Different amino acid replacements in CAAX-tetrapeptide based peptidomimetic farnesyltransferase inhibitors

In a series of CAAX-tetrapeptide based farnesyltransferase inhibitors it ha s been shown that the central AA-dipeptide can be replaced by tranexamic ac id, 4-aminobenzenesulfonic acid, and 3-amino-N-(2,3-dimethylphenyl)benzenes ulfonamide, respectively, yielding inhibitors active in the low micromolar range. Lipophilic derivatives of these compounds showed moderate anti-proli ferative activity against different tumor cell lines. A promising class of peptidomimetic farnesyltransferase inhibitors was discovered through the re placement of the terminal AAX motif of the CAAX-tetrapeptide by 2-acylamino -5-aminobenzophenones.