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ID: ALA1133818

Journal: Bioorg Med Chem Lett

Title: Discovery of heterocyclic ureas as a new class of raf kinase inhibitors: identification of a second generation lead by a combinatorial chemistry approach.

Authors: Smith RA, Barbosa J, Blum CL, Bobko MA, Caringal YV, Dally R, Johnson JS, Katz ME, Kennure N, Kingery-Wood J, Lee W, Lowinger TB, Lyons J, Marsh V, Rogers DH, Swartz S, Walling T, Wild H.

Abstract: Heterocyclic ureas, such as N-3-thienyl N'-aryl ureas, have been identified as novel inhibitors of raf kinase, a key mediator in the ras signal transduction pathway. Structure-activity relationships were established, and the potency of the screening hit was improved 10-fold to IC(50)=1.7 microM. A combinatorial synthesis approach enabled the identification of a breakthrough lead (IC(50)=0.54 microM) for a second generation series of heterocyclic urea raf kinase inhibitors.

CiteXplore: 11591521

DOI: 10.1016/s0960-894x(01)00571-6