2. Academic Validation
  3. Design, synthesis, and activity of 4-quinolone and pyridone compounds as nonthiol-containing farnesyltransferase inhibitors

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

  • Bioorg Med Chem Lett. 2004 Nov 1;14(21):5367-70. doi: 10.1016/j.bmcl.2004.08.012.
Qun Li 1,  Akiyo Claiborne,  Tongmei Li,  Lisa Hasvold,  Vincent S Stoll,  Steven Muchmore,  Clarissa G Jakob,  Wendy Gu,  Jerry Cohen,  Charles Hutchins,  David Frost,  Saul H Rosenberg,  Hing L Sham
Affiliations

Affiliation

  • 1 Cancer Research, GPRD, Abbott Laboratories, Abbott Park, IL 60064-6101, USA. [email protected]
PMID: 15454228 DOI: 10.1016/j.bmcl.2004.08.012
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.

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