Dioxo-triazines as a novel series of cathepsin K inhibitors

A series of potent and selective dioxo-triazine inhibitors of cathepsin K was identified from HTS. A novel dioxo-triazine series of cathepsin K inhibitors was identified from HTS. A rapid exploratory programme led to the discovery of potent and selective cathepsin K inhibitors, typified by compound...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2010-03, Vol.20 (5), p.1488-1490
Main Authors: Rankovic, Zoran, Cai, Jiaqiang, Fradera, Xavier, Dempster, Maureen, Mistry, Ashvin, Mitchell, Ann, Long, Clive, Hamilton, Emma, King, Angela, Boucharens, Sylviane, Jamieson, Craig, Gillespie, Jonathan, Cumming, Iain, Uitdehaag, Joost, Zeeland, Mario van
Format: Article
Language:English
Subjects:
Binding Sites
Biological and medical sciences
Bones, joints and connective tissue. Antiinflammatory agents
Catalytic Domain
Cathepsin K
Cathepsin K - antagonists & inhibitors
Cathepsin K - metabolism
Crystallography, X-Ray
Cysteine protease
Cysteine Proteinase Inhibitors - chemical synthesis
Cysteine Proteinase Inhibitors - chemistry
Cysteine Proteinase Inhibitors - pharmacology
High-Throughput Screening Assays
Humans
Medical sciences
Osteoporosis
Pharmacology. Drug treatments
Structure-Activity Relationship
Triazines - chemical synthesis
Triazines - chemistry
Triazines - pharmacology
Uracil - analogs & derivatives
Uracil - chemical synthesis
Uracil - chemistry
Uracil - pharmacology
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Summary:A series of potent and selective dioxo-triazine inhibitors of cathepsin K was identified from HTS. A novel dioxo-triazine series of cathepsin K inhibitors was identified from HTS. A rapid exploratory programme led to the discovery of potent and selective cathepsin K inhibitors, typified by compound 24 which displayed IC 50 values of 17 nM against catK and >10,000 nM in catL, catB and catS assays.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2010.01.116