title: Design of small molecule ketoamide-based inhibitors of cathepsin K.
abstract: A novel series of ketoamide-based inhibitors of cathepsin K has been identified. Modifications to P(2) and P(3) elements were crucial to enhancing inhibitory activity. Although not optimized, a selected inhibitor was effective in attenuating type I collagen hydrolysis in a surrogate assay of bone resorption.
authors.affiliation: Department of Medicinal Chemistry, GlaxoSmithKline, Research Triangle Park, NC 27709, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Catalano
authors.forename: David N
authors.initials: DN
authors.lastname: Deaton
authors.forename: Stacey T
authors.initials: ST
authors.lastname: Long
authors.forename: Robert B
authors.initials: RB
authors.lastname: McFadyen
authors.forename: Larry R
authors.initials: LR
authors.lastname: Miller
authors.forename: J Alan
authors.initials: JA
authors.lastname: Payne
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Wells-Knecht
authors.forename: Lois L
authors.initials: LL
authors.lastname: Wright
mesh_terms: D001862:Bone Resorption / Q000378:metabolism*; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D024042:Collagen Type I / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D006868:Hydrolysis; D013329:Structure-Activity Relationship
chemical_list: D024042:Collagen Type I; D015853:Cysteine Proteinase Inhibitors; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K