Design and synthesis of novel 2-pyridone peptidomimetic falcipain 2/3 inhibitors

The structure-based design, chemical synthesis and in vitro activity evaluation of various falcipain inhibitors derived from 2-pyridone are reported. These compounds contain a peptidomimetic binding determinant and a Michael acceptor terminal moiety capable of deactivating the cysteine protease active site.

Graphical abstractHere we present the design and synthesis of novel peptidomimetic falcipain inhibitors that should react as classical ‘Michael acceptors’ and in which the incorporation of a rigid scaffold moiety to define a conformation is evaluated for antimalarial activity.Figure optionsDownload full-size imageDownload as PowerPoint slide