Download MendeleyPyrazolopyridine inhibitors of B-RafV600E. Part 2: structure-activity relationships.
Wenglowsky, S., Ahrendt, K.A., Buckmelter, A.J., Feng, B., Gloor, S.L., Gradl, S., Grina, J., Hansen, J.D., Laird, E.R., Lunghofer, P., Mathieu, S., Moreno, D., Newhouse, B., Ren, L., Risom, T., Rudolph, J., Seo, J., Sturgis, H.L., Voegtli, W.C., Wen, Z.(2011) Bioorg Med Chem Lett 21: 5533-5537
- PubMed: 21802293
- DOI: https://doi.org/10.1016/j.bmcl.2011.06.097
- Primary Citation of Related Structures:
3SKC - PubMed 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.
Organizational Affiliation:
ArrayBioPharma, 3200 Walnut Street, Boulder, CO 80301, United States. wenglo1056@yahoo.com
