Cardiotonic agents. 3. Synthesis and biological activity of novel 6-(substituted 1H-imidazol-4(5)-yl)-3(2H)-pyridazinones

J Med Chem. 1986 Feb;29(2):261-7. doi: 10.1021/jm00152a015.

Abstract

Several 6-(substituted 1H-imidazol-4(5)-yl)-3(2H)-pyridazinones were synthesized and evaluated for positive inotropic activity. The 1H-imidazol-4-yl regioisomers 4,5-dihydro-6-(1-methyl-2-phenyl-1H-imidazol-4-yl)-3(2H)-pyridazinone (25a) and 6-(1-methyl-2-phenyl-1H-imidazol-4-yl)-3(2H)-pyridazinone (28a) were potent positive inotropic agents. By contrast, the corresponding 1H-imidazol-5-yl regioisomers 25b and 28b were only weak positive inotropic agents. Compounds 25a and 28a were also potent inhibitors of cardiac phosphodiesterase fraction III.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Cardiotonic Agents / chemical synthesis*
  • Cardiotonic Agents / pharmacology
  • Dogs
  • Dose-Response Relationship, Drug
  • Female
  • Male
  • Phosphodiesterase Inhibitors / pharmacology
  • Pyridazines / chemical synthesis*
  • Pyridazines / pharmacology
  • Structure-Activity Relationship

Substances

  • Cardiotonic Agents
  • Phosphodiesterase Inhibitors
  • Pyridazines