Novel and selective imidazole-containing biphenyl inhibitors of protein farnesyltransferase

  • Bioorg Med Chem Lett. 2003 Apr 7;13(7):1367-71. doi: 10.1016/s0960-894x(03)00096-9.
Michael L Curtin  1 ,  Alan S Florjancic ,  Jerome Cohen ,  Wen-Zhen Gu ,  David J Frost ,  Steven W Muchmore ,  Hing L Sham
Affiliations
  • 1. Department of Cancer Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. [email protected]
PMID: 12657284 DOI: 10.1016/s0960-894x(03)00096-9
Abstract

A series of imidazole-containing biphenyls was prepared and evaluated in vitro for inhibition of FTase and cellular Ras processing. Several of these analogues, such as 21, are potent inhibitors of FTase (<1nM), FTase/GGTase selective (>300-fold) and cellularly active (<or=80nM). An X-ray crystal structure of inhibitor 21 bound to rat farnesyltransferase is also presented.