title: Non-oxime pyrazole based inhibitors of B-Raf kinase.
abstract: The synthesis and biological evaluation of non-oxime pyrazole based B-Raf inhibitors is reported. Several oxime replacements have been prepared and have shown excellent enzyme activity. Further optimization of fused pyrazole 2a led to compound 38, a selective and potent B-Raf inhibitor.
authors.affiliation: Array BioPharma, 3200 Walnut Street, Boulder, CO 80301, United States. bnewhouse@arraybiopharma.com
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Newhouse
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Hansen
authors.forename: Jonas
authors.initials: J
authors.lastname: Grina
authors.forename: Mike
authors.initials: M
authors.lastname: Welch
authors.forename: George
authors.initials: G
authors.lastname: Topalov
authors.forename: Nicole
authors.initials: N
authors.lastname: Littman
authors.forename: Michele
authors.initials: M
authors.lastname: Callejo
authors.forename: Matthew
authors.initials: M
authors.lastname: Martinson
authors.forename: Sarah
authors.initials: S
authors.lastname: Galbraith
authors.forename: Ellen R
authors.initials: ER
authors.lastname: Laird
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Brandhuber
authors.forename: Guy
authors.initials: G
authors.lastname: Vigers
authors.forename: Tony
authors.initials: T
authors.lastname: Morales
authors.forename: Rich
authors.initials: R
authors.lastname: Woessner
authors.forename: Nikole
authors.initials: N
authors.lastname: Randolph
authors.forename: Joseph
authors.initials: J
authors.lastname: Lyssikatos
authors.forename: Alan
authors.initials: A
authors.lastname: Olivero
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D010091:Oximes / Q000737:chemistry; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D010091:Oximes; D011720:Pyrazoles; C031280:pyrazole; D048493:Proto-Oncogene Proteins B-raf