Dioxo-triazines as a novel series of cathepsin K inhibitors.
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.
Rankovic
Zoran
Z
Schering-Plough Corporation, Newhouse, Lanarkshire, ML1 5SH, Scotland, United Kingdom. zoran.rankovic@spcorp.com
Cai
Jiaqiang
J
Fradera
Xavier
X
Dempster
Maureen
M
Mistry
Ashvin
A
Mitchell
Ann
A
Long
Clive
C
Hamilton
Emma
E
King
Angela
A
Boucharens
Sylviane
S
Jamieson
Craig
C
Gillespie
Jonathan
J
Cumming
Iain
I
Uitdehaag
Joost
J
van Zeeland
Mario
M
D001665:Binding Sites; D020134:Catalytic Domain; D056657:Cathepsin K / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018360:Crystallography, X-Ray; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D057166:High-Throughput Screening Assays; D006801:Humans; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014498:Uracil / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D015853:Cysteine Proteinase Inhibitors; D014227:Triazines; D014498:Uracil; D056657:Cathepsin K