(4-Piperidinylphenyl)aminoethyl amides as a novel class of non-covalent cathepsin K inhibitors.
A series of (4-piperidinylphenyl)aminoethyl amides based on dipeptide anilines were synthesized and tested against cathepsin K, cathepsin L and cathepsin B. These new non-covalent inhibitors exhibited single-digit nM inhibition of the cysteine proteases. Compounds 3 and 7 demonstrated potency in both mouse and human osteoclast resorption assays.
Kim
Tae-Seong
TS
Department of Chemistry Research and Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. tkim@amgen.com
Hague
Andrew B
AB
Lee
Tony I
TI
Lian
Brian
B
Tegley
Christopher M
CM
Wang
Xianghong
X
Burgess
Teresa L
TL
Qian
Yi-Xin
YX
Ross
Sandra
S
Tagari
Philip
P
Lin
Chi-Hwei
CH
Mayeda
Carol
C
Dao
Jennifer
J
Jordan
Steven
S
Mohr
Christopher
C
Cheetham
Janet
J
Viswanadhan
Vellarkad
V
Tasker
Andrew S
AS
D000577:Amides / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy / Q000201:enzymology; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use
D000577:Amides; D015853:Cysteine Proteinase Inhibitors; D010880:Piperidines; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; C534132:Ctsk protein, mouse