Molecular Modeling, Synthesis, and Biological Evaluation of Macrocyclic Calpain Inhibitors

The design and elaboration of a series of macrocyclic templates that exhibit a propensity to adopt a β‐strand‐like peptide‐backbone conformation led to potent and selective inhibitors of calpain 2. Macrocycle 1 retarded calcium‐induced opacification in an ovine‐lens culture assay and is a lead compound for the development of a drug for cataract treatment. Cbz=carbobenzyloxy. magnified...