N-Heterocyclic Dipeptide Aldehyde Calpain Inhibitors

A series of Val-Leu based peptidic aldehydes containing either a furan or thiophene at the N-terminus was prepared and assayed against ovine m-calpain. In general, potency is favoured by a 2-substituted (rather than 3-substituted) heterocycle, a thiophene rather than a furan, and a shorter chain length at the N-terminus. Molecular docking experiments provide some rationale for these observations.