2. Academic Validation
  3. 4-Quinazolinyloxy-diaryl ureas as novel BRAFV600E inhibitors

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

Affiliation

  • 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.

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