Azadipeptide nitriles: Highly potent and proteolytically stable inhibitors of papain-like cysteine proteases

Article abstract of DOI:10.1002/anie.200705858

(Chemical Presented) Nitrogen instead of carbon: Azadipeptide nitriles resulting from CH/N exchange in the P¹ position (see picture) are hitherto unknown. To access these compounds by conversion of amino acid-derived hydrazides with cyanogen bromide both nitrogen atoms of the hydrazide must be substituted. Despite a methylated P²-P¹ peptide bond, the azadipeptide nitriles show a strong inhibitory activity against cysteine proteases, and a high stability towards chymotryptic hydrolysis.