| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1362201 | Bioorganic & Medicinal Chemistry Letters | 2011 | 5 Pages |
Abstract
The development of inhibitors of B-RafV600E 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.
Graphical abstractInhibitors of B-RafV600E kinase are reported for which indanone oximes are replaced with tricyclic pyrazoles and indazoles.Figure optionsDownload full-size imageDownload as PowerPoint slide
Keywords
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Li Ren, 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,