Conformationally restricted carbamate inhibitors of horse serum butyrylcholinesterase

• Published in: Bioorganic & medicinal chemistry letters Vol. 8; no. 19; pp. 2747 - 2750
• Main Authors: LIN, G, CHEN, G.-H, HO, H.-C
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 06.10.1998; Elsevier
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Butyrylcholinesterase - blood; Butyrylcholinesterase - drug effects; Carbamates - pharmacokinetics; Carbamates - pharmacology; Cholinesterase Inhibitors - pharmacokinetics; Cholinesterase Inhibitors - pharmacology; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Horses; Hydrolases; Kinetics; Molecular Conformation; Structure-Activity Relationship; Molecular rigidity; Enzyme; Epimer; Saturated compound; Enzyme inhibitor; Steric hindrance; Esterases; Tricyclic compound; In vitro; Cholinesterase; Carboxylic ester hydrolases; Vertebrata; Irreversible reaction; Mammalia; Structure activity relation; Animal; Horse; Bicyclic compound; Hydrolases; Perissodactyla; Kinetics; Chemical synthesis; Ungulata
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(98)00484-3

Conformationally restricted carbamate inhibitors, exo-2-norbornyl- N-butylcarbamate ( 1), endo-2-norbornyl- N-butylcarbamate ( 2), 1-adamantyl- N-butylcarbamate ( 3), and 2-adamantyl- N-butylcarbamate ( 4) as active site-directed irreversible inhibitors of horse serum butyrylcholinesterase are investigated for values of the dissociation constant ( K I), the carbamylation constant (k 2), and the bimolecular rate constant (k i). Compound 1 is the most potent inhibitor of the enzyme and the values of K I and k i are 20 nM and 1.1×10 5 M −1sec −1. Graphic