title: 4-Quinazolinyloxy-diaryl ureas as novel BRAFV600E inhibitors.
abstract: Aryl phenyl ureas with a 4-quinazolinoxy substituent at the meta-position of the phenyl ring are potent inhibitors of mutant and wild type BRAF kinase. Compound 7 (1-(5-tert-butylisoxazol-3-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)urea hydrochloride) exhibits good pharmacokinetic properties in rat and mouse and is efficacious in a mouse tumor xenograft model following oral dosing.
authors.affiliation: Ambit Biosciences Corporation, 4215 Sorrento Valley Boulevard, San Diego, CA 92121, USA. mholladay@ambitbio.com
authors.forename: Mark W
authors.initials: MW
authors.lastname: Holladay
authors.forename: Brian T
authors.initials: BT
authors.lastname: Campbell
authors.forename: Martin W
authors.initials: MW
authors.lastname: Rowbottom
authors.forename: Qi
authors.initials: Q
authors.lastname: Chao
authors.forename: Kelly G
authors.initials: KG
authors.lastname: Sprankle
authors.forename: Andiliy G
authors.initials: AG
authors.lastname: Lai
authors.forename: Sunny
authors.initials: S
authors.lastname: Abraham
authors.forename: Eduardo
authors.initials: E
authors.lastname: Setti
authors.forename: Raffaella
authors.initials: R
authors.lastname: Faraoni
authors.forename: Lan
authors.initials: L
authors.lastname: Tran
authors.forename: Robert C
authors.initials: RC
authors.lastname: Armstrong
authors.forename: Ruwanthi N
authors.initials: RN
authors.lastname: Gunawardane
authors.forename: Michael F
authors.initials: MF
authors.lastname: Gardner
authors.forename: Merryl D
authors.initials: MD
authors.lastname: Cramer
authors.forename: Dana
authors.initials: D
authors.lastname: Gitnick
authors.forename: Mark A
authors.initials: MA
authors.lastname: Ator
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Dorsey
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Ruggeri
authors.forename: Michael
authors.initials: M
authors.lastname: Williams
authors.forename: Shripad S
authors.initials: SS
authors.lastname: Bhagwat
authors.forename: Joyce
authors.initials: J
authors.lastname: James
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D051379:Mice; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D014508:Urea; D048493:Proto-Oncogene Proteins B-raf