Cardiotonic Agents. 5. 1,2-Dihydro-5-[4-(1H-imidazol-1-yl)phenyl]-6-methyl-2-oxo-3- Pyridinecarbonitriles and Related Compounds. Synthesis and Inotropic Activity

J Med Chem. 1987 Jun;30(6):1023-9. doi: 10.1021/jm00389a011.

Abstract

Several 1,2-dihydro-5-(substituted phenyl)-2(1H)-pyridinones were synthesized and evaluated for inotropic activity. 1,2-Dihydro-5-[4-(1H-imidazol-1-yl)phenyl]-6-methyl-2-oxo-3- pyridinecarbonitrile (5a) and the corresponding unsubstituted analogue 14a were the most potent positive inotropic agents in this series. Although the 4,6-dimethyl analogue 6a retained most of the activity of 5a, the 4-methyl analogue 8a was substantially less potent. The synthesis and structure-activity relationships are discussed.

MeSH terms

  • Animals
  • Cardiotonic Agents / chemical synthesis*
  • Cardiotonic Agents / pharmacology
  • Dogs
  • Dose-Response Relationship, Drug
  • Female
  • Imidazoles / chemical synthesis*
  • Imidazoles / pharmacology
  • Male
  • Myocardial Contraction / drug effects*
  • Nitriles / chemical synthesis
  • Nitriles / pharmacology
  • Pyridones / chemical synthesis*
  • Pyridones / pharmacology
  • Structure-Activity Relationship

Substances

  • Cardiotonic Agents
  • Imidazoles
  • Nitriles
  • Pyridones