Cardiotonic agents. 1. Novel 8-aryl-substituted imidazo[1,2-a]- and -[1,5-a]pyridines and imidazo[1,5-a]pyridinones as potential positive inotropic agents.
Several 8-arylimidazo[1,2-a]pyridines, 8-arylimidazo[1,5-a]pyridines, and 8-arylimidazo[1,5-a]pyridinones were prepared and tested in vitro for potential cardiac inotropic and electrophysiological activity. Selected analogues were further tested in vivo in canine hemodynamic and cardiac electrophysiology models. Compounds having an imidazole substituent consistently showed activity. A pharmacophoric relationship between heterocycle-phenyl-imidazole and positive inotropic activity was noted. The significance of this relationship is discussed.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D004594:Electrophysiology; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D011728:Pyridones / Q000138:chemical synthesis / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship
D007093:Imidazoles; D011725:Pyridines; D011728:Pyridones; D015105:3',5'-Cyclic-AMP Phosphodiesterases