Synthesis and antiproliferative activity of N-acylaspartic acid dimethyl esters

Farnesyl residues are found as a lipophilic modification of a number of important proteins. In addition, synthetic farnesyl derivatives display a range of biological effects. We have prepared a series of N-acylaspartates as structural analogs of farnesylpyrophosphate in which the farnesyl residue has been replaced by a number of different aliphatic and aromatic carboxylic acids and the aspartate is used as a pyrophosphate surrogate. The corresponding dimethyl esters of these aspartates were assayed against different tumor cell lines. Several N-acylaspartic acid dimethyl esters carrying an aromatic acyl residue displayed a selective antiproliferative effect against THP-1 cells with GI50 values ranging from 7.6 to 1.3 microM.