title: Cardiotonic agents. 3. Synthesis and biological activity of novel 6-(substituted 1H-imidazol-4(5)-yl)-3(2H)-pyridazinones.
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: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D002316:Cardiotonic Agents; D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines