1256757-70-6Relevant academic research and scientific papers
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
Hobbs, Heather,Bravi, Gianpaolo,Campbell, Ian,Convery, Maire,Davies, Hannah,Inglis, Graham,Pal, Sandeep,Peace, Simon,Redmond, Joanna,Summers, Declan
supporting information, p. 6972 - 6984 (2019/09/16)
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 Π-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).
MORPHOLINO SUBSTITUTED UREA DERIVATIVES AS MTOR INHIBITORS
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Page/Page column 80-81, (2011/10/03)
The invention relates to compounds of formula (I) wherein X1, X2, R1 to R4, m, n have the meaning as cited in the description and the claims. Said compounds are useful as inhibitors of mTOR for the treatment or prophylaxis of mTOR related diseases and disorders. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments.
