Peptidic 1-cyanopyrrolidines: synthesis and SAR of a series of potent, selective cathepsin inhibitors.
- R. Rydzewski, C. Bryant, Darren H. Wong
- Chemistry, BiologyBioorganic & Medicinal Chemistry
- 1 October 2002
Design and synthesis of tri-ring P3 benzamide-containing aminonitriles as potent, selective, orally effective inhibitors of cathepsin K.
Inhibition of collagen breakdown by cathepsin K inhibitors suggests this mechanism of action may be useful in osteoporosis and other indications involving bone resorption.
A novel class of nonpeptidic biaryl inhibitors of human cathepsin K.
- J. Robichaud, R. Oballa, J. Palmer
- Biology, ChemistryJournal of Medicinal Chemistry
- 16 July 2003
It was shown that inhibition of cathepsin K leads to an inhibition of this bone resorption marker in OVX rhesus monkeys and strongly suggests that inhibition by compound (R)-2 is a viable therapeutic approach for the treatment of osteoporosis.
Non-peptidic inhibitors of human leukocyte elastase. 4. Design, synthesis, and in vitro and in vivo activity of a series of beta-carbolinone-containing trifluoromethyl ketones.
- C. Veale, J. R. Damewood, G. Steelman, C. Bryant, B. Gomes, J. Williams
- Chemistry, BiologyJournal of Medicinal Chemistry
- 6 January 1995
This series of compounds are found to have excellent selectivity for HLE over a number of other proteolytic enzymes, including closely related enzymes such as porcine pancreatic elastase.
Discovery and biological activity of orally active peptidyl trifluoromethyl ketone inhibitors of human neutrophil elastase.
- P. Edwards, D. Andisik, M. Zottola
- Chemistry, BiologyJournal of Medicinal Chemistry
- 6 June 1997
By modifying the N-terminal group of tripeptidyl TFMKs, inhibitors can be designed which are effective in vivo when administered either orally or intratracheally.