2-Phenyl-9H-purine-6-carbonitrile derivatives as selective cathepsin S inhibitors.
Starting from previously disclosed equally potent cathepsin K and S inhibitor 4-propyl-6-(3-trifluoromethylphenyl)pyrimidine-2-carbonitrile 1, a novel 2-phenyl-9H-purine-6-carbonitrile scaffold was identified to provide potent and selective cathepsin S inhibitors.
Cai
Jiaqiang
J
Merck Research Laboratories, MSD, Newhouse, Lanarkshire ML1 5SH, UK. jiaqiang.cai@merck.com
Bennett
D Jonathan
DJ
Rankovic
Zoran
Z
Dempster
Maureen
M
Fradera
Xavier
X
Gillespie
Jonathan
J
Cumming
Iain
I
Finlay
William
W
Baugh
Mark
M
Boucharens
Sylviane
S
Bruin
John
J
Cameron
Kenneth S
KS
Hamilton
William
W
Kerr
Jennifer
J
Kinghorn
Emma
E
McGarry
George
G
Robinson
John
J
Scullion
Paul
P
Uitdehaag
Joost C M
JC
van Zeeland
Mario
M
Potin
Dominique
D
Saniere
Laurent
L
Fouquet
Andre
A
Chevallier
Francois
F
Deronzier
Hortense
H
Dorleans
Cecile
C
Nicolai
Eric
E
D020134:Catalytic Domain; D056657:Cathepsin K / Q000037:antagonists & inhibitors / Q000378:metabolism; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002460:Cell Line; D003198:Computer Simulation; D006801:Humans; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011687:Purines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry
C553257:2-phenyl-9H-purine-6-carbonitrile; D009570:Nitriles; D011480:Protease Inhibitors; D011687:Purines; D011743:Pyrimidines; D002403:Cathepsins; C028217:cathepsin S; D056657:Cathepsin K; C030986:pyrimidine