title: Triazines incorporating (R)-3-methylmorpholine are potent inhibitors of the mammalian target of rapamycin (mTOR) with selectivity over PI3Kalpha.
abstract: 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.
authors.affiliation: Chemical Sciences, Wyeth Research, Pearl River, NY 10965, USA. david.j.richard@pfizer.com
authors.forename: David J
authors.initials: DJ
authors.lastname: Richard
authors.forename: Jeroen C
authors.initials: JC
authors.lastname: Verheijen
authors.forename: Ker
authors.initials: K
authors.lastname: Yu
authors.forename: Arie
authors.initials: A
authors.lastname: Zask
mesh_terms: 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*
chemical_list: 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