Novel 6-aminofuro[3,2-c]pyridines as potent, orally efficacious inhibitors of cMET and RON kinases

  • Bioorg Med Chem Lett. 2013 Aug 1;23(15):4381-7. doi: 10.1016/j.bmcl.2013.05.074.
Arno G Steinig  1 ,  An-Hu Li ,  Jing Wang ,  Xin Chen ,  Hanqing Dong ,  Caterina Ferraro ,  Meizhong Jin ,  Mridula Kadalbajoo ,  Andrew Kleinberg ,  Kathryn M Stolz ,  Paula A Tavares-Greco ,  Ti Wang ,  Mark R Albertella ,  Yue Peng ,  Linda Crew ,  Jennifer Kahler ,  Julie Kan ,  Ryan Schulz ,  Andy Cooke ,  Mark Bittner ,  Roy W Turton ,  Maryland Franklin ,  Prafulla Gokhale ,  Darla Landfair ,  Christine Mantis ,  Jen Workman ,  Robert Wild ,  Jonathan Pachter ,  David Epstein ,  Mark J Mulvihill
Affiliations
  • 1. OSI Pharmaceuticals, LLC, A Wholly-Owned Subsidiary of Astellas US, 1 Bioscience Park Drive, Farmingdale, NY 11735, USA. [email protected]
PMID: 23773865 DOI: 10.1016/j.bmcl.2013.05.074
Abstract

A series of novel 6-aminofuro[3,2-c]pyridines as kinase inhibitors is described, most notably, OSI-296 (6). We discuss our exploration of structure-activity relationships and optimization leading to OSI-296 and disclose its pharmacological activity against cMET and RON in cellular assays. OSI-296 is a potent and selective inhibitor of cMET and RON kinases that shows in vivo efficacy in tumor xenografts models upon oral dosing and is well tolerated.

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