Tuesday, 11 October 2011

1P25: w) Vasodilating and antiarrhythmic activity of heteryl lactones

 L. Leite et al.63 prepared a new series of unsaturated γ- and δ-lactones with pyridyl, quinolyl and nitrophenyl substituents (143, 144), 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 (143e) displayed a significant vasodilating activity. The antiarrhythmic activity of this compound was higher, but its toxicity lowers than that of the procainamide reference drug. Five-membered lactones, particularly 3-cyano-4-(4-pyridylvinyl)-5,5-dimethyl-2(5H)-furanone (143c), 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 as shown in scheme 25.

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63. L. Leite, D. Jansone, M. Veveris, H. Cirule, Y. Popelis, G. Melikyan, A. Avetisyan, and E. Lukevics, Eur. J. Med. Chem., 1999, 34, 859.
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