title: Novel 6-aminofuro[3,2-c]pyridines as potent, orally efficacious inhibitors of cMET and RON kinases.
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.
authors.affiliation: OSI Pharmaceuticals, LLC, A Wholly-Owned Subsidiary of Astellas US, 1 Bioscience Park Drive, Farmingdale, NY 11735, USA. arnosteinig@gmail.com
authors.forename: Arno G
authors.initials: AG
authors.lastname: Steinig
authors.forename: An-Hu
authors.initials: AH
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Hanqing
authors.initials: H
authors.lastname: Dong
authors.forename: Caterina
authors.initials: C
authors.lastname: Ferraro
authors.forename: Meizhong
authors.initials: M
authors.lastname: Jin
authors.forename: Mridula
authors.initials: M
authors.lastname: Kadalbajoo
authors.forename: Andrew
authors.initials: A
authors.lastname: Kleinberg
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Stolz
authors.forename: Paula A
authors.initials: PA
authors.lastname: Tavares-Greco
authors.forename: Ti
authors.initials: T
authors.lastname: Wang
authors.forename: Mark R
authors.initials: MR
authors.lastname: Albertella
authors.forename: Yue
authors.initials: Y
authors.lastname: Peng
authors.forename: Linda
authors.initials: L
authors.lastname: Crew
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kahler
authors.forename: Julie
authors.initials: J
authors.lastname: Kan
authors.forename: Ryan
authors.initials: R
authors.lastname: Schulz
authors.forename: Andy
authors.initials: A
authors.lastname: Cooke
authors.forename: Mark
authors.initials: M
authors.lastname: Bittner
authors.forename: Roy W
authors.initials: RW
authors.lastname: Turton
authors.forename: Maryland
authors.initials: M
authors.lastname: Franklin
authors.forename: Prafulla
authors.initials: P
authors.lastname: Gokhale
authors.forename: Darla
authors.initials: D
authors.lastname: Landfair
authors.forename: Christine
authors.initials: C
authors.lastname: Mantis
authors.forename: Jen
authors.initials: J
authors.lastname: Workman
authors.forename: Robert
authors.initials: R
authors.lastname: Wild
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pachter
authors.forename: David
authors.initials: D
authors.lastname: Epstein
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Mulvihill
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; C585787:OSI-296; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D019859:Proto-Oncogene Proteins c-met; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases