title: Orally bioavailable small molecule ketoamide-based inhibitors of cathepsin K.
abstract: An orally available series of ketoamide-based inhibitors of cathepsin K has been identified. Starting from a potent inhibitor with poor oral bioavailability, modifications to P1 and P1' elements led to enhancements in solubility and permeability. These improvements resulted in orally available cathepsin K inhibitors.
authors.affiliation: Department of Medicinal Chemistry, GlaxoSmithKline, Research Triangle Park, NC 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: Larry R
authors.initials: LR
authors.lastname: Miller
authors.forename: Francis X
authors.initials: FX
authors.lastname: Tavares
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Wells-Knecht
authors.forename: Lois L
authors.initials: LL
authors.lastname: Wright
authors.forename: Hui-Qiang Q
authors.initials: HQ
authors.lastname: Zhou
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D001682:Biological Availability; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D002460:Cell Line; D004285:Dogs; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D010599:Pharmacokinetics; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K