1.
J Med Chem
; 54(1): 396-400, 2011 Jan 13.
Artigo
em Inglês
| MEDLINE
| ID: mdl-21128614
RESUMO
Using the example of cathepsin K, we demonstrate the design of highly potent and selective azadipeptide nitrile inhibitors. A systematic scan with respect to P2 and P3 substituents was carried out. Structural modifications strongly affected the enzyme-inhibitor association (but not dissociation) rate. A combination of optimized P2 and P3 substituents with a methylation of the P3-P2 amide linker resulted in the picomolar cathepsin K inhibitor 19 with remarkable selectivity over cathepsins L, B, and S.