Add time:08/30/2019         Source:sciencedirect.com

Thirty new 1,2-dihydropyridine derivatives of the general formula 4-alkyl (aryl)-6-aryl-3-cyano-2(1H)-pyridinones (1–15) and 4-alkyl (aryl)-6-aryl-3-cyano-2(1H)-iminopyridines (16–30) were synthesized using one-pot multicomponent reactions of the properly substituted acetophenone, appropriate aldehyde, ammonium acetate and ethyl cyanoacetate (1–15) or malononitrile (16–30) in ethanol. These target compounds (1–30) were evaluated for their cardiotonic activity using the spontaneously beating atria model, from reserpine-treated guinea pigs. The best pharmacological profile was obtained with 3-cyano-6-(3,4-dimethoxyphenyl)-4-(4-hydroxyphenyl)-2(1H)-pyridinone (9) which displayed selectivity for increasing the force of contraction (108.7±6.7,% change over control) rather than the frequency rate (40.8±5.3,% change over control) at a 5×10−4 M concentration. The effects of structural changes upon activity are reported.

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