Discovery of 2-ureidophenyltriazines bearing bridged morpholines as potent and selective ATP-competitive mTOR inhibitors Academic Article uri icon

Overview

MeSH Major

  • Adenosine Triphosphate
  • Intracellular Signaling Peptides and Proteins
  • Morpholines
  • Protein-Serine-Threonine Kinases
  • Triazines

abstract

  • Incorporation of bridged morpholines in monocyclic triazine PI3K/mTOR inhibitors gave compounds with increased mTOR selectivity relative to the corresponding morpholine analogs. Compounds with ureidophenyl groups gave highly potent and selective mTOR inhibitors. Potency and selectivity was demonstrated both in vitro and in vivo through biomarker suppression studies. Select compounds exhibited potent inhibition of tumor growth in nude mouse xenograft assays upon PO and IV administration.

publication date

  • April 15, 2010

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.bmcl.2010.02.045

PubMed ID

  • 20227881

Additional Document Info

start page

  • 2644

end page

  • 7

volume

  • 20

number

  • 8