Triazines incorporating (R)-3-methylmorpholine are potent inhibitors of the mammalian target of rapamycin (mTOR) with selectivity over PI3Kalpha

David J Richard; Jeroen C Verheijen; Ker Yu; Arie Zask

doi:10.1016/j.bmcl.2010.02.029

Triazines incorporating (R)-3-methylmorpholine are potent inhibitors of the mammalian target of rapamycin (mTOR) with selectivity over PI3Kalpha

Bioorg Med Chem Lett. 2010 Apr 15;20(8):2654-7. doi: 10.1016/j.bmcl.2010.02.029. Epub 2010 Feb 11.

Authors

David J Richard¹, Jeroen C Verheijen, Ker Yu, Arie Zask

Affiliation

¹ Chemical Sciences, Wyeth Research, Pearl River, NY 10965, USA. david.j.richard@pfizer.com

PMID: 20223664
DOI: 10.1016/j.bmcl.2010.02.029

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.

MeSH terms

Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
Morpholines / chemistry*
Phosphatidylinositol 3-Kinases / metabolism
Phosphoinositide-3 Kinase Inhibitors*
Protein Serine-Threonine Kinases / antagonists & inhibitors*
TOR Serine-Threonine Kinases
Triazines / chemistry
Triazines / pharmacology*

Substances

Intracellular Signaling Peptides and Proteins
Morpholines
Phosphoinositide-3 Kinase Inhibitors
Triazines
Protein Serine-Threonine Kinases
TOR Serine-Threonine Kinases