Novel and selective imidazole-containing biphenyl inhibitors of protein farnesyltransferase

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 (<1 nM), FTase/GGTase selective (>300-fold) and cellularly active (≤80 nM). An X-ray crystal structure of inhibitor 21 bound to rat farnesyltransferase is also presented.