General solid-phase method to prepare novel cyclic ketone inhibitors of the cysteine protease cruzain
Lily Huang1, Jonathan A Ellman
1Center for New Directions in Organic Synthesis, Department of Chemistry, University of California, Berkeley, CA 94720, USA.
Bioorganic & Medicinal Chemistry Letters
|September 25, 2002
Abstract:
A series of constrained ketone-based inhibitors has been developed that show low nanomolar Ki values. These ketone inhibitors showed promising activity towards cruzain, the cysteine protease implicated in Chagas' disease. This series of constrained inhibitors, which can be accessed quickly and efficiently using a solid-phase combinatorial strategy, should be applicable to other members of the cysteine protease class.
