title: Design and synthesis of 6-substituted amino-4-oxa-1-azabicyclo[3,2,0]heptan-7-one derivatives as cysteine proteases inhibitors.
abstract: A series of 6-substituted amino-4-oxa-1-azabicyclo[3,2,0]heptan-7-one compounds was designed and synthesized as a new class of inhibitors for cysteine proteases cathepsins B, L, K, and S. One compound (5S,6S)-6-(N-benzyloxycarbonyl-L-phenylalanyl) amino-4-oxa-1-azabicyclo[3,2,0]heptan-7-one showed excellent cathepsin L and K inhibition activity with IC(50) at a low nanomolar range.
authors.affiliation: SynPhar Laboratories, currently NAEJA Pharmaceutical Inc., 4290-91A Street, Edmonton, Alberta, Canada.
authors.forename: Nian E
authors.initials: NE
authors.lastname: Zhou
authors.forename: Deqi
authors.initials: D
authors.lastname: Guo
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Kaleta
authors.forename: Enrico
authors.initials: E
authors.lastname: Purisima
authors.forename: Robert
authors.initials: R
authors.lastname: Menard
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Micetich
authors.forename: Rajeshwar
authors.initials: R
authors.lastname: Singh
mesh_terms: D002403:Cathepsins / Q000037:antagonists & inhibitors; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D020128:Inhibitory Concentration 50; D007769:Lactams / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D010206:Papain / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D015853:Cysteine Proteinase Inhibitors; D007769:Lactams; C027434:4-oxa-1-azabicyclo(3.2.0)heptan-7-one; D002403:Cathepsins; D010206:Papain