title: 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.
authors.affiliation: N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prosp. 47, Moscow, 119991, Russian Federation.
authors.forename: Leonid L
authors.initials: LL
authors.lastname: Fershtat
authors.affiliation: N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prosp. 47, Moscow, 119991, Russian Federation.
authors.forename: Nina N
authors.initials: NN
authors.lastname: Makhova
mesh_terms: D020030:Nitric Oxide Donors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D010069:Oxadiazoles / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C528141:1,2,5-oxadiazole 2-oxide; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D011355:Prodrugs
keywords: drug design; furoxans; molecular diversity; nitric oxide; nitrogen heterocycles; prodrugs