title: Development of potent B-RafV600E inhibitors containing an arylsulfonamide headgroup.
abstract: A potent series of inhibitors against the B-Raf(V600E) kinase have been developed that show excellent activity in cellular assays and good oral bioavailability in rats. The key structural features of the series are an arylsulfonamide headgroup, a thiazole core, and a fluorine ortho to the sulfonamide nitrogen.
authors: GlaxoSmithKline Oncology CEDD, Research Triangle Park, NC 27709-3398, United States. john.stellwagen@amgen.com
authors: John C
authors: JC
authors: Stellwagen
authors: George M
authors: GM
authors: Adjabeng
authors: Marc R
authors: MR
authors: Arnone
authors: Scott H
authors: SH
authors: Dickerson
authors: Chao
authors: C
authors: Han
authors: Keith R
authors: KR
authors: Hornberger
authors: Alastair J
authors: AJ
authors: King
authors: Robert A
authors: RA
authors: Mook
authors: Kimberly G
authors: KG
authors: Petrov
authors: Tara R
authors: TR
authors: Rheault
authors: Cynthia M
authors: CM
authors: Rominger
authors: Olivia W
authors: OW
authors: Rossanese
authors: Kimberly N
authors: KN
authors: Smitheman
authors: Alex G
authors: AG
authors: Waterson
authors: David E
authors: DE
authors: Uehling
mesh_terms: D000284:Administration, Oral; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D005461:Fluorine / Q000737:chemistry; D008862:Microsomes, Liver / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D005461:Fluorine; D048493:Proto-Oncogene Proteins B-raf