823809-31-0

Upstream product

• 104-82-5 4-Methylbenzyl chloride 
• 1530-37-6 (4-methylbenzyl)triphenylphosphonium chloride 
• 552-89-6 2-nitro-benzaldehyde 
• 2378-86-1 4-methylbenzyltriphenylphosphonium bromide 

Downstream Products

• 823809-35-4 [2-(2-p-tolyl-vinyl)-phenylamino]-acetic acid 
• 823809-33-2 (Z)-2-amino-4'-methylstilbene 

Relevant academic research and scientific papers

Complete 1H and 13C NMR spectral assignment of cis- and trans- 3-{2-[2-(4-methylphenyl)ethenyl]phenyl}sydnones

1H and 13C NMR spectra of cis- and trans-3-{2-[2-(4-methylphenyl)ethenyl]phenyl]}sydnones, the first stilbene-substituted mezoionic oxadiazolium rings, were fully assigned combining the information in various solvents, such as deuter

Development of Tetrachlorophthalimides as Liver X Receptor β (LXRβ)-Selective Agonists

Liver X receptor (LXR) agonists are candidates for the treatment of atherosclerosis via induction of ABCA1 (ATP-binding cassette A1) gene expression, which contributes to reverse cholesterol transport (RCT) and to cholesterol efflux from the liver and intestine. However, LXR agonists also induce genes involved in lipogenesis, such as SREBP-1c (sterol regulatory binding element protein 1c) and FAS (fatty acid synthase), thereby causing an undesirable increase in plasma and hepatic triglyceride (TG) levels. Recent studies indicate that LXRα contributes to lipogenesis in liver, and selective LXRβ activation improves RCT in mice. Therefore, LXRβ-selective agonists are promising candidates to improve atherosclerosis without increasing plasma or hepatic TG levels. However, the ligand-binding domains in the two LXR isoforms α/β share high sequence identity, and few LXR ligands show subtype selectivity. In this study we identified a tetrachlorophthalimide analogue as an LXRβ-selective agonist. Structural development led to (E)-4,5,6,7-tetrachloro-2-(2-styrylphenyl)isoindoline-1,3-dione (24 a), which shows potent and selective LXRβ agonistic activity in reporter gene assays. In binding assays, compound 24 a bound to LXRβ preferentially over LXRα. It also induced the expression of ABCA1 mRNA but not SREBP-1c mRNA in cells. Compound 24 a appears to be a promising lead compound for therapeutic agents to treat atherosclerosis without the side effects induced by LXRα/β dual agonists.

Styrylphenylphthalimides as Novel Transrepression-Selective Liver X Receptor (LXR) Modulators

Anti-inflammatory effects of liver X receptor (LXR) ligands are thought to be largely due to LXR-mediated transrepression, whereas side effects are caused by activation of LXR-responsive gene expression (transactivation). Therefore, selective LXR modulators that preferentially exhibit transrepression activity should exhibit anti-inflammatory properties with fewer side effects. Here, we synthesized a series of styrylphenylphthalimide analogues and evaluated their structure-activity relationships focusing on LXRs-transactivating-agonistic/antagonistic activities and transrepressional activity. Among the compounds examined, 17l showed potent LXR-transrepressional activity with high selectivity over transactivating activity and did not show characteristic side effects of LXR-transactivating agonists in cells. This representative compound, 17l, was confirmed to have LXR-dependent transrepressional activity and to bind directly to LXRβ. Compound 17l should be useful not only as a chemical tool for studying the biological functions of LXRs transrepression but also as a candidate for a safer agent to treat inflammatory diseases.