Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1374386 | Bioorganic & Medicinal Chemistry Letters | 2006 | 6 Pages |
Abstract
We have prepared a series of cathepsin K inhibitors bearing the keto-1,3,4-oxadiazole warhead capable of forming a hemithioketal complex with the target enzyme. By modifying binding moieties at the P1, P2, and prime side positions of the inhibitors, we have achieved selectivity over cathepsins B, L, and S, and have achieved sub-nanomolar potency against cathepsin K. This series thus represents a promising chemotype that could be used in diseases implicated by imbalances in cathepsin K activity such as osteoporosis.
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Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
James T. Palmer, Bernard L. Hirschbein, Harry Cheung, John McCarter, James W. Janc, Z. Walter Yu, Gregg Wesolowski,