title: Design and synthesis of tetracyclic nonpeptidic biaryl nitrile inhibitors of cathepsin K.
abstract: The synthesis and biological profile of a novel series of potent and selective inhibitors of cysteine protease cathepsin K (Cat K) are described. Pharmacokinetic evaluation of 12 indicated that some members of this series could be suitable candidates to develop new orally active therapeutic agents for the treatment of osteoporosis.
authors.affiliation: Celera Genomics, South San Francisco, CA 94080, USA. eduardo.setti@bcglobal.net
authors.forename: Eduardo L
authors.initials: EL
authors.lastname: Setti
authors.forename: Shankar
authors.initials: S
authors.lastname: Venkatraman
authors.forename: James T
authors.initials: JT
authors.lastname: Palmer
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xie
authors.forename: Harry
authors.initials: H
authors.lastname: Cheung
authors.forename: Walter
authors.initials: W
authors.lastname: Yu
authors.forename: Gregg
authors.initials: G
authors.lastname: Wesolowski
authors.forename: Joel
authors.initials: J
authors.lastname: Robichaud
mesh_terms: D019540:Area Under Curve; D002401:Cathepsin B / Q000737:chemistry; D056657:Cathepsin K; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003546:Cysteine Endopeptidases / Q000737:chemistry; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008958:Models, Molecular; D009570:Nitriles / Q000737:chemistry*; D010024:Osteoporosis / Q000188:drug therapy*
chemical_list: D004791:Enzyme Inhibitors; D009570:Nitriles; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C028217:cathepsin S; C534130:CTSK protein, human; D056657:Cathepsin K