The discovery and optimisation of pyrido[2,3-d]pyrimidine-2,4-diamines as potent and selective inhibitors of mTOR kinase

  • Bioorg Med Chem Lett. 2009 Oct 15;19(20):5950-3. doi: 10.1016/j.bmcl.2009.08.038.
Karine Malagu  1 ,  Heather Duggan ,  Keith Menear ,  Marc Hummersone ,  Sylvie Gomez ,  Christine Bailey ,  Peter Edwards ,  Jan Drzewiecki ,  Frédéric Leroux ,  Mar Jimenez Quesada ,  Gesine Hermann ,  Stephanie Maine ,  Carrie-Anne Molyneaux ,  Armelle Le Gall ,  James Pullen ,  Ian Hickson ,  Lisa Smith ,  Sharon Maguire ,  Niall Martin ,  Graeme Smith ,  Martin Pass
Affiliations
  • 1. KuDOS Pharmaceuticals Ltd, 410 Cambridge Science Park, Milton Road, Cambridge CB4 0WG, UK.
PMID: 19762236 DOI: 10.1016/j.bmcl.2009.08.038
Abstract

We describe a novel series of potent inhibitors of the kinase activity of mTOR. The compounds display good selectivity relative to other PI3K-related kinase family members and, in cellular assays, inhibit both mTORC1 and mTORC2 complexes and exhibit good antiproliferative activity.