A series of novel derivatives of N-cinnamoyl-l-aspartic acid were designed, synthesized, and assayed for their inhibitory activities against aminopeptidase N. The preliminary biological assay showed that compound 8c has the most potent inhibitory activity against APN with an IC(50) of 11.1+/-0.9 microM, this could be used as the lead compound in future research on anticancer agents.