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Bioorg Med Chem Lett. 2011 Sep 15;21(18):5533-7. doi: 10.1016/j.bmcl.2011.06.097. Epub 2011 Jul 2.

Pyrazolopyridine inhibitors of B-RafV600E. Part 2: structure-activity relationships.

Author information

1
ArrayBioPharma, 3200 Walnut Street, Boulder, CO 80301, United States. wenglo1056@yahoo.com

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.

PMID:
21802293
DOI:
10.1016/j.bmcl.2011.06.097
[Indexed for MEDLINE]

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