2-Phenoxy-indan-1-one derivatives as acetylcholinesterase inhibitors: a study on the importance of modifications at the side chain on the activity

Bioorg Med Chem. 2008 Aug 15;16(16):7646-53. doi: 10.1016/j.bmc.2008.07.014. Epub 2008 Jul 10.

Abstract

As a part of our project aimed at developing new agents of potential application in AD, a new series of 2-phenoxy-indan-1-one derivatives which possess alkylamine side chain were designed, synthesized, and evaluated for their inhibitory activity against AChE and BuChE. Most of the compounds were found to inhibit AChE in the nanomolar range. The optimum inhibitor 3g exhibited 34-fold increase in AChE inhibition than donepezil and displayed neuroprotective effect against H(2)O(2)-induced cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry
  • Acetylcholinesterase / metabolism
  • Animals
  • Butyrylcholinesterase / chemistry
  • Butyrylcholinesterase / metabolism
  • Cell Survival / drug effects
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / pharmacology*
  • Humans
  • Hydrogen Peroxide / antagonists & inhibitors
  • Hydrogen Peroxide / pharmacology
  • Indans / chemical synthesis
  • Indans / chemistry*
  • Indans / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • PC12 Cells
  • Rats
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Infrared
  • Structure-Activity Relationship

Substances

  • Cholinesterase Inhibitors
  • Indans
  • Hydrogen Peroxide
  • Acetylcholinesterase
  • Butyrylcholinesterase