4-Quinazolinyloxy-diaryl ureas as novel BRAFV600E inhibitors.

Authors: Holladay MW, Campbell BT, Rowbottom MW, Chao Q, Sprankle KG, Lai AG, Abraham S, Setti E, Faraoni R, Tran L, Armstrong RC, Gunawardane RN, Gardner MF, Cramer MD, Gitnick D, Ator MA, Dorsey BD, Ruggeri BR, Williams M, Bhagwat SS, James J.
Publisher/Year: Bioorg Med Chem Lett. 2011 Sep 15;21(18):5342-6. Epub 2011 Jul 14.
Pub Med ID/Journal ID: PMID:21807507


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. Copyright © 2011 Elsevier Ltd. All rights reserved.