Cage amines as the stopper inhibitors of cholinesterases

Bioorg Med Chem Lett. 2003 Sep 1;13(17):2887-90. doi: 10.1016/s0960-894x(03)00599-7.

Abstract

Cage amines 1-4 are potent peripheral anionic site-bound reversible inhibitors of both acetylcholinesterase and butyrylcholinesterase. Cage amines 1-3 are selective butyrylcholinesterase inhibitor versus acetylcholinesterase. For both enzymes, the -log K(i) values linearly correlate with the difference of substituted phenyl radius of cage amines (-log K(i)=5.4+3.4Deltagamma for acetylcholinesterase, -log K(i)=5.9+3.2Deltagamma for butyrylcholinesterase). Moreover, the relationship between the enzymes and cage amines mimics that between bottles and stoppers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Anions / chemistry
  • Benzylamines / chemical synthesis
  • Benzylamines / chemistry*
  • Benzylamines / pharmacology*
  • Binding Sites
  • Butyrylcholinesterase / metabolism
  • Cations / chemistry
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / pharmacology*
  • Edrophonium / pharmacology
  • Electrophorus
  • Horses
  • Hydrolysis
  • Kinetics
  • Structure-Activity Relationship

Substances

  • Anions
  • Benzylamines
  • Cations
  • Cholinesterase Inhibitors
  • Edrophonium
  • Acetylcholinesterase
  • Butyrylcholinesterase