Derivatives of oxoisoaporphine alkaloids: a novel class of selective acetylcholinesterase inhibitors

Bioorg Med Chem Lett. 2007 Jul 1;17(13):3765-8. doi: 10.1016/j.bmcl.2007.04.015. Epub 2007 Apr 10.

Abstract

A series of 9-aminoalkanamido-1-azabenzanthrones derviatives (3a-i Ar-NHCO(CH(2))(n)NR(1)R(2)) and their quaternary methiodide salts (4a-g Ar-NHCO(CH(2))(n)N(+)(CH(3))R(1)R(2)I(-)) were designed and synthesized as acetylcholinesterase (AChE) or butyrylcholinesterase (BuChE) inhibitors. The synthetic compounds exhibited high AChE inhibitory activity with IC(50) values in the nanomolar range and high selectivity for AChE over BuChE (45- to 1980-fold). The structure-activity relationships (SARs) were discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry*
  • Alkaloids / chemistry*
  • Butyrylcholinesterase / chemistry*
  • Carbamates / chemistry
  • Cations
  • Chemistry, Pharmaceutical / methods*
  • Cholinesterase Inhibitors / chemistry*
  • Crystallography, X-Ray
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Inhibitory Concentration 50
  • Models, Chemical
  • Protein Structure, Quaternary
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Carbamates
  • Cations
  • Cholinesterase Inhibitors
  • Enzyme Inhibitors
  • Acetylcholinesterase
  • Butyrylcholinesterase