title: Highly selective azadipeptide nitrile inhibitors for cathepsin K: design, synthesis and activity assays.
abstract: We have developed a series of azadipeptide nitriles with different P3 groups. A triaryl meta-phenyl derivative, compound 13, was not only a potent inhibitor for cathepsin K (K(i) = 0.0031 nM), but also highly selective over both cathepsins B and S (~1000-fold). A protein-ligand docking study performed on the series provided a possible explanation why compound 13 could be significantly more potent than the others, especially compound 12 in the same series.
authors.affiliation: State Key Laboratory of Supramolecular Structure and Materials, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China.
authors.forename: Xing-Feng
authors.initials: XF
authors.lastname: Ren
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Li
authors.forename: Xuexun
authors.initials: X
authors.lastname: Fang
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Wu
authors.forename: Lincong
authors.initials: L
authors.lastname: Wang
authors.forename: Shuxue
authors.initials: S
authors.lastname: Zou
mesh_terms: D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D056657:Cathepsin K / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D001372:Aza Compounds; D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D009570:Nitriles; D056657:Cathepsin K