Nicorandil analogues containing NO-donor furoxans and related furazans

The synthesis and in vitro vasodilating properties of hybrid compounds in which furoxan (1,2,5-oxadiazole 2-oxide) moieties, endowed with diAerent NO-donor properties, were substituted for the nitroxy function of Nicorandil are reported. The corresponding cyanoguanidine analogues are also considered. This approach has led to a series of vasorelaxing compounds devoid of aAnity for KATP channels, whose activity is prevalently due to their ability to activate sGC, at the concentrations of the experi- ments. Related furazan (1,2,5-oxadiazole) derivatives, unable to release nitric oxide were also prepared and studied for control. The amide analogues of Nicorandil display feeble vasorelaxing action not involving the activation of K + channels, while in the guani- dine analogues, this mechanism seems to underlie this action. # 2000 Elsevier Science Ltd. All rights reserved.