Vasodilating and antiarrhythmic activity of heteryl lactones

A new series of unsaturated gamma- and delta-lactones with pyridyl, quinolyl and nitrophenyl substituents (9, 10) have been synthesized by the condensation of unsaturated methyl lactones with heteryl aldehyde or nitrobenzaldehyde in the base-catalysed aldol reaction. The antiarrhythmic, vasodilating and cardiotonic activities of the synthesized compounds have been studied in vivo and ex vivo. 3-Cyano-5,5-dimethyl-4-[4'-(4-pyridyl)-1',3'-butadienyl)]-2(5H)-furanone (9e) displayed a significant vasodilating activity. The antiarrhythmic activity of this compound was higher, but its toxicity lower than that of the procainamide reference drug. Five-membered lactones, particularly 3-cyano-4-(4-pyridylvinyl)-5,5-dimethyl-2(5H)-furanone (9c), exhibited a remarkable cardiotonic activity. The replacement of a pyridyl substituent by a nitrophenyl group in the pyranone derivative did not change the cardiovascular activity and toxicity. (C) 1999 Editions scientifiques et medicales Elsevier SAS.