Novel cyclic-imide peptidomimetics as aminopeptidase N inhibitors. Design, chemistry and activity evaluation. Part I

Abstract A series of aminopeptidase inhibitors with cyclic-imide scaffold are described. The biological characterization for the piperidinedione analogues revealed that most compounds displayed high inhibitory activity against APN. Among which 4l and 6 showed potent inhibition against APN with the IC 50 value of 5.2 μM and 3.1 μM, respectively. In addition, 6 also displayed good activity in HL-60 cell assay and in vivo anti-metastasis assay. This interesting activity profile may also guide the design of new, specific inhibitors of target mammalian aminopeptidases with ‘one-zinc’ active site.