Design and synthesis of novel chloramphenicol amine derivatives as potent aminopeptidase N (APN/CD13) inhibitors

Herein we report a series of novel chloramphenicol amine derivatives as aminopeptidase N (APN)/CD13 inhibitors. All compounds were synthesized starting from commercially available (1S,2S)-2-amino-1-(4-nitrophenyl) propane-1,3-diol. The preliminary biological screening showed that some compounds exhibited potent inhibitory activity against APN. It should be noted that one compound, 13b (IC50 = 7.1 μM), possess similar APN inhibitory activity compared with Bestatin (IC50 = 3.0 μM).

The compound 13b was built and docked into the active site of APN (PDB code: 2DQM) using sybyl7.0. The docking result of 13b is showed by Ligplot.Figure optionsDownload as PowerPoint slide