1186608-23-0Relevant articles and documents
Pyrazolopyridine inhibitors of B-RafV600E. Part 2: Structure-activity relationships
Wenglowsky, Steve,Ahrendt, Kateri A.,Buckmelter, Alex J.,Feng, Bainian,Gloor, Susan L.,Gradl, Stefan,Grina, Jonas,Hansen, Joshua D.,Laird, Ellen R.,Lunghofer, Paul,Mathieu, Simon,Moreno, David,Newhouse, Brad,Ren, Li,Risom, Tyler,Rudolph, Joachim,Seo, Jeongbeob,Sturgis, Hillary L.,Voegtli, Walter C.,Wen, Zhaoyang
, p. 5533 - 5537 (2011/10/09)
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-RafV600E 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.
