3-Acylamino-azetidin-2-one as a novel class of cysteine proteases inhibitors

• Published in: Bioorganic & medicinal chemistry letters Vol. 13; no. 1; pp. 139 - 141
• Main Authors: Zhou, Nian E., Guo, Deqi, Thomas, George, Reddy, Andhe V.N., Kaleta, Jadwiga, Purisima, Enrico, Menard, Robert, Micetich, Ronald G., Singh, Rajeshwar
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 06.01.2003; Elsevier
• Subjects: Azetidines - chemical synthesis; Azetidines - pharmacology; Biological and medical sciences; Cathepsin B - antagonists & inhibitors; Cathepsin K; Cathepsin L; Cathepsins - antagonists & inhibitors; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors - chemical synthesis; Cysteine Proteinase Inhibitors - pharmacology; Drug Design; Humans; Inhibitory Concentration 50; Lactams - chemistry; Leukocyte Elastase - antagonists & inhibitors; Medical sciences; Miscellaneous; Pharmacology. Drug treatments; Structure-Activity Relationship; Cathepsin L; Cathepsin K; Four membered ring; Enzyme; Aminoamide; Nitrogen heterocycle; Cysteine endopeptidases; Lactam; Enzyme inhibitor; Non peptide compound; Cathepsin S; In vitro; Peptidases; Structure activity relation; Azetidine derivatives; Cathepsin B; Hydrolases; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(02)00831-4

A new class of inhibitors for cysteine proteases cathepsin B, L, K and S is described. These inhibitors are based on the β-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. 3-Acylamino-azetidin-2-one derivatives with potent inhibition activities for cathepsins L, K, and S at the nanomolar or subnanomolar IC 50 values is reported.