(2-Aryl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)morpholine compounds, their use as mTOR kinase and PI3 kinase inhibitors, and their syntheses.

Abstract

The invention relates to (2-aryl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)morpholine compds. of Formula I (wherein R1, R2, R3, and R4 are independently H or C1-C6alkyl-; or either R1 and R2 or R3 and R4 together may form an C1-C3alkylene chain; R5 is C1-C8acyl-, (un)substituted C1-C6alkyl-, halo, etc.; n = 0-3; R6 is H, (un)substituted C1-C6alkyl-, (un)substituted C1-C6aminoalkyl, etc.; R7 and R8 are independently H, halo, C1-C8acyl-, etc.; Ar is Ph, naphthyl, or N-contg. mono- or bicyclic heteroaryl-) or a pharmaceutically acceptable salt thereof, compns. comprising the compds., and methods for making and using the compds. Example compd. II, prepd. by coupling intermediate 2-chloro-4-morpholin-4-yl-7H-pyrrolo[2,3-d]pyrimidine and 3-hydroxymethylphenylboronic acid, had IC50 values of 1.9 nM, 16 nM, and 0.0011 μM in assays measuring PI3Kα, and PI3Kγ, and mTOR kinase inhibition, resp. [on SciFinder(R)]