Aryl tetrahydropyridine inhibitors of farnesyltransferase: Glycine, phenylalanine and histidine derivatives

Inhibitors of farnesyltransferase are effective against a variety of tumors in mouse models of cancer. Clinical trials to evaluate these agents in humans are ongoing. In our effort to develop new farnesyltransferase inhibitors, we have discovered a series of aryl tetrahydropyridines that incorporate substituted glycine, phenylalanine and histidine residues. The design, synthesis, SAR and biological properties of these compounds will be discussed. (C) 2003 Elsevier Science Ltd. All rights reserved.