Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1374852 | Bioorganic & Medicinal Chemistry Letters | 2009 | 5 Pages |
Abstract
As part of our research effort to discover B-Raf kinase inhibitors, we prepared a series of C-3 substituted N-(3-(pyrazolo[1,5-a]pyrimidin-7-yl)phenyl)-3-(trifluoromethyl)benzamides. X-ray crystallography studies revealed that one of the more potent inhibitors (10n) bound to B-Raf kinase without forming a hinge-binding hydrogen bond. With basic amine residues appended to C-3 aryl residues, cellular activity and solubility were enhanced over previously described compounds of this class.
Graphical abstractOptimization of initial lead compound 1 provided a series of pyrazolo[1,5-a]pyrimidines 2 as potent B-Raf kinase inhibitors.Figure optionsDownload full-size imageDownload as PowerPoint slide
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Dan M. Berger, Nancy Torres, Minu Dutia, Dennis Powell, Greg Ciszewski, Ariamala Gopalsamy, Jeremy I. Levin, Kyung-Hee Kim, Weixin Xu, James Wilhelm, YongBo Hu, Karen Collins, Larry Feldberg, Steven Kim, Eileen Frommer, Donald Wojciechowicz,