title: The identification of potent, selective and CNS penetrant furan-based inhibitors of B-Raf kinase.
abstract: Modification of the potent imidazole-based B-Raf inhibitor SB-590885 resulted in the identification of a series of furan-based derivatives with enhanced CNS penetration. One such compound, SB-699393 (17), was examined in vivo to challenge the hypothesis that selective B-Raf inhibitors may be of value in the treatment of stroke.
authors.affiliation: Department of Medicinal Chemistry, Neurology and GI Centre of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. Andy.K.Takle@gsk.com
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Takle
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Bamford
authors.forename: Susannah
authors.initials: S
authors.lastname: Davies
authors.forename: Robert P
authors.initials: RP
authors.lastname: Davis
authors.forename: David K
authors.initials: DK
authors.lastname: Dean
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gaiba
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Irving
authors.forename: Frank D
authors.initials: FD
authors.lastname: King
authors.forename: Antoinette
authors.initials: A
authors.lastname: Naylor
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Parr
authors.forename: Alison M
authors.initials: AM
authors.lastname: Ray
authors.forename: Alastair D
authors.initials: AD
authors.lastname: Reith
authors.forename: Beverley B
authors.initials: BB
authors.lastname: Smith
authors.forename: Penelope C
authors.initials: PC
authors.lastname: Staton
authors.forename: Jon G A
authors.initials: JG
authors.lastname: Steadman
authors.forename: Tania O
authors.initials: TO
authors.lastname: Stean
authors.forename: David M
authors.initials: DM
authors.lastname: Wilson
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000187:drug effects*; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D007189:Indans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D020521:Stroke / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D005663:Furans; D007093:Imidazoles; D007189:Indans; C530671:L-779,450; D011725:Pyridines; C508204:SB-590885; C530670:SB-699393; D048493:Proto-Oncogene Proteins B-raf