Pharmacological Properties of Furoxans and Benzofuroxans: Recent Developments

Abstract

The chemistry of furoxans (1, 2, 5-oxadiazole-2-oxides) and benzofuroxans (benzo[1, 2-c]1, 2, 5-oxadiazole-1-oxides) is very well known. These systems are widely used in organic chemistry as intermediate compounds for the synthesis of numerous heterocycles. In the other hand, furoxan and benzofuroxan derivatives were extensively studied as bioactive compounds. They possess remarkable biological activities, such as anti-microbial and anti-parasitic properties, mutagenic, immunosuppressive and anticancer effects, anti-aggregating and vasorelaxant activity, among others. In some cases, molecular mode of action was proposed. Recently, the research and development in the medicinal chemistry of these systems have produced hybrid compounds in which furoxan or benzofuroxan moieties together with a classical drug moieties are present in a single molecule. So, new anti-ulcer drugs, calcium channel modulators and vasodilator derivatives were described and they are currently in study. In this presentation recent developments in the medicinal chemistry of furoxans and benzofuroxans will be reviewed.

Preparation and Antitumor Activity of a Tamibarotene-Furoxan Derivative

“…In this work, tamibarotene was used as a basic model drug to be coupled with furoxans, which are NO donors that display remarkable antitumor activities (Wang et al, 2002;Cerecetto et al, 2005;Huerta et al, 2008;Hirst et al, 2010), to synthesize a new compound named QT-011. QT-011 was proposed to exert synergistic effects at multiple target sites and significantly enhance efficacy by releasing NO and tamibarotene through in vivo metabolism.…”

Synthesis and E-Beam-Mediated Gas Phase Fragmentation of Thiol-Containing Furoxans for Nanopatterned Alkyne Formation on Gold Surface

“…The thiol group or thiolate that might be generated in the reaction medium interacted with the furoxan ring, resulting in the occurrence of side reactions. 16,17 The synthetic experiment involving thiol-containing furoxans required careful handling to maintain oxygen-free, neutral conditions. Thus, the liberation of a thiol group was planned at the end of the synthetic route.…”

Studies in 3,4-diaryl-1,2,5-oxadiazoles and their N-oxides: Search for better COX-2 inhibitors

“…1,2,5-oxadiazole N-oxides (furoxans) are reported (11) to be thiol dependent NO donors, whose biological activity is produced by action on the soluble guanylate cyclase--cyclic guanosine monophosphate (sGC-cGMP) pathway. Furoxans are considered to possess favorable bioactivity since they cause a slow release of NO resulting in longer duration of action without development of tolerance.…”

“…Granik and Grigor (12) proposed the mechanism for the release of NO from 1,2,5-oxadiazole N-oxides. It is also reported that release of NO from a nitric oxide donor drug produces beneficial effects such as reduction in blood pressure and prevention of atherosclerosis (11). NSAIDs possessing nitric oxide releasing capabilities are considered to be more promising drugs than the coxibs as these would be devoid of potential cardiovascular side effects associated with coxibs (11).…”

“…NSAIDs possessing nitric oxide releasing capabilities are considered to be more promising drugs than the coxibs as these would be devoid of potential cardiovascular side effects associated with coxibs (11). Recently, a report has been published discussing the synthesis of some monosubstituted 3,4-diaryl-1,2,5-oxadiazoles (11) and N-oxides (35) as selective COX-2 inhibitors, expecting them to be free from adverse cardiovascular effects (13), but we claimed synthesis of these compounds much earlier (10).…”