Cardiotonic agents: a crystallographic and quantum-chemical study of ethyl 5-cyano-1,6-dihydro-2-isopropyl-6-oxo-3-pyridine carboxylate and related compounds

The X-ray structural characterization of ethyl 5-cyano-1,6-dihydro-2-isopropyl-6-oxo-3-pyridine carboxylate is reported. Its solid state conformation has been compared with that of ethyl 2-methyl- and 2- tert -butyl-5-cyano-1,6-dihydro-6-oxo-3-pyridine carboxylate and with the results of a quantum chemical analysis at MNDO level in order to study the structure-activity relationship. Theoretical data indicate that the 2-substituent appears to be primarily responsible for the potencies and the different inotropic activities (positive or negative) of compounds 1–3 .