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Dioxo-triazines as a novel series of cathepsin K inhibitors. 2010

Zoran Rankovic, and Jiaqiang Cai, and Xavier Fradera, and Maureen Dempster, and Ashvin Mistry, and Ann Mitchell, and Clive Long, and Emma Hamilton, and Angela King, and Sylviane Boucharens, and Craig Jamieson, and Jonathan Gillespie, and Iain Cumming, and Joost Uitdehaag, and Mario van Zeeland
Schering-Plough Corporation, Newhouse, Lanarkshire, ML1 5SH, Scotland, United Kingdom. zoran.rankovic@spcorp.com

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 17nM against catK and >10,000nM in catL, catB and catS assays.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014227 Triazines Heterocyclic rings containing three nitrogen atoms, commonly in 1,2,4 or 1,3,5 or 2,4,6 formats. Some are used as HERBICIDES. Triazine,Benzotriazines
D014498 Uracil One of four nucleotide bases in the nucleic acid RNA.
D015853 Cysteine Proteinase Inhibitors Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES. Acid Cysteine Proteinase Inhibitor,Cysteine Protease Inhibitor,Cysteine Protease Inhibitors,Cysteine Proteinase Antagonist,Cysteine Proteinase Antagonists,Cysteine Proteinase Inhibitor,Cysteine Proteinase Inhibitors, Endogenous,Cysteine Proteinase Inhibitors, Exogenous,alpha-Cysteine Protease Inhibitor,Acid Cysteine Proteinase Inhibitors,alpha-Cysteine Protease Inhibitors,Antagonist, Cysteine Proteinase,Antagonists, Cysteine Proteinase,Inhibitor, Cysteine Protease,Inhibitor, Cysteine Proteinase,Inhibitor, alpha-Cysteine Protease,Inhibitors, Cysteine Protease,Inhibitors, Cysteine Proteinase,Inhibitors, alpha-Cysteine Protease,Protease Inhibitor, Cysteine,Protease Inhibitor, alpha-Cysteine,Protease Inhibitors, Cysteine,Protease Inhibitors, alpha-Cysteine,Proteinase Antagonist, Cysteine,Proteinase Antagonists, Cysteine,Proteinase Inhibitor, Cysteine,Proteinase Inhibitors, Cysteine,alpha Cysteine Protease Inhibitor,alpha Cysteine Protease Inhibitors
D056657 Cathepsin K A cysteine protease that is highly expressed in OSTEOCLASTS and plays an essential role in BONE RESORPTION as a potent EXTRACELLULAR MATRIX-degrading enzyme.
D057166 High-Throughput Screening Assays Rapid methods of measuring the effects of an agent in a biological or chemical assay. The assay usually involves some form of automation or a way to conduct multiple assays at the same time using sample arrays. High-Throughput Screening,High-Throughput Biological Assays,High-Throughput Chemical Assays,High-Throughput Screening Methods,Assay, High-Throughput Biological,Assay, High-Throughput Chemical,Assay, High-Throughput Screening,Biological Assay, High-Throughput,Chemical Assay, High-Throughput,High Throughput Biological Assays,High Throughput Chemical Assays,High Throughput Screening,High Throughput Screening Assays,High Throughput Screening Methods,High-Throughput Biological Assay,High-Throughput Chemical Assay,High-Throughput Screening Assay,High-Throughput Screening Method,High-Throughput Screenings,Screening Assay, High-Throughput,Screening Method, High-Throughput,Screening, High-Throughput
D018360 Crystallography, X-Ray The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) X-Ray Crystallography,Crystallography, X Ray,Crystallography, Xray,X Ray Crystallography,Xray Crystallography,Crystallographies, X Ray,X Ray Crystallographies
D020134 Catalytic Domain The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. Active Site,Catalytic Core,Catalytic Region,Catalytic Site,Catalytic Subunit,Reactive Site,Active Sites,Catalytic Cores,Catalytic Domains,Catalytic Regions,Catalytic Sites,Catalytic Subunits,Core, Catalytic,Cores, Catalytic,Domain, Catalytic,Domains, Catalytic,Reactive Sites,Region, Catalytic,Regions, Catalytic,Site, Active,Site, Catalytic,Site, Reactive,Sites, Active,Sites, Catalytic,Sites, Reactive,Subunit, Catalytic,Subunits, Catalytic

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