Design, synthesis and preliminary evaluation of new cinnamoyl pyrrolidine derivatives as potent gelatinase inhibitors

A series of new cinnamoyl pyrrolidine derivatives have been synthesized based on the L-hydroxyproline scaffold and inhibiting activities on gelatinase (MMP-2 and -9) and APN were tested. Structure-activity relationship studies showed that the side chain with aromatic ring at C4 in pyrrolidine ring showed better inhibitory activities on gelatinase than aliphatic side chain. Most compounds exhibited poor activities on APN compared with MMP-2. Within this series, three compounds, A8, B9 and C10, have the good potency (IC50 = 5.2-9.7 nM) and could be used as lead compounds in the future. (c) 2006 Elsevier Ltd. All rights reserved.