Triazines incorporating (R)-3-methylmorpholine are potent inhibitors of the mammalian target of rapamycin (mTOR) with selectivity over PI3Kalpha.
Potent inhibitors of the mammalian target of rapamycin (mTOR) which contain the triazine scaffold and the (R)-3-methyl morpholine moiety have been identified. Such compounds also demonstrated good selectivity over the related lipid kinase PI3Kalpha. Incorporation of additional functionality at the 4-position of the arylureidophenyl ring resulted in compounds with enhanced cellular activity.
Richard
David J
DJ
Chemical Sciences, Wyeth Research, Pearl River, NY 10965, USA. david.j.richard@pfizer.com
Verheijen
Jeroen C
JC
Yu
Ker
K
Zask
Arie
A
D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D009025:Morpholines / Q000737:chemistry*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D058570:TOR Serine-Threonine Kinases; D014227:Triazines / Q000737:chemistry / Q000494:pharmacology*
D047908:Intracellular Signaling Peptides and Proteins; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D014227:Triazines