Synthesis and evaluation of tacrine-E2020 hybrids as acetylcholinesterase inhibitors for the treatment of Alzheimer's disease

Bioorg Med Chem Lett. 2004 Sep 20;14(18):4639-42. doi: 10.1016/j.bmcl.2004.07.005.

Abstract

Tacrine-E2020 hybrids and some related compounds were prepared and their bioactivities on the Alzheimer's disease were assayed. The optimum hybrid inhibitor 3 is 37-fold more potent and 31-fold more selective than tacrine in vitro.

Publication types

  • Comparative Study

MeSH terms

  • Acetylcholinesterase / metabolism
  • Alzheimer Disease / drug therapy
  • Animals
  • Butyrylcholinesterase / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Donepezil
  • In Vitro Techniques
  • Indans / chemical synthesis
  • Indans / chemistry
  • Indans / pharmacology*
  • Ligands
  • Models, Molecular
  • Nootropic Agents / chemical synthesis
  • Nootropic Agents / chemistry
  • Nootropic Agents / pharmacology*
  • Piperidines / chemical synthesis
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Rats
  • Structure-Activity Relationship
  • Tacrine / chemical synthesis
  • Tacrine / chemistry
  • Tacrine / pharmacology*

Substances

  • Cholinesterase Inhibitors
  • Indans
  • Ligands
  • Nootropic Agents
  • Piperidines
  • Tacrine
  • Donepezil
  • Acetylcholinesterase
  • Butyrylcholinesterase