Synthesis and in vitro evaluation of 7-methoxy-N-(pent-4-enyl)-1,2,3,4-tetrahydroacridin-9-amine-new tacrine derivate with cholinergic properties

Bioorg Med Chem Lett. 2011 Nov 1;21(21):6563-6. doi: 10.1016/j.bmcl.2011.08.042. Epub 2011 Aug 22.

Abstract

Cholinesterase inhibitors are, so far, the only successful strategy for the symptomatic treatment of Alzheimer's disease. Tacrine (THA) is a potent acetylcholinesterase inhibitor that was used in the treatment of Alzheimer's disease for a long time. However, the clinical use of THA was hampered by its low therapeutic index, short half-life and liver toxicity. 7-Methoxytacrine (7-MEOTA) is equally pharmacological active compound with lower toxicity compared to THA. In this Letter, the synthesis, biological activity and molecular modelling of elimination by-product isolated during synthesis of 7-MEOTA based bis-alkylene linked compound is described.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridines / chemical synthesis*
  • Acridines / pharmacology*
  • Cholinergic Agents / chemical synthesis*
  • Cholinergic Agents / pharmacology*
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / pharmacology
  • Drug Evaluation, Preclinical
  • Half-Life
  • In Vitro Techniques
  • Models, Molecular
  • Tacrine / chemical synthesis*
  • Tacrine / pharmacology*

Substances

  • Acridines
  • Cholinergic Agents
  • Cholinesterase Inhibitors
  • Tacrine