Design and synthesis of arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 1

A series of Nα-acyl-α-amino acid-(arylaminoethyl)amides were found to be potent and noncovalent cathepsin S inhibitors. Compound 20 possessed high cathepsin S affinity (Ki = 3.3 nM) and showed excellent selectivity over cathepsin K, L, F, and V. Molecular modeling, design, synthesis, and in vitro activity are described.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide