169614-78-2

Upstream product

• 6898-86-8 3-methyl-4-phenylfuroxan 
• 104-54-1 3-Phenylpropenol 
• 140-10-3 (E)-3-phenylacrylic acid 
• 4407-36-7 (2E)-3-phenyl-2-propen-1-ol 
• 135733-30-1 3-(hydroxymethyl)-4-phenylfuroxan 

Downstream Products

• 169614-84-0 2-(2-Oxy-4-phenyl-furazan-3-ylmethyl)-isoindole-1,3-dione 
• 1370705-54-6 3-(azidomethyl)-4-phenyl-1,2,5-oxadiazole-2-oxide 
• 135733-34-5 4-phenylfuroxan-3-carboxaldehyde 
• 151733-56-1 4-phenyl-3-furoxanylcarbaldehyde oxime 
• 125520-62-9 4-phenyl-3-furoxancarbonitrile 
• 169614-87-3 3-(aminomethyl)-4-phenyl-1,2,5-oxadiazole-2-oxide 
• 135733-30-1 3-(hydroxymethyl)-4-phenylfuroxan 

Relevant academic research and scientific papers

Design, Synthesis, and in vitro Evaluation of P2X7 Antagonists

The P2X7 receptor is a promising target for the treatment of various diseases due to its significant role in inflammation and immune cell signaling. This work describes the design, synthesis, and in vitro evaluation of a series of novel derivatives bearing diverse scaffolds as potent P2X7 antagonists. Our approach was based on structural modifications of reported (adamantan-1-yl)methylbenzamides able to inhibit the receptor activation. The adamantane moieties and the amide bond were replaced, and the replacements were evaluated by a ligand-based pharmacophore model. The antagonistic potency of the synthesized analogues was assessed by two-electrode voltage clamp experiments, using Xenopus laevis oocytes that express the human P2X7 receptor. SAR studies suggested that the replacement of the adamantane ring by an aryl-cyclohexyl moiety afforded the most potent antagonists against the activation of the P2X7 cation channel, with analogue 2-chloro-N-[1-(3-(nitrooxymethyl)phenyl)cyclohexyl)methyl]benzamide (56) exhibiting the best potency with an IC50 value of 0.39 μΜ.

FUROXANS AS THERAPIES FOR NEURODEGENERATIVE DISORDERS

Furoxan compounds, compositions comprising the same, and methods of making and using the same, are described.

Furoxans (Oxadiazole-4 N-oxides) with Attenuated Reactivity are Neuroprotective, Cross the Blood Brain Barrier, and Improve Passive Avoidance Memory

Nitric oxide (NO) mimetics and other agents capable of enhancing NO/cGMP signaling have demonstrated efficacy as potential therapies for Alzheimer's disease. A group of thiol-dependent NO mimetics known as furoxans may be designed to exhibit attenuated reactivity to provide slow onset NO effects. The present study describes the design, synthesis, and evaluation of a furoxan library resulting in the identification of a prototype furoxan, 5a, which was profiled for use in the central nervous system. Furoxan 5a demonstrated negligible reactivity toward generic cellular thiols under physiological conditions. Nonetheless, cGMP-dependent neuroprotection was observed, and 5a (20 mg/kg) reversed cholinergic memory deficits in a mouse model of passive avoidance fear memory. Importantly, 5a can be prepared as a pharmaceutically acceptable salt and is observed in the brain 12 h after oral administration, suggesting potential for daily dosing and excellent metabolic stability. Continued investigation into furoxans as attenuated NO mimetics for the CNS is warranted.

Synthesis of furoxan derivatives: DABCO-mediated cascade sulfonylation/cyclization reaction of α-nitro-ketoximes

A convenient and efficient method for the synthesis of furoxan derivatives from α-nitro-ketoximes and sulfonyl chlorides is reported. A wide variety of furoxan derivatives were smoothly obtained in good yields via a DABCO-mediated cascade sulfonylation/cy

Novel nitric oxide-releasing derivatives of brusatol as anti-inflammatory agents: Design, synthesis, biological evaluation, and nitric oxide release studies

Brusatol, a biologically active natural product, was modified in four distinct positions through the covalent attachment of a furoxan moiety, which acts as a nitric oxide (NO) donor. Forty derivatives were synthesized and evaluated for their inhibitory effects on excess NO biosynthesis in activated macrophages. Among them, compound 75 demonstrated inhibition (IC50= 0.067 μM) comparable to that of brusatol but were less cytotoxic. More importantly, even at very low doses (2 μmol/kg/day), compound 75 also showed substantial inhibitory efficacy against chronic obstructive pulmonary disease (COPD)-like inflammation in the mouse model induced by cigarette smoke (CS) and lipopolysaccharide (LPS). Particularly, this compound was over 100-fold less toxic (LD50> 3852 μmol/kg) than brusatol and could be a promising lead for further studies. Notably, the improved properties of this derivative are associated with its NO-releasing capability.

Unsymmetrically Substituted Furoxans. Part 15. Bromination of Dimethylfuroxan and Related Compounds with NBS

Treatment of the dimethylfuroxan 1 and of the two methylphenylfuroxan isomers 4, 5 with N-bromosuccinimide (NBS) shows that the methyl group linked at the 3-position of the furoxan ring is selectively brominated.The same reaction run with the 3-methyl-4-nitrofuroxan 8 and with the 4-ethoxy-3-methylfuroxan 9 bears evidence that the reactivity of the 3-methyl group is dependent on the nature of the substituent at the 4-position. 3-Bromomethylfuroxan derivatives easily undergo nucleophilic substitutions to afford a variety of unsymmetrically substituted furoxans.