Nicorandil analogues containing NO-donor furoxans and related furazans

The synthesis and in vitro vasodilating properties of hybrid compounds in w hich furoxan (1,2,5-oxadiazole 2-oxide) moieties, endowed with different NO -donor properties, were substituted for the nitroxy function of Nicorandil are reported. The corresponding cyanoguanidine analogues are also considere d. This approach has led to a series of vasorelaxing compounds devoid of af finity for K-ATP channels, whose activity is prevalently due to their abili ty to activate sGC, at the concentrations of the experiments. Related furaz an (1,2,5-oxadiazole) derivatives, unable to release nitric oxide were also prepared and studied for control. The amide analogues of Nicorandil displa y feeble vasorelaxing action not involving the activation of K+ channels, w hile in the guanidine analogues, this mechanism seems to underlie this acti on. (C) 2000 Elsevier Science Ltd. All rights reserved.