Potent fluoromethyl ketone inhibitors of recombinant human calpain I

Article abstract of DOI:10.1016/0960-894X(96)00209-0

We report on a series of potent and selective dipeptide fluoromethyl ketone inhibitors of recombinant human calpain I. Compound 4f, having a tetrahydroisoquinoline containing urea motif as N-terminus capping group, is the most potent member (k(obs)/I = 276,000 M^-1 s^-1) of this class. This compound was shown to prefer calpain I by >36-fold and approximately 4-fold over the related cysteine proteases, cathepsin B and cathepsin L, respectively.