Synthesis, benzodiazepine receptor binding and molecular modelling of isochromeno[4,3-c]pyrazol-5(1H)-one derivatives

Eur J Med Chem. 2012 Aug:54:709-20. doi: 10.1016/j.ejmech.2012.06.028. Epub 2012 Jun 28.

Abstract

A series of isochromeno[4,3-c]pyrazole-5(1H)-one derivatives 7b-h were prepared and tested at 10 μM for their ability to displace specific [(3)H]flunitrazepam from bovine brain membranes. The substitution pattern of the above derivatives was shown to influence the receptor affinity. The most active compound of the series was 7e, showing a 54% inhibition of [(3)H]flunitrazepam binding. Compounds 7a-d,i were compared with the known isomers chromeno[4,3-c]pyrazole-4(1H)-ones 14a-d,i, showing that the isochromene/chromene isomerism influences the activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzopyrans / chemical synthesis*
  • Benzopyrans / chemistry
  • Benzopyrans / metabolism*
  • Cattle
  • Chemistry Techniques, Synthetic
  • Humans
  • Molecular Docking Simulation*
  • Protein Binding
  • Protein Conformation
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / metabolism*
  • Receptors, GABA-A / chemistry
  • Receptors, GABA-A / metabolism*

Substances

  • Benzopyrans
  • Pyrazoles
  • Receptors, GABA-A