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

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 IC50 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.

Novel cyclic-imide derivatives were synthesized and evaluated for their activity against APN. Most compounds displayed more potent inhibitory activity than previous work. The most active compound also showed high potency both in cells and in vivo assay.Figure optionsDownload as PowerPoint slide