title: Acyclic, orally bioavailable ketone-based cathepsin K inhibitors.
abstract: Starting from a potent ketone-based inhibitor with poor drug properties, incorporation of P(2)-P(3) elements from a ketoamide-based inhibitor led to the identification of a hybrid series of ketone-based cathepsin K inhibitors with better oral bioavailability than the starting ketone.
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: 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: Vicente
authors.initials: V
authors.lastname: Samano
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; D001682:Biological Availability; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D018360:Crystallography, X-Ray; D015853:Cysteine Proteinase Inhibitors / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D006801:Humans; D007659:Ketones / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D015853:Cysteine Proteinase Inhibitors; D007659:Ketones; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K