2. Academic Validation
  3. Identification of a novel series of potent RON receptor tyrosine kinase inhibitors

Identification of a novel series of potent RON receptor tyrosine kinase inhibitors

  • Bioorg Med Chem Lett. 2010 May 1;20(9):2745-9. doi: 10.1016/j.bmcl.2010.03.073.
Stéphane Raeppel 1,  Frédéric Gaudette,  Michael Mannion,  Stephen Claridge,  Oscar Saavedra,  Ljubomir Isakovic,  Robert Déziel,  Normand Beaulieu,  Carole Beaulieu,  Isabelle Dupont,  Hannah Nguyen,  James Wang,  A Robert Macleod,  Christiane Maroun,  Jeffrey M Besterman,  Arkadii Vaisburg
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, MethylGene Inc., 7220 rue Frederick-Banting, Montréal, QC, Canada H4S 2A1. raeppels@methylgene.com
PMID: 20363625 DOI: 10.1016/j.bmcl.2010.03.073
Abstract

A novel series of N-(3-fluoro-4-(2-substituted-thieno[3,2-b]pyridin-7-yloxy)phenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamides targeting RON receptor tyrosine kinase was designed and synthesized. SAR study of the series allowed us to identify compounds possessing either inhibitory activity of RON kinase Enzyme in the low nanomolar range with low residual activity against the closely related c-Met or potent dual inhibitory activity against RON and c-Met, with no significant activity against VEGFR2/KDR/Flk-1 in both cases.

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