PHENOL BASED TRIPEPTIDE INHIBITORS OF RAS FARNESYL PROTEIN TRANSFERASE

Abstract Preparation and activity of phenol tripeptides, a new class of inhibitors of ras farnesyl protein transferase (FPT), is described. Based on the inhibitory potency of meta-phenol 11 (I 50 = 29 uM) and the ortho-benzyl ether analog 7 (I 50 = 63 uM), regioisomeric hybrid analogs 18 and 25 were designed and evaluated as partial bisubstrate analog inhibitors of FPT ( 18 , I 50 = 157 uM; 25 , I 50 = 137 uM).