Non-thiol Farnesyltransferase Inhibitors: N-(4-Acylamino-3-benzoylphenyl)-4-nitrocinnamic Acid Amides Original Research Article

We have developed the 4-nitrocinnamoyl substituted benzophenone 4a as a novel non-thiol farnesyltransferase inhibitor. Replacement of the p-tolyl moiety of our initial lead structure 4a by different para and ortho substituted phenyl residues as well as by 1-naphthyl resulted in derivatives with considerably enhanced activity displaying IC50 values between 42 and 52 nM. These compounds represent novel, readily accessible non-thiol farnesyltransferase inhibitors being more active than the corresponding thiol-containing analogues.