4-Amino-5-vinyl-3(2H)-pyridazinones and analogues as potent antinociceptive agents: Synthesis, SARs, and preliminary studies on the mechanism of action

Bioorg Med Chem. 2007 Aug 15;15(16):5563-75. doi: 10.1016/j.bmc.2007.05.035. Epub 2007 May 18.

Abstract

A series of 4-amino-5-vinyl-3(2H)-pyridazinones and analogues were synthesized and their antinociceptive effect was evaluated in the mouse abdominal constriction model. Several of the novel compounds showed ED(50) values in the range 6-20mg/kg/sc and demonstrated to be able to completely protect all the treated animals from the effect of the noxious stimulus at 30 mg/kg/sc. SAR studies confirmed the essential role played by an amino or substituted amino function at position 4 and by a vinyl group at position 5 of the diazine system.

MeSH terms

  • Amination
  • Animals
  • Behavior, Animal / drug effects
  • Male
  • Mice
  • Molecular Structure
  • Nociceptors / metabolism*
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Pyridines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Pyridines