Inhibition of farnesyl protein transferase by new farnesyl phosphonate derivatives of phenylalanine

Abstract New farnesyl phosphonate derivatives of phenylalanine have been prepared as inhibitors of farnesyl-protein transferase (FPT). Enzyme inhibition studies with bovine brain FPT and rat liver squalene synthase show that compound 3a is a new, potent and selective FPT inhibitor. Moreover, structural modifications from 3a have provided some useful information concerning the key structural subunits necessary for optimum and selective FPT inhibition.