title: 3,4-disubstituted azetidinones as selective inhibitors of the cysteine protease cathepsin K. Exploring P2 elements for selectivity.
abstract: A novel series of 3,4-disubstituted azetidinones based inhibitors of the cysteine protease cathepsin K (Cat K) has been identified. Although not optimized, some of these compounds show at least 100-fold selectivity against other cathepsins. The use of cyclic moieties as P2 elements has proven to be crucial to achieve a high degree of selectivity.
authors.affiliation: Department of Medicinal Chemisty, Celera, 180 Kimball Way, South San Francisco, CA 94080, USA. setti@celera.com
authors.forename: Eduardo L
authors.initials: EL
authors.lastname: Setti
authors.forename: Dana
authors.initials: D
authors.lastname: Davis
authors.forename: Tobee
authors.initials: T
authors.lastname: Chung
authors.forename: John
authors.initials: J
authors.lastname: McCarter
mesh_terms: D001384:Azetidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007536:Isomerism; D007700:Kinetics; D010879:Piperazines / Q000737:chemistry; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: C104591:APC 3328; D001384:Azetidines; D015853:Cysteine Proteinase Inhibitors; D010879:Piperazines; D002403:Cathepsins; D056657:Cathepsin K