| Literature DB >> 21802293 |
Steve Wenglowsky1, Kateri A Ahrendt, Alex J Buckmelter, Bainian Feng, Susan L Gloor, Stefan Gradl, Jonas Grina, Joshua D Hansen, Ellen R Laird, Paul Lunghofer, Simon Mathieu, David Moreno, Brad Newhouse, Li Ren, Tyler Risom, Joachim Rudolph, Jeongbeob Seo, Hillary L Sturgis, Walter C Voegtli, Zhaoyang Wen.
Abstract
Structure-activity relationships around a novel series of B-Raf(V600E) inhibitors are reported. The enzymatic and cellular potencies of inhibitors derived from two related hinge-binding groups were compared and3-methoxypyrazolopyridine proved to be superior. The 3-alkoxy group of lead B-Raf(V600E) inhibitor 1 was extended and minimally affected potency. The propyl sulfonamide tail of compound 1, which occupies the small lipophilic pocket formed by an outward shift of the αC-helix, was expanded to a series of arylsulfonamides. X-ray crystallography revealed that this lipophilic pocket unexpectedly enlarges to accommodate the bulkier aryl group.Entities:
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Year: 2011 PMID： 21802293 DOI： 10.1016/j.bmcl.2011.06.097
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823