title: (4-Piperidinylphenyl)aminoethyl amides as a novel class of non-covalent cathepsin K inhibitors.
abstract: 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.
authors.affiliation: Department of Chemistry Research and Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. tkim@amgen.com
authors.forename: Tae-Seong
authors.initials: TS
authors.lastname: Kim
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Hague
authors.forename: Tony I
authors.initials: TI
authors.lastname: Lee
authors.forename: Brian
authors.initials: B
authors.lastname: Lian
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Tegley
authors.forename: Xianghong
authors.initials: X
authors.lastname: Wang
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Burgess
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Qian
authors.forename: Sandra
authors.initials: S
authors.lastname: Ross
authors.forename: Philip
authors.initials: P
authors.lastname: Tagari
authors.forename: Chi-Hwei
authors.initials: CH
authors.lastname: Lin
authors.forename: Carol
authors.initials: C
authors.lastname: Mayeda
authors.forename: Jennifer
authors.initials: J
authors.lastname: Dao
authors.forename: Steven
authors.initials: S
authors.lastname: Jordan
authors.forename: Christopher
authors.initials: C
authors.lastname: Mohr
authors.forename: Janet
authors.initials: J
authors.lastname: Cheetham
authors.forename: Vellarkad
authors.initials: V
authors.lastname: Viswanadhan
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Tasker
mesh_terms: 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
chemical_list: D000577:Amides; D015853:Cysteine Proteinase Inhibitors; D010880:Piperidines; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; C534132:Ctsk protein, mouse