2. Academic Validation
  3. Benzimidazolones and indoles as non-thiol farnesyltransferase inhibitors based on tipifarnib scaffold: synthesis and activity

Benzimidazolones and indoles as non-thiol farnesyltransferase inhibitors based on tipifarnib scaffold: synthesis and activity

  • Bioorg Med Chem Lett. 2005 Jun 2;15(11):2918-22. doi: 10.1016/j.bmcl.2005.03.049.
Qun Li 1,  Tongmei Li,  Keith W Woods,  Wen-Zhen Gu,  Jerry Cohen,  Vincent S Stoll,  Tomas Galicia,  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: 15911281 DOI: 10.1016/j.bmcl.2005.03.049
Abstract

A series of analogs of tipifarnib (1) has been synthesized as inhibitors of FTase by substituting the benzimidazolones and indoles for the 2-quinolone of tipifarnib. The novel benzimidazolones are potent and selective FTase inhibitors (FTIs) with IC(50) values of the best compounds close to that of tipifarnib. The current series demonstrate good cellular activity as measured in their inhibiting the Ras processing in NIH-3T3 cells, with compounds 2c and 2f displaying EC(50) values of 18 and 22nM, respectively.

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