Conformationally restricted carbamate inhibitors of horse serum butyrylcholinesterase

Bioorg Med Chem Lett. 1998 Oct 6;8(19):2747-50. doi: 10.1016/s0960-894x(98)00484-3.

Abstract

Conformationally restricted carbamate inhibitors, exo-2-norbornyl-N-butylcarbamate (1), endo-2-norbornyl-N-butylcarbamate (2), l-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 (KI), the carbamylation constant (k2), and the bimolecular rate constant (ki). Compound 1 is the most potent inhibitor of the enzyme and the values of KI and ki are 20 nM and 1.1 x 10(5) M-1sec-1, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Butyrylcholinesterase / blood*
  • Butyrylcholinesterase / drug effects
  • Carbamates / pharmacokinetics
  • Carbamates / pharmacology*
  • Cholinesterase Inhibitors / pharmacokinetics
  • Cholinesterase Inhibitors / pharmacology*
  • Horses
  • Kinetics
  • Molecular Conformation
  • Structure-Activity Relationship

Substances

  • Carbamates
  • Cholinesterase Inhibitors
  • Butyrylcholinesterase