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ID: ALA1137996

Journal: Bioorg Med Chem Lett

Title: Design, synthesis, and activity of 4-quinolone and pyridone compounds as nonthiol-containing farnesyltransferase inhibitors.

Authors: Li Q, Claiborne A, Li T, Hasvold L, Stoll VS, Muchmore S, Jakob CG, Gu W, Cohen J, Hutchins C, Frost D, Rosenberg SH, Sham HL.

Abstract: As a part of our efforts to identify potent inhibitors of farnesyltransferase (FTase), modification of the structure of tipifarnib through structure-based design was undertaken by replacing the 2-quinolones with 4-quinolones and pyridones, and subsequent relocation of the D-ring to the N-methyl group on the imidazole ring. This study has yielded a novel series of potent and selective FTase inhibitors. The X-ray structure of tipifarnib (1) in complex with FTase was described.

CiteXplore: 15454228

DOI: 10.1016/j.bmcl.2004.08.012