines are privileged pharmacophores for PI3K and PIKKs inhibition by virtue of the morpholine oxygen, both forming the key hydrogen bonding interaction and conveying selectivity over the broader kinome. Key to the morpholine utility as a kinase hinge binder is its ability to adopt a coplanar conformation with an adjacent aromatic core favored by the morpholine nitrogen nonbonding pair of electrons interacting with the electron deficient pyrimidine 闁?system. Few selective morpholine replacements have been identified to date. Herein we describe the discovery of a potent non-nitrogen containing morpholine isostere with the ability to mimic this conformation and its application in a potent selective dual inhibitor of mTORC1 and mTORC2 (29b). In the experiment, the researchers used many compounds, for example, 4-(2-Chloropyrimidin-4-yl)morpholine (cas: 62968-37-0Reference of 62968-37-0).
4-(2-Chloropyrimidin-4-yl)morpholine (cas: 62968-37-0) belongs to pyrimidine derivatives. The aromatic compound pyrimidine, and its derivatives, are ubiquitous in nature. They are found in nucleic acids, vitamins, amino acids, antibiotics, alkaloids, and a variety of toxins. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own.Reference of 62968-37-0
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia