14802-10-9

Upstream product

• 4648-33-3 (E)-1-methoxy-4-(4-nitrostyryl)benzene 
• 1472-68-0 1-methoxy-4-[2-(4-nitrophenyl)ethenyl]benzene 
• 824-94-2 p-methoxybenzyl chloride 
• 3462-97-3 (4-methoxybenzyl)triphenylphosphonium bromide 
• 123-11-5 4-methoxy-benzaldehyde 
• 104-03-0 4-nitrobenzeneacetic acid 

Downstream Products

• 14987-61-2 1-methoxy-4-(4-nitrophenethyl)benzene 
• 33384-05-3 4-(4-aminophenethyl)phenol 
• 1186335-62-5 N-{4-[2-(4-methoxyphenyl)ethyl]phenyl}phthalimide 
• 1186335-71-6 4,5,6,7-tetrachloro-2-(4-(4-methoxyphenethyl)phenyl)isoindoline-1,3-dione 
• 1259938-77-6 C₂₃H₁₈N₂O₅ 
• 1259938-76-5 C₂₃H₁₈N₂O₅ 

Relevant academic research and scientific papers

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.

Anti-influenza activity of phenethylphenylphthalimide analogs derived from thalidomide

Swine-origin influenza A virus has caused pandemics throughout the world and influenza A is regarded as a serious global health issue. Hence, novel drugs that will target these viruses are very desirable. Influenza A expresses an RNA polymerase essential for its transcription and replication which comprises PA, PB1, and PB2 subunits. We identified potential novel anti-influenza agents from a screen of 34 synthesized phenethylphenylphthalimide analogs derived from thalidomide (PPT analogs). For this screen we used a PA endonuclease inhibition assay, a PB2 pathogenicity-determinant domain-binding assay, and an anti-influenza A virus assay. Three PPT analogs, PPT-65, PPT-66, and PPT-67, were found to both inhibit PA endonuclease activity and retard the growth of influenza A, suggesting a correlation between their activities. PPT-28 was also found to inhibit the growth of influenza A. These four analogs have a 3,4-dihydroxyphenethyl group in common. We also discuss the possibility that 3,4-dihydroxyphenethyl group flexibility may play an important functional role in PA endonuclease inhibition. Another analog harboring a dimethoxyphenethyl group, PPT-62, showed PB2 pathogenicity-determinant domain-binding activity, but did not inhibit the growth of the virus. Our present results indicate the utility of the PA endonuclease assay in the screening of anti-influenza drugs and are therefore useful for future strategies to develop novel anti-influenza A drugs and for mapping the function of the influenza A RNA polymerase subunits.

Design and synthesis of phthalimide-based fluorescent liver X receptor antagonists

Based on our structure-activity relationship study of liver X receptor (LXR) ligands, we designed and synthesized fluorescent LXR antagonists containing an unsubstituted or substituted amino group on a phthalimide unit.

Separation of α-glucosidase-inhibitory and liver X receptor-antagonistic activities of phenethylphenyl phthalimide analogs and generation of LXRα-selective antagonists

Liver X receptor (LXR) α/β dual agonists are candidate medicaments for the treatment of metabolic syndrome, because their biological actions include increasing cholesterol efflux mediated by LXRβ. However, their clinical application is currently limited by their enhancing effect on triglyceride (TG) synthesis mediated by LXRα. Combination of an LXRα-selective antagonist with an LXRα/β dual agonist may overcome this disadvantage. In the present work, structural development studies of phenethylphenyl phthalimide 9, which possesses LXRα/β dual-antagonistic activity and α-glucosidase-inhibitory activity, led to the LXRα-selective antagonist 23f. Specific α-glucosidase inhibitors were also obtained.

The synthesis and structure-activity relationship of substituted N-phenyl anthranilic acid analogs as amyloid aggregation inhibitors

It is believed that β-amyloid aggregation is an important event in the development of Alzheimer's disease. In the course of our studies to identify β-amyloid aggregation inhibitors, a series of N-phenyl anthranilic acid analogs were synthesized and studied for β-amyloid inhibition activity. The synthesis, structure-activity relationship, and in vivo activity of these analogs are discussed.

Correspondence between Molecular Functionality and Crystal Structures. Supramolecular Chemistry of a Family of Homologated Aminophenols

The crystal structures and packing features of a family of 13 aminophenols, or supraminols, are analyzed and correlated. These compounds are divided into three groups: (a) compounds 1-5 with methylene spacers of the general type HO-C6H4-(CH2)n- C6H 4-NH2 (n = 1 to 5) and both OH and NH2 in a para position; (b) compounds la, 2a, 2b, 2c, and 3a in which one or more of the methylene linkers in 1 to 3 are exchanged with an S-atom; and (c) compounds 2d, 1b, and 6a prepared with considerations of crystal engineering and where the crystal structures may be anticipated on the basis of structures 1-5, 1a, 2a, 2b, 2c, and 3a. These 13 aminols can be described in terms of three major supramolecular synthons based on hydrogen bonding between OH and NH2 groups: the tetrameric loop or square motif, the infinite N(H)O chain, and β-As sheet. These three synthons are not completely independent of each other but interrelate, with the structures tending toward the more stable β-As sheet in some cases. Compounds 1-5 show an alternation in melting points, and compounds with n = even exhibit systematically higher melting points compared to those with n = odd. The alternating melting points are reflected in, and explained by, the alternation in the crystal structures. The n = odd structures tend toward the β-As sheet as n increases and can be considered as a variable series whereas for n = even, the β-As sheet is invariably formed constituting a fixed series. Substitution of a methylene group by an isosteric S-atom may causes a change in the crystal structure. These observations are rationalized in terms of geometrical and chemical effects of the functional groups. This study shows that even for compounds with complex crystal structures the packing may be reasonably anticipated provided a sufficient number of examples are available.

Binding of 5-Arylalkyloxytryptamines at Human 5-HT1Dβ Serotonin Receptors

Several 5-substituted tryptamine derivatives were prepared and examined for their binding at 5-HT1D serotonin receptors. Initially, a region of bulk tolerance was probed. Subsequently, a series of 5-(arylalkyloxy)tryptamines was prepared. Within a homolog