Send to

Choose Destination
See comment in PubMed Commons below
J Med Chem. 2004 Oct 7;47(21):5057-68.

Ketoamide-based inhibitors of cysteine protease, cathepsin K: P3 modifications.

Author information

  • 1Department of Medicinal Chemistry, Discovery Research Biology, GlaxoSmithKline, Research Triangle Park, NC 27709, USA.


Osteoporosis is a disease characterized by skeletal fragility. Cathepsin K, a lysosomal cysteine protease, has been implicated in the osteoclast mediated bone resorption. Inhibitors of this protease could potentially treat this skeletal disease. The present work describes exploration of the spatial requirements of the S3 subsite by the use of various sterically demanding P3 substituents. Sulfur and oxygen linked heterocycles as well as those without heteroatom linkers were found to provide potent inhibitors of cathepsin K. Representative examples from these series also afforded quite good selectivity ratios against most cathepsins tested. The tolerability of the S3 subsite for sterically demanding groups that provide potency and selectivity enhances the attractiveness of P3 changes to improve the physiochemical properties of inhibitors in the developments of compounds for the treatment of osteoporosis.

[PubMed - indexed for MEDLINE]

LinkOut - more resources

Full Text Sources

Other Literature Sources

Chemical Information

PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Chemical Society
    Loading ...
    Support Center