Homobivalent quinazolinimines as novel nanomolar inhibitors of cholinesterases with dirigible selectivity toward butyrylcholinesterase

J Med Chem. 2006 Sep 7;49(18):5411-3. doi: 10.1021/jm060682m.

Abstract

Homobivalent dimers of quinazolinimines, which bridge the imine nitrogen atoms via a hepta- and an octamethylene spacer, with different ring sizes of the alicycles were synthesized from the corresponding quinazolinethiones. The resulting compounds show >100-fold increase of inhibitory activities compared to related monomeric compounds yielding low-nanomolar inhibitors. For heptamethylene dimers, mixed inhibition profiles were obtained, whereas for the octamethylene compounds selectivity toward butyrylcholinesterase (>180) can be achieved with an eight-membered alicycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry*
  • Butyrylcholinesterase / chemistry*
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / chemistry
  • Dimerization
  • Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
  • Heterocyclic Compounds, 4 or More Rings / chemistry
  • Imines / chemical synthesis*
  • Imines / chemistry
  • Ligands
  • Quinazolines / chemical synthesis*
  • Quinazolines / chemistry
  • Structure-Activity Relationship
  • Tacrine / chemistry

Substances

  • Cholinesterase Inhibitors
  • Heterocyclic Compounds, 4 or More Rings
  • Imines
  • Ligands
  • Quinazolines
  • Tacrine
  • Acetylcholinesterase
  • Butyrylcholinesterase