Design and synthesis of 6-substituted amino-4-oxa-1-azabicyclo[3,2,0]heptan-7-one derivatives as cysteine proteases inhibitors.
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.
Zhou
Nian E
NE
SynPhar Laboratories, currently NAEJA Pharmaceutical Inc., 4290-91A Street, Edmonton, Alberta, Canada.
Guo
Deqi
D
Kaleta
Jadwiga
J
Purisima
Enrico
E
Menard
Robert
R
Micetich
Ronald G
RG
Singh
Rajeshwar
R
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
D015853:Cysteine Proteinase Inhibitors; D007769:Lactams; C027434:4-oxa-1-azabicyclo(3.2.0)heptan-7-one; D002403:Cathepsins; D010206:Papain