| Literature DB >> 16392826 |
Ion Niculescu-Duvaz1, Esteban Roman, Steven R Whittaker, Frank Friedlos, Ruth Kirk, Ian J Scanlon, Lawrence C Davies, Dan Niculescu-Duvaz, Richard Marais, Caroline J Springer.
Abstract
B-RAF, a serine/threonine kinase, plays an important role in the development of certain classes of cancer, especially melanoma. As a result of high-throughput screening of a 23,000 compound library, 2-(3,4,5-trimethoxyphenylamino)-6-(3-acetamidophenyl)pyrazine, 1, was identified as a low micromolar (IC(50) = 3.5 microM) B-RAF inhibitor. This compound was chosen as the starting point of a program aimed at producing potent inhibitors of B-RAF. We have synthesized a series of 40 novel compounds, which involved extensive modifications to the 2-(3,4,5-trimethoxyphenylamino) moiety (ring A) of 1. Their biological profiles against isolated B-RAF and mutated B-RAF in a cellular assay have been determined. These efforts led to the identification of two compounds exhibiting activities lower than 800 nM against B-RAF.Entities:
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Year: 2006 PMID： 16392826 DOI： 10.1021/jm050983g
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446