title: The discovery of potent cRaf1 kinase inhibitors.
abstract: A series of benzylidene-1H-indol-2-one (oxindole) derivatives was synthesized and evaluated as cRaf-1 kinase inhibitors. The key features of the molecules were the donor/acceptor motif common to kinase inhibitors and a critical acidic phenol flanked by two substitutions. Diverse 5-position substitutions provided compounds with low nanomolar kinase enzyme inhibition and inhibited the intracellular MAPK pathway.
authors.affiliation: Glaxo Wellcome, Inc., Research Triangle Park, NC 27709, USA. kel8725@glaxowellcome.com
authors.forename: K
authors.initials: K
authors.lastname: Lackey
authors.forename: M
authors.initials: M
authors.lastname: Cory
authors.forename: R
authors.initials: R
authors.lastname: Davis
authors.forename: S V
authors.initials: SV
authors.lastname: Frye
authors.forename: P A
authors.initials: PA
authors.lastname: Harris
authors.forename: R N
authors.initials: RN
authors.lastname: Hunter
authors.forename: D K
authors.initials: DK
authors.lastname: Jung
authors.forename: O B
authors.initials: OB
authors.lastname: McDonald
authors.forename: R W
authors.initials: RW
authors.lastname: McNutt
authors.forename: M R
authors.initials: MR
authors.lastname: Peel
authors.forename: R D
authors.initials: RD
authors.lastname: Rutkowske
authors.forename: J M
authors.initials: JM
authors.lastname: Veal
authors.forename: E R
authors.initials: ER
authors.lastname: Wood
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D019908:Proto-Oncogene Proteins c-raf