title: The discovery of furo[2,3-c]pyridine-based indanone oximes as potent and selective B-Raf inhibitors.
abstract: Virtual and high-throughput screening identified imidazo[1,2-a]pyrazines as inhibitors of B-Raf. We describe the rationale, SAR, and evolution of the initial hits to a series of furo[2,3-c]pyridine indanone oximes as highly potent and selective inhibitors of B-Raf.
authors.affiliation: Array BioPharma, 3200 Walnut Street, Boulder, CO 80301, USA.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Buckmelter
authors.forename: Li
authors.initials: L
authors.lastname: Ren
authors.forename: Ellen R
authors.initials: ER
authors.lastname: Laird
authors.forename: Bryson
authors.initials: B
authors.lastname: Rast
authors.forename: Greg
authors.initials: G
authors.lastname: Miknis
authors.forename: Steve
authors.initials: S
authors.lastname: Wenglowsky
authors.forename: Stephen
authors.initials: S
authors.lastname: Schlachter
authors.forename: Mike
authors.initials: M
authors.lastname: Welch
authors.forename: Eugene
authors.initials: E
authors.lastname: Tarlton
authors.forename: Jonas
authors.initials: J
authors.lastname: Grina
authors.forename: Joseph
authors.initials: J
authors.lastname: Lyssikatos
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Brandhuber
authors.forename: Tony
authors.initials: T
authors.lastname: Morales
authors.forename: Nikole
authors.initials: N
authors.lastname: Randolph
authors.forename: Guy
authors.initials: G
authors.lastname: Vigers
authors.forename: Matthew
authors.initials: M
authors.lastname: Martinson
authors.forename: Michele
authors.initials: M
authors.lastname: Callejo
mesh_terms: D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007189:Indans / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D008862:Microsomes, Liver / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D007189:Indans; D010091:Oximes; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C518621:indanone oxime; D048493:Proto-Oncogene Proteins B-raf; C023666:pyridine