31994-68-0

Upstream product

• 451-46-7 4-fluorobenzoic acid ethyl ester 
• 108-95-2 phenol 
• 120-47-8 Ethyl 4-hydroxybenzoate 
• 108-86-1 bromobenzene 
• 5798-75-4 Ethyl 4-bromobenzoate 
• 456-22-4 4-Fluorobenzoic acid 
• 1204518-04-6 [4-(ethoxycarbonyl)phenyl](2,4,6-trimethylphenyl)iodonium trifluoromethanesulfonate 
• 98-80-6 phenylboronic acid 
• 462-06-6 fluorobenzene 
• 99-77-4 ethyl 4-nitrobenzoate 
• 7335-27-5 ethyl 4-chlorobenzoate 
• 108-90-7 chlorobenzene 
• 591-50-4 iodobenzene 
• 51934-41-9 4-iodobenzoic acid ethyl ester 

Downstream Products

• 143667-36-1 4-phenoxy-benzoic acid hydrazide 
• 363627-78-5 N-(1-benzylpiperidine-4-yl)-4-phenoxybenzamide 

Relevant academic research and scientific papers

Hit-to-lead optimization on aryloxybenzamide derivative virtual screening hit against SIRT

Sirtuins (SIRTs) are a class of nicotinamide adenine dinucleotide (NAD+)-dependent protein histone deacetylases (HDACs) that are evolutionarily conserved from bacteria to mammals. This group of enzymes catalyses the reversible deacetylation of lysine residues in the histones or non-histone substrates using NAD+ as a cosubstrate. Numerous studies have demonstrated that the aberrant enzymatic activity of SIRTs has been linked to various diseases like diabetes, cancer, and neurodegenerative disorders. Previously, we performed a pharmacophore-based virtual screening campaign and an aryloxybenzamide derivative (1) displaying SIRT1/2 inhibitory effect was identified as a hit compound. In the current study, the hit-to-lead optimization on the hit compound was explored in order to improve the SIRT binding and inhibition. Fourteen compounds, ten of which were new, have been synthesized and subjected to in vitro biological evaluation for their inhibitory activity against SIRT1-3. By the structural modifications performed, a significant improvement was observed in selective SIRT1 inhibition for ST01, ST02, and ST11 compared to that of the hit compound. The highest SIRT2 inhibitory activity was observed for ST14, which was designed according to compatibility with pharmacophore model developed for SIRT2 inhibitors and thus, providing the interactions required with key residues in SIRT2 active site. Furthermore, ST01, ST02, ST11, and ST14 were subjected to in vitro cytotoxicity assay against MCF-7 human breast cancer cell line to determine the influence of the improvement in SIRT1/2 inhibition along with the structural modifications on the cytotoxic properties of the compounds. The cytotoxicity of the compounds was found to be correlated with their SIRT inhibitory profiles indicating the effects of SIRT1/2 inhibition on cancer cell viability. Overall, this study provides structural insights for further inhibitor improvement.

Nickel-Catalyzed Etherification of Phenols and Aryl Halides through Visible-Light-Induced Energy Transfer

Notwithstanding some progress in nickel-catalyzed etherification of alkanols and arylhalides, the ability of such a Ni-catalyzed transformation employing phenols to diaryl ethers is unsuccessful due to phenolates with much lower reduction potentials, which suppress the oxidation of nickel(II) intermediates into requisite Ni(III) species. We herein report visible-light-initiated, nickel-catalyzed O-arylation of phenols with arylhalides using t-BuNH(i-Pr) as the base and thioxanthen-9-one as the photosensitizer under visible light. This photocoupling exhibits a broad substrate scope.

Novel fatty acid-thiadiazole derivatives as potential antimycobacterial agents

The discovery of antibiotics around the middle twentieth century led to a decrease in the interest in antimycobacterial fatty acids. In order to re-establish the importance of naturally abundant fatty acid, a series of fatty acid-thiadiazole derivatives were designed and synthesized based on molecular hybridization approach. In vitro antimycobacterial potential was established by a screening of synthesized compounds against Mycobacterium tuberculosis H37Rv strain. Among them, compounds 5a, 5d, 5h, and 5j were the most active, with compound 5j exhibiting minimum inhibitory concentration of 2.34?μg/ml against M.tb H37Rv. Additionally, the compounds were docked to determine the probable binding interactions and understand the mechanism of action of most active molecules on enoyl-acyl carrier protein reductases (InhA), which is involved in the mycobacterium fatty acid biosynthetic pathway.

Design, synthesis, and structure-activity relationship studies of novel diaryl ether amides as potential antitumor agents

Sorafenib is a drug that has been verified to be effective on hepatoma cells. Three series of diaryl ethers have been designed and synthesized based on the structure of sorafenib. The 5m compound shows better inhibitory potency against HepG2 cells (IC50 = 1.96 μM) than sorafenib (IC50 = 9.61μM). These results have been verified with MTT assay and colony-forming assay. Moreover, compound 5m exhibits good antitumor activities against PLC/PRF5, HeLa, A549, and HT-29 cell lines. The excellent bioactivity of compound 5m confirms that a single optical conformation is superior to the racemate. A western blotting analysis indicates that compound 5m induces the apoptosis of HepG2 cells by enhancing the protein levels of p21 and Cl-caspase3.

Synthesis and structure–activity relationship of N-(piperidin-4-yl)benzamide derivatives as activators of hypoxia-inducible factor 1 pathways

Guided by bioisosterism and pharmacokinetic parameters, we designed and synthesized a series of novel benzamide derivatives. Preliminary in vitro studies indicated that compounds 10b and 10j show significant inhibitory bioactivity in HepG2 cells (IC50 values of 0.12 and 0.13?μM, respectively). Compounds 10b and 10j induced the expression of HIF-1α protein and downstream target gene p21, and upregulated the expression of cleaved caspase-3 to promote tumor cells apoptosis.

Visible-light-mediated synthesis of diaryl ethers from arylboronic acids and diaryliodonium salts

With visible-light irradiation, a simple and metal-free photocatalytic system for the synthesis of diaryl ethers from arylboronic acids and diaryliodonium salts has been developed. The reaction proceeded in high yield for a range of different substrates in the presence of eosin Y under mild reaction conditions.

Modular Synthesis of Arylacetic Acid Esters, Thioesters, and Amides from Aryl Ethers via Rh(II)-Catalyzed Diazo Arylation

One-pot formation of arylacetic acid esters, thioesters, and amides via Rh(II)-catalyzed arylation of a Meldrum's acid-derived diazo reagent with electron-rich arenes is described. The methodology was used to efficiently synthesize an anticancer compound.

The coupling reactions of aryl halides and phenols catalyzed by palladium and MOP-type ligands

Palladium-catalyzed coupling reactions of aryl halides and phenols are described employing the bulky and electron-rich MOP-type ligands. When K3PO4 was used as base and toluene as solvent, the catalyst system exhibited high efficiency for the coupling reaction of the activated aryl halides. When NaH was used as base and o-xylene as solvent, unactivated aryl halides can be used as substrates.

Structure-based design, structure-activity relationship analysis, and antitumor activity of diaryl ether derivatives

To identify novel therapeutic agents to treat cancer, we synthesized a series of diaryl ether derivatives. Structure-activity relationship studies revealed that the presence of a chlorine or hydroxyl at the para-position on the phenyl ring (5h or 5k) significantly enhanced antitumor activity. Compound 5h had stronger growth inhibitory activity in HepG2, A549, and HT-29 cells than compound 5k, with IC50 values of 2.57, 5.48, and 30.04 μM, respectively. Compound 5h also inhibited the growth of other cells lines, including Hep3B, PLC/PRF5, SMMC-7721, HeLa, and A375, with IC50 values of 2.76, 4.26, 29.66, 18.86, and 10.21 μM, respectively. The antitumor activity of compound 5h was confirmed by a colony forming assay. Further, our results indicated that the antitumor activity of compound 5h may be mediated by enhancing expression of p21 and cl-caspase3, and leading to apoptosis of cancer cells.

CsF/clinoptilolite: An efficient solid base in SNAr and copper-catalyzed Ullmann reactions

CsF/clinoptilolite was found to be an efficient solid base catalyst for both SNAr and Ullmann ether reactions. A general and efficient one-step procedure was developed for the synthesis of biaryl ethers via direct coupling of electron-deficient aryl halides to phenols using CsF/clinoptilolite. The protocol was also applied to electron-rich aryl halides by addition of a catalytic amount of copper oxide nanoparticles. Both SNAr and Ullmann reactions were rapid and provided good to excellent yields.