4-Quinazolinyloxy-diaryl ureas as novel BRAFV600E inhibitors

  • Bioorg Med Chem Lett. 2011 Sep 15;21(18):5342-6. doi: 10.1016/j.bmcl.2011.07.019.
Mark W Holladay  1 ,  Brian T Campbell ,  Martin W Rowbottom ,  Qi Chao ,  Kelly G Sprankle ,  Andiliy G Lai ,  Sunny Abraham ,  Eduardo Setti ,  Raffaella Faraoni ,  Lan Tran ,  Robert C Armstrong ,  Ruwanthi N Gunawardane ,  Michael F Gardner ,  Merryl D Cramer ,  Dana Gitnick ,  Mark A Ator ,  Bruce D Dorsey ,  Bruce R Ruggeri ,  Michael Williams ,  Shripad S Bhagwat ,  Joyce James
Affiliations
  • 1. Ambit Biosciences Corporation, 4215 Sorrento Valley Boulevard, San Diego, CA 92121, USA. [email protected]
PMID: 21807507 DOI: 10.1016/j.bmcl.2011.07.019
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.