Farnesyl-derived inhibitors of ras farnesyl transferase.

The synthesis and evaluation of farnesyl-derived inhibitors of ras farnesyl transferase are presented. Evaluation of inhibitors of farnesyl transferase and comparison with the previously described inhibitor was accomplished using purified enzyme and Amersham's Farnesyl:Transferase enzyme assay kit. These results show an order of magnitude increase in inhibitory activity for beta-ketophosphonic acid over beta-hydroxyphosphonic acid. Incorporation of fluorines in alpha-position, led to an increase in inhibitory activity over the nonfluorinated analogues.