Molecular Hybridization Tools in the Development of Furoxan-Based NO-Donor Prodrugs.

Abstract

The molecular hybridization of different compounds with known pharmacological activity is a particularly prominent approach for the design of potential drugs with improved pharmacokinetic profiles. Much attention over the last decade has been focused on the synthesis of hybrid structures with a nitric oxide (NO)-donor framework, as NO is a ubiquitous and crucial regulator of cellular metabolism, affecting various physiological and pathophysiological processes. 1,2,5-Oxadiazole 2-oxides (furoxans), which are capable of exogenous NO release in the presence of thiol cofactors, are an important class of prospective NO donors. As such, a wide range of hybrid compounds that combine a furoxan ring with various pharmacologically active structures have been created. This review focuses on recent results in the synthesis and pharmacological activity of furoxan-based hybrids. Special attention is given to chemo- and regioselective methods used in the preparation of these hybrid structures, and the role of synergistic effects on their pharmacological activity, associated with the furoxan fragment.