A one-pot domino synthesis and discovery of highly functionalized dihydrobenzo[b]thiophenes as AChE inhibitors

Bioorg Med Chem Lett. 2013 Apr 1;23(7):2101-5. doi: 10.1016/j.bmcl.2013.01.122. Epub 2013 Feb 8.

Abstract

A library of novel 5-amino-2,7-diaryl-2,3-dihydrobenzo[b]thiophene-4,6-dicarbonitriles have been synthesized regioselectively in good yields through the one-pot domino reactions of 5-aryldihydro-3(2H)-thiophenones, malononitrile and aromatic aldehydes in the presence of morpholine. This transformation presumably involves Knoevenagel condensation-Michael addition-intramolecular Thorpe-Ziegler cyclization-Tautomerization-Elimination sequence of reactions. These compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity and 5-amino-2,7-bis(4-methoxyphenyl)-2,3-dihydrobenzo[b]thiophene-4,6-dicarbonitrile was found to be the most potent against AChE with IC50 4.16 μmol/L.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Models, Molecular
  • Molecular Structure
  • Nitriles / chemical synthesis
  • Nitriles / chemistry
  • Nitriles / pharmacology*
  • Structure-Activity Relationship
  • Thiophenes / chemical synthesis
  • Thiophenes / chemistry
  • Thiophenes / pharmacology*

Substances

  • Cholinesterase Inhibitors
  • Nitriles
  • Thiophenes
  • Acetylcholinesterase