Different Amino Acid Replacements in CAAX-Tetrapeptide Based Peptidomimetic Farnesyltransferase Inhibitors

In a series of CAAX‐tetrapeptide based farnesyltransferase inhibitors it has been shown that the central AA‐dipeptide can be replaced by tranexamic acid, 4‐aminobenzenesulfonic acid, and 3‐amino‐N‐(2,3‐dimethylphenyl)benzenesulfonamide, respectively, yielding inhibitors active in the low micromolar range. Lipophilic derivatives of these compounds showed moderate antiproliferative activity against different tumor cell lines. A promising class of peptidomimetic farnesyltransferase inhibitors was discovered through the replacement of the terminal AAX motif of the CAAX‐tetrapeptide by 2‐acylamino‐5‐aminobenzophenones.