Selective Nitrile Inhibitors To Modulate the Proteolytic Synergism of Cathepsins S and F

Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.
Journal of Medicinal Chemistry (Impact Factor: 5.45). 06/2012; 55(12):5982-6. DOI: 10.1021/jm300734k
Source: PubMed


A series of dipeptide nitriles with different P3 substituents was designed to explore the S3 binding pocket of cathepsin S. Racemic 7-16 and the enantiopure derivative (R)-22 proved to be potent inhibitors of human cathepsin S and exhibited notable selectivity over human cathepsins L, K, and B. Inhibition of cathepsin F, the functional synergist of cathepsin S, was not observed. The azadipeptide analogue of 22, compound 26, was highly potent but nonselective.

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