title: Exploration of the P1 SAR of aldehyde cathepsin K inhibitors.
abstract: The synthesis and biological activity of a series of aldehyde inhibitors of cathepsin K are reported. Exploration of the properties of the S(1) subsite with a series of alpha-amino aldehyde derivatives substituted at the P(1) position afforded compounds with cathepsin K IC(50)s between 52 microM and 15 nM.
authors.affiliation: Department of Medicinal Chemistry, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Catalano
authors.forename: David N
authors.initials: DN
authors.lastname: Deaton
authors.forename: Eric S
authors.initials: ES
authors.lastname: Furfine
authors.forename: Annie M
authors.initials: AM
authors.lastname: Hassell
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: Lisa M
authors.initials: LM
authors.lastname: Shewchuk
authors.forename: Derril H
authors.initials: DH
authors.lastname: Willard
authors.forename: Lois L
authors.initials: LL
authors.lastname: Wright
mesh_terms: D000447:Aldehydes / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000447:Aldehydes; D011480:Protease Inhibitors; D002403:Cathepsins; D056657:Cathepsin K