title: A structural screening approach to ketoamide-based inhibitors of cathepsin K.
abstract: Several novel ketoamide-based inhibitors of cathepsin K have been identified. Starting from a modestly potent inhibitor, structural screening of P2 elements led to 100-fold enhancements in inhibitory activity. Modifications to one of these leads resulted in an orally bioavailable cathepsin K inhibitor.
authors.affiliation: Department of Medicinal Chemistry, GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Barrett
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: Aaron B
authors.initials: AB
authors.lastname: Miller
authors.forename: Larry R
authors.initials: LR
authors.lastname: Miller
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Wells-Knecht
authors.forename: Lois L
authors.initials: LL
authors.lastname: Wright
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D001665:Binding Sites; D001682:Biological Availability; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K