Discovery of phenyl alanine derived ketoamides carrying benzoyl residues as novel calpain inhibitors

Novel calpain inhibitors derived from phenyl alanine aldehydes or ketoamides carrying a benzoyl residue were prepared and evaluated for their biological potency. A brief structure–activity relationship elucidated the importance of ortho-substitutents in the benzoyl moiety. The most potent derivative, the ketoamide 19c, exhibited a Ki of 6 nM and represents a novel class of reversible, highly potent and non-peptidic calpain inhibitors.