1447047-24-6Relevant articles and documents
Synthesis and extended activity of triazole-containing macrocyclic protease inhibitors
Pehere, Ashok D.,Pietsch, Markus,Gütschow, Michael,Neilsen, Paul M.,Pedersen, Daniel Sejer,Nguyen, Steven,Zvarec, Ondrej,Sykes, Matthew J.,Callen, David F.,Abell, Andrew D.
supporting information, p. 7975 - 7981 (2013/07/11)
Peptide-derived protease inhibitors are an important class of compounds with the potential to treat a wide range of diseases. Herein, we describe the synthesis of a series of triazole- containing macrocyclic protease inhibitors pre-organized into a b-strand conformation and an evaluation of their activity against a panel of proteases. Acyclic azidoalkyne-based aldehydes are also evaluated for comparison. The macrocyclic peptidomimetics showed considerable activity towards calpain II, cathepsin L and S, and the 20S proteasome chymotrypsin-like activity. Some of the first examples of highly potent macrocyclic inhibitors of cathepsin S were identified. These adopt a well-defined b-strand geometry as shown by NMR spectroscopy, X-ray analysis, and molecular docking studies.