Design, synthesis, and in vitro hMAO-B inhibitory evaluation of some 1-methyl-3,5-diphenyl-4,5-dihydro-1H-pyrazoles

Bioorg Med Chem Lett. 2013 Sep 15;23(18):5128-30. doi: 10.1016/j.bmcl.2013.07.035. Epub 2013 Jul 23.

Abstract

A series of 1-methyl-3,5-diphenyl-4,5-dihydro-1H-pyrazoles (3a-k and 4a-u) were designed, synthesized, and evaluated for their inhibitory efficacy towards the two hMAO isoforms. Most of the derivatives were found to be potent and selective hMAO-B inhibitors. In particular, derivative 3g showed greater hMAO-B affinity than selective inhibitor selegiline coupled with high selectivity index (SI=145). The most selective hMAO-B inhibitor was the 3-methyl analogue 3f with an SI higher than 909.

Keywords: Monoamine oxidases; Pyrazole derivatives; hMAO inhibitors.

MeSH terms

  • Dose-Response Relationship, Drug
  • Drug Design*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Monoamine Oxidase / metabolism*
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Structure-Activity Relationship

Substances

  • 1-methyl-3,5-diphenyl-4,5-dihydro-1H-pyrazole
  • Enzyme Inhibitors
  • Pyrazoles
  • Monoamine Oxidase