SYNTHESIS AND CARDIOTONIC ACTIVITY OF ESTERS OF 2-SUBSTITUTED 5-ACETYL-1,6-DIHYDRO-6-OXO-3-PYRIDINECARBOXYLIC ACIDS

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-oxobutanoa te, respectively, has been described. These esters routinely gave the corresponding carboxylic acids by alkaline hydrolysis followed by acid ification. 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 r eserpine-treated guinea pigs. Among the tested compounds, ethyl l-1,6- dihydro-6-oxo-2-phenyl-3-pyridinecarboxylate was found to be more pote nt and more effective than milrinone as a positive inotropic agent, wh ile only marginally affecting the frequency rate.