title: Design and synthesis of diaminopyrrolidinone inhibitors of human osteoclast cathepsin K.
abstract: The structure-based design and synthesis of lactam-constrained azapeptide inhibitors of human cathepsin K are described. Enhanced stability to proteolytic cleavage over acyclic analogues is discussed.
authors.affiliation: Department of Medicinal Chemistry, SmithKline Beecham Pharmaceuticals, Collegeville, PA 19246, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Duffy
authors.forename: L H
authors.initials: LH
authors.lastname: Ridgers
authors.forename: R L
authors.initials: RL
authors.lastname: DesJarlais
authors.forename: T A
authors.initials: TA
authors.lastname: Tomaszek
authors.forename: M J
authors.initials: MJ
authors.lastname: Bossard
authors.forename: S K
authors.initials: SK
authors.lastname: Thompson
authors.forename: R M
authors.initials: RM
authors.lastname: Keenan
authors.forename: D F
authors.initials: DF
authors.lastname: Veber
mesh_terms: D000588:Amines / Q000737:chemistry; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018360:Crystallography, X-Ray; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D010010:Osteoclasts / Q000201:enzymology*; D010455:Peptides / Q000737:chemistry; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D015853:Cysteine Proteinase Inhibitors; D010455:Peptides; D011760:Pyrrolidinones; C121283:diaminopyrrolidinone; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K