Synthesis and cardiotonic activity of esters of 2-substituted 5-acetyl-1,6-dihydro-6-oxo-3-pyridinecarboxylic acids

Article abstract of DOI:10.1016/0223-5234(93)90037-F

The synthesis of ethyl or methyl esters of 2-substituted 5-acetyl-1,6-dihydro-6-oxo-3-pyridinecarboxylic acids 2a-d, f and 5 by reaction of sodium acetoacetamide with ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates and ethyl 2-ethoxymethylene-4,4,4-trifluoro-3-oxobutanoate, respectively, has been described. These esters routinely gave the corresponding carboxylic acids by alkaline hydrolysis followed by acidification. As milrinone analogues, the above compounds were tested on contractile activity and frequency rate of spontaneously beating atria and on contractile activity of electrically-driven left atrium from reserpine-treated guinea pigs. Among the tested compounds, ethyl 5-acetyl-1,6-dihydro-6-oxo-2-phenyl-3-pyridinecarboxylate was found to be more potent and more effective than milrinone as a positive inotropic agent, while only marginally affecting the frequency rate.