3-Acylamino-azetidin-2-one as a novel class of cysteine proteases inhibitors.
A new class of inhibitors for cysteine proteases cathepsin B, L, K and S is described. These inhibitors are based on the beta-lactam ring designed to interact with the nucleophilic thiol of the cysteine in the active site of cysteine proteases. Some 3-acylamino-azetidin-2-one derivatives showed very potent inhibition activities for cathepsins L, K and S at the nanomolar or subnanomolar IC(50) values.
Zhou
Nian E
NE
SynPhar Laboratories, currently NAEJA Pharmaceutical Inc., 4290-91A Street, Edmonton, Alberta, Canada T6E 5V2.
Guo
Deqi
D
Thomas
George
G
Reddy
Andhe V N
AV
Kaleta
Jadwiga
J
Purisima
Enrico
E
Menard
Robert
R
Micetich
Ronald G
RG
Singh
Rajeshwar
R
D001384:Azetidines / Q000138:chemical synthesis* / Q000494:pharmacology; D002401:Cathepsin B / Q000037:antagonists & inhibitors; D056657:Cathepsin K; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D007769:Lactams / Q000737:chemistry; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D001384:Azetidines; D015853:Cysteine Proteinase Inhibitors; D007769:Lactams; D002403:Cathepsins; D019272:Leukocyte Elastase; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C028217:cathepsin S; C534130:CTSK protein, human; D056657:Cathepsin K