| Literature DB >> 21251822 |
Li Ren1, Steve Wenglowsky, Greg Miknis, Bryson Rast, Alex J Buckmelter, Robert J Ely, Stephen Schlachter, Ellen R Laird, Nikole Randolph, Michele Callejo, Matthew Martinson, Sarah Galbraith, Barbara J Brandhuber, Guy Vigers, Tony Morales, Walter C Voegtli, Joseph Lyssikatos.
Abstract
The development of inhibitors of B-Raf(V600E) serine-threonine kinase is described. Various head-groups were examined to optimize inhibitor activity and ADME properties. Several of the head-groups explored, including naphthol, phenol and hydroxyamidine, possessed good activity but had poor pharmacokinetic exposure in mice. Exposure was improved by incorporating more metabolically stable groups such as indazole and tricyclic pyrazole, while indazole could also be optimized for good cellular activity.Entities:
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Year: 2010 PMID： 21251822 DOI： 10.1016/j.bmcl.2010.12.061
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823