Day: November 17, 2022

Zhang, Bo published the artcileDiscovery of novel aminophosphonate derivatives containing pyrazole moiety as potential selective COX-2 inhibitors, Quality Control of 1468-83-3, the main research area is aminophosphonate preparation anticancer pyrazole inhibitor amidation human COX MSBAR; Aminophosphonate derivatives; Anti-cancer activity; Apoptosis induction; Cyclooxygenase 2; Mitochondrion-dependent pathway; Pyrazole moiety.

Cyclooxygenase is critical for maintaining physiol. functions, whereas overexpression of COX-2 was closely implicated in various cancers. In this study, a series of novel aminophosphonate derivatives containing pyrazole moiety were synthesized with their anti-cancer activity evaluated. In vitro assays of the target compounds showed that (I) displayed excellent COX-2 inhibitory activity against COX-2 (IC50 = 0.22 ± 0.04μM) and anti-proliferative activity against MCF-7 cell (IC50 = 4.37 ± 0.49μM). The apoptosis induction of compound I was confirmed by flow cytometry and polymerase chain reaction. Further investigation demonstrated that compound I induced apoptosis of MCF-7 cells through a mitochondrion-dependent pathway and involved cell-cycle arrest in G2 phase. Overall, these results provided some new insights into the design of therapeutic drugs for COX-2 inhibitors and indicated the connection between selective COX-2 inhibition and the anti-tumor activity.

Bioorganic Chemistry published new progress about Amidation. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Quality Control of 1468-83-3.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Cruz-Monteagudo, Maykel published the artcileComputational chemistry approach for the early detection of drug-induced idiosyncratic liver toxicity, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is hepatotoxicity drug computational chem QSAR.

Idiosyncratic drug toxicity (IDT), considered as a toxic host-dependent event, with an apparent lack of dose response relationship, is usually not predictable from early phases of clin. trials, representing a particularly confounding complication in drug development. Albeit a rare event (usually <1/5000), IDT is often life threatening and is one of the major reasons new drugs never reach the market or are withdrawn post marketing. Computational methodologies, like the computer-based approach proposed in the present study, can play an important role in addressing IDT in early drug discovery. We report for the first time a systematic evaluation of classification models to predict idiosyncratic hepatotoxicity based on linear discriminant anal. (LDA), artificial neural networks (ANN), and machine learning algorithms (OneR) in conjunction with a 3D mol. structure representation and feature selection methods. These modeling techniques (LDA, feature selection to prevent over-fitting and multicollinearity, ANN to capture nonlinear relationships in the data, as well as the simple OneR classifier) were found to produce QSTR models with satisfactory internal cross-validation statistics and predictivity on an external subset of chems. More specifically, the models reached values of accuracy/sensitivity/specificity over 84%/78%/90%, resp. in the training series along with predictivity values ranging from ca. 78 to 86% of correctly classified drugs. An LDA-based desirability anal. was carried out in order to select the levels of the predictor variables needed to trigger the more desirable drug, i.e. the drug with lower potential for idiosyncratic hepatotoxicity. Finally, two external test sets were used to evaluate the ability of the models in discriminating toxic from nontoxic structurally and pharmacol. related drugs and the ability of the best model (LDA) in detecting potential idiosyncratic hepatotoxic drugs, resp. The computational approach proposed here can be considered as a useful tool in early IDT prognosis. Journal of Computational Chemistry published new progress about Algorithm. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Cai, Yuxing published the artcileN-Heterocyclic Carbene-Catalyzed 1,4-Alkylacylation of 1,3-Enynes, Product Details of C6H6OS, the main research area is allenone preparation; enyne aldehyde radical precursor alkylacylation heterocyclic carbene catalyst.

The radical relay coupling reaction recently emerged as a powerful synthetic strategy for producing tetrasubstituted allenes R(R1CHR2)C=C=C(R3)C(O)R4 (R = H, Me; R1 = trifluoromethyl, 1,1-difluoro-2-methoxy-2-oxoethyl, 3-cyanopropyl, etc.; R2 = Me, Ph, thiophen-3-yl, pyridin-3-yl, etc.; R3 = hexyl, cyclopropyl, Ph, 4-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)butyl, etc.; R4 = Ph, furan-2-yl, pyridin-3-yl, etc.). However, bond-forming processes involving the allenyl radical intermediate are mostly limited to those promoted by transition metals. In this report, a ketyl radical generated from single-electron oxidation of the Breslow intermediate, which is an excellent coupling partner of allenyl radicals is described. An organocatalytic 1,4-alkylacylation of 1,3-enynes RCH=C(R2)CCR3 occurred smoothly in the presence of an aldehyde R4CHO, a radical precursor, and an N-heterocyclic carbene catalyst. This transformation showed remarkable tolerance to both aromatic and aliphatic aldehydes, enyne substitution, and diversified radical precursors.

Organic Letters published new progress about Acylation. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Product Details of C6H6OS.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Huang, Jingjia published the artcileSynthesis of N-Alkylpyridin-4-ones and Thiazolo[3,2-a]pyridin-5-ones through Pummerer-Type Reactions, Formula: C6H6OS, the main research area is alkylpyridinone thiazolopyridinone preparation Pummerer.

N-Alkylated 4-pyridones were obtained through a one-pot procedure involving either normal or interrupted Pummerer reactions between triflic anhydride-activated sulfoxides and 4-fluoropyridine derivatives, followed by hydrolysis. However, triflic anhydride-activated benzyl 6-fluoro-2-pyridyl sulfoxide could react with alkenes or alkynes to afford thiazolo[3,2-a]pyridin-5-ones, via the pyridinium salt intermediates.

Journal of Organic Chemistry published new progress about Hydrolysis. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Formula: C6H6OS.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

McGinnity, Dermot F. published the artcileEvaluation of time-dependent cytochrome P450 inhibition using cultured human hepatocytes, Synthetic Route of 40180-04-9, the main research area is drug cytochrome P450 inhibition human hepatocyte.

Primary human hepatocytes in culture are commonly used to evaluate cytochrome P 450 induction via an enzyme activity endpoint. However, other processes can confound data interpretation. To this end, the impact of time-dependent P 450 inhibition in this system was evaluated. Using a substrate-cassette approach, P 450 activities were determined after incubation with the prototypic inhibitors tienilic acid (CYP2C9), erythromycin, troleandomycin, and fluoxetine (CYP3A4). Kinetic anal. of enzyme inactivation in hepatocytes was used to describe the effect of these time-dependent inhibitors and derive the inhibition parameters kinact and Kl, which generally were in good agreement with the values derived using recombinant P450s and human liver microsomes (HLMs). Tienilic acid selectively inhibited CYP2C9-dependent diclofenac 4′-hydroxylation activity, and erythromycin, troleandomycin, and fluoxetine inhibited CYP3A4-dependent midazolam 1′-hydroxylation in a time- and concentration-dependent manner. Fluoxetine also inhibited CYP2C19-dependent S-mephenytoin 4′-hydroxylation in a time- and concentration-dependent manner in hepatocytes, HLMs, and recombinant CYP2C19 (Kl 0.4 μM and kinact 0.5 min-1). As expected, the effect of fluoxetine on CYP2D6 in hepatocytes was consistent with potent yet reversible inhibition. A very weak time-dependent CYP2C9 inhibitor (AZ1, a proprietary AstraZeneca compound; Kl 30 μM and kinact 0.02 min-1) effectively abolished CYP2C9 activity over 24 h at low (micromolar) concentrations in primary cultured human hepatocytes. This work demonstrates that caution is warranted in the interpretation of enzyme induction studies with metabolically stable, weak time-dependent inhibitors, which may have dramatic inhibitory effects on P 450 activity in this system. Therefore, in addition to enzyme activity, mRNA and/or protein levels should be measured to fully evaluate the P 450 induction potential of a drug candidate.

Drug Metabolism and Disposition published new progress about Hepatocyte. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Synthetic Route of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Tan, Ming published the artcileRoasting treatments affect physicochemical, aroma and nutritional quality of strong fragrant rapeseed oil, Related Products of benzothiophene, the main research area is roasting aroma nutritional quality rapeseed oil.

The strong fragrant rapeseed oil (SFRO) attracts the growing interest in China due to its fragrant flavor, attractive color, and phys. and oxidative stability. It is usually produced with simple processes including rapeseed roasting, mech. pressing, and degumming with hot water (80-90°C). To produce SFROs with high quality and nutritional contents, the seed roasting parameters including temperature up to 220°C and time ranging from 10 min to 30 min were investigated. Results showed that 20-min roasting at temperature 160°C resulted in the highest oil extraction yield of 33.20% with the lowest water content of 0.121%. The produced SFRO had the roasted, nutty and soft tastes with the maximum overall score, the highest total tocopherol and sterol contents of 789.73 mg/kg and 4582.80 mg/kg, resp., and high CoQ10 content of 65.57 mg/kg. Over-roasting at roasting temperature of over 180°C and time of over 30 min led to the high Lovibond red readings, off-flavors, and increased concentrations of high saturated fatty acids and Benzo[a]pyrene (BaP). Our findings would provide a reference to produce SFROs with the highest extraction yield and nutrient contents, acceptable physicochem. properties, optimal profile of the fatty acids and the key aroma compounds, and relatively-low BaP concentration

Journal of Food Composition and Analysis published new progress about Extraction. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Related Products of benzothiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Hicks, Michael B. published the artcileAssessment of coulometric array electrochemical detection coupled with HPLC-UV for the absolute quantitation of pharmaceuticals, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is coulometry electrochem detection liquid chromatog pharmaceutical.

The use of a coulometric array detector in tandem with HPLC-UV was evaluated for the absolute quantitation of pharmaceutical compounds without standards, an important capability gap in contemporary pharmaceutical research and development. The high-efficiency LC flow-through electrochem. detector system allows for the rapid evaluation of up to 16 different potentials, aiding in the identification and quantitation of electrochem. reactive species. By quantifying the number of electrons added or removed from an analyte during its passage through the detector, the number of moles of the analyte can be established. Herein we demonstrate that mols. containing common electroactive functional groups (e.g. anilines, phenols, parabens and tertiary alkyl amines) can in some cases be reliably quantified in HPLC-EC-UV without the need for authentic standards Furthermore, the multichannel nature of the CoulArray detector makes it well suited for optimizing the conditions for electrochem. reaction, allowing the impact of changes in potential, flow rate, temperature and pH to be conveniently studied. The electrochem. oxidation of albacivir, zomepirac, diclofenac, rosiglitazone and several other marketed drugs resulted in large linear ranges, predictable recoveries and excellent quantitation using the total moles of electrons and back-calculating using Faraday’s law. Importantly, we observed several instances where subtle structural changes within a given class of mols. (e.g. aromatic ring isomers) led to unanticipated changes in electrochem. behavior. Consequently, some care should be taken when applying the technique to the routine quantitation of compound libraries where standards are not available.

Analyst (Cambridge, United Kingdom) published new progress about Coulometry. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Cavasin, Anna Theresa published the artcileReliable and Performant Identification of Low-Energy Conformers in the Gas Phase and Water, Safety of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is low energy conformer gas phase water.

Prediction of compound properties from structure via quant. structure-activity relationship and machine-learning approaches is an important computational chem. task in small-mol. drug research. Though many such properties are dependent on three-dimensional structures or even conformer ensembles, the majority of models are based on descriptors derived from two-dimensional structures. Here we present results from a thorough benchmark study of force field, semiempirical, and d. functional methods for the calculation of conformer energies in the gas phase and water solvation as a foundation for the correct identification of relevant low-energy conformers. We find that the tight-binding ansatz GFN-xTB shows the lowest error metrics and highest correlation to the benchmark PBE0-D3(BJ)/def2-TZVP in the gas phase for the computationally fast methods and that in solvent OPLS3 becomes comparable in performance. MMFF94, AM1, and DFTB+ perform worse, whereas the performance-optimized but far more expensive functional PBEh-3c yields energies almost perfectly correlated to the benchmark and should be used whenever affordable. On the basis of our findings, we have implemented a reliable and fast protocol for the identification of low-energy conformers of drug-like mols. in water that can be used for the quantification of strain energy and entropy contributions to target binding as well as for the derivation of conformer-ensemble-dependent mol. descriptors.

Journal of Chemical Information and Modeling published new progress about Conformers. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Safety of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Takakusa, Hideo published the artcileMarkers of electrophilic stress caused by chemically reactive metabolites in human hepatocytes, Quality Control of 40180-04-9, the main research area is drug hepatotoxicity reactive metabolite heme oxygenase biomarker.

The metabolic activation of a drug to an electrophilic reactive metabolite and its covalent binding to cellular macromols. is considered to be involved in the occurrence of idiosyncratic drug toxicity (IDT). As a cellular defense system against oxidative and electrophilic stress, phase II enzymes are known to be induced through a Kelch-like ECH-associated protein 1/nuclear factor E2-related factor 2/antioxidant response element system. We presumed that it is important for the risk assessment of drug-induced hepatotoxicity and IDTs to observe the biol. responses evoked by exposure to reactive metabolites, and then investigated the mRNA induction profiles of phase II enzymes in human hepatocytes after exposure to problematic drugs associated with IDTs, such as ticlopidine, diclofenac, clozapine, and tienilic acid, as well as safe drugs such as levofloxacin and caffeine. According to the results, the problematic drugs exhibited inductive effects on heme oxygenase 1 (HO-1), which contrasted with the safe drugs; therefore, the induction of HO-1 mRNA seems to be correlated with the occurrence of drug toxicity, including IDT caused by electrophilic reactive metabolites. Moreover, glutathione-depletion and cytochrome P 450-inhibition experiments have shown that the observed HO-1 induction was triggered by the electrophilic reactive metabolites produced from the problematic drugs through P 450-mediated metabolic bioactivation. Taken together with our present study, this suggests that HO-1 induction in human hepatocytes would be a good marker of the occurrence of metabolism-based drug-induced hepatotoxicity and IDT caused by the formation of electrophilic reactive metabolites.

Drug Metabolism and Disposition published new progress about Biomarkers. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Quality Control of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Bala, Snega published the artcileMolecular characterization and identification of copper transport in Wilson disease, Quality Control of 40180-04-9, the main research area is ATP7B diuretic copper mol docking Wilson disease.

Wilson’s disease or hepatolenticular degeneration in an autosomal recessive genetic disorder in which copper accumulates in tissues. The condition is due to mutations in Wilson disease protein (ATP7B). A special feature of WD is that medical therapy is used to treat presymptomatic as well as symptomatic individuals, and hepatic transplantation can reverse the metabolic abnormality. In the present research work, an attempt has been made to map the binding site residues of ATP7B protein (receptor). The 3D structure of the monomeric protein was not yet not been exptl. elucidated for which the theor. structure was determined by homol. modeling using 2UVC as template and the structure was validated and refined by SAVS and MODELLER. The generated 3D structure of ATP7B protein was solvated at 310k and energy minimized using Gromacs. Similarly, 2D structures of several diuretic compounds were retrieved, refined and energy minimized using Arguslab software. The diuretic compounds were then subjected to analyze their adsorption, distribution, metabolism, excretion and their toxicity properties. This anal. was done using the online server PREADME/TOX. The protein-ligand interactions between the ATP7B protein and the diuretic compounds were analyzed using Autodock – PyRx and the docking models were visualized and analyzed by PyMol. Based on the output of the docking models and the binding energies the best lead compound was determined which can be used for fighting against the Wilson disease.

Journal of Computational Methods in Molecular Design published new progress about Asteraceae. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Quality Control of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem