Design, synthesis and SAR studies of tripeptide analogs with the scaffold 3-phenylpropane-1,2-diamine as aminopeptidase N/CD13 inhibitors

Aminopeptidase N (APN), belonged to metalloproteinase, is an essential peptidase involved in the process of tumor invasion and metastasis. A series of tripeptide analogs with the scaffold 3-phenylpropane-1,2-diamine were designed, synthesized and evaluated for their ability to inhibit APN. Preliminary activity evaluation showed that most of target compounds possessed potent inhibitory activities against APN. With in this series, compound A6 and B6 exhibited good potency with the IC50 values of 8.8 ± 1.3 μM and 8.6 ± 1.1 μM, respectively.

The representative compound B6 was built and docked into the active site of APN (PDB code: 2DQM) using sybyl7.0. The docking result was showed by PyMOL.Figure optionsDownload as PowerPoint slide