The identification of potent, selective, and bioavailable cathepsin S inhibitors.
Highly potent, selective, and bioavailable inhibitors of human, mouse, or rat cathepsin S are described. The key structural features combine a sulfonyl moiety attached to a large group in P2 and a small substituent in P3.
Gauthier
Jacques Yves
JY
Merck Frosst Centre for Therapeutic Research, Department of Medicinal Chemistry, Kirkland, QUE, Canada. jacques-yves_gauthier@merck.com
Black
W Cameron
WC
Courchesne
Isabelle
I
Cromlish
Wanda
W
Desmarais
Sylvie
S
Houle
Robert
R
Lamontagne
Sonia
S
Li
Chun Sing
CS
Massé
Frédéric
F
McKay
Daniel J
DJ
Ouellet
Marc
M
Robichaud
Joël
J
Truchon
Jean-François
JF
Truong
Vouy-Linh
VL
Wang
Qingping
Q
Percival
M David
MD
D000818:Animals; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011485:Protein Binding; D051381:Rats; D013329:Structure-Activity Relationship
D015853:Cysteine Proteinase Inhibitors; D002403:Cathepsins; C028217:cathepsin S